bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental Health Trends in India from 2020 to 2022: Association with Financial Stress, Food Insecurity, and COVID-19-related Illness Concerns
Authors: Yang Youqi , Sun Anqi , Zimmermann Lauren , Mukherjee Bhramar 
Published: March 2024

AbstractThis study examines the impact of pandemic-related worries on mental health in the Indian general adult population from 2020 to 2022. Using data from the Global COVID-19 Trends and Impact Survey (N = 2,576,174 respondents aged≥18 years in India; an average weekly sample size of around 25,000), it explores the associations between worry variables (namely financial stress, food insecurity, and COVID-19-related health worries) and self-reported symptoms of depression and nervousness. The statistical analysis was conducted using complete cases only (N = 747,996). Our analysis used survey-weighted models, focusing on the three pandemic-related worries as the exposures, while also adjusting for various other covariates, including demographics and calendar time. The study finds significant associations between these worries and mental health outcomes, with financial stress being the most significant factor affecting both depression (adjusted odds ratio: 2.36, 95% confidence interval: [2.27, 2.46]) and nervousness (adjusted odds ratio: 1.91, 95% confidence interval: [1.81, 2.01]) during the first phase of the study period (June 27, 2020, to May 19, 2021). The fully adjusted models also identify additional factors related to mental health, including age, gender, residential status, geographical region, occupation, and education. Moreover, the research highlights that males and urban residents had higher odds ratios for self-reported mental health problems regarding the worry variables than females and rural residents, respectively. Furthermore, the study reveals a rise in the prevalence of self-reported depression and nervousness and their association with COVID-19-related health worries during the lethal second wave of the pandemic in May 2021 compared to the onset of the pandemic. This study shows that social media platforms like Facebook can deploy surveys to a large number of participants globally and can be useful tools in capturing mental health trends and uncovering associations during a public health crisis.
Recapitulation of Cellular Senescence, Inflammation, and Fibrosis in Human Kidney-Derived Tubuloids by Repeated Cisplatin Treatment
Authors: Nakao Yuki , Mori Yutaro , Mori Makiko , Mandai Shintaro , Fujiki Tamami , Kikuchi Hiroaki , Ando Fumiaki , Susa Koichiro , Mori Takayasu , Waseda Yuma , Yoshida Soichiro , Fujii Yasuhisa , Sohara Eisei , Uchida Shinichi 
Published: March 2024

AbstractIn the pursuit of more accurate pathophysiological models for assessing renal drug response, the development of kidney organoids derived from human pluripotent stem cells represents a significant step forward. However, recapitulating aging/senescence-associated pathophysiology within these models remains challenging. Here, we present an innovative approach to generate more homogeneous epithelial-like structures known as “tubuloid” using primary human renal proximal tubular epithelial cells (hRPTECs) cultured from human resected kidneys, as a refined alternative. We evaluated the efficacy of tubuloids using cisplatin treatment at three different concentrations: 0.2, 2.0, and 20.0 µg/mL. Tubuloids showed highly differentiated structures with proximal tubular epithelial cells that expressed lotus tetragonolobus lectin and LRP2/Megalin. Upon exposure to cisplatin, γH2AX expression increased in a dose-dependent manner, indicating DNA damage. Cisplatin treatment also resulted in the expression of Kidney Injury Molecule-1 (KIM-1) and Cleaved Caspase-3, which are indicators of kidney injury and apoptotic signaling, respectively. Repeated cisplatin administration resulted in upregulation of the cellular senescence marker p16, alongside increased secretion of inflammatory cytokines IL-1β and IL-6, indicating the induction of a senescence-associated secretory phenotype (SASP). Furthermore, supernatant collected from cisplatin-treated tubuloids induced myofibroblast activation, indicating the onset of renal fibrosis. We successfully established a tubuloid-based model of cisplatin-induced kidney injury using hRPTECs. Tubuloids provide a novel platform for studying the response of renal epithelial cells to toxins and therapeutics. Tubuloids can replicate cellular senescence, SASP, and fibrosis, making them a promising pathophysiological model for chronic kidney disease (CKD), providing insights into the disease’s fibrotic mechanisms.Translational StatementRecapitulating aging/senescence-associated pathophysiological reaction in kidney organoids remains challenging. Our study reveals that tubuloids could be novel candidate for chronic kidney disease (CKD) model.
Sex-dependent associations between human milk oligosaccharides and malaria outcomes in breastfeeding Ugandan children
Authors: Mwangi Victor Irungu , Owalla Tonny Jimmy , Moukarzel Sara , Okurut Emmanuel , Yonemitsu Chloe , Bode Lars , Egwang Thomas G. 
Published: March 2024

