On 2014 Jan 08, Tom Kindlon commented:

Numerous exercise abnormalities been found in Chronic Fatigue Syndrome (CFS)

One curious omission from this interesting review[1] is Chronic Fatigue Syndrome (CFS), which is also sometimes known as Myalgic Encephalomyelitis (ME). An abnormal response to physical activity is an essential part of widely used ME/CFS clinical criteria for adults[2] and children[3]. The most frequently used research criteria for CFS [4] require that patients, along with suffering from chronic debilitating fatigue lasting at least 6 months, have at least 4 out of a list of 8 symptoms, one of which is “postexertional malaise lasting more than 24 hours.”

There is a growing body of research on abnormal responses to exercise in CFS. A recent review[5] covers the issue in a fairly comprehensive manner - here's a summary: “Exertion induces post-exertional malaise with a decreased physical performance/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, "fatigue", and weakness, and a long lasting "recovery" time. This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis.”

High rates of adverse reactions to graded exercise programs have been reported in patients with CFS – sometimes 50% or greater[6].

CFS remains a fairly poorly understood condition. There is increasing evidence that CFS is heterogeneous and this heterogeneity could be of relevance to therapeutic programs involving exercise [7,8]. Those interested in researching abnormal responses to physical activity, including dysregulated inflammatory responses, could find much of interest if they chose to study CFS.

References:

1) Cooper DM, Radom-Aizik S, Schwindt C, Zaldivar F Jr. Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity. J Appl Physiol. 2007 Aug;103(2):700-9. Epub 2007 May 10.

2) Carruthers BM, Jain AK, De Meirleir KL, Petersn DL, Klimas MD, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, van de Sande MI (2003). "Myalgic encephalomyelitis.chronic fatigue syndrome: Clinical working definition, diagnostic and treatment protocols". Journal of Chronic Fatigue Syndrome 11 (1): 7-36.

3) Jason LA, Porter N, Shelleby E, Bell DS, Lapp CW, Rowe K, & De Meirleir K. (2008). A case definition for children with Myalgic Encephalomyelitis/ chronic fatigue syndrome. Clinical Medicine: Pediatrics, 1, 53-57.

4) Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9.

5) Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro Endocrinol Lett. 2009;30(3):284-99.

6) Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too soon to dismiss reports of adverse reactions. J Rehabil Med. 2010 Feb;42(2):184; author reply 184-6.

7) Jason LA, Corradi K, Torres-Harding S, Taylor RR, & King C. Chronic fatigue syndrome: The need for subtypes. Neuropsychology Review 2005, 15, 29-58.

8) Kindlon T. Stratification using biological factors should be performed in more CFS studies. Psychol Med. 2010 Feb;40(2):352. Epub 2009 Oct 12.

On 2014 Aug 31, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/08/28/cancer-researcher-has-correction-upgraded-to-retraction/ It's the second retraction for the last author: http://retractionwatch.com/2014/08/28/cancer-researcher-has-correction-upgraded-to-retraction/

On 2015 Jun 23, Prof.Dr.Jogenananda Pramanik commented:

Delayed diagnosis of MDR-TB and TB with co-infection of HIV – A major concern!

Tuberculosis (TB) is emerging as an dreaded communicable disease in Malaysia, with the death rate even higher than that of dengue (Ministry of Health, Malay Mail, 2014). Besides being a deadly disease, TB is also an expensive disease which is adding additional economic burden to the health system of the country. Delayed diagnosis of tuberculosis (TB) may lead to an increased period of infectivity in the community, a delay in treatment and a severe form of the disease like MDR-TB and TB with HIV co-infection.(1-7) We appreciate the insightful attempts of Chang CT1, Esterman A.(1) in analyzing the delay in diagnosis of tuberculosis in two perspectives: (A) period between the onset of TB symptoms to any first medical consultation (patients' delay); and (B) period between the first medical consultation to the diagnosis of TB (diagnosis delay). Moreover, we would like to emphasize that there is a need to reduce the time lag between the first inoculations of patient’s sample in solid or liquid culture media till appearance of macroscopically detectable AFB colonies. One of the priorities in the control of tuberculosis is to cure patients with the disease, given that the most effective way to prevent transmission and avoid the appearance of drug-resistant strains is to detect cases of tuberculosis early and treat them appropriately. As a routine practice, all patients suspected of having PTB should submit at least two sputum specimens for microscopic examination in a quality-assured laboratory. These techniques while remaining an important baseline modality of investigations currently, they lack the desired sensitivity or are time consuming. Hence, Nucleic Acid Amplification Tests for the detection of Mycobacterium tuberculosis are useful tools for rapid diagnosis of TB, both pulmonary and extra-pulmonary. These tests are also useful for the rapid screening of patients suspected of MDR-TB. Nucleic Acid Amplification Tests (NAAT) provide rapid results within 24 - 48 hours and has greater PPV (>95%) with AFB smear positive specimens. They have the ability to confirm rapidly the presence of Mycobacterium in 50 - 80% AFB smear negative, culture positive specimens. However, Molecular assays may supplement but cannot replace conventional methods for culture and sensitivity. Moreover their high cost and requirement for sophisticated laboratory infrastructure limit their use in routine diagnosis. Laboratories with advanced infrastructure are limited in most of the peripheral diagnostic laboratories in Malaysia(6-7).

To balance the lack of sophisticated laboratory infrastructure for performing TB identification and drug sensitivity tests to exclude MDR-TB cases with speed and accuracy, there is an urgent need of inexpensive, non-invasive, robust diagnostic and culture sensitivity test. To achieve this goal an attempt was made to incorporate thyroxine hormone in solid and liquid media for culture of AFB in vitro (8-12) Presently, we planned to evaluate the effectiveness of this thyroxine supplemented culture media for culture of AFB from clinical samples in vitro and also to standardize use of this method in comparison to routine AFB culture procedure. This study may prove to be a useful technique for rapid culture isolation of AFB in vitro.

References:

1.Chang CT1, Esterman A.Diagnostic delay among pulmonary tuberculosis patients in Sarawak, Malaysia: a cross-sectional study. Rural Remote Health. 2007 Apr-Jun;7(2):667. Epub 2007 May 11. 2. Alison Rodger, Shabbar Jaffar, Stuar Paynter et al., Delay in the diagnosis of pulmonary tuberculosis, London, 1998-2000: analysis of surveillance data: BMJ 2003; 326 doi: http://dx.doi.org/10.1136/bmj.326.7395.909 (Published 26 April 2003)<br> 3. Zahar JR, Azoulay E, Klement E et al., Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure. Intensive Care Med 2001; 27: 513–520 4. Wares D.. Delay in diagnosis of tuberculosis: of remaining concern in England and Wales. J Public Health Med 1999; 21: 355–356 5. Aldhubhani AH1, lzham MI, Pazilah I, Anaam MS (2013)Effect of delay in diagnosis on the rate of tuberculosis among close contacts of tuberculosis patients. East Mediterr Health J. 2013 Oct;19(10):837-42. 6. Ying Li1†, John Ehiri2†, Shenglan Tang et al., 3(2013)Research article Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis:BMC Medicine 2013, 11:156 doi:10.1186/1741-7015-11-156 7. Timothy William123, Uma Parameswaran12, Wai Khew Lee4 et al., Pulmonary tuberculosis in outpatients in Sabah, Malaysia: advanced disease but low incidence of HIV co-infection: BMC Infectious Diseases 2015, 15:32 doi:10.1186/s12879-015-0758-6 8. Pramanik J, Lodam AN, Reddy MVR, Narang P and Harinath BC. Increased yield of excretory-secretory antigen with thyroxine supplementation in in vitro culture of tubercle bacilli. Ind. J. tub. 1997; 44: 185-190. 9. Pramanik J, Lodam AN, Badole CM, Reddy MVR, Patond KR and Harinath BC. Detection of tubercular antibody and antigen in sera of bone and joint tuberculosis. Ind. J. Clin. Biochem. 2000; 15 (1): 22–28. 10. Lodam AN, Pramanik J, Reddy MVR and Harinath BC. Diagnostic potential of fractionated Mycobacterium tuberculosis H37Ra excretory-secretory (EST-DE1) antigen in pulmonary tuberculosis. Ind. J. Clin. Biochem. 1997; 12 (1): 71-77. 11. Pramanik.J. BMJ.2003.http://www.bmj.com/rapid-response/2011/10/30/delays-diagnosis-tuberculosislet-us-use-thyroxine-supplemented-culture-med: Delays in diagnosis of tuberculosis? Let us use thyroxin supplemented culture medium for early lab-diagnosis. 12. Pramanik.J. BMJ: 2004.http://www.bmj.com/rapid-response/2011/10/30/early-diagnosis-tuberculosis-reported-third-world-country Early diagnosis of tuberculosis-reported from third world country:A research letter from India.

On 2014 Apr 01, Christopher Southan commented:

This is Open Access with full text in the Transactions link. Note also the approaches outlined were used in a 2013 paper on the evolutionary history of BACE1 and BACE2 and their substrates http://www.ncbi.nlm.nih.gov/pubmed/24381583

On 2014 Jun 25, Chandra Boosani commented:

Many articles from this journal are not found on their website including this one.

