bluuebunny/crossref_metadata_2025_split huggingface dataset:
GST polymorphism as a predictive biomarker for modulating the susceptibility to chronic obstructive pulmonary disease: A North Indian study
Authors: Yadav Harsh , Pandit Depanshi , Singh Sidhartha , Sharma Parul , Garg Kranti , Girdhar Nidhi , Sharma Karan , Chopra Vishal , Chopra Siddharth , Sharma Siddharth 
Published: November 2023

AbstractChronic obstructive pulmonary disease (COPD) is commonly characterized by shortness of breath, coughing or expectoration. Smoking is the leading cause of COPD development, but only a small percentage of smokers develop symptoms, implying a genetic component. Glutathione S‐transferase enzymes are responsible for detoxifying cigarette smoke components. The role of glutathione S‐transferase T1 (GSTT1) and glutathione S‐transferase M1 (GSTM1) gene polymorphism was assessed with COPD susceptibility and associated clinical parameters in the North Indian population. This was a cross‐sectional study involving 200 COPD patients and 200 healthy individuals, with peripheral blood sampling and adequate questionnaires. Multiplex PCR was used for genotyping GSTT1 and GSTM1 gene polymorphism. Logistic regression was used to calculate the odds ratio and 95% confidence intervals to assess the COPD risk and GST polymorphisms. The GSTT1 gene deletion rate was higher in COPD cases (34.5%) than in healthy individuals (20.5%). A statistical relationship between the GSTT1(−) null genotype and COPD risk was observed (odds ratio = 2.04, 95% CI = 1.30–3.20, P = 0.0019). After adjusting for covariates like age, sex and smoking status, a significant association was found for GSTT1(−) null genotype and COPD risk (adjusted odds ratio = 2.90, 95% CI = 1.43–5.87, P = 0.003). The GSTT1(−) genotype was also significantly correlated with clinical parameters for COPD risk. Another primary observation was that females with the GSTT1(−) null genotype were more vulnerable to COPD than males with the same gene deletion. The GSTT1(−) null genotype strongly correlates with COPD development, while no association was observed in the GSTM1(−) null genotype in the North Indian population.
Eukaryotic genomes from a global metagenomic data set illuminate trophic modes and biogeography of ocean plankton
Authors: Alexander Harriet , Hu Sarah K. , Krinos Arianna I. , Pachiadaki Maria , Tully Benjamin J. , Neely Christopher J. , Reiter Taylor 
Published: November 2023

ABSTRACT
Metagenomics is a powerful method for interpreting the ecological roles and physiological capabilities of mixed microbial communities. Yet, many tools for processing metagenomic data are neither designed to consider eukaryotes nor are they built for an increasing amount of sequence data. EukHeist is an automated pipeline to retrieve eukaryotic and prokaryotic metagenome-assembled genomes (MAGs) from large-scale metagenomic sequence data sets. We developed the EukHeist workflow to specifically process large amounts of both metagenomic and/or metatranscriptomic sequence data in an automated and reproducible fashion. Here, we applied EukHeist to the large-size fraction data (0.8–2,000 µm) from Tara Oceans to recover both eukaryotic and prokaryotic MAGs, which we refer to as TOPAZ (Tara Oceans Particle-Associated MAGs). The TOPAZ MAGs consisted of >900 environmentally relevant eukaryotic MAGs and >4,000 bacterial and archaeal MAGs. The bacterial and archaeal TOPAZ MAGs expand upon the phylogenetic diversity of likely particle- and host-associated taxa. We use these MAGs to demonstrate an approach to infer the putative trophic mode of the recovered eukaryotic MAGs. We also identify ecological cohorts of co-occurring MAGs, which are driven by specific environmental factors and putative host-microbe associations. These data together add to a number of growing resources of environmentally relevant eukaryotic genomic information. Complementary and expanded databases of MAGs, such as those provided through scalable pipelines like EukHeist, stand to advance our understanding of eukaryotic diversity through increased coverage of genomic representatives across the tree of life.

