bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of prior outpatient diabetes screening with cardiovascular events and mortality among people with incident diabetes: a population-based cohort study
Authors: Ke Calvin , Chu Anna , Shah Baiju R. , Tobe Sheldon , Tu Karen , Fang Jiming , Vaid Haris , Liu Peter , Cader Aishah , Lee Douglas S. 
Published: August 2023

Abstract
Background
Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada.

Methods
We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014–2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death.

Results
We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63–0.69) and mortality (0.68, 0.64–0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77–0.88) and mortality (0.71, 0.66–0.78) outcomes than a result in the normoglycemic range.

Conclusions
Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults.
Discovery of novel JAK1 inhibitors through combining machine learning, structure-based pharmacophore modeling and bio-evaluation
Authors: Wang Zixiao , Sun Lili , Xu Yu , Liang Peida , Xu Kaiyan , Huang Jing 
Published: August 2023

Abstract
Background
Janus kinase 1 (JAK1) plays a critical role in most cytokine-mediated inflammatory, autoimmune responses and various cancers via the JAK/STAT signaling pathway. Inhibition of JAK1 is therefore an attractive therapeutic strategy for several diseases. Recently, high-performance machine learning techniques have been increasingly applied in virtual screening to develop new kinase inhibitors. Our study aimed to develop a novel layered virtual screening method based on machine learning (ML) and pharmacophore models to identify the potential JAK1 inhibitors.

Methods
Firstly, we constructed a high-quality dataset comprising 3834 JAK1 inhibitors and 12,230 decoys, followed by establishing a series of classification models based on a combination of three molecular descriptors and six ML algorithms. To further screen potential compounds, we constructed several pharmacophore models based on Hiphop and receptor-ligand algorithms. We then used molecular docking to filter the recognized compounds. Finally, the binding stability and enzyme inhibition activity of the identified compounds were assessed by molecular dynamics (MD) simulations and in vitro enzyme activity tests.

Results
The best performance ML model DNN-ECFP4 and two pharmacophore models Hiphop3 and 6TPF 08 were utilized to screen the ZINC database. A total of 13 potentially active compounds were screened and the MD results demonstrated that all of the above molecules could bind with JAK1 stably in dynamic conditions. Among the shortlisted compounds, the four purchasable compounds demonstrated significant kinase inhibition activity, with Z-10 being the most active (IC50 = 194.9 nM).

Conclusion
The current study provides an efficient and accurate integrated model. The hit compounds were promising candidates for the further development of novel JAK1 inhibitors.
Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy
Authors: Hoffmann Emily , Schache Daniel , Höltke Carsten , Soltwisch Jens , Niland Stephan , Krähling Tobias , Bergander Klaus , Grewer Martin , Geyer Christiane , Groeneweg Linda , Eble Johannes A. , Vogl Thomas , Roth Johannes , Heindel Walter , Maus Bastian , Helfen Anne , Faber Cornelius , Wildgruber Moritz , Gerwing Mirjam , Hoerr Verena 
Published: August 2023

Abstract
Background
With metabolic alterations of the tumor microenvironment (TME) contributing to cancer progression, metastatic spread and response to targeted therapies, non-invasive and repetitive imaging of tumor metabolism is of major importance. The purpose of this study was to investigate whether multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST-MRI) allows to detect differences in the metabolic profiles of the TME in murine breast cancer models with divergent degrees of malignancy and to assess their response to immunotherapy.

Methods
Tumor characteristics of highly malignant 4T1 and low malignant 67NR murine breast cancer models were investigated, and their changes during tumor progression and immune checkpoint inhibitor (ICI) treatment were evaluated. For simultaneous analysis of different metabolites, multiparametric CEST-MRI with calculation of asymmetric magnetization transfer ratio (MTRasym) at 1.2 to 2.0 ppm for glucose-weighted, 2.0 ppm for creatine-weighted and 3.2 to 3.6 ppm for amide proton transfer- (APT-) weighted CEST contrast was conducted. Ex vivo validation of MRI results was achieved by 1H nuclear magnetic resonance spectroscopy, matrix-assisted laser desorption/ionization mass spectrometry imaging with laser postionization and immunohistochemistry.

Results
During tumor progression, the two tumor models showed divergent trends for all examined CEST contrasts: While glucose- and APT-weighted CEST contrast decreased and creatine-weighted CEST contrast increased over time in the 4T1 model, 67NR tumors exhibited increased glucose- and APT-weighted CEST contrast during disease progression, accompanied by decreased creatine-weighted CEST contrast. Already three days after treatment initiation, CEST contrasts captured response to ICI therapy in both tumor models.

