bluuebunny/crossref_metadata_2025_split huggingface dataset:
flowVI: Flow Cytometry Variational Inference
Authors: Inecik Kemal , Meric Adil , König Lars , Theis Fabian J. 
Published: November 2023

AbstractSingle-cell flow cytometry stands as a pivotal instrument in both biomedical research and clinical practice, not only offering invaluable insights into cellular phenotypes and functions but also significantly advancing our understanding of various patient states. However, its potential is often constrained by factors such as technical limitations, noise interference, and batch effects, which complicate comparison between flow cytometry experiments and compromise its overall impact. Recent advances in deep representation learning have demonstrated promise in overcoming similar challenges in related fields, particularly in the context of single-cell transcriptomic sequencing data analysis. Here, we proposeflowVI, a multimodal deep generative model, tailored for integrative analysis of multiple massively parallel cytometry datasets from diverse sources. By effectively modeling noise variances, technical biases, and batch-specific heterogeneity using probabilistic data representation, we demonstrate that flowVI not only excels in the imputation of missing protein markers but also seamlessly integrates data from distinct cytometry panels. FlowVI thus emerges as a potent tool for constructing comprehensive flow cytometry atlases and enhancing the precision of flow cytometry data analyses. The source code for replicating these findings is hosted onGitHub, ‘theislab/flowVI’
Human trophoblast stem cells can be used to model placental susceptibility toToxoplasma gondiiand highlight the critical importance of the trophoblast cell surface in pathogen resistance
Authors: da Silva Rafaela J. , Cabo Leah F. , George Jada L. , Cahoon Laty A. , Yang Liheng , Coyne Carolyn B. , Boyle Jon P. 
Published: November 2023

ABSTRACTThe placenta is a critical barrier against viral, bacterial, and eukaryotic pathogens. For most teratogenic pathogens, the precise molecular mechanisms of placental resistance are still being unraveled. Given the importance to understand these mechanisms and challenges in replicating trophoblast-pathogeninteractions usingin vitromodels, we tested an existing stem-cell derived model of trophoblast development for its relevance to infection withToxoplasma gondii. We grew human trophoblast stem cells (TSCT) under conditions leading to either syncytiotrophoblast (TSSYN) or cytotrophoblast (TSCYT) and infected them withT. gondii. We evaluatedT. gondiiproliferation and invasion, cell ultrastructure, as well as for transcriptome changes after infection. TSSYNscells showed similar ultrastructure compared to primary cells and villous explants when analyzed by TEM and SEM, a resistance toT. gondiiadhesion could be visualized on the SEM level. Furthermore, TSSYNswere highly refractory to parasite adhesion and replication, while TSCYTwere not. RNA-seq data on mock-treated and infected cells identified differences between cell types as well as how they responded toT. gondiiinfection. We also evaluated if TSSC-derived SYNs and CYTs had distinct resistance profiles to another vertically transmitted facultative intracellular pathogen,Listeria monocytogenes. We demonstrate that TSSYNsare highly resistant toL. monocytogenes, while TSCYTsare not. LikeT. gondii, TSSYNresistance toL. monocytogeneswas at the level of bacterial adhesion. Altogether, our data indicate that stem-cell derived trophoblasts recapitulate resistance profiles of primary cells toT. gondiiand highlight the critical importance of the placental surface in cell-autonomous resistance to teratogens.
Modifications in the T arm of tRNA globally determine tRNA maturation, function and cellular fitness
Authors: Schultz Sarah K. , Katanski Christopher D. , Halucha Mateusz , Pena Noah , Fahlman Richard P. , Pan Tao , Kothe Ute 
Published: November 2023

AbstractAll elongator tRNAs harbor 5-methyluridine 54 and pseudouridine 55 in the T arm, which are generated by the enzymes TrmA and TruB, respectively.Escherichia coliTrmA and TruB both act as tRNA chaperones, and strains lackingtrmAortruBare outcompeted by wildtype. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion oftrmAandtruBinE. colicauses a global decrease in aminoacylation and alters other tRNA modification such as acp3U47. Whereas overall protein synthesis is not affected in ΔtrmAand ΔtruBstrains, the translation of a specific subset of codons is significantly impaired, and the expression of many specific proteins is translationally changed. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing tRNA maturation, tRNA aminoacylation, and translation, thereby improving cellular fitness and explainingtrmAandtruBconservation.
Sterility-Independent Enhancement of Proteasome Function via Floxuridine-Triggered Detoxification inC. elegans
Authors: Dubey Abhishek Anil , Szulc Natalia A. , Piechota Małgorzata , Serwa Remigiusz A. , Pokrzywa Wojciech 
Published: November 2023

