bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Determinants of Academic Bullying Among Junior Doctors in Sierra Leone
Authors: Jalloh Fatima , Bah Ahmed Tejan , Kanu Alieu , Jalloh Mohamed Jan , Agboola Kehinde , Faulkner Monalisa M.J. , Foray Foray M. , Abiri Onome T. , Sillah Arthur , Lebbie Aiah , Jalloh Mohamed B. 
Published: November 2024

AbstractBackgroundAcademic bullying among junior doctors—characterized by repeated actions that undermine confidence, reputation, and career progression—is associated with adverse consequences for mental health and professional development. We aimed to investigate the prevalence and determinants of academic bullying among junior doctors in Sierra Leone.MethodsWe conducted a cross-sectional survey of 126 junior doctors at the University of Sierra Leone Teaching Hospitals Complex (USLTHC) in Freetown between January 1 and March 30, 2024. Participants were selected through random sampling. Data were collected using a semi-structured, self-administered questionnaire and analyzed with descriptive statistics and multivariable logistic regression.ResultsOf the 126 participants (61.1% male; mean age 31.9 years), 86 (68.3%) reported experiencing academic bullying. Among those, 54.6% experienced it occasionally and 35.2% very frequently. The most common forms were unfair criticism (73.3%), verbal aggression (66.3%), and derogatory remarks (47.7%). Consultants and senior doctors were the main perpetrators, with incidents primarily occurring during ward rounds, clinical meetings, and academic seminars. No statistically significant predictors of bullying were found for gender (odds ratio [OR] 2.07, 95% CI 0.92–4.64; p=0.08) or less than two years of practice (OR 0.30, 95% CI 0.05–1.79; p=0.19).ConclusionAcademic bullying is pervasive among junior doctors at USLTHC, with significant implications for their mental health and professional development. Urgent implementation of comprehensive strategies—including culturally sensitive policies, targeted training programs, confidential reporting mechanisms, and leadership development—is essential to address this issue. Promoting ethical leadership and fostering a culture of respect may mitigate incivility and burnout, enhancing the work environment for junior doctors.
Risk-averse optimization of genetic circuits under uncertainty
Authors: Kobiela Michal , Oyarzún Diego A. , Gutmann Michael U. 
Published: November 2024

AbstractSynthetic biology aims to engineer biological systems with specified functions. This requires navigating an extensive design space, which is challenging to achieve with wet lab experiments alone. To expedite the design process, mathematical modelling is typically employed to predict circuit functionin silicoahead of implementation, which when coupled with computational optimization can be used to automatically identify promising designs. However, circuit models are inherently inaccurate which can result in sub-optimal or non-functionalin vivoperformance. To mitigate this issue, here we propose to combine Bayesian inference, Thompson sampling, and risk management to find optimal circuit designs. Our approach employs data from non-functional designs to estimate the distribution of the model parameters and then employs risk-averse optimization to select design parameters that are expected to perform well given parameter uncertainty and biomolecular noise. We illustrate the approach by designing robust adaptation circuits and genetic oscillators with a prescribed frequency. The proposed approach provides a novel methodology for the design of robust genetic circuitry.
A Chaperonin Complex Regulates Organelle Proteostasis in Malaria Parasites
Authors: Tissawak Amanda , Rosin Yarden , Shahar Michal , Trabelsi Nirit , Furman-Schueler Ora , Johnson Steven M , Florentin Anat 
Published: November 2024

