GroupPresentingHPOs: HP:0001324, HP:0001270, HP:0002205, HP:0002098, HP:0001635, HP:0001640, HP:0011968

HPOsFreeText: IOPD, reduced GAA activity, paucity of movements

GroupNotHPOs:

NumberMales: 14

NumberFemales: 11

CountryOrigin: mainland China; 12 patients from southern China, 13 from northern China

Ethnicity: Chinese

Race: Chinese

AgeRange: median age at symptom onset = 3.4mo, median age at diagnosis = 4.9mo

*TotalNumber: 25

FamilyInfo: Parents of those individuals with mutations were sequenced

NoFamily: n/a

GroupAddInfo: all patients diagnosed with IOPD between 2013 and 2016 at Shanghai Children's Medical Center. Of the 24 untreated patients, non survived beyond 1.5yrs, only surviving (Patient 25) was 7mo at last follow-up.

GroupPreviousTesting: IOPD diagnosed via reduced GAA enzyme activity in leukocytes or DBS (PMID: 16702880)

GroupGenotypingMethod: DNA isolated from blood samples, coding exons (2-20) and intron/exon boundaries of GAA gene amplified via PCR (primers: PMID: 10338092), resulting DNA was sequenced with ABI3730XL sequencer then was analyzed with Mutation Survey or DNA Variant Analysis software, novel mutations were screened in 60 normal individuals (120 alleles) via direct sequencing and no novel variants were found among these suggesting those found in study patients are uncommon polymorphisms.

fragments containing a mutation in the patients were amplified and sequenced for the corresponding parents

Phylogenetic conservation of missense mutations analyzed with ClustalX program, and pathogenicity of novel variants predicited with MutationTaster, sorting intolerant from tolerant (SIFT), and PolyPhen-2

Variant: NM_000152.4(GAA):c.2662G>T (p.Glu888Ter)

this was identified (by present study) as the most common variant in northern Chinese patients, heterozygous for 5 patients, homozygous for one patient

ClinVar: 578595, https://www.ncbi.nlm.nih.gov/clinvar/variation/578595/

gnomAD: 1.65e-05, http://exac.broadinstitute.org/variant/17-78092467-G-T

GroupPresentingHPOs: HP:0005952, HP:0030197

HPOsFreeText: LOPD confirmed by enzyme analysis in leukocytes or fibroblasts and mutation analysis, median GAA activity in leukocytes = 1.0 nmol glucose/mg hour, median GAA activity in fibroblasts = 12.9 nmol 4MU/mg hour, median MRC sum score = 80.8, 7 patients had total wheelchair dependence, 17 patients had partial wheelchair dependence, median upright FVC = 71.9%, median supine FVC = 54.0%, 4 patients required invasive ventilation, 18 required NIV, 13 patients experienced infusion associated reactions

GroupNotHPOs:

NotHPOsFreeText: no ERT treatments prior to study, no pregnant patients

NumberMales: 37

NumberFemales: 36

CountryOrigin: n/a

Ethnicity: n/a

Race: n/a

AgeRange: at symtom onset = 1.4-62.6yrs, at diagnosis = 1.4-72.7yrs, at ERT start = 26.2-74.0yrs

TotalNumber: 73

FamilyInfo: n/a

NoFamily: n/a

GroupAddInfo: all patients received ERT of 20mg/kg/2wk alglucosidase alfa intravenoulsy, minimum 5 months of treatment. Median duration of disease = 8.2yrs

GroupPreviousTesting: anti-rhGAA antibody titers determined in plasma or serum using ELISA, neutralizing effects of antibodies determined by addition of alglucosidase alfa and patient serum to medium of GAA-deficient fibroblasts then by measurement of GAA activity in cells and medium, manual muscle testing to assess skeletal muscle strength, FVC in upright and supine positions, 46 patients developed anti-rhGAA titers about background of 1:250 (16 high, 29 intermediate, 28 low to no)

GroupGenotypingMethod: mutation analysis (PMID: 18425781)

Variant1: NM_000152.4(GAA):c.-32-13T>G this was carried by all but 1 patient

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

The following are the four most common variants on the second allele

Variant2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Variant3: NC_000017.11:g.(?80118193)(80118357_?)del

ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

gnomAD: n/a

Variant4: NM_000152.4(GAA):c.1548G>A (p.Trp516Ter)

ClinVar: 189025, https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

gnomAD: n/a

Variant5: NM_000152.4(GAA):c.925G>A (p.Gly309Arg)

ClinVar: 188797, https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

gnomAD: 4.609e-05, http://exac.broadinstitute.org/variant/17-78081665-G-A

Statistics of the number of Catholics by regions, collected as of June 30, 2024.