ABSTRACTThe ubiquitin-proteasome system (UPS) functionality is vital for proteostasis, contributing to stress resilience, lifespan, and thermal adaptability. InCaenorhabditis elegans, proteasome constituents such as the RPN-6 and PBS-6 subunits or the PSME-3 activator are respectively linked to heat resistance, survival at low temperatures (4°C), and longevity at moderate cold (15°C). Since the inhibition of germline stem cells proliferation is associated with robust proteostasis in worms, we utilized floxuridine (FUdR), a compound known for inducing sterility, to examine whether it could reinforce UPS under proteasome dysfunction, particularly to foster cold survival. We demonstrate that FUdR promotes proteasome resilience during its inhibition or subunit deficits, supporting normal lifespan and facilitating adaptation to cold. FUdR’s elevation of the UPS activity occurs independently of main proteostasis regulators and is partly driven by SKN-1-regulated transcription, especially under reduced proteasome function. Additionally, we uncover a FUdR-stimulated detoxification pathway, distinct from both SKN-1 and the germline, with GST-24 emerging as a critical mediator of the UPS buffering. This research underscores FUdR’s role in the UPS modulation and its contribution to survival of worms in low-temperature conditions.HIGHLIGHTSFloxuridine (FUdR) enhances ubiquitin-proteasome system activity inC. elegans, independent of primary proteostasis regulators.FUdR permits worms to maintain a normal lifespan and facilitates their adaptation to cold in the context of proteasome deficits.Acting independently of the germline and SKN-1, FUdR triggers a detoxification pathway, with GST-24 as a pivotal component in modulating the ubiquitin-proteasome system.
The perceived problem‐solving potential of deliberative minipublics: Evidence from a survey of Belgian citizens
Authors: VAN DIJK LISA , WERNER HANNAH , MARIEN SOFIE 
Published: November 2023

AbstractConcerns about widespread democratic dissatisfaction have prompted a search for remedies, such as increasing citizens’ role in politics. While the public seems supportive, it remains unclear whether such newly introduced procedures can effectively tackle citizens’ dissatisfaction with present‐day politics. This paper develops a problem‐solving approach to studying this question. It proposes that combining insights on what ‘pushes’ and ‘pulls’ people to support procedural reform is crucial: Only then can we uncover if and how people consider procedural reform as addressing the problem(s) they see in the representative system today. Using the example of deliberative minipublics and original, pre‐registered survey data from Belgium (n = 1,579), we find that respondents generally think of minipublics as problem‐solvers rather than problem‐creators, albeit to different degrees. For instance, this perceived problem‐solving potential is more pronounced among discontent citizens. This study sheds new light on the importance of studying citizens’ reasoning about the roots and remedies for political dissatisfaction.
Does encouraging mastery goals benefit performance in a scoring exercise? It may depend on chronic self‐adopted achievement goals
Authors: Winkens Jim , Hamstra Melvyn R. W. 
Published: November 2023

IntroductionMastery goals (aims to learn or attain skill) have traditionally been portrayed in achievement‐motivation literature as the optimal goal for ensuring objective performance and well‐being outcomes (relative to performance goals – aims to outperform others). This portrayal often yielded the recommendation that those in applied settings, such as coaches, managers, and teachers, should encourage those whom they lead to pursue mastery goals. We put this assertion to a test by examining whether the effect of situationally induced goals depends on the goals that individuals personally self‐adopt.MethodsWe hypothesized that inducing mastery goals would be beneficial for individuals who self‐adopt performance goals (Hypothesis 1), while inducing performance goals would be beneficial for individuals who self‐adopt mastery goals (Hypothesis 2). We conducted an experiment among amateur field hockey players to test these hypotheses in a scoring exercise.ResultsWe found that encouraging a mastery goal (compared with a performance goal) led to higher scoring accuracy among players high in self‐adopted performance goals (supporting Hypothesis 1) but also unexpectedly for individuals low in self‐adopted mastery goals. We did not find support for Hypothesis 2.ConclusionThe findings indicate that situationally inducing a mastery goal may be beneficial for individuals who do not already self‐adopt mastery goals strongly.
Production of recombinant humanized monoclonal anti‐human neutrophil antigen (HNA) antibodies with potential applicability as standard antibodies
Authors: Ishimoto Yuko , Taniguchi Kikuyo , Bayat Behnaz , Tobita Ryutaro , Miyazaki Toru , Onodera Rie , Kurita Emi , Kobayashi Masao , Muroi Kazuo , Tsuno Nelson Hirokazu 
Published: November 2023