AbstractHuman milk oligosaccharides (HMOs), whose compositions vary between secretor and non-secretor mothers, protect breastfeeding children against various diseases. We investigated the relationship between HMOs in Ugandan secretor mothers and malaria outcomes in their children. Malaria outcomes in breastfeeding children followed up over seven months were classified as malaria-free and asymptomatic, mild, or severe malaria. A single human milk sample collected from each mother was analyzed for HMOs. Significantly higher 2’fucosyllactose (2’FL) and lacto-N-fucopentaose I (LNFP I) concentrations were observed in mothers of malaria-free children, and significantly higher lacto-N-tetraose (LNT) concentrations were observed in mothers of children with asymptomatic malaria. Concentrations of five HMOs, 3-fucosyllactose (3 FL), 3’sialyllactose (3’SL), difucosyllactose (DFLac), lacto-N-fucopentaose II (LNFP II), and sialyllacto-N-tetraose b (LSTb); and two HMOs, difucosyllacto-N-tetrose (DFLNT) and fucosyllacto-N-hexaose (FLNH) were significantly higher in mothers of malaria-infected children and children with severe malaria, respectively. Sex-dependent associations were observed for some HMOs.
Evaluating public and patient involvement in interventional research – a newly developed checklist (EPPIIC) with application to the COB-MS feasibility trial
Authors: Pyne Elise , Joyce Robert , Dwyer Christopher P. , Hynes Sinéad M. 
Published: March 2024

AbstractPublic and patient involvement (PPI) has been identified as an increasingly desired and, often, required component of trial methodology – leading to higher quality, more accessible and relevant clinical research, alongside increased recruitment, funding success and insight into research impact. However, despite the great variety of frameworks and checklists available for assessing PPI, most are limited with respect to important features (e.g. applicable in specific contexts only, fail to clarify what should be assessed and reported, lack the necessary comprehensiveness or are biased in favour of researcher reporting). Thus, the current research aimed to address such limitations through the development of a new checklist, the EPPIIC, through review, thematic analysis and ‘meta-evaluation’ in conjunction with PPI engagement. A further aim was to pilot the EPPIIC through its application to and reporting on the COB-MS trial, which utilised PPI throughout the research’s life-cycle. Upon completion of the EPPIIC, three thematic ‘sub-scales’ emerged: (1) Policy & Practice, (2) Participatory Culture and (3) Influence & Impact. All findings are presented and discussed in light of theory and research. Notably, findings recommend EPPIIC as a useful means of assessing PPI in future trials.
Initial respiratory support outcomes and associated factors among preterm neonates with respiratory distress syndrome admitted at Moi Teaching and Referral hospital Eldoret, Kenya
Authors: Ndeto Joyce Kalekye , Nyandiko Winstone M , Chepkemoi Audrey K , Mwangi Ann W 
Published: March 2024

AbstractBackgroundRespiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm neonates. Early management of RDS is crucial in determining short- and long-term outcomes and studies have established initial respiratory support (IRS) among other factors as an important determinant. Despite preexisting guidelines and advancements in the management of RDS, IRS failure with noninvasive ventilation is common and is associated with unfavorable outcomes.ObjectiveThis study evaluated the non-invasive initial respiratory support outcomes and associated factors among preterm neonates with respiratory distress syndrome admitted in the newborn unit (NBU) at Moi Teaching and Referral Hospital Eldoret (MTRH), KenyaMethodsUsing a prospective observational hospital-based study, preterm neonates ≤ 35weeks admitted at the newborn unit with clinical RDS were followed up for 28 days. The primary outcome was IRS success or failure characterized by not stepping up or stepping up the respiratory support respectively within 72 hours of life and associated maternal and neonatal factors. Descriptive statistics was described using mean ± (SD) for continuous variables and frequencies and percentages for categorical variables. Simple and multinomial regression analysis was performed to evaluate relationship between different IRS methods with outcome variables and a p-value of < 0.05 was considered significant.ResultsWe enrolled 320 neonates, 172(53.8%) were male with a mean (SD) gestation age of 30.9 (2.95) weeks. The mothers mean age was 27 years, ranging (15–43). 70(22.4%) 95%CI:17.95,27.47] had IRS failure and 243(77.6%) had IRS success. On multivariate analysis IRS success was associated with primiparity (AOR=2.81;95%CI: 1.42, 7.99), birthweight > 1300g (AOR= 5.04;95%CI 1.81, 14.6), low modified Downes score (AOR=26.395%CI 3.37, 230) and normal admission temperatures (AOR=0.32;95%CI 0.12, 0.72) (p= <0.001).ConclusionNoninvasive ventilation had a high initial respiratory support success. Primiparity, birthweight >1300g, normal admission temperatures and low Downes score were associated with IRS success.
Assessing Red Blood Cell Distribution Width in Vietnamese Heart Failure Patients: A Cross-Sectional Study
Authors: Dang Hai Nguyen Ngoc , Luong Thang Viet , Cao Mai Thi Thu , Bui Vinh Trung , Tran Thanh Thien , Nguyen Hung Minh 
Published: March 2024

AbstractHeart failure (HF) is a growing public health concern, with red cell distribution width (RDW) gaining recognition as a cost-effective marker for predicting HF onset and progression. This study, conducted from February 2022 to February 2024 at Hue Central Hospital, aimed to assess RDW levels in hospitalized Vietnamese HF patients and its predictive value for HF severity, involving a cross-sectional analysis of 351 patients categorized into HF and non-HF groups. HF patients exhibited higher median RDW levels (14.90% [13.70% - 17.00%]) compared to non-HF individuals (13.10% [12.23% - 13.78%]). RDW was higher in HF patients with left ventricular ejection fraction (LVEF) < 50% (15.30%) than LVEF ≥ 50% (14.70%). ROC curve analysis for acute heart failure (AHF) prediction yielded an AUC of 0.651 (p < 0.001), with a cutoff point of 13.85%, sensitivity of 86.05%, and specificity of 36.94%. Elevated RDW levels were associated with HF risk (OR: 1.844, p < 0.001) and AHF (OR: 3.612, p < 0.001). Multivariate analysis identified associations between RDW and hemoglobin (Hb) (β = 2.431, p = 0.040) and hematocrit (HCT) (β = −3.355, p = 0.007) in HF. RBC and RDW > 13.85% were independent risk factors for AHF. This suggests that RDW levels can serve as biomarkers for diagnosing HF and predicting its severity. Their accessibility and cost-effectiveness indicate the potential utility of RDW in managing HF, particularly in settings with limited resources.
Training-free Design of Deep Networks as Ensembles of Clinical Experts
Authors: Wu Tinghui , Wu Jieke , Zhang Zijun , Chen Wuyang 
Published: March 2024

