bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Risk Factors and the Establishment of a Predictive Model for Thrombosis in Patients with immune thrombocytopenia
Authors: Liang Hui , Duan Lingxue , Long Manyu , Tie Songyuan , Sun Changyan , Ma Sha , Wang Jing , Wang Shuya 
Published: August 2024

AbstractObjectivesTo explore the risk factors for thrombi occurring in patients with immune thrombocytopenia (ITP) and establish a risk prediction model to better predict the risk of thrombosis in patients with ITP.MethodsWe retrospectively analyzed 350 ITP patients who had been hospitalized in The First People’s Hospital of Yunnan Province between February to June 2024. For all patients, we recorded demographic characteristics and clinical data, analyzed the risk factors for thrombosis in ITP patients and then developed a risk prediction model.ResultsStepwise logistic regression analysis indicated that a high complement D-dimer level, a low PLT and a high Padua score were independent risk factors for thrombosis in ITP patients. According to multivariate analysis, a predictive model for thrombus risk was successfully established; the area under the ROC curve(AUC) was 0.673 (95% CI: 0.615-0.730) and the maximum Youden index, sensitivity and specificity were 0.272, 47.0% and 80.2%, respectively.ConclusionA high complement D-dimer level, low PLT level, and a high Padua score were shown to be independent risk factors for thrombosis in ITP patients. We developed a risk prediction model based on these three risk factors that could predict the risk of thrombosis in ITP patients to some extent.
Glucokinase activity controls peripherally-located subpopulations of β-cells that lead islet Ca2+oscillations
Authors: Jin Erli , Briggs Jennifer K. , Benninger Richard K.P. , Merrins Matthew J. 
Published: August 2024

AbstractOscillations in insulin secretion, driven by islet Ca2+waves, are crucial for glycemic control. Prior studies, performed with single-plane imaging, suggest that subpopulations of electrically coupled β-cells have privileged roles in leading and coordinating the propagation of Ca2+waves. Here, we used 3D light- sheet imaging to analyze the location and Ca2+activity of single β-cells within the entire islet at >2 Hz. In contrast with single-plane studies, 3D network analysis indicates that the most highly synchronized β-cells are located at the islet center, and remain regionally but not cellularly stable between oscillations. This subpopulation, which includes ‘hub cells’, is insensitive to changes in fuel metabolism induced by glucokinase and pyruvate kinase activation. β-cells that initiate the Ca2+wave (‘leaders’) are located at the islet periphery, and strikingly, change their identity over time via rotations in the wave axis. Glucokinase activation, which increased oscillation period, reinforced leader cells and stabilized the wave axis. Pyruvate kinase activation, despite increasing oscillation frequency, had no effect on leader cells, indicating the wave origin is patterned by fuel input. These findings emphasize the stochastic nature of the β-cell subpopulations that control Ca2+oscillations and identify a role for glucokinase in spatially patterning ‘leader’ β-cells.Highlights• Studies of islet Ca2+oscillations by 3D light-sheet imaging provide a more complete picture of β- cell subpopulations than prior 2D studies.• Highly synchronized β-cells (including ‘hub cells’) are a regionally-stable subpopulation located at the islet center that is insensitive to metabolic perturbation.• Glucokinase activation patterns the Ca2+wave axis, which originates from stochastic β-cell subpopulations on the islet periphery that change between oscillations.• The stochasticity of ‘leader’ β-cells, and the stability of ‘hubs’, is geographically consistent with the peripheral location of α/δ-cells in mouse islets.
Genetic Polymorphisms Associated with Insulin Resistance Risk in Normal BMI Indians
Authors: Thummala Sabitha , Khan Ghori Junaid Ahmed , Saikia Katherine , Fathima Sarah , Kruthi Nithya , Balamurali AR , Ranganathan Rahul 
Published: August 2024

ABSTRACTBackgroundInsulin resistance (IR) contributes significantly to the onset of metabolic disorders, such as type 2 diabetes mellitus and cardiovascular diseases. Identifying genetic markers associated with IR can offer insights into its mechanisms and potential therapeutic targets.ObjectiveThis study investigated the association between four single nucleotide polymorphisms (SNPs) and insulin resistance among 191 individuals in the Indian population.MethodsA literature review identified four SNPs linked to IR. Participants were divided into groups based on insulin resistance and sensitivity, determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA2-IR). DNA was extracted for genotyping using Illumina Infinium Global Screening Array (GSA) V3. Case-control analysis assessed SNP-genotype associations with insulin resistance and other clinical parameters.ResultsAmong 191 participants, 57 were insulin-resistant and 134 were insulin-sensitive. Significant associations (P < 0.05) were found between selected SNPs and IR. SNP rs920590 showed the strongest association, with the T allele associated with increased IR risk (odds ratio = 4.01, 95% CI 1.55-10.34; p < 0.0014). Additionally, serum LDL cholesterol, serum triglycerides, HbA1c, Insulin fasting and fat mass show significant differences in cases and controls.ConclusionThis study validates genetic markers linked to insulin resistance (IR) in the Indian population and elucidates their roles in IR pathogenesis. Understanding these markers can inform personalised therapeutic strategies for metabolic disorders.
Insulin Resistance Risk in Normal BMI Individuals: Investigating the Role of Genetic Polymorphisms in RNF138, ABCA1, and ESRRG-GPATCH2 Genes - A Case-Control Study in the Indian Population
Authors: Thummala Sabitha , Fathima Sarah , Kruthi Nithya , Ghori Junaid Ahmed Khan , Saikia Katherine , Belde Vivek , Balamurali AR , Ranganathan Rahul 
Published: August 2024

AbstractBackgroundIndia, characterised as the “diabetes capital” of the world, faces a rapidly increasing diabetes crisis with over 65 million cases diagnosed. Despite the growing prevalence, the genetic underpinnings of insulin resistance (IR) among Indians with normal BMI remain understudied. This research aims to fill the knowledge gap by investigating the association of specific gene variants (RNF138, ABCA1, andESRRG-GPATCH2) with IR risk in this demographic.MethodsA total of 191 participants (90 men, 101 women) were recruited for this cross-sectional study. Participants were categorized into cases (HOMA2-IR > 2) and controls (HOMA2-IR < 2) based on Homeostasis Model Assessment Insulin Resistance values. Genotyping for rs4799327 (RNF138), rs2275543 (ABCA1), and rs1497828 (ESRRG-GPATCH2) was performed using the Illumina Infinium Global Screening Array. Statistical analyses, including odds ratios (ORs), 95% confidence intervals (CIs), and inheritance model analysis, were conducted to assess the association between genotypes and IR.ResultsSignificant associations were found between IR and genetic variants rs4799327 in RNF138 and rs1497828 inESRRG-GPATCH2(dominant inheritance model) and rs2275543 in ABCA1 (additive model). The study highlights a notable susceptibility to IR linked to these genetic markers among normal BMI individuals in the Indian population.ConclusionsThis study underscores the importance of genetic factors in the risk of developing insulin resistance among Indians with normal BMI, suggesting a complex interplay of genetics beyond traditional risk factors. These findings necessitate further research into the functional significance of these associations and their potential implications for targeted interventions and preventive strategies in high-risk populations.Trial registrationNot applicable.
Study the Prevalence of Multidrug resistant bacteria from air samples collected from Mumbai & Suburban areas
Authors: Shah Janvi , Ghosh Sourav 
Published: August 2024

AbstractIntroductionAir comprises mixture of airborne bacteria & air pollutants in near surface of atmosphere. Air pollution is one of the major threat around the world due to change in physical and chemical parameters because of natural and anthropogenic activities; leading to climate change.Materials and MethodsA systematic analysis of AQI included air pollutants PM2.5, PM10, CO, SO2, NO2, O3, NH3using SAMEER app developed by CPCB and meteorological parameters including wind speed and relative humanity. The overuse of antibiotics since last two decades has lead pathogenic bacteria gaining resistance.ResultsThe study was carried out to identify the prevalence of MDR bacteria in air from 8 different spatial variations of Mumbai & Suburban areas. 32 isolates from air were collected by settle plate technique. Enumeration and characterization of bacteria was performed. Antibiotic susceptibility test against 10 antibiotics; test showed that all bacterial isolates were sensitive to Tigecycline. The bacteria were highly resistant to Methicillin by 81.25 %. ARI of two isolates was 0.9 & MRI of Vasai, 0.625 was the highest. The prominent pollutant among 8 locations was found to be PM2.5, CO & PM10. PCA & hierarchical cluster analysis showed that MRI is not correlated to 8 parameters but, distinctly related to NH3.ConclusionsThe MDR bacteria travel from soil, plants, water, humans, places, inanimate objects into the air. Hence, it is necessary to maintain the sanitation, ecological balance & usage of antibiotics when necessary.
Comparative Analysis of Stress Responses in Medical Students Using Virtual Reality Versus Traditional 3D-Printed Mannequins for Pericardiocentesis Training
Authors: Rubio-López Alberto , García Carmona Rodrigo , Zarandieta Román Laura , Rubio Navas Alejandro , González Pinto Ángel , Cardinal-Fernández Pablo 
Published: August 2024

ABSTRACTBackgroundAs medical education evolves, innovative methods like virtual reality (VR) and 3D-printed mannequins are increasingly used to simulate high-stress medical scenarios realistically. This study investigates the effectiveness of VR and 3D-printed mannequins in replicating stress levels during pericardiocentesis training, comparing their impact on the emotional and physiological responses of learners.MethodsWe enrolled 108 final-year medical students who were randomized to train with both VR and 3D-printed mannequins. Heart rate variability (HRV) analysis was employed to assess stress responses. Additionally, a secondary analysis examined the influence of demographic factors, lifestyle, medication use, and academic stress on these responses.ResultsBoth VR and traditional mannequin-based training methods proved equally effective in simulating the stress levels encountered in real medical procedures. Our findings indicate significant interactions between stress markers and demographic factors, which highlights the complex nature of stress responses in medical education and underscores the necessity for personalized training approaches.ConclusionThe study validates the use of VR as a viable alternative to traditional mannequins, capable of simulating the technical skills and emotional pressures of medical procedures such as pericardiocentesis. Incorporating VR into medical training programs may enhance learning outcomes and accessibility, particularly in settings constrained by resources.
Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score
Authors: Ritchie Scott C. , Taylor Henry J. , Liang Yujian , Manikpurage Hasanga D. , Pennells Lisa , Foguet Carles , Abraham Gad , Gibson Joel T. , Jiang Xilin , Liu Yang , Xu Yu , Kim Lois G. , Mahajan Anubha , McCarthy Mark I. , Kaptoge Stephen , Lambert Samuel A , Wood Angela , Sim Xueling , Collins Francis S. , Denny Joshua C. , Danesh John , Butterworth Adam S. , Di Angelantonio Emanuele , Inouye Michael 
Published: August 2024

AbstractCombining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score.
A modular encapsulation system for precision delivery of proteins, nucleic acids and therapeutics
Authors: Luong T. D. , Martel N. , Rae J. , Lo H. P. , Lim Y-W. , Wu Y. , McMahon K-A. , Fletcher N. , Thurecht K. , Johnston A.P.R. , Ariotti N. , Hall T. E. , Parton R.G. 
Published: August 2024

AbstractTargeted nanoparticles have the potential to revolutionize therapeutics for medical applications. Here, we demonstrate the utility of a flexible precision nanovesicle delivery system for functional delivery of DNA, RNA, proteins and drugs into target cells. Nanovesicles generated by the membrane sculpting protein caveolin, termed caveospheres, can be loaded with RNA, DNA, proteins or drugs post-synthesis or incorporate genetically-encoded cargo proteins during production without the need for protein purification. Functionalized fluorescently-labeled caveospheres form a modular system that shows high stability in biological fluids, specific uptake by target-positive cells, and can deliver proteins, drugs, DNA, and mRNA directly to the cytoplasm and nuclei of only the target cells. We demonstrate their application as a targeted transfection system for cells in culture, as a system to study endosomal escape, and critically, their efficacy in precision tumor killingin vivo.
Counting on AR: EEG responses to incongruent information with real-world context
Authors: Wimmer Michael , Pepicelli Alex , Volmer Ben , ElSayed Neven , Cunningham Andrew , Thomas Bruce H. , Müller-Putz Gernot R. , Veas Eduardo E. 
Published: August 2024

AbstractAugmented Reality (AR) technologies enhance the real world by integrating contextual digital information about physical entities. However, inconsistencies between physical reality and digital augmentations, which may arise from errors in the visualized information or the user’s mental context, can considerably impact user experience. This study characterizes the brain dynamics associated with processing incongruent information within an AR environment. We designed an interactive paradigm featuring the manipulation of a Rubik’s cube serving as a physical referent. Congruent and incongruent information regarding the cube’s current status was presented via symbolic (digits) and non-symbolic (graphs) stimuli, thus examining the impact of different means of data representation. The analysis of electroencephalographic (EEG) signals from 19 participants revealed the presence of centro-parietal N400 and P600 components following the processing of incongruent information, with significantly increased latencies for non-symbolic stimuli. Additionally, we explored the feasibility of exploiting incongruency effects for brain-computer interfaces. Hence, we implemented decoders using linear discriminant analysis, support vector machines, and EEGNet, achieving comparable performances with all methods. The successful decoding of incongruency-induced modulations can inform systems about the current mental state of users without making it explicit, aiming for more coherent and contextually appropriate AR interactions.
PI(4)P recruits CIDE proteins to promote the formation of unilocular lipid droplets during adipogenesis and hepatic steatosis
Authors: Wu Jin , Gao Mingming , Wu Xiaoqin , Liu Yang , Du Ximing , Liang Yan , Ma Chengxin , Li Peng , Chen Fung-Jung , Yang Hongyuan 
Published: August 2024

ABSTRACTLipid droplets (LDs) are evolutionarily conserved organelles that play important roles in metabolism. Each LD is enclosed by a monolayer of phospholipids, distinct from bilayer membranes. The composition of LD surface phospholipids and their impact on LD growth and function remain to be clearly defined. Phosphoinositides mark cellular organelles and regulate cell signalling and organellar function. Here, we demonstrate that PI(4)P decorates a subset of LDs to recruit and activate the CIDE proteins. Enhanced expression of ORP2 and ORP5, LD-associated lipid transfer proteins that remove PI(4)P from LDs, abolished the localization and function of CIDE proteins. Blocking the synthesis of PI(4)P on LD surface via knocking down PI4K2A also impaired the localization and function of CIDE proteins. In adipocytes, depleting PI(4)P dramatically reduced the size of LDs, as well as adipose tissue mass. In severe steatotic liver, depleting PI(4)P reduced LD accumulation. Our results thus identify a key function of LD surface PI(4)P under physiological conditions and unveil how CIDE proteins are recruited to LDs.
Confinement and Catalysis WithinDe NovoDesigned Peptide Barrels
Authors: Petrenas Rokas , Hawkins Olivia A. , Jones Jacob F. , Scott D. Arne , Fletcher Jordan M. , Obst Ulrike , Lombardi Lucia , Pirro Fabio , Leggett Graham J. , Oliver Thomas A.A. , Woolfson Derek N. 
Published: August 2024

ABSTRACTDe novoprotein design has advanced such that many peptide assemblies and protein structures can be generated predictably and quickly. The drive now is to bring functions to these structures, for example, small-molecule binding and catalysis. The formidable challenge of binding and orienting multiple small molecules to direct chemistry is particularly important for paving the way to new functionalities. To address this, here we describe the design, characterization, and application of small-molecule:peptide ternary complexes in aqueous solution. This uses α-helical barrel (αHB) peptide assemblies, which comprise 5 or more α-helices arranged around central channels. These channels are solvent accessible, and their internal dimensions and chemistries can be altered predictably. Thus, αHBs are analogous to ‘molecular flasks’ made in supramolecular, polymer, and materials chemistry. Using Förster resonance energy transfer as a readout, we demonstrate that specific αHBs can accept two different organic dyes, 1,6-diphenyl-1,3,5-hexatriene and Nile Red in close proximity. In addition, two anthracene molecules can be accommodated within an αHB to promote photocatalytic anthracene-dimer formation. However, not all ternary complexes are productive, either in energy transfer or photocatalysis, illustrating the control that can be exerted by judicious choice and design of the αHB.
Pharmacological CDK4/6 inhibition promotes vulnerability to lysosomotropic agents in breast cancer
Authors: Nehme Jamil , Maassen Sjors , Bravaccini Sara , Zanoni Michele , Gianni Caterina , Giorgi Ugo De , Soto-Gamez Abel , Altulea Abdullah , Gheorghe Teodora , Wang Boshi , Demaria Marco 
Published: August 2024

AbstractBreast cancer is a leading cause of mortality worldwide. Pharmacological inhibitors of Cyclin- Dependent Kinases (CDK) 4 and 6 (CDK4/6i) inhibit breast cancer growth by inducing a senescent-like state. However, the long-term treatment efficacy remains hindered by the development of drug resistance. Clearance of senescent-like cancer cells may extend the durability of treatment. In this study, we showed that CDK4/6i-treated breast cancer cells exhibit various senescence-associated phenotypes, but remain insensitive to common senolytic compounds. By searching for novel vulnerabilities, we identified a significantly increased lysosomal mass and altered lysosomal structure across various breast cancer cell types upon exposure to CDK4/6i in preclinical systems and clinical specimens. We demonstrated that these lysosomal alterations render breast cancer cells sensitive to lysosomotropic agents, such as L- leucyl-L-leucine methyl ester (LLOMe) and salinomycin. Importantly, sequential treatment with CDK4/6i/lysosomotropic agents effectively reduced the growth of both Hormone Receptor- positive (HR+) and triple-negative breast cancer (TNBC) cells in vivo. This sequential therapeutic strategy offers a promising approach to eliminate CDK4/6i-induced senescent(-like) cells, potentially reducing tumor recurrence and enhancing the overall efficacy of breast cancer therapy.
Selection can favor a recombination landscape that limits polygenic adaptation
Authors: Parée Tom , Noble Luke , Roze Denis , Teotónio Henrique 
Published: August 2024

AbstractMeiotic crossover positions are uneven along eukaryotic chromosomes, giving rise to heterogeneous recombination rate landscapes. Genetic modifiers of local and genome-wide crossover positions have been described, but the selective pressures acting on them and their potential effect on adaptation in already-recombining populations remain unclear. We performed experimental evolution using a mutant that modifies the position of crossovers along chromosomes in the nematodeCaenorhabditis elegans, without any detectable direct fitness effect. Our results show that when the recombination landscape is fixed, adaptation is facilitated by the modifier allele that, on average, increases recombination rates in genomic regions containing heritable fitness variation. However, in polymorphic populations containing both the wild-type and mutant modifier alleles, the allele that facilitates adaptation tends to decrease in frequency. This is likely because the allele that reduces recombination between selected loci at the genome-wide scale increases recombination in its chromosomal vicinity, and may thus benefit from local associations it establishes with beneficial genotype combinations. These results demonstrate that indirect selection acting on a recombination modifier mainly depends on its local effect, which may be decoupled from its consequences on genome-wide polygenic adaptation.