bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults
Authors: Kuo Chia-Ling , Chen Zhiduo , Liu Peiran , Pilling Luke C. , Atkins Janice L. , Fortinsky Richard H. , Kuchel George A. , Diniz Breno S. 
Published: December 2023

AbstractBeyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2,923 plasma proteins assessed using the Olink Explore 3072 assay®. The Spearman correlation between PAC proteomic age and chronological age was 0.77. A total of 10.9% of the participants died during a mean follow-up of 13.3 years, with the mean age at death 70.1 years. We developed a proteomic aging clock (PAC) for all-cause mortality risk as a surrogate of BA using a combination of least absolute shrinkage and selection operator (LASSO) penalized Cox regression and Gompertz proportional hazards models. PAC showed robust age-adjusted associations and predictions for all-cause mortality and the onset of various diseases in general and disease-free participants. The proteins associated with PAC were enriched in several processes related to the hallmarks of biological aging. Our results expand previous findings by showing that age acceleration, based on PAC, strongly predicts all-cause mortality and several incident disease outcomes. Particularly, it facilitates the evaluation of risk for multiple conditions in a disease-free population, thereby, contributing to the prevention of initial diseases, which vary among individuals and may subsequently lead to additional comorbidities.
CDRxAbs: Antibody Small-Molecule Conjugates with Computationally Designed Target-Binding Synergy
Authors: Wang Jingzhou , Aceves Aiden J. , Mayo Stephen L. 
Published: December 2023

AbstractAntibody-drug conjugates (ADCs) combine the advantages and offset the disadvantages of their constituent parts to achieve a refined spectrum of action. We combine the concept of ADCs with the full atomic simulation capability of computational protein design to define a new class of molecular recognition agents: CDR-extended antibodies, abbreviated as CDRxAbs. A CDRxAb incorporates a covalently attached small molecule into an antibody/target binding interface using computational protein design to create an antibody small-molecule conjugate that binds tighter to the target of the small molecule than the small molecule would alone. CDRxAbs are also expected to increase the target binding specificity of their associated small molecules. In a proof-of-concept study using monomeric streptavidin/biotin pairs at either a nanomolar or micromolar-level initial affinity, we designed nanobody-biotin conjugates that exhibited >20-fold affinity improvement against their protein targets with step-wise optimization of binding kinetics and overall protein stability. The workflow explored through this process promises a novel approach to optimize small-molecule based therapeutics and to explore new chemical and target space for molecular-recognition agents in general.SignificanceWe defined a general method for optimizing molecular recognition reagents that involve small molecules and demonstrated an application of this method using a model system. Instead of using traditional approaches for modifying a small molecule to improve its binding properties, we use computational protein design to build an antibody/small molecule conjugate that allows the target-binding strength (and specificity) of the small molecule to be tuned through changes in the amino acid sequence of the antibody scaffold. This method introduces a novel approach for optimizing the binding properties of small molecules and expands the potential application scenarios for antibody-drug conjugates.
Structure of an insect gustatory receptor
Authors: Frank Heather M. , Walujkar Sanket , Walsh Richard M. , Laursen Willem J. , Theobald Douglas L. , Garrity Paul A. , Gaudet Rachelle 
Published: December 2023

SUMMARYGustatory Receptors (GRs) are critical for insect chemosensation and are potential targets for controlling pests and disease vectors. However, GR structures have not been experimentally determined. We present structures ofBombyx moriGr9 (BmGr9), a fructose-gated cation channel, in agonist-free and fructose-bound states. BmGr9 forms a tetramer similar to distantly related insect Olfactory Receptors (ORs). Upon fructose binding, BmGr9’s ion channel gate opens through helix S7b movements. In contrast to ORs, BmGR9’s ligand-binding pocket, shaped by a kinked helix S4 and a shorter extracellular S3-S4 loop, is larger and solvent accessible in both agonist-free and fructose-bound states. Also unlike ORs, fructose binding by BmGr9 involves helix S5 and a binding pocket lined with aromatic and polar residues. Structure-based sequence alignments reveal distinct patterns of ligand-binding pocket residue conservation in GR subfamilies associated with distinct ligand classes. These data provide insight into the molecular basis of GR ligand specificity and function.
Mantis: high-throughput 4D imaging and analysis of the molecular and physical architecture of cells
Authors: Ivanov Ivan E. , Hirata-Miyasaki Eduardo , Chandler Talon , Cheloor-Kovilakam Rasmi , Liu Ziwen , Pradeep Soorya , Liu Chad , Bhave Madhura , Khadka Sudip , Arias Carolina , Leonetti Manuel D. , Huang Bo , Mehta Shalin B. 
Published: December 2023