On 2016 May 24, Daniel Schwartz commented:

Calculate the Alvarado score online or using a mobile app http://qxmd.com/calculate/calculator_269/alvarado-score-for-acute-appendicitis

Conflict of interest: Medical Director, QxMD

On 2014 Nov 23, Harri Hemila commented:

A comment is available at: http://hdl.handle.net/10250/8280

On 2014 Jan 11, Brett Snodgrass commented:

Dear Authors,

Thank you for the excellent article. Please provide your kind attention to the distinction between the Thebesian veins and the vessels of Wearn.

1. http://bit.ly/JTWearn

2. http://bit.ly/vasaThebesii

3. http://bit.ly/ThebesianByPratt

4. http://www.ncbi.nlm.nih.gov/pubmed/22704295

The vessels described are probably better described as vessels of Wearn as they are (1) not Thebesian veins*, (2) not studied by Thebesius, and (3) they were described by Wearn et al.

Given that there was the prior intervention of stent placement, it may be possible that these connections are "true fistula" in that they are not normally present. Perhaps angiogenesis formed the fine connections identified by injection of contrast material into the left coronary artery.

Another hypothesis is that the procedure caused tissue injury which resulted in vasodilation and increased prominence of the normally present vessels of Wearn.

My opinion is that accurate anatomic terminology is a basic principle underlying good medical science, and I ask others to consider whether the aforementioned definitions are appropriate. If this comment is not helpful, please let me know how it might be improved.

Comments and suggestions are welcome.

Thank you very much.

On 2014 Jan 08, Tom Kindlon commented:

Does the use of the "Role emotional" subscale of the SF-36 help with sensitivity and specificity rates? Can we find out the prevalence rate if this subscale hadn't been used?

It is to be welcomed that attempts are being made to operationalize the CDC (94) CFS criteria [1], enabling easier comparisons between studies and making it easier for researchers to try to replicate findings. So, for example, having some sort of numerical value on a symptom so that one can say whether a symptom is present or not in a patient seems to be a good idea.

However, if one is aiming to do this, it would seem preferable to choose methods that have good sensitivity and specificity rates for the condition in question. And it's questionnable whether the methods used in this study have good sensitivity and specificity.

The authors claim that they "used stringent (i.e., <= 25th percentile population norms on any of the 4 SF-36 scales) to define severe functional impairment". One of the SF-36 subscales in question is the "role emotional" subscale. This involves questions such as: "During the past 4 weeks, have you accomplished less than you would like as a result of any emotional problems?" Does this really capture whether there has been a "substantial reduction in previous levels of .. personal activities"? [Full quote from paper[1]: 1) clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is of new or definite onset [has not been lifelong]; is not the result of ongoing exertion; is not substantially alleviated by rest; and results in substantial reduction in previous levels of occupational, educational, social, or personal activities] Perhaps the other three sub-scales cover this? For example, a better measure of whether the condition is having an effect on somebody's "personal activities" might be got from using the physical functioning subscales which asks about ability to walk distances, bath or dress oneself, etc. If this score is low, it's likely one's ability to do "personal activities" has been impaired.

Baraniuk[2] used the CDC '94 not operationalized in the same way as this study and found that CFS patients scores did have lower scores on some of the SF-36 subscales - but role emotional was one of the ones that weren't different (the others that weren't different were mental health and general health change). Would it be possible for the authors to calculate the all important overall prevalence rate if those people who only satisfied this part of the "functional impairment" criteria are excluded? This data would be be useful not just in the US but around the world - countries around the world have been depending on the US to undertake such large scale (and expensive) studies on CFS.

Even before the recent broadening of the criteria, it had been felt by some that the CDC '94 criteria lacked specificity. For example, Kennedy[3] investigated "patients with self-reported symptoms which developed sporadically (sCFS, n=48); after Gulf War service (GW, n=24); and following exposure to organophosphate insecticides (OP, n=25)" all of whom fulfilled the CDC '94 criteria[1]. Based on their findings, they concluded that "differences in simple, easily performed clinical outcome measurements can be observed between groups of patients, all of whom fulfill the CDC-1994 criteria for CFS. It is likely that their response to treatment may also vary. The specificity of the CFS case definition should be improved to define more homogeneous groups of patients for the purposes of treatment and research."

Perhaps what is required is a totally new set of criteria?

References:

[1] Fukuda, K., Straus, S.E., Hickie, I., Sharpe, M.C., Dobbins, J.G., & Komaroff, A. (1994). The chronic fatigue syndrome: A comprehensive approach to its definition and study. Annals of Internal Medicine, 121 (12):953-959. http://www.annals.org/cgi/content/full/121/12/953

[2] James N Baraniuk, Begona Casado, Hilda Maibach, Daniel J Clauw, Lewis K Pannell and Sonja Hess S. A chronic fatigue syndrome - related proteome in human cerebrospinal fluid. BMC Neurology 2005, 5:22 doi:10.1186/1471-2377-5-22http://www.biomedcentral.com/1471-2377/5/22

[3] Kennedy G, Abbot NC, Spence V.A, Underwood C, Belch JJF. The specificity of the CDC-1994 criteria for chronic fatigue syndrome: comparison of health status in three groups of patients who fulfil the criteria. Ann Epidemiol 2004; 14: 95–100.

On 2014 Jan 08, Tom Kindlon commented:

Questioning the use of the Role Emotional (RE) subscale of the SF-36 questionnaire in the diagnosis of CFS

As background to my previous comment, I thought I'd point out that if people would like to see what makes up the Role Emotional (RE) subscale of the SF-36, a copy of a sample SF-36 questionnaire can be seen at: https://clinicalresearch.ccf.org/fsgs/docs/WEBdocs/Form36.pdf .It is question 14 i.e. 3 questions with only yes or no as possible answers.

The cut off point used in the current study is less than or equal to a score of 66 [1], so two "yes" answers (out of the three questions) is the cut off point for functional impairment.

References:

[1] Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study. William C Reeves, Dieter Wagner, Rosane Nisenbaum, James F Jones, Brian Gurbaxani, Laura Solomon, Dimitris A Papanicolaou, Elizabeth R Unger, Suzanne D Vernon and Christine Heim BMC Medicine 2005, 3:19 doi:10.1186/1741-7015-3-19 http://www.biomedcentral.com/1741-7015/3/19

On 2014 Jan 06, Tom Kindlon commented:

Caution required when extrapolating prevalence rates to the full population

This editorial [1] says, with regard to the CDC study[2]: "The CDC has now repeated and extended the Wichita study in Georgia, and found a prevalence of between six and ten times greater, with 2.5% of the population suffering from CFS. If this prevalence was both accurate and representative of the USA as a whole, this would suggest that some 7.5 million Americans were sufferers, compared to the previous estimates of 0.7 to 1.2 million."

Before the 7.5 million figure is quoted, it might be useful to point out that the figure makes a number of assumptions, including that the prevalence rate for those under 18 and over 60 would be similar. However previous studies have suggested this is unlikely to be the case, with prevalence rates for young children in particular being much lower.

The round figure of 7.5 million would be equivalent to a population of 295,275,591. Using this data the population estimate for 2005 was 296,410,404 (i.e. a similar figure). Using the same data: The population under 18 years was 73,469,580, the population over 60 was 49,791,976 and population aged 18-60 was 173,148,444.

For a population of those aged over 18 and under 60 of this size, a back of the envelope calculation for CFS prevalence using the prevalence rate of 2.64%[2] would give: (173,148,444*0.0264)= 4,397,971.

References:

[1] How common is chronic fatigue syndrome; how long is a piece of string? Peter D White Population Health Metrics 2007, 5:6 doi:10.1186/1478-7954-5-6

[2] Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural GeorgiaWilliam C Reeves , James F Jones , Elizabeth Maloney , Christine Heim , David C Hoaglin , Roumiana S Boneva , Marjorie Morrissey and Rebecca Devlin. Population Health Metrics 2007, 5:5 doi:10.1186/1478-7954-5-5

On 2014 Jan 06, Tom Kindlon commented:

Reference to obesity a red herring?

In his editorial, Prof White says: "Georgia may not be representative of the USA as a whole. For instance, we do not know the body mass index (BMI) of the Georgian sample. The Wichita sample of CFS cases contained 43% of subjects with a BMI of 30 or over, representing significant obesity [9]. This compares with 20% in the USA as a whole [13]. Since obesity is associated with fatigue [14], a similar proportion in Georgia might inflate the prevalence of CFS."

Firstly, just because obesity can cause fatigue is quite a different from obesity causing the syndrome CFS. Using this logic, perhaps we should be saying that prevalence studies on any condition which can involve disabling fatigue (for example multiple sclerosis) may be questionable if there is a higher rate of obesity within the sample population. It is important to consider cause and effect i.e. just because people with a condition may be more obese when they are sampled years after having the illness is not the same as saying they were more obese before getting the illness and this caused them to develop the condition.

Also the Wichita study[1], to which Prof. White refers, found a relatively low prevalence rate, of 0.235%, for CFS compared to other random-number studies including the one under review. So it seems curious to refer to this study to try to justify a hypothesis that the obesity rate in the Georgia study artificially increased the prevalence rate.

References:

[1] Prevalence and Incidence of Chronic Fatigue Syndrome in Wichita, Kansas Michele Reyes, PhD; Rosane Nisenbaum, PhD; David C. Hoaglin, PhD; Elizabeth R. Unger, PhD, MD; Carol Emmons, PhD; Bonnie Randall, MCP; John A. Stewart, MD; Susan Abbey, MD; James F. Jones, MD; Nelson Gantz, MD; Sarah Minden, MD; William C. Reeves, MD, MSPH Arch Intern Med. 2003;163:1530-1536.