AbstractBackgroundAntibodies against human neutrophil antigen (HNA) are involved in the pathogenesis of neonatal alloimmune neutropenia, autoimmune neutropenia, and transfusion‐related acute lung injury. The present methods for anti‐HNA antibody identification strongly depend on the presence of standard antisera with known allo/isospecificities. Here, we aimed to produce recombinant humanized antibodies to HNA from available mouse monoclonal antibodies (MoAbs).Study Design and MethodsRNAs were extracted from available hybridoma cells producing mouse anti‐HNA antibodies recognizing HNA‐1a (TAG‐1), ‐1b (TAG‐2), ‐2 (TAG‐4), and FcγRIIIb, and the cDNA was synthesized. Recombinant fragments consisting of the variable regions of the H and L chains of the mouse MoAb ligated to the constant region of human IgG were incorporated into an expression vector and transfected into CHO cells. Antibody specificity of the selected humanized monoclonal antibodies was confirmed, and tested by the participants of the ISBT Granulocyte Immunobiology Working Party (GIWP) workshop 2020.ResultsGIFT results confirmed the specific reactivity of TAGH‐1 to ‐4, except for a cross‐reactivity of TAGH‐2 with HNA‐1a/a neutrophils, only in flow‐cytometry. MAIGA results showed clear specificity of all humanized antibodies, but the selection of the appropriate capture monoclonal antibody was essential for the test. The results of the ISBT GIWP showed high concordance among the labs.ConclusionsThese are the first humanized monoclonal antibodies to HNA‐1 and HNA‐2 antigens produced and they will be important standard reagents for laboratories testing for neutrophil antibodies. We plan to have these humanized MoAbs available through WHO.
A decoupling interpretation of an old argument for Vinogradov's Mean Value Theorem
Authors: Cook Brian , Hughes Kevin , Li Zane Kun , Mudgal Akshat , Robert Olivier , Yung Po‐Lam 
Published: November 2023

AbstractWe interpret into decoupling language a refinement of a 1973 argument due to Karatsuba on Vinogradov's mean value theorem. The main goal of our argument is to answer what precisely solution counting in older partial progress on Vinogradov's mean value theorem corresponds to in Fourier decoupling theory.
USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice
Authors: Gong Yang , Yu Tingting , Shuai Wei , Chen Tao , Zhang Jingjing , Huang He 
Published: November 2023

Abstract
Background
Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear.

Methods
In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms.

Results
Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent.

Conclusions
USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.
Is the association between blood pressure and cognition in the oldest-old modified by physical, vascular or brain pathology markers? The EMIF-AD 90 + Study
Authors: Legdeur Nienke , Moonen Justine E. , Badissi Maryam , Sudre Carole H. , Pelkmans Wiesje , Gordon Mark Forrest , Barkhof Frederik , Peters Mike , Visser Pieter Jelle , Muller Majon 
Published: November 2023

AbstractBackgroundPrior studies suggest a changing association between blood pressure (BP) and cognition with aging, however work in the oldest-old has yielded ambiguous results. Potentially, these mixed results can be explained by modifying factors. The aim of this study was to establish whether physical, vascular or brain pathology markers that describe a state of increased vulnerability, affect the association between BP and cognition in the oldest-old. Results may influence clinicians’ decisions regarding the use of antihypertensives in this age group.MethodsWe included 122 individuals (84 without cognitive impairment and 38 with cognitive impairment) from the EMIF-AD 90 + Study (mean age 92.4 years). First, we tested cross-sectional associations of systolic and diastolic BP with a cognitive composite score. Second, we tested whether these associations were modified by physical markers (waist circumference, muscle mass, gait speed and handgrip strength), vascular markers (history of cardiac disease, carotid intima media thickness as a proxy for atherosclerosis and carotid distensibility coefficient as a proxy for arterial stiffness) or brain pathology markers (white matter hyperintensities and cortical thickness).ResultsIn the total sample, there was no association between BP and cognition, however, waist circumference modified this association (p-value for interaction with systolic BP: 0.03, with diastolic BP: 0.01). In individuals with a high waist circumference, higher systolic and diastolic BP tended to be associated with worse cognition, while in individuals with a low waist circumference, higher systolic BP was associated with better cognition. The others physical, vascular and brain pathology markers did not modify the association between BP and cognition.ConclusionsWhen examining various markers for physical, vascular and brain vulnerability, only waist circumference affected the association between BP and cognition. This warrants further research to evaluate whether waist circumference may be a marker in clinical practice influencing the use of antihypertensives in the oldest-old.
Novel biomarkers to predict treatment response and prognosis in locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy
Authors: Guan Bingjie , Xu Meifang , Zheng Rong , Guan Guoxian , Xu Benhua 
Published: November 2023

Abstract
Purpose
To identify genes associated with treatment response and prognosis for locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (NCRT).