GroupPresentingHPOs: HP:0003325, HP:0003457, HP:0012548, HP:0004887, HP:0010535, HP:0001712, HP:0031296

HPOsFreeText: hyperCKaemia+LGMW, BMI, mean (SD) 25.2±5.8, Serum CK, mean (SD) 600±302, vacuolar myopathy, Muscle GAA %, mean (SD) 9.4±3.8, myogenic EMG, abnormal MRI, %Predicted FVC, mean (SD) 73±11, 6MWT, mean (SD) 452±9, vacuolisation of myofibers with variable glycogen storage, AP staining low in 6 individuals, medium in five, and high in 2 individuals. Low residual GAA activity in muscles,

GroupNotHPOs:

NotHPOsFreeText:

NumberMales: 8

NumberFemales: 9

CountryOrigin: n/a

AgeRange: mean (SD) 40±14.36

TotalNumber: 14

GroupAddInfo: mean age at disease onset was 40±14.3 years, median age at disease diagnosis was 47±14 years. 14 of the individuals underwent enzyme replacement therapy. Blood CK levels increased in all but one individual.

GroupGenotypingMethod: GAA gene sequencing

Variant 1: NM_000152.4(GAA):c.-32-13T>G

ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant 2: p.P522A, NM_000152.4(GAA):c.1564C>G (p.Pro522Ala)

ClinVar: 371277, https://www.ncbi.nlm.nih.gov/clinvar/variation/371277/

gnomAD: n/a

GroupPresentingHPOs: HP:0003701, HP:0003327, HP:0003325, HP:0003236

HPOsFreeText: average GAA activity with inhibitor of 0.18 nmol/punch × 21 hours

GroupNotHPOs: n/a

NotHPOsFreeText: n/a

NumberMales: 32 (44%)

NumberFemales: 42 (56%)

CountryOrigin: n/a

Ethnicity: n/a

Race: n/a

AgeRange: 18-81 years, median = 48 years

TotalNumber: 74

FamilyInfo: n/a

NoFamily: n/a

GroupPreviousTesting: DBS collected from peripheral vein analyzed with fluorometric assay

GroupGenotypingMethod: Sanger sequencing of coding and exon flanking region of GAA gene

Variant Count: 74

Variant: NM_000152.4(GAA):c.-32-13T>G

ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

GroupPresentingHPOs: HP:0001324, HP:0001270, HP:0002205, HP:0002098, HP:0001635, HP:0001640, HP:0011968

HPOsFreeText: IOPD, reduced GAA activity, paucity of movements

GroupNotHPOs:

NumberMales: 14

NumberFemales: 11

CountryOrigin: mainland China; 12 patients from southern China, 13 from northern China

Ethnicity: Chinese

Race: Chinese

AgeRange: median age at symptom onset = 3.4mo, median age at diagnosis = 4.9mo

TotalNumber: 25

FamilyInfo: Parents of those individuals with mutations were sequenced

NoFamily: n/a

GroupAddInfo: all patients diagnosed with IOPD between 2013 and 2016 at Shanghai Children's Medical Center. Of the 24 untreated patients, non survived beyond 1.5yrs, only surviving (Patient 25) was 7mo at last follow-up.

GroupPreviousTesting: IOPD diagnosed via reduced GAA enzyme activity in leukocytes or DBS (PMID: 16702880)

GroupGenotypingMethod: DNA isolated from blood samples, coding exons (2-20) and intron/exon boundaries of GAA gene amplified via PCR (primers: PMID: 10338092), resulting DNA was sequenced with ABI3730XL sequencer then was analyzed with Mutation Survey or DNA Variant Analysis software, novel mutations were screened in 60 normal individuals (120 alleles) via direct sequencing and no novel variants were found among these suggesting those found in study patients are uncommon polymorphisms.

fragments containing a mutation in the patients were amplified and sequenced for the corresponding parents

Phylogenetic conservation of missense mutations analyzed with ClustalX program, and pathogenicity of novel variants predicited with MutationTaster, sorting intolerant from tolerant (SIFT), and PolyPhen-2

Variant: NM_000152.4(GAA):c.2662G>T (p.Glu888Ter)

this was identified (by present study) as the most common variant in northern Chinese patients, heterozygous for 5 patients, homozygous for one patient

ClinVar: 578595, https://www.ncbi.nlm.nih.gov/clinvar/variation/578595/

gnomAD: 1.65e-05, http://exac.broadinstitute.org/variant/17-78092467-G-T

GroupPresentingHPOs: HP:0002013, HP:0001263 (vomiting, developmental delay)

HPOsFreeText: increased urinary excretion of methylmalonate and methylcitric acids. Elevated propionylcarnitine.

