bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using extracted data from Kaplan-Meier curves to compare COVID-19 vaccine efficacy
Authors: Tansawet Amarit , Numthavaj Pawin , Oranratnachai Songporn , Filbertine Grace , Kiertiburanakul Sasisopin , McKay Gareth J , Attia John , Thakkinstian Ammarin 
Published: April 2023

AbstractAlthough various COVID-19 vaccines have shown efficacy against placebo in randomized clinical trials, no head-to-head comparisons are yet available. This study aims to compare the efficacy of available COVID-19 vaccines. Vaccine trials searched in May 2021 were included. Data were extracted from Kaplan-Meier (KM) curves using the WebPlotDigitizer program for the individual participant (IP) data simulation. A mixed-effect acceleration failure model with log-logistic and Weibull distributions was used to estimate relative effects for individual vaccines as well as grouped by class: inactivated virus, mRNA, and viral vector. Primary studies were considered as the random effect in the model. Hazard ratios (HR) were estimated and compared across vaccine groups. All vaccines were efficacious in lowering symptomatic infection compared to placebo. CoronaVac, Ad26.COV2.S, ChAdOx1 nCoV-19, rAd26/rAd5, WIV04, HB02, and BNT162b2 showed 7.61 (4.50, 12.87), 6.77 (4.08, 11.24), 5.01 (2.93, 8.57), 4.50 (2.52, 8.01), 3.90 (2.04, 7.45), 3.18 (1.62, 6.21), and 2.15 (1.22, 3.78) times significantly higher risk of infection than mRNA-1273. mRNA vaccines were the most efficacious vaccine group compared to inactivated virus and viral vectors with HRs (95% CI) of 0.27 (0.20, 0.37) and 0.28 (0.21, 0.37), respectively. Although all vaccines showed significant protection compared to no vaccination. mRNA vaccines, including mRNA-1273 and BNT162b2, showed the highest efficacy in preventing symptomatic COVID-19 infection. Simulated IP data from the KM curve might allow treatment comparison when there is no primary study comparing active treatments.
Healthcare seeking behavior and delays in case of drug-resistant Tuberculosis patients in Bangladesh: Findings from a cross-sectional survey
Authors: Noman Md. Zulqarnine Ibne , Islam Shariful , Akter Shaki , Parray Ateeb Ahmad , Amando Dennis G , Karki Jyoti , Atsna Zafria , Mitra Dipak , Hossain Shaikh A. Shahed 
Published: April 2023

AbstractBackground:The emergence of Drug-Resistant Tuberculosis (DR-TB) has become a major threat globally and Bangladesh is no exception. Delays in healthcare seeking, proper diagnosis and initiation of treatment cause continuous transmission of the resistant tubercule bacilli through the communities. This study aimed to assess the different health care-seeking behaviors and delays among DR-TB patients in Bangladesh.Method:A prospective cross-sectional study was conducted from November to December 2018, among 92 culture positive and registered DR-TB patients in four selected hospitals in Bangladesh. Data were collected through face-to-face interviews with survey questionnaire as well as record reviews.Result:Among the 92 study participants, the median patient delay was 7 (IQR 3, 15) days, the median diagnostic delay was 88 (IQR 36.5, 210), the median treatment delay was 7 (IQR 4,12) days, and the median total delay among DR-TB patients was 108.5 (IQR 57.5, 238) days. 81.32% sought initial care from informal healthcare providers. The majority (68.48%) of the informal healthcare providers were drug sellers while 60.87% of patients sought care from more than four healthcare points before being diagnosed with DR-TB. The initial care seeking from multiple providers was associated with diagnostic and total delays.Conclusion:In Bangladesh, DR-TB cases usually seek care from multiple providers, particularly from informal providers, and among them, alarmingly higher healthcare-seeking related delays were noted. Immediate measures should be taken both at the health system levels and, in the community, to curb transmission and reduce the burden of the disease.
Role of T and B lymphocyte cannabinoid type 1 and 2 receptors in major depression and suicidal behaviors: effects of in vitro cannabidiol administration
Authors: Maes Michael , Rachayon Muanpetch , Jirakran Ketsupar , Sughondhabirom Atapol , Almulla Abbas F. , Sodsai Pimpayao 
Published: April 2023

AbstractEarly flow cytometry studies revealed T cell activation in major depressive disorder (MDD) (Maes et al., 1990-1993). MDD is characterised by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS), including deficits in T regulatory (Treg) cells. This study examines the number of cannabinoid type 1 (CB1) and type 2 (CB2) receptor bearing T/B lymphocytes in MDD, and the effects of in vitro cannabidiol (CBD) administration on CB1/CB2. Using flow cytometry, we determined the percentage of CD20+CB2+, CD3+CB2+, CD4+CB2+, CD8+CB2 and FoxP3+CB1+ cells in 19 healthy controls and 29 MDD patients in 5 conditions: baseline, stimulation with anti-CD3/CD28 with or without 0.1 µg/mL, 1.0 µg/mL or 10.0 µg/mL CBD. We found that CB2+ was significantly higher in CD20+ than CD3+ and CD4+, and CD8+ cells. Stimulation with anti-CD3/CD8 beads increases the number of CB2-bearing CD3+, CD4+, and CD8+ cells, as well as CB1-bearing FoxP3+ cells. There was an inverse association between the number of reduced CD4+CB2+ and IRS profiles, including M1 macrophage, T helper-(Th)-1 and Th-17 phenotypes. MDD is characterized by lowered basal FoxP3+CB1+% and higher CD20+CB2+%. 33.2% of the variance in the depression phenome (including severity of depression, anxiety, and current suicidal behaviors) is explained by CD20+CB2+% (positively) and CD3+CB2+% (inversely). All 5 immune cell populations were significantly increased by 10 µg/mL CBD administration. In conclusion, reductions in FoxP3+CB1+% and CD3+/CD4+CB2+% contribute to deficits in immune homeostasis in MDD, while increased CD20+CB2+% may contribute to the pathophysiology of MDD by activating T-independent humoral immunity.SummationsLowered CD4+CB2+ T cells are associated with increased immune-inflammatory responses (IRS) in major depressive disorder (MDD)Lowered CD3+CB2+% and increased CD20+CB2+% predict severity of depression and suicidal behaviorsLowered CD3/CD4+CB2+ may impact the immune homeostatic processes leading to enhanced IRS in MDDIncreased CD20+CB2+% may activate T-independent humoral immunity and enhance IRS responses.ConsiderationsDepletion of CB1 bearing T regulatory and CB2 bearing T and T helper cells and increased CB2+ bearing B cells are new drug targets in MDD.The findings deserve replication in other countries and cultures.Future research should examine CB2 bearing macrophages, dendritic cells, and natural killer cells in MDD
Prevalence of Bacteriologically-Confirmed Tuberculosis in Urban Blantyre, Malawi 2019-20: Substantial Decline Compared to 2013-14 National Survey
Authors: Feasey Helena R A , Khundi McEwen , Nzawa Soko Rebecca , Nightingale Emily , Burke Rachael M , Henrion Marc Y R , Phiri Mphatso D , Burchett Helen E , Chiume Lingstone , Nliwasa Marriott , Twabi Hussein H , Mpunga James A , MacPherson Peter , Corbett Elizabeth L 
Published: April 2023

AbstractRecent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 215 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters. Consenting eligible participants (household residents ≥ 18 years) were interviewed, including for cough (any duration), and offered HIV testing and chest X-ray; participants with cough and/or abnormal X-ray provided two sputum samples for microscopy, Xpert MTB/Rif and mycobacterial culture. TB disease prevalence and risk factors for prevalent TB were calculated using complete case analysis, multiple imputation, and inverse probability weighting. Of 20,899 eligible adults, 15,897 (76%) were interviewed, 13,490/15,897 (85%) had X-ray, and 1,120/1,395 (80%) sputum-eligible participants produced at least one specimen, giving 15,318 complete cases (5,895, 38% men). 29/15,318 had bacteriologically-confirmed TB (189 per 100,000 complete case (cc) / 150 per 100,000 with inverse weighting (iw)). Men had higher burden (cc: 305 [95% CI:144-645] per 100,000) than women (cc: 117 [95% CI:65-211] per 100,000): cc adjusted odds ratio (aOR) 2.70 (1.26-5.78). Other significant risk factors for prevalent TB on complete case analysis were working age (25-49 years) and previous TB treatment, but not HIV status. Multivariable analysis of imputed data was limited by small numbers, but previous TB and age group 25-49 years remained significantly associated with higher TB prevalence.TB prevalence for Blantyre was considerably lower than the 1,014 per 100,000 for urban Malawi in the 2013-14 national survey, at 150-189 per 100,000 adults, but some groups, notably men, remain disproportionately affected. TB case-finding is still needed for TB elimination in Blantyre, and similar urban centres, but should focus on reaching the highest risk groups, such as older men.
Mpox: Seroepidemiology and risk factors amidst increasing cases in Ghana
Authors: Donkor Irene Owusu , Dorcoo Christopher , Gyamfi Grace Opoku , Sumboh Jeffrey Gabriel , Asare Ama Akyampomaa Owusu , Ohene Sally-ann , Bonney Joseph H. K. , Munster Vincent , Fischer Robert 
Published: April 2023

