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Fulltext Perception of Gastrointestinal Endoscopy Personnel on Society Recommendations on Personal Protective Equipment, Case Selection, and Scope Cleaning During Covid-19 Pandemic: An International Survey Study

Mekaroonkamol P, Tiankanon K, Pittayanon R, Ridtitid W, Shams F, Tayyab GUN, et al.

Clin Endosc, 2021 Sep 29.
PMID: 34583452 DOI: 10.5946/ce.2021.051

Background/Aims: The Thai Association for Gastrointestinal Endoscopy published recommendations on safe endoscopy during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to assess the practicality and applicability of the recommendations and the perceptions of endoscopy personnel on them.
Methods: A validated questionnaire was sent to 1290 endoscopy personnel globally. Of these, the data of all 330 responders (25.6%) from 15 countries, related to the current recommendations on proper personal protective equipment (PPE), case selection, scope cleaning, and safety perception, were analyzed. Ordinal logistic regression was used to determine the relationships between the variables.
Results: Despite an overwhelming agreement with the recommendations on PPE (94.5%) and case selection (95.5%), their practicality and applicability on PPE recommendations and case selection were significantly lower (p=0.001, p=0.047, p<0.001, and p=0.032, respectively). Factors that were associated with lower sense of safety in endoscopy units were younger age (p=0.004), less working experience (p=0.008), in-training status (p=0.04), and higher national prevalence of COVID-19 (p=0.003). High prevalent countries also had more difficulty implementing the guidelines (p<0.001) and they considered the PPE recommendations less practical and showed lower agreement with them (p<0.001 and p=0.008, respectively). A higher number of in-hospital COVID-19 patients was associated with less agreement with PPE recommendations (p=0.039).
Conclusions: Using appropriate PPE and case selection in endoscopic practice during a pandemic remains a challenge. Resource availability and local prevalence are critical factors influencing the adoption of the current guidelines.
Fulltext Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Milne RL, Kuchenbaecker KB, Michailidou K, Beesley J, Kar S, Lindström S, et al.

Nat Genet, 2017 Dec;49(12):1767-1778.
PMID: 29058716 DOI: 10.1038/ng.3785

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10-8 with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Fulltext Quality evaluation of compounds in leaves of six Taxus species based on UPLC-MS/MS and chemometrics

Cai Q, Song Q, Jiang K, Lin Y, Zhang Y, Zhang J, et al.

Front Chem, 2023;11:1193188.
PMID: 37324558 DOI: 10.3389/fchem.2023.1193188

Introduction: Taxus species are used as medicinal plants all over the world. The leaves of Taxus species are sustainable medicinal resources that are rich in taxoids and flavonoids. However, traditional identification methods cannot effectively identify Taxus species on the basis of leaces used as raw medicinal materials, because their appearance and morphological characteristics are almost the same, and the probability of error identification increases in accordance with the subjective consciousness of the experimenter. Moreover, although the leaves of different Taxus species have been widely used, their chemical components are similar and lack systematic comparative research. Such a situation is challenging for quality assessment. Materials and methods: In this study, ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry combined with chemometrics was applied for the simultaneous determination of eight taxoids, four flavanols, five flavonols, two dihydroflavones, and five biflavones in the leaves of six Taxus species, namely, T. mairei, T. chinensis, T. yunnanensis, T. wallichiana, T. cuspidata, and T. media. Chemometric methods, including hierarchical cluster analysis, principal component analysis, orthogonal partial least squares-discriminate analysis, random forest iterative modeling, and fisher linear discriminant analysis, were utilized to differentiate and evaluate the six Taxus species. Results: This proposed method exhibited good linearity (R 2 = 0.9999-0.9972) with a lower quantification limits of 0.94-3.05 ng/mL for all analytes. The intra- and inter-day precisions were within 6.83%. Six compounds, namely, 7-xylosyl-10-deacetyltaxol, ginkgetin, rutin, aromadendrin, 10-deacetyl baccatin III, and epigallocatechin, were identified through chemometrics for the first time. These compounds can be used as important chemical markers to distinguish the above six Taxus species rapidly. Conclusion: This study established a method for determination of the leaves of six Taxus species, and revealing the differences in the chemical components of these six Taxus species.
Notes on Amanita section Caesareae from Malaysia

Tang LP, Lee SS, Zeng NK, Cai Q, Zhang P, Yang ZL

Mycologia, 2017 12 04;109(4):557-567.
PMID: 29200380 DOI: 10.1080/00275514.2017.1394789

Some Amanita specimens collected from Malaysia are critically investigated by morphological examination and molecular analysis of two gene fragments, the nuc rDNA partial 28S (28S) gene and the internal transcriber spacer (ITS1-5.8S-ITS2 = ITS) regions. Six phylogenetic species of Amanita section Caesareae are recognized among the studied collections. One of them is described as new, A. malayensis. Four of the phylogenetic species correspond with existing morphology-based taxa: A. aporema, A. javanica, A. princeps, and A. similis. The remaining species is not described because of the paucity of material. Detailed descriptions and the distribution of these southeastern Asian species are provided, along with a key to the species of section Caesareae from Malaysia.
Fulltext Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1

Cai Q, Zhang B, Sung H, Low SK, Kweon SS, Lu W, et al.

Nat Genet, 2014 Aug;46(8):886-90.
PMID: 25038754 DOI: 10.1038/ng.3041

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
Fulltext Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics

Jia G, Ping J, Shu X, Yang Y, Cai Q, Kweon SS, et al.

Am J Hum Genet, 2022 Dec 01;109(12):2185-2195.
PMID: 36356581 DOI: 10.1016/j.ajhg.2022.10.011

By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p
Fulltext Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Shu X, Long J, Cai Q, Kweon SS, Choi JY, Kubo M, et al.

Nat Commun, 2020 Mar 05;11(1):1217.
PMID: 32139696 DOI: 10.1038/s41467-020-15046-w

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P
Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry

Wen W, Shu XO, Guo X, Cai Q, Long J, Bolla MK, et al.

Breast Cancer Res, 2016 12 08;18(1):124.
PMID: 27931260

BACKGROUND: Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry.
METHODS: We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk.
RESULTS: We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P
Fulltext Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

Zeng C, Guo X, Long J, Kuchenbaecker KB, Droit A, Michailidou K, et al.

Breast Cancer Res, 2016 06 21;18(1):64.
PMID: 27459855 DOI: 10.1186/s13058-016-0718-0

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.
METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.
RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P
Fulltext Fine-scale mapping of the 4q24 locus identifies two independent loci associated with breast cancer risk

Guo X, Long J, Zeng C, Michailidou K, Ghoussaini M, Bolla MK, et al.

Cancer Epidemiol Biomarkers Prev, 2015 Nov;24(11):1680-91.
PMID: 26354892 DOI: 10.1158/1055-9965.EPI-15-0363

BACKGROUND: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored.
METHODS: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium.
RESULTS: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10(-4); OR, 1.04; 95% confidence interval (CI), 1.02-1.07] and rs77928427 (P = 1.86 × 10(-4); OR, 1.04; 95% CI, 1.02-1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r(2) ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor-binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue.
CONCLUSION: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2.
IMPACT: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.

Autophagy, 2016;12(1):1-222.
PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
Fulltext Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

Akkerman O, Aleksa A, Alffenaar JW, Al-Marzouqi NH, Arias-Guillén M, Belilovski E, et al.

Int J Infect Dis, 2019 Jun;83:72-76.
PMID: 30953827 DOI: 10.1016/j.ijid.2019.03.036

The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

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