Methods
In our cohort, gene expression profiles of 64 tumor biopsy samples before NCRT were examined and generated. Weighted gene co-expression network analysis was performed to identify gene modules. External validation datasets included GSE3493, GSE119409, and GSE133057. The expression of candidate genes was evaluated using immunohistochemistry (IHC). TIMER was used to assess immune infiltration.

Results
We identified and validated the capability to predict the treatment response of CCT5 and ELF1 using our data and external validation datasets. The trends of survival differences of candidate genes in the GSE133057 dataset were similar to our cohort. High levels of CCT5 and ELF1 expression were associated with NCRT resistance and poor prognosis. Furthermore, the expression of CCT5 and ELF1 were also assessed in 117 LARC patients’ samples by the IHC method. Based on IHC results and Cox analysis, the risk score model with CCT5 and ELF1 was constructed and performed well. The risk score was an independent prognostic factor for progression-free survival and overall survival in LARC patients and was then used to build nomogram models. The underlying mechanisms of CCT5 and ELF1 were explored using gene set enrichment analysis. The underlying pathway including apoptosis, cell cycle, and other processes. CCT5 and ELF1 expressions were significantly correlated with immune cell infiltration.

Conclusion
CCT5 and ELF1 were determined as biomarkers for treatment response and prognosis in LARC patients. The risk score model and nomograms helped predict treatment response and survival outcomes for LARC patients undergoing NCRT.
Evaluation of the Acute flaccid paralysis surveillance indicators in Zambia from 2015–2021: a retrospective analysis
Authors: Bessing Barnabas , Dagoe Edward A. , Tembo Deborah , Mwangombe Alice , Kanyanga Muzala K. , Manneh Fadinding , Matapo Belem B. , Bobo Patricia M. , Chipoya Musole , Eboh Victor A. , Kayeye Princess L. , Masumbu Penelope K. , Muzongwe Chilweza , Bakyaita Nathan N. , Zomahoun Delayo , Tuma Jude N. 
Published: November 2023

Abstract
Background
The resurgence of poliovirus infection in previously polio free regions and countries calls for renewed commitment to the global polio eradication efforts including strengthening of Acute Flaccid Paralysis (AFP) surveillance systems. Zambia is one of the countries substantially at risk for the importation of poliovirus infection from neighbouring countries including Malawi, Mozambique, and Democratic Republic of the Congo (DRC). This study describes a seven-year AFP surveillance, assesses the surveillance indicators, and highlights areas for improvement.

Methods
We conducted retrospective analysis of the routinely collected AFP surveillance data from January 2015 to December 2022. The AFP surveillance indicators performance was assessed using the World Health Organisation’s recommended minimum AFP surveillance indicators performance.

Results
Cumulatively, a total of 1715 AFP cases were reported over the study period. More than half, 891 (52%) of reported cases were aged < 5 years with 917 (53.5%) of males. More than half, 1186 (69.2%) had fever at onset, 718 (41.9%) had asymmetric paralysis and 1164 (67.9%) had their paralysis progressed within 3 days of onset. The non-polio AFP rate ranges from 3.4 to 6.4 per 100,000 children < 15 years old and stool adequacy ranging from 70.9% to 90.2% indicating sensitive surveillance with late detection of cases. The percentage of cases with early stool collection, timely transportation was above the World Health Organisation (WHO) minimum of 80% but with declining proportion of stools arriving in the laboratory in optimal condition. Completeness of 60-days follow-up evaluation was suboptimal ranging from 0.9% to 28.2%.

Conclusion
The AFP surveillance system in Zambia is doing well. However, additional efforts are needed to improve early detection of cases; stool sample collection, transportation and monitoring to ensure arrival in good condition in the laboratory; and improve 60-days follow-up evaluation for evidenced-based classification of inadequate AFP cases and proper care.
The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study
Authors: Murakami Taku , Yamamoto Akira , Hagiya Hideharu , Obika Mikako , Mandai Yasuhiro , Miyoshi Tomoko , Kataoka Hitomi , Otsuka Fumio 
Published: November 2023

AbstractBackgroundSimulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties.MethodsThis study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents’ medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups.ResultsA total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation.ConclusionSimulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties.