Full Summary Research Articles

Transcatheter aortic valve replacement and the value of increasing treatment for severe symptomatic aortic stenosis: a plain language summary

Plain Language Summary What is this summary about? This article summarizes an economic evaluation of transcatheter aortic valve replacement (TAVR), a treatment for severe symptomatic aortic stenosis (SSAS). SSAS occurs when the aortic valve, which allows blood to leave the heart, becomes very narrow. This reduces blood flow to the body, causing symptoms like tiredness, chest pain, dizziness, or fainting. Treating SSAS requires replacing the valve. Untreated SSAS results in heart failure and death. Before TAVR, SSAS patients had two options, medical management and surgical aortic valve replacement (SAVR). Medical management helps with symptoms but does not replace the valve, leading patients to eventually die from SSAS. SAVR replaces the valve through open-heart surgery, which is invasive, involving making a large cut through the chest bone. Concerns about this invasiveness led many patients to avoid SAVR, leaving their SSAS untreated. TAVR was introduced in 2010. It is less invasive than SAVR, involving inserting a new valve through a small cut in the leg. TAVR has become popular and twice as many patients now undergo TAVR compared to SAVR. We measure TAVR’s net benefits as the value of its health benefits minus its healthcare costs. We measure these net benefits in three patient groups aged 65 and above in the United States. Group 1 patients are ineligible for SAVR, so TAVR is their only treatment option. Group 2 patients would have received SAVR if TAVR were not available. Group 3 patients are eligible for SAVR but concerned about its invasiveness, and so would have stayed untreated without TAVR. Economic evaluation: A type of study that measures the benefits and costs of a treatment like TAVR and judges whether the benefits are sufficiently large to justify the costs (or put another way, whether the technology represents good value-for-money). Transcatheter aortic valve replacement (TAVR): Replacement of the aortic valve in SSAS patients using a thin tube called a catheter that enters the body through a small cut near the leg and delivers and installs a valve replacement. New treatment option for SSAS from 2010 onwards. A minimally invasive treatment. Aortic stenosis (AS): A heart condition where a heart valve called the aortic valve becomes very narrow, forcing the heart to work harder and limiting blood flow to the rest of the body. Severe Symptomatic Aortic Stenosis (SSAS): Severe form of AS when the narrowing of the aortic valve is significant and accompanied by symptoms like fatigue, chest pain, shortness of breath, dizziness, or fainting. What were the key takeaways? Net benefits per patient are significant in all groups, roughly equal in groups 1 and 2, and over six times larger in group 3. When net benefits are added up across patients, group 3’s total net benefit is 30 times larger than that of groups 1 and 2 combined. What are the main conclusions? Past studies ignored TAVR’s value in helping treat patients who might go untreated because of concerns over SAVR’s invasiveness. But this is TAVR’s largest value to SSAS patients. Our findings support continuing and increasing access to TAVR among SSAS patients, especially those who may go untreated because of concerns about invasive treatment. Aortic valve: One of the four heart valves. It connects the left side of the heart with the aorta, which is the large artery carrying oxygen-rich blood to the body. The aortic valve controls blood flow into the aorta, ensuring it moves in one direction. Medical management (MM): Involves medication and monitoring of SSAS patients but no treatment in the form of valve replacement. Associated with high risk of death. Surgical aortic valve replacement (SAVR): Replacement of the aortic valve in SSAS patients through open heart surgery. The sole treatment option for SSAS before 2010. A highly invasive treatment given its use of open-heart surgery. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text Link to original article here

Getting Help During Active Pain Crises in Sickle Cell Disease: Patient and Caregiver Perspectives in Canada