NumberMales: 0

NumberFemales: 3

CountryOrigin: Iran

AgeRange: 3 d-22 mo (age at diagnosis)

TotalNumber: 3

FamilyInfo: 3

NoFamily: 0

GroupAddInfo: All probands are products of consanguineous marriages.

Group (Level 2)

VariantCount: 3

NonVariant: 0

OtherVariant: 0

GroupPreviousTesting: urine organic acid analysis with urease treatment extraction with gas chromatography-mass spectrometry, after showing high levels of propionylcarnitine (umol/L) through tandem mass spectrometry

GroupMethod1: PCR

GroupGenotypingMethod: Genomic DNA was extracted from peripheral blood samples by the salting out method. MUT gene was analyzed by PCR and sequencing of both DNA strands of the entire coding region and highly-conserved exon-intron splice junctions. Reference sequence is NM_000255.3. Amplification was confirmed by electrophoresis, and products of the sequencing reaction were analyzed by DNA Sequencher 4.7. The phase of the mutation was confirmed by sequencing DNA from the patients parents.

GroupPresentingHPOs: HP:0001987, HP:0001942, HP:0003128, HP:0002912 (hyperammonemia, metabolic acidosis, lactic acidosis, methylmalonic acidemia)

HPOsFreeText: elevated blood levels of propionylcarnitine (C3) (median 13.56 umol/L), and elevated C3 to acetylcarnitine (C2) ratio (median 0.85). elevated urine methylmalonate levels (median 598.96 mmol/mol creatinine). 28/73.7% displayed recurrent vomiting (HP:0002572). 28/73.7% displayed disturbances of consciousness (HP:0004372). 23/60.5% displayed feeding difficulties in infancy (HP:0008872), 20/52.6% displayed respiratory distress (HP:0002098), 20/52.6% displayed failure to thrive (HP:0001508), 20/52.6% displayed dystonia (HP:0001332), 14/36.8% displayed mental retardation, 12/31.6% displayed convulsions.

GroupNotHPOs: normal plasma total homocysteine

NotHPOsFreeText:

NumberMales: 27

NumberFemales: 16

CountryOrigin: China

Ethnicity: Chinese

AgeRange: 33d- 10.3 y at last follow up

TotalNumber 43

FamilyInfo: 43

NoFamily: 0

GroupAddInfo: 9 identified by NBS, 34 recruited after being suspected of inherited metabolism disorders. 42 families from 14 provinces of the Mainland of China. 8 died during acute metabolic crisis, 7 lost to follow up, 28 alive at end of study.

Group (Level 2)

VariantCount: 43 (35 had two mutant alleles)

NonVariant: 0

OtherVariant: 0

GroupPreviousTesting: tandem mass spectrometry for blood levels, gas chromatography-mass spectrometry for urine,

GroupMethod1: PCR

GroupGenotypingMethod: genomic DNA extracted from peripheral blood leukocytes from patients and their parents. Exonic and flanking intronic regions of the MUT gene were amplified through PCR. PCR products were sequenced directly using forward and reverse primers on ABI 3700 sequencer. Mutation analysis using MUT reference NM_000255.3. Nucleotide numbering reflects cDNA numbering (initiation codon= codon1). All detected mutations were confirmed in the patients' parents. Novel variants were screened in 100 alleles from 50 control children. Novel variants were considered pathogenic when predicted to be deleterious by two algorithms.

Case 1: Family A: AII-1, female

Born at 37 weeks, consanguineous family, APGAR = 9, tachypnea developed shortly after birth. At 20 weeks, skeletal abnormalities and kidney and liver cysts were detected. Died at 7 weeks from renal insufficiency.