AbstractThe apicoplast ofPlasmodiumparasites serves as a metabolic hub that synthesize essential biomolecules. Like other endosymbiotic organelles, 90% of the apicoplast proteome is encoded by the cell nucleus and transported to the organelle. Evidence suggests that the apicoplast has minimal control over the synthesis of its proteome and therefore it is unclear how organelle proteostasis is regulated. Here, we identified and investigated a large and conserved chaperonin (CPN) complex with a previously unknown function. Using genetic tools, we demonstrated that its main subunit, CPN60, localizes to the apicoplast and is essential for parasite’s asexual replication due to its organellar functions. Unlike its close orthologues in other prokaryotic and eukaryotic cells, CPN60 is not upregulated during heat shock (HS) and does not affect HS response in the parasite. Instead, we found that it is directly involved in proteostasis through interaction with a proteolytic complex called Clp (caseinolytic protease) that degrades organellar proteins in a regulated manner. We showed that CPN60 physically binds both the active and inactive forms of the Clp complex, and manipulates its stability. Using computational prediction tools, we modeled the interaction between these two large complexes to understand how a stable interface is attained. Finally, we screened a library of inhibitors for the bacterial CPN60 orthologue GroEL, in order to test the potential of chaperonin inhibition as antimalarial. These inhibitors demonstrated an anti-Plasmodialactivity that was not restricted to apicoplast function. Taken together, this work reveals how balanced activities of proteolysis and refolding safeguard the apicoplast proteome.Significance StatementThe cell of the human malaria parasite,Plasmodium falciparum, has a unique organelle called the apicoplast that produces essential metabolites. Most apicoplast proteins are encoded by the nucleus and it is unclear how the organelle maintains a stable proteome. Here, we address the question of organelle proteostasis by investigating the function of a large chaperonin complex. We show that it is essential for parasite’s viability due to its role in apicoplast functions. We demonstrate that it binds and stabilizes another large proteolytic complex, and further explore its potential as a drug target. This study reveals how balanced refolding and proteolysis safeguard the apicoplast proteome and opens a new avenue for antimalarial drug discovery.
ConsolidatingUlvafunctional genomics: Gene editing and new selection systems
Authors: Blomme Jonas , Arraiza Ribera Júlia , Clerck Olivier De , Jacobs Thomas B. 
Published: November 2024

SummaryThe green seaweedUlva compressais a promising model for functional biology. In addition to historical research on growth and development, -omics data and molecular tools for stable transformation are available. However, more efficient tools are needed to study gene function. Here, we expand the molecular toolkit forUlva. We screened the survival ofUlvaand its mutualistic bacteria on 14 selective agents and establish that Blasticidin deaminases (BSD or bsr) can be used as selectable markers to generate stable transgenic lines. We show that Cas9 and Cas12a RNPs are suitable for targeted mutagenesis and can generate genomic deletions up to 20 kb using the marker gene ADENINE PHOSPHORIBOSYLTRANSFERASE (APT). We demonstrate that targeted insertion of a selectable marker via homology-directed repair or co-editing with APT is possible for non- marker genes. We evaluated 31 vector configurations and found that bicistronic fusion of Cas9 to a resistance marker or incorporation of introns in Cas9 led to the most mutants. We used this to generate mutants in three non-marker genes using a co-editing strategy. This expanded molecular toolkit now enables us to reliably make gain- and loss-of-function mutants, additional optimizations will be necessary to allow for vector-based multiplex genome editing inUlva.
A blueprint for biomolecular condensation driven by bacterial microcompartment encapsulation peptides
Authors: Trettel Daniel S. , López Cesar A. , Rodriguez Eliana , Marrone Babetta L. , Gonzalez-Esquer Cesar Raul 
Published: November 2024

SummaryBacterial microcompartments (BMC) are protein organelles with diverse metabolic capabilities. Their functional diversity is determined by an enzymatic core that is sequestered within a structurally conserved protein shell architecture. Segregation of protein cargo into the BMC is enabled by encapsulation peptides (EPs), which are short helical domains fused to core proteins through a disordered linker. Here, we investigate how EPs drive multicomponent cargo assembly into biomolecular condensates.In vitroexperiments supported by molecular dynamics simulations demonstrate the importance of both conserved hydrophobic packing and electrostatic interactions in stabilizing trimeric EP bundles. Topological rearrangements of EP domains can drive programmable liquid-or gel-like partitioningin vitroandin vivo. This partitioning is found to be EP-specific, modular and can co-assemble at least three fluorescent reporters. In summary, we describe the molecular features necessary to drive biomolecular condensation using a widespread peptide tag. This work can serve as a blueprint for implementing EP biotechnology across diverse applications.
G protein-coupled receptor 17 inhibits glucagon-like peptide-1 secretion via a Gi/o-dependent mechanism in enteroendocrine cells
Authors: Conley Jason M. , Jochim Alexander , Evans-Molina Carmella , Watts Val J. , Ren Hongxia 
Published: November 2024