Conclusion
Multiparametric CEST-MRI enables non-invasive assessment of metabolic signatures of the TME, allowing both for estimation of the degree of tumor malignancy and for assessment of early response to immune checkpoint inhibition.
Immune response in influenza virus infection and modulation of immune injury by viral neuraminidase
Authors: Jiang Hongyu , Zhang Zongde 
Published: August 2023

AbstractInfluenza A viruses cause severe respiratory illnesses in humans and animals. Overreaction of the innate immune response to influenza virus infection results in hypercytokinemia, which is responsible for mortality and morbidity. The influenza A virus surface glycoprotein neuraminidase (NA) plays a vital role in viral attachment, entry, and virion release from infected cells. NA acts as a sialidase, which cleaves sialic acids from cell surface proteins and carbohydrate side chains on nascent virions. Here, we review progress in understanding the role of NA in modulating host immune response to influenza virus infection. We also discuss recent exciting findings targeting NA protein to interrupt influenza-induced immune injury.
Inequalities in early initiation of breastfeeding in Bangladesh: an estimation of relative and absolute measures of inequality
Authors: Kundu Satyajit , Chowdhury Syed Sharaf Ahmed , Hasan Md Tamzid , Sharif Azaz Bin 
Published: August 2023

Abstract
Background
Evidence suggested that inequalities based on education, wealth status, place of residence, and geographical regions significantly influence the key breastfeeding indicators including early initiation of breastfeeding. This study aimed to estimate the trends and magnitude of inequalities in early initiation of breastfeeding practice in Bangladesh from 2004 to 2017 applying both absolute and relative measures of inequality.

Methods
We used data from the last five Bangladesh Demographic Health Survey (BDHS) from 2004 to 2017 to measure the inequalities in early initiation of breastfeeding practice using the WHO’s Health Equity Assessment Toolkit (HEAT) software. Following summary measures were estimated to measure the inequalities: Population Attributable Risk (PAR), Population Attributable Fraction (PAF), Difference (D), and Ratio (R) where the equity dimensions were wealth status, education level, sex of child, place of residence, and subnational regions (divisions). For each measure, point estimates along with a 95% confidence interval (CI) were reported.

Results
An uprising pattern in the prevalence of early initiation of breastfeeding was found, where early initiation of breastfeeding increased from 24.9% to 2004 to 59.0% in 2017. We found significant wealth-driven inequalities in early initiation of breastfeeding practice in every wave of survey favoring the poorest wealth quintile (in 2017, D -10.5; 95% CI -16.6 to -4.3). We also identified geographical disparities in early initiation of breastfeeding practice (in 2017, PAF 11.1; 95% CI 2.2 to 19.9) favoring the Rangpur (65.5%), and Sylhet (65.3%) divisions. Education-related disparities were observed in 2004 only, but not in later survey years, which was due to a much lower level of adherence among those with secondary or higher education. There were no significant disparities in early initiation of breastfeeding based on the urban vs. rural residence and sex of the child.

Conclusions
The highest attention should be placed in Bangladesh to attain the WHO’s 100% recommendation of timely initiation of breastfeeding. This study emphasizes on addressing the existing socioeconomic and geographic inequalities. Awareness-raising outreach programs focusing the mothers from wealthier sub-groups and divisions with lower prevalence should be planned and implemented by the joint effort of the government and non-government organizations.
A high-resolution genotype–phenotype map identifies the TaSPL17 controlling grain number and size in wheat
Authors: Liu Yangyang , Chen Jun , Yin Changbin , Wang Ziying , Wu He , Shen Kuocheng , Zhang Zhiliang , Kang Lipeng , Xu Song , Bi Aoyue , Zhao Xuebo , Xu Daxing , He Zhonghu , Zhang Xueyong , Hao Chenyang , Wu Jianhui , Gong Yan , Yu Xuchang , Sun Zhiwen , Ye Botao , Liu Danni , Zhang Lili , Shen Liping , Hao Yuanfeng , Ma Youzhi , Lu Fei , Guo Zifeng 
Published: August 2023

Abstract
Background
Large-scale genotype–phenotype association studies of crop germplasm are important for identifying alleles associated with favorable traits. The limited number of single-nucleotide polymorphisms (SNPs) in most wheat genome-wide association studies (GWASs) restricts their power to detect marker-trait associations. Additionally, only a few genes regulating grain number per spikelet have been reported due to sensitivity of this trait to variable environments.