Plain Language Summary What is this summary about? This is a plain language summary of an article originally published in Patient Preference and Adherence. This study aimed to identify the notable symptoms and impacts of sickle cell disease from the point of view of individuals living with sickle cell disease and their caregivers. The study also sought to understand the factors involved in individuals living with sickle cell disease’ and caregivers’ decisions and preferences if and when they seek care during a pain crisis. This summary describes: the symptoms experienced by adolescents and adults living with sickle cell disease and their severity; the treatments they and their caregivers prefer to use when they are experiencing a pain crisis; and the factors that go into deciding when and whether individuals living with sickle cell disease and their caregivers should seek outside help -- to go to a hospital, for example - during a pain crisis. What were the results? Individuals living with sickle cell disease undergoing an acute pain crisis and their caregivers consider many factors when deciding whether to seek care at a medical facility. These include: The intensity of their symptoms If the facility has a treatment plan for them already in place If the facility has long wait times If the facility has an understanding and compassionate staff The individual's age and ability to manage their daily responsibilities Racial bias, shown in the actions and lack of empathy of Emergency Department staff toward individuals living with sickle cell disease, frequently factored into the individuals' and caregivers’ decision-making and hinders their ability to get the treatment needed during a pain crisis. What do the results mean? There is a need for a unified care team at medical facilities that treats all individuals living with sickle cell disease with the same high level of empathy and treatment quality and for a strong support system for individuals living with sickle cell disease outside of the hospital or clinic. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text Link to original article here

Roles of Histone H2B, H3 and H4 Variants in Cancer Development and Prognosis.

Histone variants are the paralogs of core histones (H2A, H2B, H3 and H4). They are stably expressed throughout the cell cycle in a replication-independent fashion and are capable of replacing canonical counterparts under different fundamental biological processes. Variants have been shown to take part in multiple processes, including DNA damage repair, transcriptional regulation and X chromosome inactivation, with some of them even specializing in lineage-specific roles like spermatogenesis. Several reports have recently identified some unprecedented variants from different histone families and exploited their prognostic value in distinct types of cancer. Among the four classes of canonical histones, the H2A family has the greatest number of variants known to date, followed by H2B, H3 and H4. In our prior review, we focused on summarizing all 19 mammalian histone H2A variants. Here in this review, we aim to complete the full summary of the roles of mammalian histone variants from the remaining histone H2B, H3, and H4 families, along with an overview of their roles in cancer biology and their prognostic value in a clinical context.

Can AI Make a Case? AI Vs. Lawyer in The Dutch Legal Context

The integration of AI, specifically GPT-4, into the legal field is a subject of both potential promise and intricate challenges. This thesis delves into the transformational possibilities of AI within the Dutch legal context, examining not only the quality and persuasiveness of AI-generated legal argumentation but also its competence in information retrieval, as measured by models’ ability to spot relevant legal issues. An experiment was conducted with 25 legal professionals, using a real-world Dutch case with the purpose to assess GPT-4’s capabilities against that of a human lawyer. To enable GPT-4 to handle case documents, the author first performed so-called co-reference resolution to remove ambiguities. Given the token limitations of GPT-4, a so-called prompt reducer technique was used to compress the text, retaining essential information. The above methods produced a coherent and full case summary within GPT-4’s token constraints. This case summary, together with original lawyer’s letter (denoted as Text A) was fed to ChatGPT-4 to obtain its AI-written alternative (Text B). The study subjects were presented with a case summary as well as both texts and asked for their preferences. The outcome of the experiment is as follow: 80% of participants chose the AI’s composed legal document, demonstrating a strong preference for both its linguistic competencies as well its ability to spot relevant legal issues. This preference for GPT-4 writing is very consistent among genders, age groups and professions surveyed. Contextualising these findings within the broader implications for legal practice, the thesis explores potential benefits including increased access to justice and transformation of certain legal procedures. Insights and recommendations are offered for legal professionals, considering the technological evolution and ethical considerations inherent in AI integration. Acknowledging the need for further exploration, the study recognises its own limitations and encourages replication to solidify the understanding of AI’s transformative role in the legal realm. GPT-4, AI, AI vs Lawyer, Legal Writing, Language Technology, LLM, Dutch Legal Context

Effectiveness of tenapanor for treating hyperphosphatemia in patients receiving dialysis: a plain language summary of the OPTIMIZE study