Withdrawal StatementThe authors have withdrawn their manuscript to run confirmatory assays to confirm the initial results obtained. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have anyquestions,please contact the corresponding author. The authors will resubmit an updated version of the manuscriptin due time.
Self-Supervised Contrastive Learning to Predict Alzheimer’s Disease Progression with 3D Amyloid-PET
Authors: Kwak Min Gu , Su Yi , Chen Kewei , Weidman David , Wu Teresa , Lure Fleming , Li Jing 
Published: April 2023

AbstractEarly diagnosis of Alzheimer’s disease (AD) is an important task that facilitates the development of treatment and prevention strategies and may potentially improve patient outcomes. Neuroimaging has shown great promise, including the amyloid-PET which measures the accumulation of amyloid plaques in the brain – a hallmark of AD. It is desirable to train end-to-end deep learning models to predict the progression of AD for individuals at early stages based on 3D amyloid-PET. However, commonly used models are trained in a fully supervised learning manner and they are inevitably biased toward the given label information. To this end, we propose a self-supervised contrastive learning method to predict AD progression with 3D amyloid-PET. It uses unlabeled data to capture general representations underlying the images. As the downstream task is given as classification, unlike the general self-supervised learning problem that aims to generate task-agnostic representations, we also propose a loss function to utilize the label information in the pre-training. To demonstrate the performance of our method, we conducted experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. The results confirmed that the proposed method is capable of providing appropriate data representations, resulting in accurate classification.
Three-Dimensional Echocardiographic Evaluation of Longitudinal and Non-Longitudinal Components of Right Ventricular Contraction Results from the World Alliance of Societies of Echocardiography Study
Authors: Cotella Juan I. , Kovacs Attila , Addetia Karima , Fabian Alexandra , Asch Federico M. , Lang Roberto M. 
Published: April 2023

AbstractBackgroundRight ventricular (RV) functional assessment is mainly limited to its longitudinal component. However, due to the complex orientation of the myofibers, the RV contraction involves coordinated motion along multiple planes. Recently developed 3-dimensional echocardiography (3DE) software has enabled the separate assessment of the non-longitudinal components of RV systolic function and their relative contribution to RV performance. The aims of this study were 1) to establish normal values for 3D-derived longitudinal, radial, and anteroposterior RV ejection fraction (LEF, REF, AEF respectively) and their relative contributions to global RVEF, 2) to calculate 3D RV strain normal values and, 3) to determine sex, age and race related differences in these parameters in a large group of normal subjects (WASE study)Methods1043 healthy adult subjects prospectively enrolled at 17 centers in 15 countries were used in this study. 3DE RV wide-angle datasets were analyzed to generate a 3D mesh model of the RV cavity (TomTec). Then, dedicated software (ReVISION) was used to analyze RV motion along the three main anatomical planes and the ejection fraction (EF) values corresponding to each plane were identified as LEF, REF, and AEF. Relative contributions were determined by dividing each EF component by the global RVEF. RV strain analysis included longitudinal, circumferential, and global area strains (GLS, GCS and GAS, respectively). Results were categorized by sex, age (18-40, 41-65 and >65 years), and race.ResultsAbsolute REF, AEF, LEF and global RVEF were higher in women than in men (p < .001). With aging, both sexes exhibited a decline in all the determinants of longitudinal shortening (p <.001). In elderly women, the lower global RVEF was partially compensated by an increase in radial shortening. Both Black men and women showed lower RVEF, and GAS values compared to White and Asian subjects of the same sex (p < .001). Black men showed significantly higher REF/RVEF and lower LEF/RVEF compared to Asian and White men. These differences in RV contraction patterns across races were not present in women.Conclusion3DE evaluation of the non-longitudinal components of RV contraction provides additional information regarding RV physiology, including sex, age and race - related differences in RV contraction patterns that may prove useful in disease states involving the RV.
NR4A3 deficiency in CD8+T cells improves adoptive T cell therapy of cancer
Authors: Odagiu Livia , Maurice De Sousa Dave , Boulet Salix , Labrecque Nathalie 
Published: April 2023