Results
We perform a large-scale GWAS using approximately 40 million filtered SNPs for 27 spike morphology traits. We detect 132,086 significant marker-trait associations and the associated SNP markers are located within 590 associated peaks. We detect additional and stronger peaks by dividing spike morphology into sub-traits relative to GWAS results of spike morphology traits. We propose that the genetic dissection of spike morphology is a powerful strategy to detect signals for grain yield traits in wheat. The GWAS results reveal that TaSPL17 positively controls grain size and number by regulating spikelet and floret meristem development, which in turn leads to enhanced grain yield per plant. The haplotypes at TaSPL17 indicate geographical differentiation, domestication effects, and breeding selection.

Conclusion
Our study provides valuable resources for genetic improvement of spike morphology and a fast-forward genetic solution for candidate gene detection and cloning in wheat.
A machine learning classifier using 33 host immune response mRNAs accurately distinguishes viral and non-viral acute respiratory illnesses in nasal swab samples
Authors: Pandya Rushika , He Yudong D. , Sweeney Timothy E. , Hasin-Brumshtein Yehudit , Khatri Purvesh 
Published: August 2023

Abstract
Background
Viral acute respiratory illnesses (viral ARIs) contribute significantly to human morbidity and mortality worldwide, but their successful treatment requires timely diagnosis of viral etiology, which is complicated by overlap in clinical presentation with the non-viral ARIs. Multiple pandemics in the twenty-first century to date have further highlighted the unmet need for effective monitoring of clinically relevant emerging viruses. Recent studies have identified conserved host response to viral infections in the blood.

Methods
We hypothesize that a similarly conserved host response in nasal samples can be utilized for diagnosis and to rule out viral infection in symptomatic patients when current diagnostic tests are negative. Using a multi-cohort analysis framework, we analyzed 1555 nasal samples across 10 independent cohorts dividing them into training and validation.

Results
Using six of the datasets for training, we identified 119 genes that are consistently differentially expressed in viral ARI patients (N = 236) compared to healthy controls (N = 146) and further down-selected 33 genes for classifier development. The resulting locked logistic regression-based classifier using the 33-mRNAs had AUC of 0.94 and 0.89 in the six training and four validation datasets, respectively. Furthermore, we found that although trained on healthy controls only, in the four validation datasets, the 33-mRNA classifier distinguished viral ARI from both healthy or non-viral ARI samples with > 80% specificity and sensitivity, irrespective of age, viral type, and viral load. Single-cell RNA-sequencing data showed that the 33-mRNA signature is dominated by macrophages and neutrophils in nasal samples.

Conclusion
This proof-of-concept signature has potential to be adapted as a clinical point-of-care test (‘RespVerity’) to improve the diagnosis of viral ARIs.
Pancreatic draining lymph nodes (PLNs) serve as a pathogenic hub contributing to the development of type 1 diabetes
Authors: Sun Fei , Yang Chun-Liang , Wang Fa-Xi , Rong Shan-Jie , Luo Jia-Hui , Lu Wan-Ying , Yue Tian-Tian , Wang Cong-Yi , Liu Shi-Wei 
Published: August 2023

AbstractType 1 diabetes (T1D) is a chronic, progressive autoinflammatory disorder resulting from the breakdown of self-tolerance and unrestrained β cell-reactive immune response. Activation of immune cells is initiated in islet and amplified in lymphoid tissues, especially those pancreatic draining lymph nodes (PLNs). The knowledge of PLNs as the hub of aberrant immune response is continuously being replenished and renewed. Here we provide a PLN-centered view of T1D pathogenesis and emphasize that PLNs integrate signal inputs from the pancreas, gut, viral infection or peripheral circulation, undergo immune remodeling within the local microenvironment and export effector cell components into pancreas to affect T1D progression. In accordance, we suggest that T1D intervention can be implemented by three major ways: cutting off the signal inputs into PLNs (reduce inflammatory β cell damage, enhance gut integrity and control pathogenic viral infections), modulating the immune activation status of PLNs and blocking the outputs of PLNs towards pancreatic islets. Given the dynamic and complex nature of T1D etiology, the corresponding intervention strategy is thus required to be comprehensive to ensure optimal therapeutic efficacy.
Milk oligosaccharide-driven persistence of Bifidobacterium pseudocatenulatum modulates local and systemic microbial metabolites upon synbiotic treatment in conventionally colonized mice
Authors: Larke Jules A. , Heiss Britta E. , Ehrlich Amy M. , Taft Diana H. , Raybould Helen E. , Mills David A. , Slupsky Carolyn M. 
Published: August 2023

Abstract
Background
Bifidobacteria represent an important gut commensal in humans, particularly during initial microbiome assembly in the first year of life. Enrichment of Bifidobacterium is mediated though the utilization of human milk oligosaccharides (HMOs), as several human-adapted species have dedicated genomic loci for transport and metabolism of these glycans. This results in the release of fermentation products into the gut lumen which may offer physiological benefits to the host. Synbiotic pairing of probiotic species with a cognate prebiotic delivers a competitive advantage, as the prebiotic provides a nutrient niche.

Methods
To determine the fitness advantage and metabolic characteristics of an HMO-catabolizing Bifidobacterium strain in the presence or absence of 2′-fucosyllactose (2′-FL), conventionally colonized mice were gavaged with either Bifidobacterium pseudocatenulatum MP80 (B.p. MP80) (as the probiotic) or saline during the first 3 days of the experiment and received water or water containing 2′-FL (as the prebiotic) throughout the study.

Results
16S rRNA gene sequencing revealed that mice provided only B.p. MP80 were observed to have a similar microbiota composition as control mice throughout the experiment with a consistently low proportion of Bifidobacteriaceae present. Using 1H NMR spectroscopy, similar metabolic profiles of gut luminal contents and serum were observed between the control and B.p. MP80 group. Conversely, synbiotic supplemented mice exhibited dramatic shifts in their community structure across time with an overall increased, yet variable, proportion of Bifidobacteriaceae following oral inoculation. Parsing the synbiotic group into high and moderate bifidobacterial persistence based on the median proportion of Bifidobacteriaceae, significant differences in gut microbial diversity and metabolite profiles were observed. Notably, metabolites associated with the fermentation of 2′-FL by bifidobacteria were significantly greater in mice with a high proportion of Bifidobacteriaceae in the gut suggesting metabolite production scales with population density. Moreover, 1,2-propanediol, a fucose fermentation product, was only observed in the liver and brain of mice harboring high proportions of Bifidobacteriaceae.

Conclusions
This study reinforces that the colonization of the gut with a commensal microorganism does not guarantee a specific functional output.
Risk of imported malaria infections in Zanzibar: a cross-sectional study
Authors: Fakih Bakar S. , Holzschuh Aurel , Ross Amanda , Stuck Logan , Abdul Ramadhan , Al-Mafazy Abdul-Wahid H. , Irema Imani , Mbena Abdallah , Thawer Sumaiyya G. , Shija Shija J. , Aliy Safia M. , Ali Abdullah , Fink Günther , Yukich Joshua , Hetzel Manuel W. 
Published: August 2023

Abstract
Background
Zanzibar has made substantial progress in malaria control with vector control, improved diagnosis, and artemisinin-based combination therapy. Parasite prevalence in the population has remained around 1% but imported infections from mainland Tanzania contribute to sustained local transmission. Understanding travel patterns between mainland Tanzania and Zanzibar, and the risk of malaria infection, may help to control malaria importation to Zanzibar.

Methods
A rolling cross-sectional survey linked to routine reactive case detection of malaria was carried out in Zanzibar between May 2017 and October 2018. Households of patients diagnosed with malaria at health facilities were surveyed and household members were tested for malaria using rapid diagnostic tests and a sub-sample by quantitative PCR (qPCR). Interviews elicited a detailed travel history of all household members who had travelled within the past two months, including trips within and outside of Zanzibar. We estimated the association of malaria infection with travel destinations in pre-defined malaria endemicity categories, trip duration, and other co-variates using logistic regression.

Results
Of 17,891 survey participants, 1177 (7%) reported a recent trip, of which 769 (65%) visited mainland Tanzania. Among travellers to mainland Tanzania with travel destination details and a qPCR result available, 241/378 (64%) reported traveling to districts with a ‘high’ malaria endemicity and for 12% the highest endemicity category was ‘moderate’. Travelers to the mainland were more likely to be infected with malaria parasites (29%, 108/378) than those traveling within Zanzibar (8%, 16/206) or to other countries (6%, 2/17). Among travellers to mainland Tanzania, those visiting highly endemic districts had a higher odds of being qPCR-positive than those who travelled only to districts where malaria-endemicity was classified as low or very low (adjusted odd ratio = 7.0, 95% confidence interval: 1.9–25.5). Among travellers to the mainland, 110/378 (29%) never or only sometimes used a mosquito net during their travel.

Conclusions
Strategies to reduce malaria importation to Zanzibar may benefit from identifying population groups traveling to highly endemic areas in mainland Tanzania. Targeted interventions to prevent and clear infections in these groups may be more feasible than attempting to screen and treat all travellers upon arrival in Zanzibar.