Plain Language Summary What is this summary about? This summary provides a review of the OPTIMIZE study, the results of which were published in Kidney360 in February 2024. The OPTIMIZE study looked at how well tenapanor tablets work to treat patients receiving dialysis who have high levels of phosphate in their blood, a condition called hyperphosphatemia. In the OPTIMIZE study, researchers wanted to understand if tenapanor would decrease phosphate levels in the blood to the target range. They also tested different ways of starting tenapanor treatment in patients. In the human body, kidneys are organs that filter blood and remove waste products. In chronic kidney disease, sometimes referred to as CKD, a patient’s kidneys do not work as well at filtering their blood and removing waste products. This can allow phosphate to build up in the blood. Phosphate levels may remain high despite patients receiving treatment such as dialysis, using pills that keep phosphate in the intestines (called phosphate binders) to prevent phosphate from being absorbed into the blood, and eating a low-phosphate diet. Phosphate levels may remain high despite these treatments because they can be difficult to follow. Most people receiving dialysis take 7–8 phosphate binder pills every day, and over half of those people have reported skipping at least one dose in the past month. Additionally, low-phosphate diets can be difficult to follow and people often struggle to meet their other nutritional needs. What are the key takeaways? Tenapanor used in combination with phosphate binders led to lower phosphate levels in the blood with the use of fewer phosphate-lowering pills. Tenapanor also lowered phosphate levels in patients who were not previously on phosphate binders but needed phosphate-lowering treatment. What were the main conclusions reported by the researchers? Tenapanor can help patients receiving dialysis better control their hyperphosphatemia. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text Link to original article here

Integrating Genetic and Transcriptomic Data to Identify Genes Underlying Obesity Risk Loci.

Genome-wide association studies (GWAS) have identified numerous body mass index (BMI) loci. However, most underlying mechanisms from risk locus to BMI remain unknown. Leveraging omics data through integrative analyses could provide more comprehensive views of biological pathways on BMI. We analyzed genotype and blood gene expression data in up to 5,619 samples from the Framingham Heart Study (FHS). Using 3,992 single nucleotide polymorphisms (SNPs) at 97 BMI loci and 20,692 transcripts within 1 Mb, we performed separate association analyses of transcript with BMI and SNP with transcript (PBMI and PSNP, respectively) and then a correlated meta-analysis between the full summary data sets (PMETA). We identified transcripts that met Bonferroni-corrected significance for each omic, were more significant in the correlated meta-analysis than each omic, and were at least nominally associated with BMI in FHS data. Among 308 significant SNP-transcript-BMI associations, we identified seven genes (NT5C2, GSTM3, SNAPC3, SPNS1, TMEM245, YPEL3, and ZNF646) in five association regions. Using an independent sample of blood gene expression data, we validated results for SNAPC3 and YPEL3. We tested for generalization of these associations in hypothalamus, nucleus accumbens, and liver and observed significant (PMETA<0.05 & PMETA<PSNP & PMETA<PBMI) results for YPEL3 in nucleus accumbens and NT5C2, SNAPC3, TMEM245, YPEL3, and ZNF646 in liver. The identified genes help link the genetic variation at obesity risk loci to biological mechanisms and health outcomes, thus translating GWAS findings to function.

The causal relationship between gut microbiota and immune skin diseases: A bidirectional Mendelian randomization.

Increasing evidence suggests that alterations in gut microbiota are associated with a variety of skin diseases. However, whether this association reflects a causal relationship remains unknown. We aimed to reveal the causal relationship between gut microbiota and skin diseases, including psoriasis, atopic dermatitis, acne, and lichen planus. We obtained full genetic association summary data for gut microbiota, psoriasis, atopic dermatitis, acne, and lichen planus from public databases and used three methods, mainly inverse variance weighting, to analyze the causal relationships between gut microbiota and these skin diseases using bidirectional Mendelian randomization, as well as sensitivity and stability analysis of the results using multiple methods. The results showed that there were five associated genera in the psoriasis group, seven associated genera were obtained in the atopic dermatitis group, a total of ten associated genera in the acne group, and four associated genera in the lichen planus group. The results corrected for false discovery rate showed that Eubacteriumfissicatenagroup (P = 2.20E-04, OR = 1.24, 95%CI:1.11-1.40) and psoriasis still showed a causal relationship. In contrast, in the reverse Mendelian randomization results, there was no evidence of an association between these skin diseases and gut microbiota. We demonstrated a causal relationship between gut microbiota and immune skin diseases and provide a new therapeutic perspective for the study of immune diseases: targeted modulation of dysregulation of specific bacterial taxa to prevent and treat psoriasis, atopic dermatitis, acne, and lichen planus.