ABSTRACTNR4A3 is a transcription factor that is rapidly induced in CD8+T cells following antigenic recognition. We have previously shown that NR4A3 deficiency induces an early molecular program that promotes memory generation and enhances effector functions, which are two essential attributes for the success of adoptive cell therapy (ACT). Therefore, we tested the hypothesis thatNr4a3-/-CD8+T cells would have outstanding efficacy in ACT of cancer. Our results show that ACT of melanoma-bearing mice withNr4a3-/-effector CD8+T cells provides a better tumor control than their wild-type counterpart. The therapeutic effect observed withNr4a3-/-effector CD8+T cells is even better than the one observed with ACT ofNr4a3+/+effector CD8+T cells in combination with anti-PD-L1 treatment. scRNA-seq analysis reveals a huge heterogeneity of tumor-infiltrating lymphocytes (TILs) states following ACT. The better tumor control observed with ACT ofNr4a3-/-CD8+effectors without anti-PD-L1 treatment correlates with an enrichment of TILs within the clusters that are associated with the anti-PD-L1 response of wild-type TILs. Moreover, the clusters that are enriched inNr4a3-/-TILs are the ones that are enriched for effector functions. Furthermore,Nr4a3-/-andNr4a3+/+effectors generate distinct progenitor populations. Pseudotime analysis suggests that these progenitors have different differentiation trajectories, which may explain why ACT withNr4a3-/-effectors is more efficient. Therefore, modulation of NR4A3 activity may represent a new strategy to generate long-lived and highly functional T cells for ACT.
Transfer learning on structural brain age models to decode cognition in MS: a federated learning approach
Authors: Denissen Stijn , Grothe Matthias , Vaněčková Manuela , Uher Tomáš , Laton Jorne , Kudrna Matěj , Horáková Dana , Kirsch Michael , Motýl Jiří , De Vos Maarten , Chén Oliver Y. , Van Schependom Jeroen , Sima Diana Maria , Nagels Guy 
Published: April 2023

IntroductionClassical deep learning research requires lots of centralised data. However, data sets are often stored at different clinical centers, and sharing sensitive patient data such as brain images is difficult. In this manuscript, we investigated the feasibility of federated learning, sending models to the data instead of the other way round, for research on brain magnetic resonant images of people with multiple sclerosis (MS).MethodsUsing transfer learning on a previously published brain age model, we trained a model to decode performance on the symbol digit modalities test (SDMT) of patients with MS from structural T1 weighted MRI. Three international centers in Brussels, Greifswald and Prague participated in the project. In Brussels, one computer served as the server coordinating the FL project, while the other served as client for model training on local data (n=97). The other two clients were Greifswald (n=104) and Prague (n=100). Each FL round, the server sent a global model to the clients, where its fully connected layer was updated on the local data. After collecting the local models, the server applied a weighted average of two randomly picked clients, yielding a new global model.ResultsAfter 22 federated learning rounds, the average validation loss across clients reached a minimum. The model appeared to have learned to assign SDMT values close to the mean with a mean absolute error of 9.04, 10.59 and 10.71 points between true and predicted SDMT on the test data sets of Brussels, Greifswald and Prague respectively. The overall test MAE across all clients was 10.13 points.ConclusionFederated learning is feasible for machine learning research on brain MRI of persons with MS, setting the stage for larger transfer learning studies to investigate the utility of brain age latent representations in cognitive decoding tasks.
The stem cell-type transcriptome of bioenergy sorghum reveals the spatial regulation of secondary cell wall networks
Authors: Fu Jie , McKinley Brian , James Brandon , Chrisler William , Markillie Lye Meng , Gaffrey Matthew J , Mitchell Hugh D , Orr Galya , Swaminathan Kankshita , Mullet John , Marshall-Colon Amy 
Published: April 2023

AbstractBioenergy sorghum is a low-input, drought-resilient, deep-rooting annual crop that has high biomass yield potential enabling the sustainable production of biofuels, biopower, and bioproducts. Bioenergy sorghum’s 4-5 m stems account for ∼80% of the harvested biomass. Stems accumulate high levels of sucrose that could be used to synthesize bioethanol and useful biopolymers if information about stem cell-type gene expression and regulation was available to enable engineering. To obtain this information, Laser Capture Microdissection (LCM) was used to isolate and collect transcriptome profiles from five major cell types that are present in stems of the sweet sorghum Wray. Transcriptome analysis identified genes with cell-type specific and cell-preferred expression patterns that reflect the distinct metabolic, transport, and regulatory functions of each cell type. Analysis of cell-type specific gene regulatory networks (GRNs) revealed that unique TF families contribute to distinct regulatory landscapes, where regulation is organized through various modes and identifiable network motifs. Cell-specific transcriptome data was combined with a stem developmental transcriptome dataset to identify the GRN that differentially activates the secondary cell wall (SCW) formation in stem xylem sclerenchyma and epidermal cells. The cell-type transcriptomic dataset provides a valuable source of information about the function of sorghum stem cell types and GRNs that will enable the engineering of bioenergy sorghum stems.
Saracatinib synergizes with enzalutamide to downregulate androgen receptor activity in castration resistant prostate cancer
Authors: White Ralph E. , Bannister Maxwell , Day Abderrahman , Bergom Hannah E. , Tan Victor M. , Hwang Justin , Nguyen Hai Dang , Drake Justin M. 
Published: April 2023

AbstractProstate cancer (PCa) remains the most diagnosed non-skin cancer amongst the American male population. Treatment for localized prostate cancer consists of androgen deprivation therapies (ADTs), which typically inhibit androgen production and the androgen receptor (AR). Though initially effective, a subset of patients will develop resistance to ADTs and the tumors will transition to castration-resistant prostate cancer (CRPC). Second generation hormonal therapies such as abiraterone acetate and enzalutamide are typically given to men with CRPC. However, these treatments are not curative and typically prolong survival only by a few months. Several resistance mechanisms contribute to this lack of efficacy such as the emergence of AR mutations, AR amplification, lineage plasticity, AR splice variants (AR-Vs) and increased kinase signaling. Having identified SRC kinase as a key tyrosine kinase enriched in CRPC patient tumors from our previous work, we evaluated whether inhibition of SRC kinase synergizes with enzalutamide or chemotherapy in several prostate cancer cell lines expressing variable AR isoforms. We observed robust synergy between the SRC kinase inhibitor, saracatinib, and enzalutamide, in the AR-FL+/AR-V+ CRPC cell lines, LNCaP95 and 22Rv1. We also observed that saracatinib significantly decreases AR Y534phosphorylation, a key SRC kinase substrate residue, on AR-FL and AR-Vs, along with the AR regulome, supporting key mechanisms of synergy with enzalutamide. Lastly, we also found that the saracatinib-enzalutamide combination reduced DNA replication compared to the saracatinib-docetaxel combination, resulting in marked increased apoptosis. By elucidating this combination strategy, we provide pre-clinical data that suggests combining SRC kinase inhibitors with enzalutamide in select patients that express both AR-FL and AR-Vs.
Health impact of nuclear waste water discharge from the Fukushima Daiichi nuclear plant
Authors: Liao Huipeng , Sun Danyi , Yang Zifan , Huang Wenyu , Di Qian 
Published: April 2023

ABSTRACTTokyo Electric Power Company announced to discharge the contaminated radioactive water resulting from the Fukushima nuclear accident into the ocean after purification from 2023. Concerns remain about safety and removal efficiency of radionuclides. This study calculated the total radioactivity and simulated the marine transport of137Cs,90Sr, and tritium. It assessed activity concentration in ocean and marine products, lifetime doses from marine product consumption, and associated cancer risks. We found the radionuclides would be globally distributed and penetrate into deep ocean, with the highest concentrations along Japan’s eastern coast. If137Cs and90Sr were not removed, related cancer risks would range between 8.64 – 33.35 cases per 100,000 people, depending on age and discharge scenario. Risks would be below one case per 100,000 if only tritium is present. Efficient removal of radionuclides is crucial to mitigating health risks. This study provides evidence of potential health risks and recommendations for prevention.