IMPORTANCE
Single-celled eukaryotes play ecologically significant roles in the marine environment, yet fundamental questions about their biodiversity, ecological function, and interactions remain. Environmental sequencing enables researchers to document naturally occurring protistan communities, without culturing bias, yet metagenomic and metatranscriptomic sequencing approaches cannot separate individual species from communities. To more completely capture the genomic content of mixed protistan populations, we can create bins of sequences that represent the same organism (metagenome-assembled genomes [MAGs]). We developed the EukHeist pipeline, which automates the binning of population-level eukaryotic and prokaryotic genomes from metagenomic reads. We show exciting insight into what protistan communities are present and their trophic roles in the ocean. Scalable computational tools, like EukHeist, may accelerate the identification of meaningful genetic signatures from large data sets and complement researchers’ efforts to leverage MAG databases for addressing ecological questions, resolving evolutionary relationships, and discovering potentially novel biodiversity.
Development of a CRISPR-Cas12a system for efficient genome engineering in clostridia
Authors: Zhang Yanchao , Kubiak Aleksandra M. , Bailey Tom S. , Claessen Luuk , Hittmeyer Philip , Dubois Ludwig , Theys Jan , Lambin Philippe 
Published: November 2023

ABSTRACT

Clostridium
species have gained attention in industrial and medical applications, and the development of genetic tools has enabled the advancement of the CRISPR-Cas systems for these bacteria. Compared to the primarily used Cas9 from
Streptococcus pyogenes
, the utilization of Cas12a (previously known as Cpf1) proteins remains incomplete in clostridia, although they exhibit potential advantages, including T-rich recognition for
Clostridium
genomes and lower toxicity. In this study, we expanded the CRISPR-Cas tools in clostridia by establishing a CRISPR-Cas12a system with two different
cas12a
genes (
Ascas12a
from
Acidaminococcus
and
Fncas12a
from
Francisella novicida
). The optimized tetracycline-inducible systems were initially determined by the glucuronidase reporter and were used to drive expression of the
cas12a
genes and crRNAs. Our results demonstrate that the CRISPR-FnCas12a system offers flexible target selection in clostridia, and a specific folding pattern of the precursor crRNA is important to enable high mutation generation efficiency. By using
sacB
(encoding levansucrase) as a negative marker for plasmid curing and determining the optimal size of the donor DNA template for gene integration in the CRISPR-FnCas12a system, we achieved highly efficient and rapid genome modification, exemplified by the successful engineering of clostridia (
Clostridium butyricum
and
Clostridium sporogenes
) to produce near-infrared fluorescence from biliverdin and hemin.

IMPORTANCE

Continued efforts in developing the CRISPR-Cas systems will further enhance our understanding and utilization of
Clostridium
species. This study demonstrates the development and application of a genome-engineering tool in two
Clostridium
strains,
Clostridium butyricum
and
Clostridium sporogenes
, which have promising potential as probiotics and oncolytic agents. Particular attention was given to the folding of precursor crRNA and the role of this process in off-target DNA cleavage by Cas12a. The results provide the guidelines necessary for efficient genome engineering using this system in clostridia. Our findings not only expand our fundamental understanding of genome-engineering tools in clostridia but also improve this technology to allow use of its full potential in a plethora of biotechnological applications.
CD4
+
T cells reverse surface antigen persistence in a mouse model of HBV replication
Authors: Bailey Jacob T. , Moshkani Safiehkhatoon , Rexhouse Catherine , Cimino Jesse L. , Robek Michael D. 
Published: November 2023

ABSTRACT

Hepatitis B virus (HBV) is responsible for over 800,000 deaths yearly worldwide. While chronic HBV infection currently has no highly effective cure, immunotherapy has generated interest as a potential therapeutic solution due to the connection between viral chronicity and the magnitude of HBV-specific immune responses. Suitable animal models for studying successful immune responses to HBV are limited due to the lack of natural viral tropism for rodents. Using a mouse model of HBV replication, we found that CD4
+
T cells are essential for the antibody-mediated clearance of hepatitis B surface antigen (HBsAg) and that early transient inhibition of the CD4
+
T cell-B cell axis imparts HBsAg persistence through CD4
+
T cell functional impairment. HBsAg resolution in BALB/c mice transduced with an adeno-associated virus encoding the HBV genome (AAV-HBV) depended on B cells, MHCII, and CD4
+
T cells, but not CD8
+
T cells, indicative of antibody-mediated control. Furthermore, disrupting the CD40-CD40L interaction blunted HBsAg clearance and the generation of HBsAg-specific B cells. Finally, HBsAg persistence induced by transient CD4 depletion was reversible by the transfer of total splenocytes or purified CD4
+
T cells from immunized mice. These findings demonstrate the T cell-dependent nature of HBsAg-resolving antibody responses as well as the ability of CD4
+
T cells to reverse HBsAg persistence.

IMPORTANCE
Hepatitis B virus (HBV) is a leading causative agent of viral hepatitis. A preventative vaccine has existed for decades, but only limited treatment options are available for people living with chronic HBV. Animal models for studying HBV are constrained due to narrow viral tropism, impeding understanding of the natural immune response to the virus. Here, using a vector to overcome the narrow host range and establish HBV replication in mice, we identified the role of helper T cells in controlling HBV. We show that helper T cells promote the B cell’s ability to generate antibodies that remove HBV and its associated surface antigen from the blood and that transfer of purified helper T cells from HBV-immunized mice can reverse the accumulation of virus and antigen, furthering our understanding of the immune response to HBV.
Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study
Authors: Pradhan Richeek , Yu Oriana H Y , Platt Robert W , Azoulay Laurent 
Published: November 2023

IntroductionThe dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas.Research design and methodsUsing the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019. For melanoma, the cohort included 96 739 DPP-4 inhibitor users and 209 341 sulfonylurea users, and 96 411 DPP-4 inhibitor users and 208 626 sulfonylurea users for non-melanoma skin cancer. Propensity score fine stratification weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs of melanoma and non-melanoma skin cancer, separately.ResultsOverall, DPP-4 inhibitors were associated with a 23% decreased risk of melanoma compared with sulfonylureas (49.7 vs 65.3 per 100 000 person-years, respectively; HR 0.77, 95% CI 0.61 to 0.96). The HR progressively reduced with increasing cumulative duration of use (0–2 years HR 1.14, 95% CI 0.84 to 1.54; 2.1–5 years HR 0.44, 95% CI 0.29 to 0.66; >5 years HR 0.33, 95% CI 0.14 to 0.74). In contrast, these drugs were not associated with the incidence of non-melanoma skin cancer, compared with sulfonylureas (448.1 vs 426.1 per 100 000 person-years, respectively; HR 1.06, 95% CI 0.98 to 1.15).ConclusionsIn this large, population-based cohort study, DPP-4 inhibitors were associated with a reduced risk of melanoma but not non-melanoma skin cancer, compared with sulfonylureas.
Ethnic disparities in progression rates for sight-threatening diabetic retinopathy in diabetic eye screening: a population-based retrospective cohort study
Authors: Olvera-Barrios Abraham , Owen Christopher G , Anderson John , Warwick Alasdair N , Chambers Ryan , Bolter Louis , Wu Yue , Welikala Roshan , Fajtl Jiri , Barman Sarah A , Remagnino Paolo , Chew Emily Y , Ferris Frederick L , Hingorani Aroon D , Sofat Reecha , Lee Aaron Y , Egan Catherine , Tufail Adnan , Rudnicka Alicja R 
Published: November 2023

IntroductionThe English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse multi-ethnic population.Research design and methodsNorth East London DESP cohort data (January 2012 to December 2021) with 137 591 PLD with no retinopathy, or non-STDR at baseline in one/both eyes, were used to calculate STDR incidence rates by sociodemographic factors, diabetes type, and duration. HR from Cox models examined associations with STDR.ResultsThere were 16 388 incident STDR cases over a median of 5.4 years (IQR 2.8–8.2; STDR rate 2.214, 95% CI 2.214 to 2.215 per 100 person-years). People with no retinopathy at baseline had a lower risk of sight-threatening diabetic retinopathy (STDR) compared with those with non-STDR in one eye (HR 3.03, 95% CI 2.91 to 3.15, p<0.001) and both eyes (HR 7.88, 95% CI 7.59 to 8.18, p<0.001). Black and South Asian individuals had higher STDR hazards than white individuals (HR 1.57, 95% CI 1.50 to 1.64 and HR 1.36, 95% CI 1.31 to 1.42, respectively). Additionally, every 5-year increase in age at inclusion was associated with an 8% reduction in STDR hazards (p<0.001).ConclusionsEthnic disparities exist in a health system limited by capacity rather than patient economic circumstances. Diabetic retinopathy at first screen is a strong determinant of STDR development. By using basic demographic characteristics, screening programmes or clinical practices can stratify risk for sight-threatening diabetic retinopathy development.
A collective autoethnography of coproduction in mental health research by academic researchers and young people in Brazil
Authors: Siston Felipe Rodrigues , Murta Sheila Giardini , Mendes Josimar Antônio de Alcântara , Ferreira Julyana Alves , Santos Victor Hugo de Lima , Seabra Brenda Thallys Rocha , de Souza Rafa Ribeiro Alves , da Cunha Rafaela de Oliveira , Pavarini Gabriela 
Published: November 2023

IntroductionCoproduction of mental health research and interventions involving researchers and young people is increasingly common. However, this model raises challenges, related, for instance, to communication, power and control. This paper narrates—from a collective first-person perspective—the lived experience of coproduction of a digital intervention by institutional researchers and young citizen researchers in Brazil.MethodThis study employed a collaborative autoethnographic methodology, utilising autobiographical data such as meeting recordings, individual notes and collective guided reflections on the coproduction process. Our analysis focused on challenges and solutions that arose during the process.ResultsThroughout the project, we created formal and informal mechanisms for accountability, transparency and fair inclusion of multiple voices. We engaged in mutual capacity-building, invested in building interpersonal knowledge, and implemented practices to reduce overload and promote equitable participation. Through ongoing reflection and readjustment in response to challenges, we progressively embraced more democratic and egalitarian values. The collective care invested in the process fostered synergy, trust, and intergroup friendship.ConclusionOur experience points to the value of creating a space for multiple research identities: the citizen young person and the institutional researcher, both of whom critically reflect on their roles in the research process. Our focus on coproduced care calls into question participation metaphors that represent the process via a single axis—young people—who linearly progress from minimal participation to full autonomy. Instead, our analysis highlights the importance of a social and caring bond that supports the radical co-production of innovative health solutions in contexts of vulnerability.
Gender disparities, causes and predictors of immediate and short-term cardiovascular readmissions following COVID-19-related hospitalisations in the USA
Authors: Vardar Ufuk , Shaka Hafeez , Kumi Dennis , Gajjar Rohan , Bess Olva , Kanemo Philip , Shaka Abdultawab , Baskaran Naveen 
Published: November 2023

ObjectivesIn this study, we aimed to identify the causes, predictors and gender disparities of 30-day and 90-day cardiovascular readmissions after COVID-19-related hospitalisations using National Readmission Database (NRD) 2020.SettingWe used the NRD from 2020 to identify hospitalised adults with a principal diagnosis of COVID-19 infection.ParticipantsWe included subjects who were readmitted within 30 days and 90 days after index admission. We excluded subjects with elective and traumatic admissions. We used a multivariate Cox regression model to identify independent predictors of readmission.Primary and secondary outcomes measuresOur outcomes were inpatient mortality, 30-day and 90-day cardiovascular readmission rates following COVID-19 infection.ResultsDuring the study period, there were 1 024 492 index hospitalisations with a primary diagnosis of COVID-19 infection in the 2020 NRD database, 644 903 (62.9%) were included for 30-day readmission analysis, and 418 122 (40.8%) were included for 90-day readmission analysis. Of patients involved in the 30-day analysis, 7140 (1.1%) patients had a readmission within 30 days; of patients involved in the 90-day analysis, 8379 (2.0%) had a readmission within 90 days due to primarily cardiovascular causes. Cox regression analysis revealed that the female sex (aHR 0.89; 95% CI 0.82 to 0.95; p=0.001) was associated with a lower hazard of 30-day cardiovascular readmissions; however, congestive heart failure (aHR 2.45; 95% CI 2.2 to 2.72; p<0.001), arrhythmias (aHR 2.45; 95% CI 2.2 to 2.72; p<0.001) and valvular disease (aHR 2.45; 95% CI 2.2 to 2.72; p<0.001) had a higher hazard. The most common causes of cardiovascular readmissions were heart failure (34.3%), deep vein thrombosis/pulmonary embolism (22.5%) and atrial fibrillation (9.5%).ConclusionOur study demonstrates that male gender, heart failure, arrhythmias and valvular disease carry higher hazards of 30-day and 90-day cardiovascular readmissions. Identifying risk factors and common causes of readmission may assist with lowering the burden of cardiovascular disease in patients with COVID-19 infection.
Investigating the ability to adhere to cardiometabolic medications with different properties: a retrospective cohort study of >500 000 patients in the USA
Authors: Lauffenburger Julie C , Tesfaye Helen , Solomon Daniel H , Antman Elliott M , Glynn Robert J , Lee Su Been , Tong Angela , Choudhry Niteesh K 
Published: November 2023

ObjectivePoor medication adherence remains highly prevalent and adversely affects health outcomes. Patients frequently describe properties of the pills themselves, like size and shape, as barriers, but this has not been evaluated objectively. We sought to determine the extent to which oral medication properties thought to be influential translate into lower objectively-measured adherence.DesignRetrospective cohort study.SettingUS nationwide commercial claims database, 2016–2019.ParticipantsAmong patients initiating first-line hypertension, diabetes or hyperlipidaemia treatment based on clinical guidelines, we measured pill size, shape, colour and flavouring, number of pills/day and fixed-dose combination status as properties.Outcome measuresOutcomes included discontinuation after the first fill (ie, never filling again over a minimum of 1-year follow-up) and long-term non-adherence (1-year proportion of days covered <0.80). We estimated associations between each property and outcomes, by therapeutic class (eg, statins), with multivariable logistic regression.ResultsAcross 604 323 patients, 14.6% discontinued after filling once (ie, were non-persistent), and 54.0% were non-adherent over 1-year follow-up. Large pill size was associated with non-adherence, except for thiazides (eg, metformin adjusted OR (aOR): 1.12, 95% CI: 1.06 to 1.18). Greater pill burden was associated with a higher risk of non-adherence across all classes (eg, metformin aOR: 1.58, 95% CI: 1.53 to 1.64 for two pills/day). Taking less than one pill/day was also associated with higher risk of non-adherence and non-persistence (eg, non-persistence statin aOR: 1.29, 95% CI: 1.20 to 1.38). Pill shape, colour, flavouring and combination status were associated with mixed effects across classes.ConclusionsPill burden and pill size are key properties affecting adherence for almost all classes; others, like size and combination, could modestly affect medication adherence. Clinical interventions could screen patients for potential intolerance to medication and potentially implement more convenient dosing schedules.
Laser and radiofrequency for treating genitourinary syndrome of menopause in breast cancer survivors: a systematic review and meta-analysis protocol
Authors: Serquiz Nicoli , Sarmento Ayane Cristine Alves , Almeida Natalie Rios , Nobre Maria Luisa , Medeiros Kleyton Santos , Oliveira Ronnier de , Costa Ana Paula Ferreira , Gonçalves Ana Katherine 
Published: November 2023

IntroductionBreast cancer survivors (BCSs) experience more severe symptoms of genitourinary syndrome of menopause (GSM) than healthy postmenopausal women. As hormonal therapy with oestrogen should be avoided in BCSs, finding an effective and safe therapy to address vaginal symptoms and sexual dysfunction is urgently needed. Physical methods may be promising alternatives for the specificities of this group of women. This review aims to evaluate the efficacy and safety of physical methods (laser and radiofrequency) for treating GSM in BCSs.Methods and analysisThe PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases will be searched. A search strategy was developed to retrieve clinical trials that evaluate the efficacy and safety of any physical method (laser or radiofrequency) used for GSM in BCSs. No date or language restrictions will be imposed. Two authors will independently select studies by title, abstract and full text to meet the inclusion criteria. Data will be extracted, and the risk of bias will be evaluated using the Cochrane risk-of-bias tool (RoB 2). Review Manager 5.4.1 will be used for data synthesis. The Grading of Recommendations, Assessment, Development and Evaluation will be used to assess the strength of the evidence.Ethics and disseminationThis study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42023387680.