CAN AI MAKE A CASE?AI VS. LAWYER IN THE DUTCH LEGAL CONTEXT

The integration of AI, specifically GPT-4, into the legal field is a subject of both potential promise and intricate challenges. This thesis delves into the transformational possibilities of AI within the Dutch legal context, examining not only the quality and persuasiveness of AI-generated legal argumentation but also its competence in information retrieval, as measured by models’ ability to spot relevant legal issues. An experiment was conducted with 25 legal professionals, using a real-world Dutch case with the purpose to assess GPT-4’s capabilities against that of a human lawyer. To enable GPT-4 to handle case documents, the author first performed so-called co-reference resolution to remove ambiguities. Given the token limitations of GPT-4, a so-called prompt reducer technique was used to compress the text, retaining essential information. The above methods produced a coherent and full case summary within GPT-4’s token constraints. This case summary, together with original lawyer’s letter (denoted as Text A) was fed to ChatGPT-4 to obtain its AI-written alternative (Text B). The study subjects were presented with a case summary as well as both texts and asked for their preferences. The outcome of the experiment is as follow: 80% of participants chose the AI’s composed legal document, demonstrating a strong preference for both its linguistic competencies as well its ability to spot relevant legal issues. This preference for GPT-4 writing is very consistent among genders, age groups and professionssurveyed. Contextualising these findings within the broader implications for legal practice, the thesis explores potential benefits including increased access to justice and transformation of certain legal procedures. Insights and recommendations are offered for legal professionals, considering the technological evolution and ethical considerations inherent in AI integration. Acknowledging the need for further exploration, the study recognises its own limitations and encourages replication to solidify the understanding of AI’s transformative role in the legal realm.

Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.

Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.

#FTDQuickQuestions: An FTD Disorders Registry (FTDDR) Monthly Engagement Survey to Gather Real‐time Insights to Inform Research

AbstractBackgroundFrontotemporal degeneration is a group of rare brain diseases that cause progressive changes to behavior, personality, language, and movement with onset typically before age 60. There are no treatments or cures. FTDDR is an international, web‐based registry (participants n&gt;5,700) that facilitates clinical trial enrollment by collecting disease insights, summarizing data, and mobilizing potential research volunteers. FTDDR uses various data collection and engagement tools to interact with participants and the community at large. Quick Questions was concepted as a mechanism to gather real‐time, cross‐sectional, anonymous data from a broad response‐base not limited by Registry participation.Method#FTDQuickQuestions campaign incorporates social, email, and web to reach members and visitors to collect their data, strengthen existing relationships, connect with people who could benefit from Registry services, and inform research. Each month a pre‐approved question was posted to Facebook and Twitter, linking to a webform with polling options and collected for 2 weeks. Respondent’s location is indexed through IP address. Additionally, the question was emailed to FTDDR participants with brief highlights of the previous survey and a link to view results for it and prior surveys. Full summaries were posted as weblogs.ResultThe survey was launched in June 2022 with the question: Have you tried to get genetic testing for FTD over the last 3 years? Questions have related to FTD research participation, age of diagnosis, age first symptom appeared, where diagnosed person lived. At least one other demographic question is asked to characterize the respondent, including gender or relationship to FTD‐diagnosed person. Number of respondents for the first 7 questions ranged between 555‐857; monthly average 735. Except the initial survey, &gt;75% of responses were received within 24 hours of email. Responses reflect 41 countries; including all 50 U.S. states and the District of Columbia; and 10 Canadian provinces/territories. Majority are women (62%); a third men (35%); 3% declined providing gender.ConclusionFTDDR’s #FTDQuickQuestions is a successful monthly engagement mechanism that enables quick, timely responses to questions about this disease and the people affected by it. While related questions cannot be compared nor connected, this valuable information serves as a cross‐sectional snapshot to inform FTD research.