On 2014 Jan 06, Tom Kindlon commented:

Obesity and arbitrary criteria

Firstly, I thought I would clarify that I did not make my point about obesity rates based simply on the one study, the Wichita study[1]: the Chicago Study[2] found a prevalence of 0.422% using the same (or very similar) methodology and method of operationalizing the criteria as the Wichita study, producing a much higher score than the 0.235% score found in the Wichita study.

However this correspondence has caused to me to reflect on the issue: I still remain to be convinced that because the residents of Wichita were more obese than the general population, the prevalence figure for CFS (as defined then) of 0.235% was artificially increased; however perhaps if the new broadened criteria lack sensitivity and specificity, the figures in the latest studies could be artificially inflated because of a higher background obesity rate?

I think there is an important issue of a lack of sensitivity and specificity with the new method of operationalizing the criteria. As Peter White says, the current criteria are "arbitrary". Whether they are being used by a "jobbing physician", an epidemiologist or a researcher, one of the aims of criteria should be that they have good sensitivity and specificity rates. Perhaps a direction for discourse and research in the future should be trying to arrive at CFS criteria that reach that aim?

If necessary, having different criteria for different circumstances: for example, have one set of criteria when looking for expensive biological work but perhaps less stringent criteria for use in some clinical settings?

References:

[1] Prevalence and Incidence of Chronic Fatigue Syndrome in Wichita, Kansas Michele Reyes, PhD; Rosane Nisenbaum, PhD; David C. Hoaglin, PhD; Elizabeth R. Unger, PhD, MD; Carol Emmons, PhD; Bonnie Randall, MCP; John A. Stewart, MD; Susan Abbey, MD; James F. Jones, MD; Nelson Gantz, MD; Sarah Minden, MD; William C. Reeves, MD, MSPH Arch Intern Med. 2003;163:1530-1536.

[2]. Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S: A community-based study of chronic fatigue syndrome. Arch Int Med 1999, 159:2129-2137.

On 2014 Jan 06, Tom Kindlon commented:

Caution required when making numerical comparisons between Wessely (1997) and the current study

In his editorial[1], Prof. White says: "Comorbid psychiatric conditions may have inflated the prevalence. A previous study found an equally high point prevalence of CFS (2.6%), by surveying United Kingdom primary care patients [10]. However, when those patients who also had a comorbid psychiatric disorder were excluded, the prevalence fell to 0.5%."

Reference to this paper[2] is also made in the editorial's concluding paragraph and in the accompanying Reeves paper[3].

A close inspection of table 2 of the referenced paper[2] reveals some strange figures (with regard to the estimates for the CDC '94 criteria mentioned above): (i) The Oxford criteria for CFS were found to have a lower prevalence, of 2.2%. Given that the CDC 94 criteria would be seen as more restrictive than the Oxford criteria (e.g. requiring symptoms as well as fatigue lasting six months), this suggests an error with one or both of the figures? (ii) the mean and 95% confidence intervals given for the prevalence rates without co-morbid psychological disorders for CFS (CDC 94) are given as 0.5 (0.1, 0.3) which makes no sense (the confidence intervals should be above and below the mean).

So these two observations mean that I'm not sure how much faith should be placed with some of the figures given in that study.

The methodology of the Wessely study was also different, using attendance at primary care physicians to screen for patients, which could lead to skewed data. The random number methodology in the Reeves study seems stronger.

It should also be remembered that the authors of the Reeves study[3] did exclude many patients with psychological disorders before giving the diagnosis of CFS. So even if one accepts the curious data presented in Table 2 in Wessely et al[2], it seems unlikely we can extrapolate from the drop in the figures found the Wessely study to produce a similar drop in figures found in the current study[3].

References:

[1] How common is chronic fatigue syndrome; how long is a piece of string? Peter D White Population Health Metrics 2007, 5:6 doi:10.1186/1478-7954-5-6

[2] Wessely S, Chalder T, Hirsch S, Wallace P, Wright D. The prevalence and morbidity of chronic fatigue and chronic fatigue syndrome: a prospective primary care study. Am J Pub Health 1997, 87:1449-1455.Available online at:http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1380968

[3] Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. William C Reeves, James F Jones, Elizabeth Maloney, Christine Heim, David C Hoaglin, Roumiana S Boneva , Marjorie Morrissey and Rebecca Devlin. Population Health Metrics 2007, 5:5 doi:10.1186/1478-7954-5-5

On 2015 May 07, Jeff Kiefer commented:

DAVID is continuously being used as evidenced by its numerous citations in current biomedical literature http://bit.ly/1FS1JgT. However, the data resources used by DAVID appear to not have been updated since 2009 http://david.abcc.ncifcrf.gov/helps/update.html. The fact that DAVID has not been updated going on 5 years calls into question the current utility of using this tool.

On 2016 May 26, Jeff Kiefer commented:

It looks like DAVID has been updated May 2016 https://david-d.ncifcrf.gov/content.jsp?file=release.html.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2013 Oct 27, Tom Kindlon commented:

"Recovery" (from fatigue) does not necessarily mean recovery from CFS (in terms, for example, of activity levels)

In this paper, some variant of the word "recovered" is used 12 times, generally to describe some of the Chronic Fatigue Syndrome (CFS) patients who had taken part in a cognitive behaviour therapy (CBT) trial for CFS[1].

Actometer data from this study has subsequently been released[2]. This paper reported that CBT did not cause an increase in physical activity at the end of treatment. Before CBT, the patients did a mean 67.4 units of activity (standard deviation(SD): 21.8); following CBT, patients did 68.8 units of activity (SD: 25.2). The authors report that a previous study [3] found healthy controls had a mean Actometer score of 91 (S.D.=25). There was also no increase in activity levels in two other CBT trials examined[4,5].

The authors[2] also found that in the three CBT studies, changes in physical activity were not related to changes in fatigue. So "recovery from fatigue" does not necessarily mean recovery from CFS in terms of achieving normal activity levels.

In another Dutch CBT study[6], 37% of patients were said to be recovered from fatigue, where recovery was defined as no longer scoring on any of the 3 negative factors of the Fatigue Quality List (FQL). However when low scores on other questionnaires were also required to fulfil "full recovery", only 23% of the sample were said to be in "full recovery". Note that only subjective measures were used in that definition of full recovery - a return to a normal level of activity, as measured by an actometer, was not required.

Incidentally, a paper was subsequently published which also examined language used to describe fatigue by CFS patients and healthy controls[7]. It is slightly different as phrases rather than adjectives were used to describe the fatigue e.g. "Mentally tired after the slightest effort", "Lack the energy to talk to anyone", etc. Factor analyses revealed a five-factor structure for participants with ME/CFS but only a one-factor solution for the control group. The five factors for fatigue in ME/CFS participants were described as: "Post-Exertional", "Wired", "Brain-Fog", "Energy" and "Flu-Like".

References:

[1] Prins JB, Bleijenberg G, Bazelmans E, Elving L, de Boo Th, Severens JL, van der Wilt GJ, Spinhoven Ph, van der Meer JWM: Cognitive behaviour therapy for chronic fatigue syndrome: A multicentre randomised controlled trial. Lancet 2001, 357:841-847.

[2] Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G. How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity. Psychol Med. 2010 Jan 5:1 -7. [Epub ahead of print]

[3] van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW, Bleijenberg G (2000). Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. Journal of Psychosomatic Research 49, 373–379.

[4] Knoop H, van der Meer JW, Bleijenberg G (2008). Guided self-instructions for people with chronic fatigue syndrome: randomised controlled trial. British Journal of Psychiatry 193, 340-341.

[5] Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G (2005). Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. British Medical Journal 330. Published online : 7 December 2004. doi :10.1136/bmj.38301.587106.63.

[6] Knoop H, Bleijenberg G, Gielissen MFM, Van der Meer JWM, White PD: Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 2007, 76:171-176.

[7] Jason, L.A., Jessen, T., Porter, N., Boulton, A., Njoku, M.G., & Friedberg, F. Examining types of fatigue among individuals with ME/CFS. Disability Studies Quarterly, 2009, 29, 3. Full text at: http://www.dsq-sds.org/article/view/938/1113

On 2015 Aug 02, Jorge H Ramírez commented:

Any reason not to retract this publication?

http://chaoticpharmacology.com/?s=quetiapine

On 2015 Aug 02, Jorge H Ramírez commented:

Any reason not to retract this publication?

http://chaoticpharmacology.com/?s=quetiapine

On 2015 Jul 18, Jan Tunér commented:

A problem with most studies trying to treat tinnitus with laser light is the lack of proper diagnosis of the patients. Quite a few of these have a somatosensory background (the problem is basicly muscluar). Irradiation into the ear will then have no effect.

References: Bjorne A, Agerberg G. Reduction in sick leave and costs to society of patients with Ménière´s disease after treatment of temporomandibular and cervical spine disorders: A controlled 6-year cost-benefit study. Cranio. 2003; 21 (2): 136-143. Bernhardt O, Gesch D, Schwahn C, Bitter K et al. Signs of temporomandibular disorders in tinnitus patients and in a population-based group of volunteers: results of the Study of Health in Pomerania. J Oral Rehabil. 2004; 31 (4): 311-319. Levine RA, Abel M, Cheng H. CNS somatosensory-auditory interactions elicit or modulate tinnitus. Exp Brain Res. 2003; 153 (4): 643-648. Tullberg M, Ernberg M. Long-term effect on tinnitus by treatment of temporomandibular disorders: a two-year follow-up by questionnaire. Acta Odontol Scand. 2006; 64 (2): 89- 96.

On 2015 Dec 18, Ahmed Adeel commented:

The figures given for PCR-corrected treatment failure with AS/SP do not seem to be consistent in the Abstract and in the Results sections. This needs to be clarified.

ABSTRACT:"However, when PCR-corrected, 6.5% (5/77) of patients treated with AS/SP maintained parasites from their primary infection."

RESULTS: "In the AS/SP group, five patients (41.7 %) showed different allelic forms and were classified as reinfection, while seven (58.3) retained the same allelic pattern and were classified as recrudescence of parasites."

On 2016 Sep 24, Morten Oksvold commented:

There is a response to this reply by Kaufmann T et al., which is well worth to read. This response was published in the same number of Cell, but unfortunately hidden as a "linked article" and not searchable in PubMed.

Title of the response: "Does Bid Play a Role in the DNA Damage Response?".

Link: http://www.cell.com/cell/fulltext/S0092-8674(07)00842-2

On 2016 Aug 21, Morten Oksvold commented:

Please note that this article represents one of eleven publications which were found to contain false data, after an investigation led by ORI in 2015:

https://ori.hhs.gov/content/case-summary-dasmahapatra-girija

This article should therefor not be cited.

On 2016 Oct 25, FREDERICK DOMANN commented:

U87MG cells are not what they used to be !!

The U87MG cells used in this study were obtained from ATCC. A recent (2016) DNA sequencing study by Bengt Westermark revealed that these cells were likely contaminated at some point as their genetic signature did not match the parental tumor of their origin. Below are links to the story and an interview with Dr. Westermark.

http://www.igp.uu.se/research/neuro-oncology/bengt-westermark/

http://www.the-scientist.com/?articles.view/articleNo/46929/title/Popular-Tumor-Cell-Line-Contaminated/

http://stm.sciencemag.org/content/8/354/354re3

On 2015 Jan 03, Harri Hemila commented:

The review by Caruso TJ, 2007 is misleading about the effect of zinc on the common cold

In their systematic review, Caruso TJ, 2007 identified 14 zinc trials. They used the quality scoring approach so that for the identified trials they gave 1 point for each of 11 quality items when the requirements were satisfied. In 2 tables and 1 figure, Caruso et al. described the distribution of quality scores and the individual quality features of the trials.

Caruso TJ, 2007 considered that only studies with the full 11 points were valid: “Four studies met all 11 criteria. Three of these studies reported no therapeutic effect from zinc lozenge or nasal spray. One study reported positive results from zinc nasal spray.” On the basis of this 3 vs. 1 comparison (so called “vote counting”) Caruso et al. concluded that “the therapeutic effectiveness of zinc lozenges has yet to be established.” They proposed that the positive findings for zinc could be explained by methodological faults in the trials.

The approach to evaluate the quality of trials by a set of explicit criteria was initiated by Thomas Chalmers in the 1980s, see Chalmers TC, 1981. Thereafter dozens of quality scales have been developed. However, the approach was not successful and indeed it is discouraged eg in the Cochrane Handbook (sec 8.3.3; Jan 2015), which states that:

“The use of [quality] scales for assessing quality or risk of bias is explicitly discouraged in Cochrane reviews. While the approach offers appealing simplicity, it is not supported by empirical evidence. Calculating a summary score inevitably involves assigning ‘weights’ to different items in the scale, and it is difficult to justify the weights assigned. Furthermore, scales have been shown to be unreliable assessments of validity and they are less likely to be transparent to users of the review. It is preferable to use simple approaches for assessing validity that can be fully reported (i.e. how each trial was rated on each criterion).”

One major problem of quality scoring is the focus on reporting in contrast to the scientific quality of the trial. For example, Caruso et al. gave 1 point if there was “measurement of dropout rate” in the trial. This means that a trial might report a high dropout rate, which means low scientific quality, yet the trial would get 1 point from Caruso et al., because the high dropout rate was reported explicitly. Caruso et al. also gave 1 point for “sample size calculation” which is important when a trial is planned, because it can show that the planned trial is too small. However, this is irrelevant after the trial is published, because then the confidence interval reveals the accuracy of the result. Most of Caruso et al.’s remaining 9 quality items have similar problems, see detailed comments in a separate document.

Although it is important to consider the methods of a trial, there are no simple criteria that decide whether a trial is reliable or not. For example, in a meta-analysis of 276 RCTs, Balk EM, 2002 concluded that “double blinding and allocation concealment, two quality measures that are frequently used in meta-analyses, were not associated with the treatment effect” meaning that valid estimates of treatment effect can be reached without them. Furthermore, Glasziou P, 2007 pointed out that in some cases firm conclusions of treatment benefits can be drawn even without any control groups.

Caruso TJ, 2007 did not present any numerical results of the trials, simply classifying them as positive (statistically significant effect) or negative (no statistically significant effect), even though such a “vote counting” approach is strongly discouraged eg by the Cochrane Handbook (sec 9.4.11; Jan 2015), which states that:

“Two problems can occur with vote counting, which suggest that it should be avoided whenever possible. Firstly, problems occur if subjective decisions or statistical significance are used to define ‘positive’ and ‘negative’ studies… Secondly, vote counting takes no account of the differential weights given to each study.”

Vote counting can lead to false negative conclusions because it ignores the quantitative findings. For example, a large number of placebo-controlled trials on vitamin C and the common cold found non-significant effects on common cold duration, but the results consistently favoured vitamin C. Quantitative pooling of the results shows a statistically highly significant benefit from the vitamin, see Hemilä H, 2013 and Douglas RM, 2005. Vote counting would simply look at the proportion of studies with P<0.05, ignoring the actual mean and SD values, thereby vote counting would lead to false negative conclusions about the effects of vitamin C.

Caruso TJ, 2007 did not discuss the possibility that the dose of zinc or the lozenge composition might have an effect on trial results, nor did they refer to any of the numerous papers that discussed the possibility that the level of free zinc ion might be an important variable in zinc lozenge trials by Godfrey JC, 1988, Eby GA, 1988, Martin RB, 1988, Eby GA, 1997, Eby GA, 2001, Eby GA, 2004.

Although Caruso et al. focused on the methodological features that are mostly irrelevant to trial validity, they stated that a “common deficiency [in the zinc trials] was proof of blinding which was lacking in 7 studies. The placebo effect in the treatment of colds was first shown >70 years ago and has since been demonstrated in subsequent studies.” As a justification for this statement, Caruso et al. refer to the Thomas Chalmers review (1975), Chalmers TC, 1975, and the Thomas Karlowski and Thomas Chalmers trial (1975), Karlowski TR, 1975.

However, when Caruso TJ, 2007 wrote those sentences in their zinc review, they had already been informed that those 2 papers were erroneous, because I had pointed out problems with those 2 papers in a criticism of a previous Caruso TJ, 2005 review on echinacea and the common cold. In a letter-to-the-editor, I wrote that: “The Chalmers review (1975) was shown to be erroneous a decade ago; it has data inconsistent with the original study publications, errors in calculations, and other problems”, see the letter Hemilä H, 2005.

The Karlowski TR, 1975 trial found statistically significant benefits of vitamin C against the common cold, yet paradoxically Karlowski et al. concluded that “the effects [of vitamin C] demonstrated might be explained equally well by a break in the double blind.” My comments on the Caruso TJ, 2005 review on echinacea and the common cold briefly summarized the problems of the Karlowski trial (1975) as follows: “the [Karlowski] subgroup analysis excluded 105 episodes of common cold (42% of all episodes of cold), even though the 2 subgroups were presented as if they were complementary. There are numerous additional problems with Karlowski’s placebo effect explanation, and, consequently, it is not a valid interpretation to the study results.” see the letter Hemilä H, 2005.

My letter-to-the-editor, Hemilä H, 2005 referred to studies that documented in detail the problems of the Chalmers review (1975) in Hemilä H, 1995, and the problems of the Karlowski trial (1975) in Hemilä H, 1996. Thus, in their zinc and the common cold review in 2007, Caruso TJ, 2007 still referred to those old erroneous papers by Chalmers and Karlowski although they were aware of my criticisms, since they had read and responded to my letter-to-the-editor.

See specific comments on the quality items of the Caruso et al. 11 point scoring system in a separate document.

Another systematic review on zinc lozenges concluded that there is strong evidence that high dose zinc acetate lozenges shorten the duration of colds by 42%, see Hemilä H, 2011.

On 2015 Aug 27, Bernard Friedenson commented:

For more recent information please see the article entitled "Mutations in Breast Cancer Exome Sequences Predict Susceptibility to Infection and Converge on the Same Signaling Pathways" This article is available at http://la-press.com/article.php?article_id=5029

On 2015 Jun 29, Torsten Seemann commented:

The software can be obtained from here: http://www.ieu.uzh.ch/wagner/software/IScan/index.html

On 2017 May 31, David Nunan commented:

Readers may not be aware of concerns with duplicate data in this paper and another paper (Parrinello G, 2009) by the same group published in the Journal of Cardiac Failure in 2009. Both these papers were also included in a 2012 systematic review published in BMJ Open Heart which was subsequently retracted. A notice of concern was raised with the Journal of Cardiac Failure paper. No such notice has been made for this paper and neither individual papers have been retracted.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2017 Apr 12, Konstantinos Fountoulakis commented:

This is a paper on the efficacy of adjunctive aripiprazole on the reduction of prolactin levels in patients with antipsychotic-induced hyperprolactinaemia (1). In that particular study, adding aripiprazole in stabilized patients with schizophrenia already under haloperidol (mean dosage around 20 mg daily) was not accompanied by an increase in side-effects or destabilization of the patients. However, the unusually low Simpson Angus scale scores for haloperidol treated patients, implies the use of anticholinergics; this could have masked an increase in EPS. If on the contrary no anticholinergics were used, then this could be a special population of patients. The Simpson Angus scale does not rate akathisia, (a major problem with aripiprazole) thus it is rather inadequate for that study. A crude explanation of the lowering of prolactin levels could be that adding aripiprazole reduced the overall antidopaminergic effect of haloperidol but this could had been achieved just by lowering the haloperidol dosage. Another explanation suggests that aripiprazole as a partial dopamine agonist leads to internalization of dopamine receptors (2). However, when spared activated receptors are not available, it is unlikely that aripiprazole could exert its ‘partial agonist’ properties and manifest a more artidopaminergic effect, thus leading to more EPS (3). A preferential agonist action of aripiprazole in the pituitary implies also the presence of spare D2 receptors in the pituitary and it is in contrast with the literature (4). The only remaining explanation is that since it has been consistently shown that aripiprazole possesses a higher affinity to D2 receptors than haloperidol, it also completely replaced haloperidol on the D2 receptor. Shim et al discuss it however they do not follow it explicitly. The magnitude of this replacement should be considered to be almost complete since it has been suggested that aripiprazole is effective when >90% of D2 receptors are occupied (5). Thus it does not seem that the conclusions of Shim et al are justified. In essence what their trial showed is that it is needless to add aripiprazole; the therapist should either reduce the dosage of the original antipsychotic or switch to aripiprazole or to another appropriate agent

References

1. Shim JC, Shin JG, Kelly DL, Jung DU, Seo YS, Liu KH, Shon JH, Conley RR: Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry 2007; 164(9):1404-10
2. Laruelle M: Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 2000; 20(3):423-51
3. Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB: Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 2002; 302(1):381-9
4. Dean B, Pavey G, Scarr E, Goeringer K, Copolov DL: Measurement of dopamine D2-like receptors in postmortem CNS and pituitary: differential regional changes in schizophrenia. Life Sci 2004; 74(25):3115-31
5. Hamamura T, Harada T: Unique pharmacological profile of aripiprazole as the phasic component buster. Psychopharmacology (Berl) 2007; 191(3):741-3

On 2015 May 07, Jeff Kiefer commented:

DAVID is continuously being used as evidenced by its numerous citations in current biomedical literature http://bit.ly/1FS1JgT. However, the data resources used by DAVID appear to not have been updated since 2009 http://david.abcc.ncifcrf.gov/helps/update.html. The fact that DAVID has not been updated going on 5 years calls into question the current utility of using this tool.

On 2016 May 26, Jeff Kiefer commented:

It looks like DAVID has been updated May 2016 https://david-d.ncifcrf.gov/content.jsp?file=release.html.

On 2016 Nov 20, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2014 Feb 01, Jan Tunér commented:

The treatment time is said to be 10 minutes per patient regardless of wound size. Wound size in the laser group was in the range 4-52 cm2 (average 12 cm2). With an average output power of 4 mW and a treatment time of 600 seconds (10 minutes), an energy of 2.4 joules were emitted from the laser in each session. If the whole wound area was treated, the dose (energy density) for the smallest wounds (4 cm2) must have been 0.6 J/cm2 and for the largest wounds (52 cm2) the dose was 0.046 J/cm2. As the stated dose was 1.96 J/cm2, something seem to be wrong. Further, according the manufacturer of the laser equipment (Irradia AB, Sweden), a GaAs laser with as low power as 4 mW has never been produced and a pulse frequency of 3800 Hz is not available with any of their equipment. Neither has a GaAs laser with a beam divergence of 70 mrad (collimated) been available.

On 2013 Oct 27, Tim D. Smith commented:

This paper is a deep and friendly introduction to and comparison of decomposition methods for shape representations of cells. It is, moreover, a pleasure to read; the figures are excellent case studies in clear, evocative, and aesthetic illustration of the data they represent. The software tool described in the article has moved and is, as of this writing, available under a GPL license from Dr. Pincus' website.

On 2015 Dec 11, Harri Hemila commented:

Available at http://dx.doi.org/10.1016/0923-2508(91)90055-F

On 2017 Sep 10, Erik Gotfredsen commented:

Two ways of misspelling. "Delphinium tiantaishanense" in heading, "Delphinium tiantaishan" in abstract the correct (according to botanical litterature) is "Delphinium tianshanicum"

On 2013 Dec 29, Keizo Takao commented:

The raw data of behavioral tests, which are not described in this paper, are shown in the Mouse Phenotype Database (http://www.mouse-phenotype.org/). "ImageLD", "ImageEP", and "ImageFZ", image analysis application softwares used in this article, are now freely available from http://www.mouse-phenotype.org/software.html.

On 2016 Aug 25, thomas samaras commented:

Geneticist and statistician Francis Galton calculated the risk of being hit in combat was 33% greater for taller, heavier men. This increased risk makes sense since larger men make bigger targets. Certainly, in attacking enemy trenches, it would seem to be true. In addition, if a soldier is in a defensive position and is being attacked by three enemy soldiers, I'm sure the defender would focus on the larger of the three attackers since he would be more dangerous in hand-to-hand combat.

Sarna et al. researched Finish athletes who were in WWII. They found that tall basketball players had the highest mortality rate from combat compared to shorter athletes.

In view of the preceding, it appears that some other factors led to the study results that taller, bigger men had better survival.

On 2016 Jan 04, Wouter Hendrickx commented:

I used this great tool before but since december 2015 it seems the domain this tool is hosted on went offline ? I hope this tool will be made available elsewhere.

On 2014 Apr 01, Christopher Southan commented:

A 2009 update of this work is reported at http://www.ncbi.nlm.nih.gov/pubmed/20298516. An open text version of this article is at http://figshare.com/articles/Complementarity_between_public_and_commercial_databases_new_opportunities_in_medicinal_chemistry_informatics/979201

On 2016 Aug 23, Ben Goldacre commented:

This article has two incorrect trial registry IDs associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The first incorrect ID given is NCT00209795. We believe the correct ID, which we have found by hand searching, is NCT00209794.

The second ID given is NCT88523834. This trial ID does not appear in clinicaltrials.gov. We have contacted the corresponding author on the study to ask them for the correct trial ID on 18/08/2016, but received no reply. We have also searched manually for this trial on clinicaltrials.gov and found no matching study. We therefore believe that this trial may not have not been registered on ClinicalTrials.gov.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2014 Aug 18, Paul Brookes commented:

I did not discover the following; these comments were sent to me by an anonymous correspondent, and I agree with their assessment of the data, so am posting here using my own name even though this is not a paper I have either read, or am familiar with the field of...

There appears to be duplication of several bands in Supplemental Figure 1. Specifically, the anti-EGFP blot in Figure S1A, the anti-Myc blot in Figure S1B (rotated by 180 degrees), and the left two lanes of the anti-GFP blot in Figure S1C are all remarkably similar considering their allegedly different sample origins.

In Figure 2 of the main manuscript, there also appear to be several undisclosed splicing events. In the anti-myc blot (lower panel) of Figure 2B, enhanced contrast seems to suggest that several images were used to compile this image. Furthermore in Figure 2D, left panel, the anti-EGFP blot lower panel) contains a splicing seam in between the 1st and second lanes.

Finally, bringing the story full-circle, in the right panel of Figure 2D, the bands in the anti-GST blot (middle panel) appear to resemble those discussed above WRT Figure S1, but flipped horizontally and stretched vertically.

FYI, another paper from the same group Schwamborn JC, 2007 has also been flagged by the same person, and I have/will left a comment there too. I am reliably informed that the DFG (German equivalent of the NIH) is aware of these data problems, as are the journals involved. However more than 6 months has now passed with no actions taken.

On 2015 Jul 02, Leonid Schneider commented:

This paper has now been retracted, June 19th, 2015: http://www.jbc.org/content/290/25/15391

On 2014 Apr 10, Pedro Silva commented:

Current URL is http://homepage.ufp.pt/pedros/HCA_db/index.htm

Data may be downloaded from Figshare http://dx.doi.org/10.6084/m9.figshare.994209

On 2013 Nov 01, Dale D O Martin commented:

An updated list of new post-translationally myristoylated proteins including the anti-apoptotic protein Mcl-1 and the causative agent of Huntington Disease, Huntingtin, can be found here: http://www.ncbi.nlm.nih.gov/pubmed/21965604 Herein, we used a post-translational myristoylation assay, that was dependent on caspase cleavage, to verify previously identified substrates and to identify new post-translationally myristoylated proteins.

On 2014 Feb 07, Dale D O Martin commented:

We have since shown that caspase-cleavage of HTT releases an autophagy-inducing domain that requires its post-translational myristoylation. http://www.ncbi.nlm.nih.gov/pubmed/24459296

Videos can be seen here: http://hmg.oxfordjournals.org/content/early/2014/01/22/hmg.ddu027/suppl/DC1

On 2014 Sep 30, Dale D O Martin commented:

Post-translational myristoylation of both Bap31 and CD-IC2 have recently been confirmed endogenously in Thinon et al found here http://www.ncbi.nlm.nih.gov/pubmed/25255805

On 2014 Feb 01, Jan Tunér commented:

In this study, a 6 mW HeNe laser or a placebo HeNe laser was used to treat leg ulcers twice weekly for 12 weeks. The stated dose was 4 J/cm2. The area of the ulcers varied from 3 cm2 to 32 cm2. To achieve the stated dose, the treatment time of each session of therapy would thus have had to vary from 33 minutes to 6 hours. It is questioned that the patients really would have been treated for 6 hours. The method by which the dose was calculated is therefore questionable. No indication is given of the method of treatment. If a scanning laser with an unexpanded beam was used, the power density would have been about 0.15 W/cm2. If the beam was expanded to a diameter capable of illuminating the whole area of the ulcer at once, the power density when treating the largest ulcer would have been about 0.00019 W/cm2, which is close to the level of moonlight. Unless more parameters are accounted for, it is impossible to evaluate this study. The possibility of performing a double blind study with red light is also questionable. The authors have been reluctant to answer questions on this paper.

On 2014 Aug 24, Ivan Oransky commented:

This study has been retracted: http://retractionwatch.com/2014/07/25/paper-about-widely-touted-but-unapproved-cure-for-cancer-autism-retracted/ It's one of two recent retractions by the group: http://retractionwatch.com/2014/08/21/second-study-of-widely-touted-cancer-and-hiv-cure-retracted/

On 2015 Jul 02, Pedro Silva commented:

The code used to locate the minimum-energy-crossing points in this work is publicly available as:

Silva, Pedro (2015): Program for the computation of MECP using the Firefly Quantum Chemistry program. figshare. http://dx.doi.org/10.6084/m9.figshare.1471648

On 2016 Dec 02, Stephen Strum commented:

This is a landmark publication and should be required reading of all those caring for patients with cancer that involves bone mets. In my medical oncology practice I rarely see attention paid to bone integrity and what is called the the vicious cycle of bone resorption & tumor cell proliferation (VC). The implications of how we assess patients at diagnosis and during the course of their care as it relates to VC and the associated increase in cytokines is of immense prognostic and even diagnostic value. I continue to see men with prostate cancer who never have any lab assessment that relates to bone resorption markers (BRMs). This paper beautifully portrays the importance of bone integrity & the underlying mechanisms of action.

On 2016 Feb 08, Mwidimi Ndosi commented:

My research student Hannah Cumpstey picked this up in the methods section: "A p-value >0.05 was accepted as being statistically different" (Akbari et al, 2007, P.633).

In the results section however, the interpretation of the null hypothesis significance testing seem to follow the conventional significance level, where a p=0.03 is interpreted as significant and p=0.95 not significant (p.634).

Could the authors please comment, just to reassure other readers?

Akbari A, Moodi H, Ghiasi F, Sagheb HM, Rashidi H. (2007) Effects of vacuum-compression therapy on healing of diabetic foot ulcers: randomized controlled trial. J Rehabil Res Dev. 44(5): 631-6.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00535031. We believe the correct ID, which we have found by hand searching, is NCT00535431.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2015 May 07, Jeff Kiefer commented:

DAVID is continuously being used as evidenced by its numerous citations in current biomedical literature http://bit.ly/1FS1JgT. However, the data resources used by DAVID appear to not have been updated since 2009 http://david.abcc.ncifcrf.gov/helps/update.html. The fact that DAVID has not been updated going on 5 years calls into question the current utility of using this tool.

On 2016 May 26, Jeff Kiefer commented:

It looks like DAVID has been updated May 2016 https://david-d.ncifcrf.gov/content.jsp?file=release.html.

On 2013 Jun 30, Swapnil Hiremath commented:

This is a fascinating attempt at resolving heterogeneity in this field of contrast nephropathy. The ACT study, done later by Berwanger et al in Circulation 2011 http://www.ncbi.nlm.nih.gov/pubmed/21859972, proved conclusively that NAC is not useful. However, this paper, by trying to resolve the cause of the heterogeneity is a fascinating read beyond just the summary outcome measure. As Prof Stoto would say, while doing a systematic review, try to think, 'What is the Story?'

On 2014 Dec 11, Ibrahim Masoodi commented:

We have found Fecal Lactoferrin an effective biomarker too.This co relates well the UC activity and severity

On 2015 Oct 05, Jan Egger commented:

Videos demonstrating the virtual stenting can be found here: https://www.youtube.com/c/JanEgger/videos

Best wishes, Jan

On 2014 Nov 23, Harri Hemila commented:

A comment is available at: http://hdl.handle.net/10138/25297

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2015 May 04, Raphael Levy commented:

This post is co-authored by Raphael Levy and David Mason.

Note: We contacted Chad Mirkin and EMD Millipore for comments. Chad Mirkin replied but prefers to keep his comments for the peer reviewed literature rather than blogs. EMD Millipore has provided a response (reproduced below) and is keen to further engage in the discussion. They wrote that they "look forward to responding to [the questions you pose at the end of the post] after your blog is posted so other researchers who may have the same questions can follow our discussion online."

To image proteins in cells, biologists have powerful tools based on the Green Fluorescent Protein (GFP) for which Osamu Shimomura, Martin Chalfie and Roger Y. Tsien obtained the 2008 Nobel Prize in Chemistry. RNA molecules play crucial roles in cells such as coding, decoding, regulation, and expression of genes, yet they are much more difficult to study. SmartFlares are nanoparticle-based probes for the detection and imaging of RNA in live cells. Could they become the GFP of the RNA world?

Read more at https://raphazlab.wordpress.com/2015/03/11/how-smart-are-smartflares/

On 2017 Sep 15, Raphael Levy commented:

A new paper confirms that spherical nucleic acids / nano-flares / SmartFlares do no detect mRNA. SmartFlares fail to reflect their target transcripts levels

See also the Guest post by the authors of the above study at my blog.

On 2015 May 12, David Gortler commented:

This trial supports the findings of the older CARDS trials which also showed that "lower is better" when it comes to LDL, and there is additive benefit to driving LDL levels beyond 70mg/dL (the current NECP goal) to even as low as 40mg/dL. Since this publication, it has been additionally shown that elevation of hsCRP is associated with increased risk of type 2 diabetes development in patients with all levels of metabolic syndrome.

In type 1 and type 2 diabetes mellitus, hemoglobin A1c significantly correlates with hsCRP levels and future cardiovascular risk indicating that diabetes has inflammatory fundamentals. Also, hsCRP levels increase with the stage of beta-cell dysfunction and insulin resistance. Non-diabetic drugs that have been shown to reduce hsCRP concentrations include aspirin, statins, cyclooxygenase-2 inhibitors, and fibrates.

On 2014 May 10, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/05/09/more-retractions-for-researcher-who-says-he-will-no-longer-publish/

On 2017 Dec 06, Misha Koksharov commented:

The link to the full text: http://dx.doi.org/10.1139/y91-257

On 2016 Nov 20, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2015 Jun 18, Bill Cayley commented:

A great example of "Less is More" in Medicine: https://lessismoreebm.wordpress.com/2015/06/17/effect-of-honey-dextromethorphan-and-no-treatment-on-nocturnal-cough-and-sleep-quality-for-coughing-children-and-their-parents/

On 2014 Oct 13, Ivan Oransky commented:

This paper has been retracted, the third retraction of a paper by Nobutu Yamamoto about GcMAF: http://retractionwatch.com/2014/10/10/yet-another-study-of-widely-touted-cancer-cure-retracted/

On 2014 Nov 26, Harri Hemila commented:

A manuscript version is available at handle

On 2013 Oct 23, MARK VRABEL commented:

For the latest evidence on ondansetron, granisetron, other antiemetics, and nonpharmacologic interventions for CINV, see the Oncology Nursing Society Putting Evidence Into Practice http://www.ons.org/Research/PEP/Nausea and http://esource.ons.org/ProductDetails.aspx?sku=INPU0638

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0037. We believe the correct ID, which we have found by hand searching, is NCT00371982.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2017 Feb 26, Bill Noble commented:

Please note that the particular strategy proposed here for estimating false discovery rates in the context of tandem mass spectrometry has subsequently been shown to be biased. Evidence for this bias, and discussion of alternative protocols, is given in this paper: https://www.ncbi.nlm.nih.gov/pubmed/26152888

On 2013 Nov 01, Dale D O Martin commented:

It should be noted that N-myristoylation can only occur on N-terminal Glycines, hence the name N-myristoylation. This occurs either co-translationally on the nascent polypeptide following the removal of the initiator Met or it can occur posttranslationally following proteolysis, which exposes a new N-terminal Gly. The latter has only been shown to occur in caspase-cleaved proteins. In this case, the Gly follows an Asp residue where caspase will cleave. The authors here predict internal myristoylation at very unlikely positions. Furthermore, the general consensus sequence for myristoylation is GXXXS/C/T where X is any amino acid, except for large bulky residues, and S/C/T are preferred in position 5 (counting from Gly). The first site they predict is GAAPP and is very unlikely to be myristoylated. Caution should be taken when predicting internal myristoylation sites. Unless it is predicted to be cleaved to expose an N-terminal Gly.

On 2014 Apr 17, Carl Denef commented:

An update of this review is available in an on line database at the following URL:

https://perswww.kuleuven.be/~u0009251/index.htm

This database is updated

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2017 Jan 19, Denise Fernandez-Twinn commented:

I am an author on this paper, however because my name is listed as Twinn DF, I am not getting the cites for this really important paper. Is there something PubMed can do to change the way my name is listed to Fernandez-Twinn DS. I have other collaborative work with some of the other authors on this paper (Ozanne SE and Samuelson AM), so it would be easy to verify my identity and contribution on this paper. Thank you. Kind Regards, Denise S Fernandez-Twinn

On 2014 Nov 17, Raphael Levy commented:

A key paper in the stripy controversy. Discussed here.

More broadly, the evidence behind the structure and special properties of “striped” nanoparticles has been challenged by Cesbron Y, 2012. The publication in 2012 of Cesbron Y, 2012 took three years and has been followed by post-publication peer review of the various existing and new stripy articles on my blog, PubPeer, etc.

A detailed analysis of this body of work is published today in PloS One by Stirling et al; from the abstract: “through a combination of an exhaustive re-analysis of the original data with new experimental measurements of a simple control sample comprising entirely unfunctionalised particles, we conclusively show that all of the STM evidence for striped nanoparticles published to date can instead be explained by a combination of well-known instrumental artefacts, strong observer bias, and/or improper data acquisition/analysis protocols.”

On 2013 Oct 22, DAVID SANDERS commented:

None

On 2013 Oct 25, DAVID SANDERS commented:

This article twice claims that Alvarado J, 2006 hypothesizes that there are two distinct active sites on the E. coli Ppx.

"However, the bifunctional aspect of pppGpp hydrolysis was linked to the presence of two active sites in one study Alvarado J, 2006 but was in favor of a common active site in the other."

"The structural analysis by Alvarado et al. identified domain III as a second PPX active site responsible for pppGpp hydrolysis."Alvarado J, 2006

However, no such statement is made in Alvarado J, 2006.

On 2014 Nov 23, Harri Hemila commented:

Reply to this comment is available at DOI

On 2014 May 12, G L Francis commented:

This paper sought to find a chemically-defined medium to maintain human embryonic stem cells (hESCs) in long-term culture, necessary for expansion of cell numbers to enable production platforms required to provide differentiated cells for the clinical trial of cell-mediated therapeutics and beyond. Although this paper in now six years old the authors raise some important points still relevant today, however, I believe they misinterpreted a key finding for the relative importance of the components of ‘lipid rich albumin’ by underestimating the contribution of the albumin carrier itself. The studies initially utilized KnockOut™ Serum Replacement (KOSR) and then AlbuMAX®, a chromatographically purified lipid-rich bovine serum albumin (BSA) preparation, which they established was the active component in KOSR, moreover, both products are problematic themselves when developing production methods for human clinical products, due to their animal origins . None the less, the importance of the albumin borne lipid components in sustaining pluripotency markers of hESCs, indicating self-renewal over five passages, was correctly established (Fig. 2 & Fig.3). They extend this finding to claim evidence for the exclusive role of lipids, and attribute no role for the associated albumin carrier protein, in supporting the self-renewal of the hESC lines (Fig 3 A-E). It is the latter conclusion I take odds with, and in fact believe the results also support another conclusion - that while lipid components are essential to the action of the lipid-rich albumin preparations used, albumin promotes the action of its lipid ligands, to maximize the response as seen for both KOSR and AlbuMAX®. Indeed careful examination of the data (Fig 3B and Fig3D) reported allows the conclusion that the presence of intact albumin increases the expression of the pluripotency markers TRA-1-60 and NANAOG by around 25%, and only that of OCT4 is unchanged. Also in this series of experiments the authors could have included another control treatment where they mixed the intact AlbuMAX® with trypsin inhibitor before adding the protease trypsin. Next the authors correctly proved that after the repeated passage (X7) of hESCs they actually retained pluripotency and the capacity to differentiate into ectoderm, endoderm, and mesoderm, by displaying the appropriate markers, GFAP & Sox1, Sox17 & Pdx1 (latter not shown), and cardiac Troponin T, respectively (Fig.4A). Differentiation of hESCs passaged under all conditions resulted in a drastic reduction of pluripotency markers Oct4 and NANAOG and the appropriate increase of differentiation marker for each germ layer of the generated embroid bodies (EBs). However, for the AlbuMAX® + Trypsin media passaged hESCs the resulting embroid bodies displayed for each germ layer the relevant markers, but numerically (by inspection) reduced by 47% GFAP and 25% SOX1 (ectoderm), 10% SOX17 and ??% Pdx1 (endoderm), and 42% cardiac Troponin T (mesoderm) compared to EBs derived from hESCs cultured with intact AlbuMAX®. This difference was not addressed by the authors to my knowledge, and if all experimental variables are controlled and assuming these differences are statistically robust - then possibly a more complex role for albumin in facilitating the subsequent differentiation of these cell lines is indicated. Furthermore, the presence of lipid-rich albumin (i.e. BSA present in 10% Fetal Bovine Serum) during hESC differentiation and EB growth suggests the observed marker differences result from earlier genetic or epigenetic modifications to the hESCs during the serial passaging phase. While the possible involvement of other endogenous or exogenous ligands of albumin were considered to no avail, reasonably the authors could not cover the full spectrum of effects that albumin could promote directly or indirectly in mammalian cells, many of which I have reviewed more recently (2010-PMID: 20373019 [PubMed]).<br> I wish to sincerely thank the authors for the wide range of issues they raised in relation to this topic and I hope my comments are of some value to them or others.

On 2016 Feb 18, Kristina Hanspers commented:

The network in figure 2 is available in the "Open Access Publication" collection at WikiPathways: http://www.wikipathways.org/index.php/Pathway:WP2636. This pathway can be downloaded for use in network analysis tools such as Cytoscape and PathVisio.

On 2015 Sep 27, S Sundar commented:

We noticed re-induction of hormone sensitivity in more patients and we presented our experience at the ASCO GU conference in 2008. The conference abstract is unfortunately no longer available from ASCO website.

We have reproduced our submission below for the benefit of clinicians and researchers interested in our manuscript.

Citation:<br> Cox RA, Sundar S. Re-induction of sensitivity to diethylstilbestrol in docetaxel-treated androgen refractory prostate cancer. In: American Society of Clinical Oncology Genitourinary Symposium. 2008. Abstract No: 172. ....................................

Control/Tracking Number: 08-AB-20299-ASCOGU Activity: Abstract Submission Current Date/Time: 1/29/2008 10:04:47 AM

Re-induction of sensitivity to Diethylstilbestrol in Docetaxel treated androgen refractory prostate cancer

Author Block: S. Sundar, R. Cox; Nottingham City Hospital, Nottingham, United Kingdom

Abstract:

Introduction: Diethylstilbestrol (DES) is a standard second line hormone therapy for prostate cancer in the UK. Following introduction of Docetaxel, DES is increasingly being used as third line therapy. We audited our patients (pts) response to DES after treatment with Docetaxel.

Methods: Pts (n=56) who received Docetaxel within an 18-month period were identified from a pharmacy database and the sub-group (n=16) treated with DES after Docetaxel was identified. PSA Response rate (50% decline) to Docetaxel was 60%. All pts had androgen refractory disease and had castrate levels of testosterone (LHRH-agonist therapy/orchidectomy). Pts with a history of ischaemic heart disease, stroke, pulmonary embolism (PE) or thrombosis were not offered DES. Pts were treated with DES 1mg daily with aspirin 75mg daily for thrombotic prophylaxis.

Results: 16 pts subsequently received DES on disease progression following Docetaxel. (1 pt unable to tolerate DES due to nausea was excluded from analysis). Median age of pts given DES after Docetaxel was 70yrs (52-79). 12 of 15 (80%) responded to DES 'after' Docetaxel, with 6 (50%) having a >50% reduction in PSA. Significantly 7 pts were treated with DES 'prior' to Docetaxel. 6 of these 7 pts (86%) who were previously refractory to DES 'prior' to Docetaxel responded to retreatment with DES 'following' Docetaxel chemotherapy. Currently, 6 pts remain on therapy after a median follow up of 2.5 months. 5 pts who progressed, did so after a median treatment duration of 4 months. 1 responding patient stopped after 2 months due to a PE. DES was otherwise very well tolerated. 1 patient stopped treatment after 1 week due to nausea. There were no other documented cardiovascular, cerebrovascular or thrombotic events.

Conclusions: DES is an option for patients with androgen refractory prostate cancer who have relapsed after treatment with Docetaxel. Previous work (Shamash et al, Br.J.Cancer.2005) found re-induction of hormone sensitivity following failure of Chlorambucil and Lomustine chemotherapy. Further investigation of this interesting phenomenon of re-induction of DES sensitivity could provide further insight into molecular mechanisms underlying androgen refractory prostate cancer. : Author Disclosure Information: S. Sundar, None; R. Cox, None. ..........................................................................