AbstractGut peptides, including glucagon-like peptide-1 (GLP-1), regulate metabolic homeostasis and have emerged as the basis for multiple state-of-the-art diabetes and obesity therapies. We previously showed that G protein-coupled receptor 17 (GPR17) is expressed in intestinal enteroendocrine cells (EECs) and modulates nutrient-induced GLP-1 secretion. However, the GPR17-mediated molecular signaling pathways in EECs have yet to be fully deciphered. Here, we expressed the human GPR17 long isoform (hGPR17L) in GLUTag cells, a murine EEC line, and we used the GPR17 synthetic agonist MDL29,951 together with pharmacological probes and genetic approaches to quantitatively assess the contribution of GPR17 signaling to GLP-1 secretion. Constitutive hGPR17L activity inhibited GLP-1 secretion, and MDL29,951 treatment further inhibited this secretion, which was attenuated by treatment with the GPR17 antagonist HAMI3379. MDL29,951 promoted both Gi/o and Gq protein coupling to mediate cyclic AMP (cAMP) and calcium signaling. hGPR17L regulation of GLP-1 secretion was Gq-independent and dependent upon Gi/o signaling, but was not correlated with MDL29,951-induced whole-cell cAMP signaling. Our studies revealed key signaling mechanisms underlying the role of GPR17 in regulating GLP-1 secretion and suggest future opportunities for pharmacologically targeting GPR17 with inverse agonists to maximize GLP-1 secretionGraphical Abstract
Telomeric transposons are pervasive in linear bacterial genomes
Authors: Hsieh Shan-Chi , Fülöp Máté , Schargel Richard , Petassi Michael T. , Barabas Orsolya , Peters Joseph E. 
Published: November 2024

AbstractEukaryotes have linear DNA and their telomeres are hotspots for transposons, which in some cases took over telomere maintenance. While many bacteria also have linear chromosomes and plasmids, no transposons were known to target bacterial telomeres. Here we show several families of independently evolved telomeric transposons in cyanobacteria andStreptomyces. While these elements have one specific transposon end sequence with the second boundary being the telomere, we can show they move using two transposon ends. Telomeres are transiently bridged by the telomere maintenance systems, providing a duplex substrate for mobilization of the element and the associated telomere. We identify multiple instances where telomeric transposons have replaced native telomeres, making the host cell dependent on the new telomere system for genome maintenance. This work indicates how telomeric transposons can promote gene transfer both between and within genomes, significantly influencing the evolutionary dynamics of linear genomes.
Dysregulation of synaptic-related genes of neuroimmune networks within peripheral blood mononuclear cells in major depressive disorder
Authors: Adri Anny Silva , Nóbile Adriel Leal , de Alburquerque Débora Gomes , Barcelos Pedro Marçal , do Vale Fernando Yuri Nery , Bahia Ian Antunes F. , Freire Paula P. , Nava Roseane Galdioli , Correa Yohan Lucas G. , Cabral-Miranda Gustavo , Dalmolin Rodrigo , Schimke Lena F. , Fonseca Dennyson Leandro M. , Filgueiras Igor Salerno , Nakaya Helder I. , Rezende Rafael Machado , Dias Haroldo Dutra , Cabral-Marques Otavio 
Published: November 2024

ABSTRACTMajor depressive disorder (MDD) involves complex neuroimmune interactions linked to gene modulation. Our study investigates synaptic-related gene dysregulation in peripheral blood mononuclear cells (PBMCs) from MDD patients, showing how these immune cells mirror neural processes. Using RNA-seq data, we identified 1,383 differentially expressed genes (DEGs) related to neuroimmune crosstalk, with 49 DEGs effectively distinguishing MDD patients from controls based on synaptic functions. Synaptic genes, enriched for roles like vesicle transport, suggest mechanistic links between immune cells and neural signaling. Eleven synaptic-related DEGs were shared between PBMCs and brain regions involved in mood regulation, highlighting a common molecular signature. Among them,ADORA3andRPS28emerged as potential biomarkers. These findings highlight the potential of PBMCs in the diagnosis and treatment of MDD, reinforcing the development of future neuroimmune-targeted therapies for depression.
Joint consideration of selection and microbial generation count provides unique insights into evolutionary and ecological dynamics of holobionts
Authors: Pearman William S. , Rodrigo Allen G. , Santure Anna W. 
Published: November 2024

AbstractThe relationship between, and joint selection on, a host and its microbes – the holobiont – can impact evolutionary and ecological outcomes of the host and its microbial community. Here we present a novel agent-based modelling framework for understanding the ecological dynamics of hosts and their microbiomes. Our model explicitly incorporates numerous microbial generations per host generation allowing for selection on both host and microbe. We apply our model to explore community fitness and diversity in the face of rapid environmental change. We demonstrate that multiple microbial generations can buffer changes experienced across host lifetimes by smoothing environmental transitions. Our simulations reveal that microbial fitness and host fitness may be at odds with each other when considering the impact of vertical inheritance of microbial communities from a host to its offspring – where high values favour microbial fitness, while low values favour host fitness – these tradeoffs are minimized when microbial generation count per host generation is high. We suggest that these results arise from ‘cross-generational priority effects’ which maintain diversity within the community and can subsequently be acted upon by selection. Our model is readily extensible into new areas of holobiont research and provides novel insights into holobiont evolution under variable environmental conditions.
Brain Aging Among Individuals with Classical Trigeminal Neuralgia
Authors: Cruz-Almeida Yenisel , Valdes-Hernandez Pedro A. , Liang Yun , Ding Mingzhou , Neubert John K. 
Published: November 2024

AbstractTrigeminal neuralgia (TN) is a complex orofacial neuropathic pain condition with limited understanding of underlying mechanisms and therapeutic options. Emerging evidence suggests the involvement of the brain in persons with TN including widespread brain changes when employing a widely used brain aging biomarker that estimates a predicted brain age difference or brain age gap. The aim of the present cross-sectional study was to assess the predicted brain age difference (brain-PAD) or brain age gap across two discrete TN subtypes (classical TN, and secondary/idiopathic TN) in comparison with age-and sex-matched pain-free controls and its association with several clinical and psychological characteristics. Thirty-four individuals diagnosed with Classical TN, 17 diagnosed with secondary/idiopathic TN were age- and sex-matched to pain-free controls (n=54). All participants underwent a T1 brain MRI and completed clinical and psychological measures. There were significant differences in brain-PAD among TN subtypes (ANCOVA p = 0.0078, effect size f2= 0.282), with individuals diagnosed with Classical TN having a brain-PAD significantly greater than the controls by 3.87 years (p = 0.01, Bonferroni-corrected). There were no significant brain-PAD differences between secondary/idiopathic TN and pain-free controls. Brain-PAD had a significant positive association with both pain catastrophizing (p = 0.032) and pain-related anxiety (p = 0.041), but no significant association with disease duration (p = 0.519) or usual pain intensity (p = 0.443). We report here accelerated brain aging processes in patients with classical TN, but not in persons diagnosed with secondary/idiopathic TN. Our study replicates previous findings and adds to the literature that accelerated brain aging may not occur across all TN subtypes. Given the increased use of MRI for TN diagnostics, combined with our own recent work deriving our brain aging biomarker from clinical-grade scans, future studies within clinical settings are feasible and needed to understand this debilitating condition.
Accumulation of Dietary and Non-Enzymatic Oxysterols in Preeclamptic Placentas: Insights into Cholesterol Dynamics in Pregnancy Complications
Authors: Zou Lisa , Maldonado-Pereira Lisaura , Ticiani Elvis , Sethuraman Visalakshi , Olomu Isoken Nicholas , Long Robert , Veiga-Lopez Almudena , Medina-Meza Ilce Gabriela 
Published: November 2024

AbstractPregnancy involves a series of intricately coordinated events, including decidualization, placentation, and parturition, with oxidative stress playing a central role in both normal and pathological pregnancy progression. Placental complications in pregnancy, including preeclampsia, characterized by hypertension and proteinuria after 20 weeks of gestation. Excessive ROS production disrupts cell physiology, affecting bioactive lipids such as cholesterol. Cholesterol’s oxidative derivatives, oxysterols, function as active biological molecules regulating cholesterol synthesis and immune function. Oxysterols arise from both enzymatic and non-enzymatic pathways; non-enzymatic oxysterols, including dietary sources, may amplify oxidative stress under pathological conditions. This study aims to characterize dietary and non-enzymatic oxysterol presence in the human placenta, analyzing profiles in uncomplicated and preeclamptic pregnancies delivered preterm and at term. Findings indicate significantly higher oxysterol levels in preeclamptic placentas, particularly for 7-ketcholesterol (7-Keto) and 5α,6β-cholestanetriol, (Triol) regardless of gestational age. 5β,6β-epoxycholesterol (5β,6β-Epoxy) was elevated in term preeclampsia, while total cholesterol levels were notably lower in preeclamptic placentas. Oxysterols levels and cholesterol concentrations positively correlated with certain oxysterols yet inversely with others, highlighting unique oxidative signatures in preeclamptic conditions. These insights reveal oxysterols as potential biomarkers for preeclampsia and deepen our understanding of oxidative processes in pregnancy complications.
An impact analysis of global governance and economic indicators in shaping bank lending in India
Authors: Khan Imran , Akhtar Mohammed Anam 
Published: November 2024

PurposeThe objective of the research is to examine the impact of global governance and macroeconomic indicators on the lending capacity of banks in India.Design/methodology/approachEmploying a comprehensive time series dataset spanning from 1996 to 2022, we utilize the Nonlinear Autoregressive Distributed Lag model approach to investigate the short-run and long-run impact of government policy (GP) effectiveness, lending interest rates and remittance inflows (RI) on the lending capacity of banks in India.FindingsThe findings of the study indicate that lending interest rates have a statistically insignificant impact on lending capacity in the short term. However, in the long run, an increase in the lending interest rate leads to a decrease in lending capacity, whereas a decrease in the lending interest rate has a non-significant impact. On the other hand, the effectiveness of GPs affects both short-term and long-term lending capacity. In the short run, positive or negative changes in GP effectiveness lead to a decline in lending capacity. Whereas in the long run, a positive shock in GP effectiveness increases lending capacity, while a negative shock decreases it. Lastly, RI indicated no significant short-term impact on the lending capacity of the banks. Conversely, in the long run, a positive change in RI enhances lending capacity, whereas a negative change in RI reduces it, with a more pronounced effect.Originality/valueThe novelty of the study lies in the fact that it is a pioneering study that utilizes global governance and macroeconomic indicators to examine the impact on the lending capacity of banks and financial institutions in India. Moreover, the study adopts a non-linear approach to examine the relationship between the chosen variables, which enables an understanding of the impact of both positive and negative shocks on the dependent variable both in the short and long run. Lastly, the examination sheds light on the achievement of Sustainable Development Goal 8.10, which is related to financial inclusion and it is a major concern for a large developing nation like India.
Determinants of consumer purchase decisions of plant-based milk alternatives: the role of preferences for product attributes
Authors: Su Wenfan , Gao Zhifeng , Li Songhan , Sheng Jiping 
Published: November 2024

PurposeThe study aims to investigate consumer preferences across 25 attributes of plant-based milk (PBM) products and examine the key predictors and underlying mechanisms of consumer purchase decisions of PBM alternatives.Design/methodology/approachThis study employed a multidimensional approach to investigate consumer preferences and the determinants of PBM purchasing decisions. Drawing on data from 819 online surveys conducted in the Jing-Jin-Ji region of China in 2021, we measured consumer preferences across 25 specific attributes and other individual characteristics. Purchasing decisions were framed as a two-stage process – the decision to purchase (frequency) and the decision on how much to pay (WTP). The Least Absolute Shrinkage and Selection Operator (LASSO) model was utilized to examine these dimensions separately, and the selected predictors were incorporated into OLS linear and Heckman’s two-stage regression analyses to establish the underlying mechanisms.FindingsThe findings indicate that consumers exhibit a strong preference for freshness and the absence of spoilage, followed by taste experiences such as taste and aroma. Preferences for milk preservation significantly increase the purchase frequency of PBM, while preference for calorie content has a negative and significant impact. Preferences for milk preservation, aroma and processing methods can also significantly increase WTP. Preferences vary across PBM categories. Social influence, knowledge and advertising exposure positively impact purchase frequency and WTP. Consumers with low food neophobia tend to be more responsive to product-related factors, such as freshness, calorie content and processing methods, in their purchase decisions.Originality/valueThis study contributes to the extant literature by comprehensively examining the determinants of consumer purchase decisions for PBM alternatives. The findings provide practical implications for marketers and policymakers, highlighting the strategic product attributes, consumer segments and marketing levers that can effectively target and cater to consumer preferences for PBM alternatives.