A Prospective, Exploratory, Phase II Study of the Xpo-1 Inhibitor Selinexor in Combination with RCHOP in Double/Triple-Hit Large B-Cell Lymphoma

Background Double-hit (DH) lymphoma or triple-hit (TH) lymphoma, according to 2016 WHO Classification Criteria, is recognized as a distinct subset of non-Hodgkin lymphoma. The optimal treatment for DH/TH lymphoma remains unclear, although outcomes are inadequate with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) alone. Selinexor is a first-in-class, oral therapeutic that forms a slowly reversible covalent bond with cytoplasm by exportin 1 (XPO1/CRM1), leading to its inactivation. The U.S. Food and Drug Administration has approved selinexor monotherapy for relapsed/refractory DLBCL. Previous studies also suggested that selinexor was used to treat 5 patients with relapsed/refractory DH lymphoma, and 1 patient achieved CR and 2 achieved PR. Here, we report on the efficacy and safety of selinexor in combination with RCHOP as first-line treatment in patients with DH or TH lymphoma. Methods This prospective, phase 2, exploratory study was conducted in Zhejiang Cancer Hospital. The primary endpoint of the study was to evaluate the objective response rate (ORR), including complete remission (CR) rate and partial remission (PR) rate. In addition, diagnostic tumor tissue was prepared to conduct NGS analysis, and dynamic peripheral blood samples were collected before treatment, after 4 cycles when achieving CR from first-line chemotherapy, and progression of disease, to conduct ctDNA analysis. The initial dose of each drug in this regimen is as follows (repeat every 21 days, 6 cycles in total): rituximab: 375mg/m 2, d0; vindesine 4mg, d1; epirubicin 75mg/m 2, d1 (or liposomal doxubicin 35mg/m 2, d1); cyclophosphamide: 750mg/m 2, d1; prednisone: 100mg, d1-5; selinexor 60mg orally once a week. AEs were assessed according to the National Cancer Institute Common Terminology Criteria (CTCAE, version 4.0). Results From May, 2022, 8 patients were enrolled in the study, including 5 females and 3 males. All patients had received at least 2 cycles of selinexor with RCHOP. A full summary of patient baseline characteristics and response to chemotherapy was shown in Table 1. Four patients have completed full cycles of chemotherapy, while 2 patients are still undergoing treatment, and 2 patients suspended subsequent chemotherapy due to rejection of antitumor treatment. A total of 34 cycles of chemotherapy have been completed. Best responses after induction as assessed by positron emission tomography/CT were 5 CRs and 3 PRs. Two patients received ASCT as consolidation therapy after achieving CR. CNS prophylaxis with intrathecal methotrexate was administered to all patients for 2-6 cycles. No patient experienced disease progression, and no patient had CNS involvement during follow-up period (Figure 1A). All patients were assessable for toxicity. All patients in the study received prophylactic granulocyte colony-stimulating factor after each cycle of chemotherapy. The most common hematologic toxicities included anemia (15/34, 44.1%), neutropenia (20/34, 58.8%), thrombocytopenia (13/34, 38.2%), leukopenia (10/34, 29.4%). Other nonhematologic toxicities included fever (6/34, 17.6%), nausea (16/34, 47.1%), vomiting (13/34, 38.2%), fatigue (20/34, 58.9%), and infection (5/34, 14.7%). NGS was conducted successfully in 3 patients, while another 5 patients could not provide NGS data due to insufficient tumor tissue. 139 somatic alterations were detected in 3 patients, with a median of 30 mutations per sample. BCL6/IGLL5/TMSB4X were the most frequently mutated gene in 100% of patients followed by 66.7% who had BTG2/ETS1/EZH2/MYC/NFKBIE/OSBPL10/SOCS1/TNFRSF14 mutations. TP53 mutations were detected in 33.3% of the patient (Figure 1B). In 71.4% (5/7) of the cases, we were able to detect a total of 143 variants in the ctDNA from pretreatment serum samples. 80 variants were detected in both tumor tissue and peripheral blood samples. 4 variants were detected only in the ctDNA, and 59 were detected only in the tissue biopsy. Serial ctDNA monitoring results showed that 100% (8/8) reduction to zero in ctDNA after 4 cycles of chemotherapy. Conclusions Selinexor combined with RCHOP may be an effective first-line regimen for patients with DH/TH lymphoma. Dynamic testing of ctDNA demonstrated deep remission to chemotherapy. Based on the encouraging results of the current study, a large scale, multicenter trial is needed to further investigate this promising regimen.

Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis

Recently, large scale genomic projects such as All of Us and the UK Biobank have introduced a new research paradigm where data are stored centrally in cloud-based Trusted Research Environments (TREs). To characterize the advantages and drawbacks of different TRE attributes in facilitating cross-cohort analysis, we conduct a Genome-Wide Association Study of standard lipid measures using two approaches: meta-analysis and pooled analysis. Comparison of full summary data from both approaches with an external study shows strong correlation of known loci with lipid levels (R2 ~ 83–97%). Importantly, 90 variants meet the significance threshold only in the meta-analysis and 64 variants are significant only in pooled analysis, with approximately 20% of variants in each of those groups being most prevalent in non-European, non-Asian ancestry individuals. These findings have important implications, as technical and policy choices lead to cross-cohort analyses generating similar, but not identical results, particularly for non-European ancestral populations.

Pharmacognostic and Pharmacolgical Profile of Amomum subulatum, ‘Black Cardamom’

Abstract: Amomum subulatum is a well-known aromatic spice that has been used for many years to treat a wide range of health issues. The literature search was limited to English-language research papers using PubMed, Google Scholar, Elsevier, NCBI, Springer, Wiley Online Library, Web of Science, Scopus, and Science Direct databases. For the review, significant information on the pharmacological activities of A. subulatum, such as anti-inflammatory, nephroprotective, hepatoprotective, antioxidant, antidiabetic, and so on, was gathered. The profusion of secondary metabolites found in this medicinal herb may be responsible for its pharmacological activities. Preliminary phytochemical screening revealed a high concentration of terpenoids, flavonoids, steroids, minerals, vitamins, and other compounds. The significant phytochemicals reported from A. subulatum include limonene, 1,8-cineole, terpineol, and many others. The current review provides a full summary of current knowledge on A. subulatum, including its phytoconstituents and pharmacological applications.

Improving the Accuracy of Marginal Approximations in Likelihood-Free Inference via Localization

Likelihood-free methods are an essential tool for performing inference for implicit models which can be simulated from, but for which the corresponding likelihood is intractable. However, common likelihood-free methods do not scale well to a large number of model parameters. A promising approach to high-dimensional likelihood-free inference involves estimating low-dimensional marginal posteriors by conditioning only on summary statistics believed to be informative for the low-dimensional component, and then combining the low-dimensional approximations in some way. In this article, we demonstrate that such low-dimensional approximations can be surprisingly poor in practice for seemingly intuitive summary statistic choices. We describe an idealized low-dimensional summary statistic that is, in principle, suitable for marginal estimation. However, a direct approximation of the idealized choice is difficult in practice. We thus suggest an alternative approach to marginal estimation which is easier to implement and automate. Given an initial choice of low-dimensional summary statistic that might only be informative about a marginal posterior location, the new method improves performance by first crudely localizing the posterior approximation using all the summary statistics to ensure global identifiability, followed by a second step that hones in on an accurate low-dimensional approximation using the low-dimensional summary statistic. We show that the posterior this approach targets can be represented as a logarithmic pool of posterior distributions based on the low-dimensional and full summary statistics, respectively. The good performance of our method is illustrated in low to moderate dimensional examples. Computer code to implement the methods for the examples of this article is available at https://github.com/cdrovandi/ABC-marginal-approximations.

Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population.

We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns. The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed. In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10-83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10-6 (0.05/13,114); DEFB108B had the lowest p=5.94×10-15, followed by FAM86C1 (p=1.74×10-14), PSCA (p=1.81×10-14), and KLHDC4 (p=5.00×10-10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway. While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.

Volatile Organic Compound Emissions from Disinfectant Usage in the Home and Office.

Volatile Organic Compound Emissions from Disinfectant Usage in the Home and Office.

The hepato-ovarian axis: genetic evidence for a causal association between non-alcoholic fatty liver disease and polycystic ovary syndrome

BackgroundRecent studies found associations between non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS), but the causal nature of this association is still uncertain.MethodsWe performed a bidirectional two-sample Mendelian randomization (MR) analysis to test for the causal association between NAFLD and PCOS using data from a large-scale biopsy-confirmed NAFLD genome-wide association study (GWAS) (1483 cases and 17,781 controls) and PCOS GWAS (10,074 cases and 103,164 controls) in European ancestries. Data from glycemic-related traits GWAS (in up to 200,622 individuals) and sex hormones GWAS (in 189,473 women) in the UK Biobank (UKB) were used in the MR mediation analysis to assess potential mediating roles of these molecules in the causal pathway between NAFLD and PCOS. Replication analysis was conducted using two independent datasets from NAFLD and PCOS GWASs in the UKB and a meta-analysis of data from FinnGen and the Estonian Biobank, respectively. A linkage disequilibrium score regression was conducted to assess genetic correlations between NAFLD, PCOS, glycemic-related traits, and sex hormones using full summary statistics.ResultsIndividuals with higher genetic liability to NAFLD were more likely to develop PCOS (OR per one-unit log odds increase in NAFLD: 1.10, 95% CI: 1.02–1.18; P = 0.013). Indirect causal effects of NAFLD on PCOS via fasting insulin only (OR: 1.02, 95% CI: 1.01–1.03; P = 0.004) and further a suggestive indirect causal effect via fasting insulin in concert with androgen levels were revealed in MR mediation analyses. However, the conditional F statistics of NAFLD and fasting insulin were less than 10, suggesting likely weak instrument bias in the MVMR and MR mediation analyses.ConclusionsOur study suggests that genetically predicted NAFLD was associated with a higher risk of developing PCOS but less evidence for vice versa. Fasting insulin and sex hormones might mediate the link between NAFLD and PCOS.

Community pharmacists' attitudes towards, and experiences of, providing medication reviews after hospital discharge: a questionnaire survey.

To investigate the attitudes and experiences of community pharmacists providing medicines-use review (MUR) and post-discharge medicines-use review (PD-MUR) services. An online survey for community pharmacists who had experience providing the MUR service. In total, 495 community pharmacists responded to the survey. A total of 89% (n = 382) of community pharmacists wanted to receive the patient's full discharge summary and 79% (n = 363) preferred electronic communication. Community pharmacists thought they could build trusted relationships with patients and felt that patients were willing to discuss post-discharge medicines-related issues with them. Less experienced pharmacists conducted more MURs than more experienced pharmacists (P = 0.004), and pharmacists working in large multiples (>50 pharmacies) conducted more MURs than those working in independent pharmacies (<5 pharmacies) (P = 0.001). Community pharmacists working in independent pharmacies conducted more PD-MURs than those working in large multiples (P = 0.004). Community pharmacists working in rural areas also thought they were best placed to provide PD-MURs while those working in urban areas thought that practice pharmacists were best suited to provide this service (P = 0.007). Community pharmacists believe they have a vital role in supporting patients after hospital discharge. They can build long-lasting, trusted relationships with patients and patients are willing to discuss medication issues with them. By providing community pharmacists in all locations with timely access to accurate discharge information, they could use their knowledge and skills to better support patients after hospital discharge.

The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.

The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to>200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for>45 000 published GWAS across>5000 human traits, and>40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.

The Use of Corpus in English Writing: Scholarly Development and Implications

Corpus linguistics, as a methodological paradigm, is one of the striking fields in recent scholarly advancement. Its use in theoretical and practical explorations is generally accepted as a productive and efficient approach to provide affirmative support and empirical data and therefore, is wildly seen in disciplines of languages, linguistics and education. English writing, one of the commonest English language skills and a key area of studies for applied linguistics, has also aroused many interests in its integration with corpus linguistics. The use of corpus in English writing, though having achieved rich products in scholarly studies, still lacks a systematic investigation or a full summary on what have been developed and inspired. To fill in this gap, this study is aimed: by a bibliometric-and-corpus analysis on the titles, abstracts, and keywords, etc. of the scholarly articles of corpus and English writing, to find out their concerns, conclusions and implications.