On 2015 Jun 28, Erick H Turner commented:

Below are DOIs and links to FDA review documents for the 8 older antidepressant drugs whose reviews are not available on the FDA website Drugs@FDA.

doi:10.6083/M4542M8J Bupropion SR http://digitalcommons.ohsu.edu/fdadrug/21

doi:10.6083/M41C1VJT Fluoxetine http://digitalcommons.ohsu.edu/fdadrug/22

doi:10.6083/M48W3C0Z Mirtazapine http://digitalcommons.ohsu.edu/fdadrug/20

doi:10.6083/M4WM1C2X Nefazodone http://digitalcommons.ohsu.edu/fdadrug/23

doi:10.6083/M4HD7TC4 Paroxetine http://digitalcommons.ohsu.edu/fdadrug/26

doi:10.6083/M4CN72MB Sertraline http://digitalcommons.ohsu.edu/fdadrug/27

doi:10.6083/M4RV0MCN Venlafaxine http://digitalcommons.ohsu.edu/fdadrug/24

doi:10.6083/M4N58K2D Venlafaxine XR http://digitalcommons.ohsu.edu/fdadrug/25

Because they were not acquired directly from the FDA but rather indirectly through colleagues who had obtained them via FOIA requests, the order of the 'hard copy' pages may have been shuffled in some cases. For a 'cleaner' copy, one might need to place a new FOIA request with the FDA (http://www.accessdata.fda.gov/scripts/foi/FOIRequest/requestinfo.cfm).

As for the 4 newer antidepressant drugs, as stated in the article, those reviews are downloadable from Drugs@FDA. If assistance is needed in navigating to and through that site, the "cookbook" article of mine available at http://www.bmj.com/content/347/bmj.f5992 may be useful.

On 2016 Sep 22, Lydia Maniatis commented:

Please see comments on PubPeer.

On 2013 Oct 28, DAVID SANDERS commented:

Identical Env deletions to those described in this article ("The Env truncated at 616 exhibits maximum fusogenicity in cell-to-cell fusion assay. By comparison, full tail Env (632) and the Env truncated to residue 601 mediated fusion at 40%.") are analyzed in Taylor GM, 2003, which is not cited by this article and contains an alternative hypothesis that there is a trimeric coiled coil in the cytoplasmic domain. This hypothesis has gained recent support. Löving R, 2012

Analysis of the effects of Env mutations in Li M, 2001, Yang C, 1997, and Taylor GM, 2003, which is inconsistent with the hypothesis proposed by the authors of this Exp Mol Pathol article, was also ignored by them.

On 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle

On 2013 Dec 15, Eduardo Palencia-Herrejón commented:

Surprised with the Le Gall statement against the involvement of family in "hard decisions"... Perhaps the full text provides an adequate explanation, but the bare statement sounds like paternalistic...

On 2015 Jul 02, Pedro Silva commented:

The code used to locate the minimum-energy-crossing points in this work is publicly available as:

Silva, Pedro (2015): Program for the computation of MECP using the Firefly Quantum Chemistry program. figshare. http://dx.doi.org/10.6084/m9.figshare.1471648

On 2013 Oct 26, Graham Coop commented:

The heritable variation in hotspot usage that we found in this article was later mapped to the gene prdm9, see Baudat et al ( Baudat F, 2010 ) and related articles.

On 2014 Nov 24, Claudia Paiva commented:

I think that the possible link between autoimmune thyroiditis and Meniere's disease may be the deposition of antibody+thyroid antigen immune complexes instead of autoimmunity against other antigens. The evidences do not point to hormone levels as the link.

On 2014 Sep 29, Ivan Oransky commented:

This paper has been retracted, one of three studies by the late first author to have been retracted: http://retractionwatch.com/2014/09/26/deceased-researcher-has-two-more-papers-retracted/

On 2017 Oct 14, Eric Yarnell commented:

Authors should be Peng A, Gu Y, Gui DK, Zhu QY, Zhu KY, Lin SY (family and given names have been switched)

On 2015 Oct 15, Nanjiang Shu commented:

Link to the web-server has been changed to http://predzinc.bioshu.se

On 2015 Jun 16, Bill Cayley commented:

A great example of when "Less" is more: https://lessismoreebm.wordpress.com/2015/06/16/systematic-review-of-randomized-controlled-trials-examining-written-action-plans-in-children-what-is-the-plan/

On 2013 Jun 17, Mike Fay commented:

This paper shows an improved way to calculate the variance when using multiple imputation with interval censored data. Huang, Lee and Yu show this is better than calculating the variance by using a correction for multiple imputation developed by Rubin for a different situation, that was used in earlier papers.

Another advantage of this test (not studied in the original paper) is that it retains the type I error fairly well even when the assessment times depend on treatment (see my paper with Joanna Shih Fay MP, 2012).

Software to calculate this test is available in the interval R package, http://cran.r-project.org/web/packages/interval/index.html.

On 2017 May 23, Morten Oksvold commented:

This article was retracted April 27 2017 together with eight other articles from the same group due to data manipulations.

Please note that the retraction notice is visible in the PDF document only.

http://www.jbc.org/content/283/17/11176.full.pdf?sid=a8d5dc2c-dd64-4b19-bf5e-c46f7deb9f49

"This article has been withdrawn by the authors. The authors were recently made aware of issues in Figs. 1A and 2A. In Fig. 1A, the actERK2 panel was manipulated inappropriately, and the GST panel was duplicated in Fig. 1C as the GST panel. In Fig. 2A, the P-Elk panels for ERK2 were duplicated, and the right actERK2 panel for RSK was duplicated in the right actERK2 panel for cFOS. Because the original data are no longer available, in the interest of maintaining accuracy in the published scientific literature, the authors wish to withdraw this article. However, the authors have full confidence in the findings and conclusions of this paper and have replicated the findings in subsequent work."

On 2014 Jan 03, Alexander Lerchl commented:

None

On 2014 Jan 16, Franz Adlkofer commented:

None

On 2014 Feb 11, Franz Adlkofer commented:

Two papers from a research team at the Medical University of Vienna (MUV), the one above and a previous one [1], point to a genotoxic potential of radiofrequency electromagnetic fields. Both papers result from the REFLEX project, a multi-national study on biological effects of electromagnetic fields funded by the European Union, which I coordinated [2]. About three years after REFLEX had been completed all of a sudden the claim was circulated that the Vienna results might have been faked. With this allegation the editors of the two peer-reviewed scientific journals should be forced to retract the respective papers. However, they carried out their own investigations, and in both editorial boards the outcome of a thorough scrutiny led to the conclusion that there is no evidence of fraud.

At the same time, the MUV mandated its Council for Scientific Ethics to investigate in detail how the Vienna REFLEX data were generated. This Council confirmed already at its first meeting and without any investigation the suspected fraud, and recommended the retraction of the two papers. By chance, it turned out that its chairman was a lawyer from the Austrian telecommunication industry. After his replacement the new Council came to the decision that the allegation is unfounded and that there is no reason to further pursue the case. Unhappy with this acquittal, the matter was finally transferred to the newly established Austrian Agency for Research Integrity that after a further scrutiny followed the Council’s decision [3].

Criticism of scientific data is absolutely necessary, but to claim fraud in order to get rid of them is unacceptable, whatever the reasons behind.

1. Diem E, Schwarz C, Adlkofer F, Jahn O, Rüdiger HW (2005) Non-thermal DNA breakage by mobile phone radiation (1800 MHz) in human fibroblasts and transformed GFSH-R17 rat granulosa cells in vitro. Mutat Res 583:178-83.
2. See „REFLEX Final Report“ in http://www.itis.ethz.ch/assets/Downloads/Papers-Reports/Reports/REFLEXFinal-Report171104.pdf
3. See “Part I. A campaign to destroy scientific findings” in http://www.kompetenzinitiative.net/assets/broschuerenreihe_heft-5_eng_screen.pdf

On 2014 Aug 10, Alexander Lerchl commented:

None

On 2014 Nov 26, Harri Hemila commented:

A comment on this study was published in DOI.

A response to that comment was published in DOI.

On 2017 Jul 31, valentina di pietro commented:

Notes: The substitution I226T has never been found in patients affected by Canavan disease. Bioinformatics tools recently deployed to predict mutations did not confirm substitution of I226T as a mutation. According to PredictSNP (https://loschmidt.chemi.muni.cz/predictsnp1/) which combines six different methods (MAPP, Phd-SNP, Poly-phen1, Poly-phen2, SIFT, SNAP) into a consensus classifier, this is a neutral substitution with an 83% level of confidence. Meta-SNP (http://snps.biofold.org/meta-snp/), a meta-predictor which combines the outputs of PANTHER, PhD-SNP, SIFT and SNAP gives a final score of 0.242 . Only a score >0.5 indicates prediction of disease mutations.

On 2015 Feb 15, James Tsung commented:

Link to Focused Cardiac Ultrasound video: https://youtu.be/40tJLGzvmMU?list=PL-HeZidYNe37Rzd6i7OeFHO4Gk3l5NHQP

On 2014 Mar 26, Tom Kindlon commented:

"Actometer readings would have provided more objective data"

My e-letter replying to this paper, "Actometer readings would have provided more objective data", can be read here: http://pediatrics.aappublications.org/content/121/3/e619/reply