AbstractArtificial intelligence (AI) techniques such as deep learning hold tremendous potential for improving clinical practice. However, clinical data complexity and the need for extensive specialized knowledge represent major challenges in the current, human-driven model design. Moreover, as human interpretation of a clinical problem is inherently encoded in the model, the conventional single model paradigm is subjective and cannot fully capture the prediction uncertainty. Here, we present a fast and accurate framework for automated clinical deep learning, TEACUP (training-free assembly as clinical uncertainty predictor). The core of TEACUP is a newly developed metric that faithfully characterizes the quality of deep networks without incurring any cost for training of these networks. When compared to conventional, training-based approaches, TEACUP reduces computation costs by more than 50% while achieving improved performance across distinct clinical tasks. This efficiency allows TEACUP to create ensembles of expert AI models, contributing to recommendations in clinical practice by mimicking the approach of using multiple human experts when interpreting medical data. By combining multiple perspectives, TEACUP provides more robust predictions and uncertainty quantification, paving the way for more reliable clinical AI.
Prevalence and Sociodemographic Covariates of Human Papillomavirus in the United States: Findings from the 2008 to 2020 National Inpatient Sample Database
Authors: Dantes Emily , Bhuiyan Mohammad Alfrad Nobel , Bourg Margaret , Smith Corey D. , Bhuiyan Md. Shenuarin , Smith Deborah G 
Published: March 2024

AbstractHuman papillomavirus (HPV) infection is widespread worldwide, leading to a significant burden of HPV-related cancers. This study aimed to identify the prevalence of HPV infection in the United States based on a large nationwide inpatient sample database. We used the Nationwide Inpatient Sample (NIS) database from 2008 to 2020 and identified HPV cases using the International Classification of Diseases, Ninth (ICD-9) and Tenth Revision (ICD-10) codes. Pearson’s chi-square and independent-sample t-test were used for the analysis. The prevalence ratio was calculated using logistic regression models and the Cochran Armitage trend test to examine trends. A total of 47,506 HPV infections were identified from 2008 to 2020 among adults aged >18 years. Most patients were female (99.72%), with a higher prevalence among the 26-40 age group and white individuals. HPV infections were more prominent among low-income individuals and in the southern region of the United States. From 2008 to 2020, HPV increased from 6.76% to 10.91%. This study provides insights into the epidemiology of HPV infection in the United States. Understanding the trends and characteristics of HPV infection can contribute to public health interventions aimed at prevention and early detection.
IDRWalker: A Random Walk based Modeling Tool for Disordered Regions in Proteins
Authors: Chen Guanglin , Zhang Zhiyong 
Published: March 2024

AbstractMotivationWith the advancement of structural biology techniques, the elucidation of increasingly large protein structures has become possible. However, the structural modeling of intrinsically disordered regions in proteins remains challenging. Particularly in the case of large protein complexes, it is difficult to rapidly construct models for all intrinsically disordered regions using existing methods. In the nuclear pore complex, a gigantic protein machine of interest, intrinsically disordered regions play a crucial role in the function of the nuclear pore complex. Therefore, there is a need to develop a modeling tool suitable for intrinsically disordered regions in large protein complexes.ResultsWe have developed a program named IDRWalker based on self-avoiding random walks, enabling convenient and rapid modeling of intrinsically disordered regions in large protein complexes. Using this program, modeling of all disordered regions within the nuclear pore complex can be completed in a matter of minutes. Furthermore, we have addressed issues related to peptide chain connectivity and knot that may arise during the application of random walks.Availability and implementationIDRWalker is an open-source Python package. Its source code is publicly accessible on GitHub (https://github.com/zyzhangGroup/IDRWalker).
Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition
Authors: Fahoum Jamal , Billan Maria , Varga Julia K , Padawer Dan , Elgrably-Weiss Maya , Basu Pallabi , Stolovich-Rain Miri , Baraz Leah , Cohen-Kfir Einav , Kumari Sujata , Oiknine-Dijan Esther , Kumar Manoj , Zelig Orly , Mayer Guy , Isupov Michail N , Wolf Dana G , Altuvia Shoshy , Wiener Reuven , Schueler-Furman Ora , Rouvinski Alexander 
Published: March 2024

AbstractSARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which extracellular NP on uninfected cells contributes to COVID-19 pathogenicity. We show that NP binds to cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of its RNA-binding sites facilitated by the flexible, positively charged, linker. Coating of uninfected lung-derived cells with purified NP attracted anti-NP-IgG from lung fluids and sera collected from COVID-19 patients. The magnitude of this immune recognition was significantly elevated in moderate compared to mild COVID-19 cases. Importantly, binding of anti-NP-IgG present in sera generated clusters that triggered C3b deposition by the classical complement pathway. Heparin analog enoxaparin outcompeted NP-binding, rescuing cells from anti-NP IgG-mediated complement deposition. Our findings unveil how extracellular NP may exacerbate COVID-19 tissue damage, and suggest leads for preventative therapy.Abstract FigureHighlightsIgG from patients’ sera target NP-bound cells resulting in complement activationThe flexible linker allows NP to both bind linear sulfated GAGs and wrap around RNAHeparin analogs prevent NP surface binding and alleviate complement activationCell-ELISA anti-NP IgG levels differ between mild and moderate COVID-19
Integrative spatial omics reveals distinct tumor-promoting multicellular niches and immunosuppressive mechanisms in African American and European American patients with TNBC
Authors: Zhu Qian , Balasubramanian Akhila , Asirvatham Jaya Ruth , Piyarathna Badrajee , Kaur Jaspreet , Mohamed Nada , Wu Ling , Chatterjee Megha , Wang Stacy , Pourfarrokh Niloufar , Rasaily Uttam , Xu Yitian , Zheng Junjun , Jebakumar Deborah , Rao Arundathi , Chen Shu-hsia , Li Yi , Chang Eric , Li Xiaoxian , Aneja Ritu , Zhang Xiang H.-F. , Sreekumar Arun 
Published: March 2024

AbstractRacial disparities in triple-negative breast cancer (TNBC) outcomes have been reported. However, the biological mechanisms underlying these disparities remain unclear. We integrated imaging mass cytometry and spatial transcriptomics, to characterize the tumor microenvironment (TME) of African American (AA) and European American (EA) patients with TNBC. The TME in AA patients was characterized by interactions between endothelial cells, macrophages, and mesenchymal-like cells, which were associated with poor patient survival. In contrast, the EA TNBC-associated niche is enriched in T-cells and neutrophils suggestive of an exhaustion and suppression of otherwise active T cell responses. Ligand-receptor and pathway analyses of race-associated niches found AA TNBC to be “immune cold” and hence immunotherapy resistant tumors, and EA TNBC as ‘inflamed’ tumors that evolved a distinctive immunosuppressive mechanism. Our study revealed the presence of racially distinct tumor-promoting and immunosuppressive microenvironments in AA and EA patients with TNBC, which may explain the poor clinical outcomes.Statement of SignificanceWe have uncovered distinct tumor-promoting and immunosuppressive microenvironments that may contribute to the observed disparities in patient outcomes. Our findings lay the groundwork for developing race-specific therapeutic interventions, potentially improving outcomes for patients with TNBC. Given that chemotherapy and anti-PD1 therapy are currently available treatments for TNBC, our finding of race-specific spatial multicellular niche-associated cell-cell interactions suggest that these treatments may have racially distinct response profiles among TNBC patients. Hence, our novel insights on molecular and cellular interactions in TNBC stratified by race has the potential to inform personalized treatment strategies.
Biguanide-PROTACs: Modulating Mitochondrial Proteins in Pancreatic Cancer Cells
Authors: Vatté Julie , Bourdeau Véronique , Ferbeyre Gerardo , Schmitzer Andreea R. 
Published: March 2024

AbstractThis study focuses on the synthesis of Biguanide-PROTACs, formed by conjugating the biguanide motif with diverse E3 enzyme ligands and spacers. Evaluation of their activity on pancreatic cancer cell (KP4) proliferation established a correlation between membrane permeability and median effective concentration. Mechanistic insights revealed that only two compounds exhibited biguanide-like AMPK activation, while only one hydrophobic compound uniquely altered mitochondrial protein levels. The prospect of developing and expanding the Biguanide-PROTAC library holds promises, offering potential insights into biguanide mechanisms and the creation of more potent anticancer agents. This study contributes to understanding the intricate interplay between compound structure, permeability, and anticancer activity, paving the way for targeted drug development in pancreatic cancer treatment.