HPO Terms: HP:0002652, HP:0001999, HP:0002789, HP:0005562, HP:0001407, HP:0009826, HP:0000926, HP:0001156, HP:0000085, HP:0000083, HP:0002079, HP:0002119, HP:0030747, HP:0011839

Previous Testing: Found autosomal recessive variant in CHST9 (MIM: 610191; c.1133A>G [p.Asn378Ser] [GenBank: NM_031422])

Genotyping Method: WES, CNV performed on WES data, EXTL3 fibroblast localization tested and compared to non-affected controls using immunocytochemistry

Variant: p.Arg513Cys, g.28575113, c.1537C>T

ClinVar ID: n/a

gnomAD: http://gnomad.broadinstitute.org/variant/8-28575113-C-T

Inheritance: autosomal recessive

Variant Evidence:

GroupPresentingHPOs: HP:0008344 (elevated A keto acids in urine)

HPOsFreeText:

GroupNotHPOs:

NotHPOsFreeText:

NumberMales: 4

NumberFemales: 4

CountryOrigin: mainland China

Ethnicity:

Race: Chinese

AgeRange: 2 y 3 mo- 4 y 3 mo (present age)

TotalNumber: 8

VariantCount: 8 (subunits of BKDC: either BCKDHA, BCKDHB, or DBT)

NonVariant: 0

OtherVariant: 0

GroupPreviousTesting: n/a

GroupMethod1: PCR

GroupMethod2: Multiple sequence alignments

GroupGenotypingMethod: genomic DNA extracted from peripheral blood lymphocytes of patients and parents using TIANamp Blood DNA Kit. Exons and flanking intronic regions of BCKDHA, BCKDHB, and DBT were amplified with PCR and sequenced. Results compared with reference sequences in UCSC genome (BCKDHA (NM_000709), BCKDHB (NM_183050), DLD (NM_000108), DBT (NM_001918)), and compared with integrated set of variants from 1000 Genome Project to identify mutations. PolyPhen-2 and Mutationtaster program predicted the impact of missense alterations on protein function. Multiple sequence alignments obtained using BLAST.

This statement raises questions about the demographics of the users and the sustainability of the verification process, especially in relation to the promised cryptocurrency.

for - climate crisis - 2023 U.S. poll - demographics - climate communication - 2023 U.S. poll - demographics - climate change - 2023 U.S. poll - demographics - U.S. Hispanic / Latinos - 2023 - high concern about climate crisis - U. S. African American - 2023 - high concern about climate change - U.S. Gen Z - 2023 - high concern about climate change

Katherine Ognyanova. (2022, February 15). Americans who believe COVID vaccine misinformation tend to be more vaccine-resistant. They are also more likely to distrust the government, media, science, and medicine. That pattern is reversed with regard to trust in Fox News and Donald Trump. Https://osf.io/9ua2x/ (5/7) https://t.co/f6jTRWhmdF [Tweet]. @Ognyanova. https://twitter.com/Ognyanova/status/1493596109926768645

christoph chorherr. (2022, January 13). Bleibt allergrößtes menschliches Rätsel für mich. Das zu wissen, und sich “aus Überzeugung”, “trotzdem” nicht impfen zu lassen. Https://t.co/WlGGk5vmeN [Tweet]. @chorherr. https://twitter.com/chorherr/status/1481505797867724803

just demographic indicators such as age, gender, region and SES are strongly linked with academic performance in online-based learning.

This deserves to be delved into more deeply. This sounds like a bizarre stop on the creation of institutional racism.

How do these sorts of abstraction hurt the move towards equality?

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117th Congress

Hasn't contraception been a major reason for the fall in birth rates in all countries?

Wrong solution to economic problem: demand- vs. supply-side economics

Won't that birth rate continue to fall, as has been the pattern in other countries?

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Implications for libraries...

Author Ted Mitchell is the President of the American Council on Education. The article outlines solid numbers of Higher Education demographics and the changes that have occurred over the years and what that means for the future of students, especially those who have lived their entire lives in a digital era. The article is a great approach to reflecting on the future of technology and questions we can answer in this area and is not so much a focus on certain technologies.

Rating: 9/10

simple demographics viz from Grawe

Pennsylvania had a high number of immigrants from Germany. The English colonies received many immigrants from other parts of Europe as well as the forced migration of enslaved people from Africa.

We should not look at predictors that will not help us to make accurate interventions. Statistics should not be used to support bias.

Quoted from Michael Oren in Commentary.