AbstractHigh-throughput dynamic imaging of cells and organelles is essential for understanding complex cellular responses. We report Mantis, a high-throughput 4D microscope that integrates two complementary, gentle, live-cell imaging technologies: remote-refocus label-free microscopy and oblique light-sheet fluorescence microscopy. Additionally, we report shrimPy, an open-source software for high-throughput imaging, deconvolution, and single-cell phenotyping of 4D data. Using Mantis and shrimPy, we achieved high-content correlative imaging of molecular dynamics and the physical architecture of 20 cell lines every 15 minutes over 7.5 hours. This platform also facilitated detailed measurements of the impacts of viral infection on the architecture of host cells and host proteins. The Mantis platform can enable high-throughput profiling of intracellular dynamics, long-term imaging and analysis of cellular responses to perturbations, and live-cell optical screens to dissect gene regulatory networks.Significance StatementUnderstanding the dynamics and interactions of cellular components is crucial for biological research and drug discovery. Current dynamic fluorescence microscopy methods can only image a few fluorescent labels, providing a limited view of these complex processes. We developed Mantis, a high-throughput 3D microscope that maps interactions among components of dynamic cell systems. Mantis combines light-sheet fluorescence imaging of multiple fluorophores with quantitative label-free microscopy and is complemented by shrimPy, our open-source software for high-throughput data acquisition and high-performance analysis. Mantis enabled simultaneous 3D time-lapse imaging of 20 cell lines and quantitative analysis of responses to perturbations like viral infection at single-cell resolution. This approach can accelerate the analysis of cellular dynamics and image-based drug discovery.
Epithelial Folding Irreversibility is Controlled by Elastoplastic Transition via Mechanosensitive Actin Bracket Formation
Authors: Teranishi Aki , Mori Misato , Ichiki Rihoko , Toda Satoshi , Shioi Go , Okuda Satoru 
Published: December 2023

AbstractDuring morphogenesis, epithelial sheets undergo sequential folding to form three-dimensional organ structures. The resulting folds are irreversible, ensuring that morphogenesis progresses in one direction. However, the mechanism establishing the irreversibility of folding remains unclear. Here, we report a novel mechanical property of epithelia that is responsible for folding irreversibility. Using a newly developed mechanical indentation assay, we demonstrate that short-term or low-curvature folding induces an elastic, shape-restoring response. In contrast, combined long-term, high-curvature folding results in plastic, irreversible deformation. This elastic-to-plastic transition occurs in a switch-like manner, with critical thresholds for the folding curvature and duration. Specific cells at the fold initiate this transition, sensing the curvature and duration of folding on their apical side via mechanosensitive signaling pathways, including transient receptor potential canonical (TRPC) 3/6-mediated calcium influx and ligand-independent epidermal growth factor receptor activation. These pathways induce F-actin accumulation into a bracket-like structure across the fold, establishing the transition. The duration threshold is determined and tunable by the actin polymerization rate. These results demonstrate that cells control the irreversibility of epithelial folding by detecting folding characteristics and adaptively switching between elastic and plastic responses. This finding resolves a long-standing question about the directionality of morphogenesis.
The effectiveness of human resource management practices, work engagement and self-efficacy in minimizing talent turnover intention
Authors: Alhajaj Wejdan Eissa , Ahmad Syed Zamberi 
Published: December 2023

PurposeThis study examines the impact of perceived human resource management practices on talent turnover intention, with work engagement mediating and self-efficacy moderating the relationship. It examines how employees' perceptions of pay satisfaction, empowerment, participation and communication are related to their turnover intentions.Design/methodology/approachA total of 283 valid questionnaires from UAE government employees were used for data analysis. Partial least squares structural equation modeling (PLS-SEM) was used to examine the proposed hypothesis.FindingsThe results reveal that employees' perceptions of pay satisfaction, empowerment, participation and communication are significant contributors to work engagement. The findings further demonstrate that work engagement significantly negatively affects talent turnover intention and acts as a mediator between employees' perceptions of individual human resource management practices and talent turnover intention. However, the results contradict the hypothesis that self-efficacy moderates the association between work engagement and talent turnover intention.Originality/valueThis study focuses on the impact of perceived human resource management practices on talent turnover intention, an area that has received limited attention in literature. By focusing on perceived human resource management practices, this study illuminates employees' subjective experiences and how they perceive human resource management practices intended to reduce talent turnover intention. The inclusion of the mediating effect of work engagement offers a more profound understanding of how employees' perceptions of human resource management practices influence their turnover intentions. This comprehensive approach to understanding the interplay between these variables provides valuable insights for organizations seeking to improve their human resource management practices and talent turnover intention.
Why Bangkokians use online food delivery services after COVID-19 restrictions have been lifted
Authors: Weiler Arissara Suratanon , Gilitwala Bhumiphat 
Published: December 2023

PurposeThe growth of the internet has transformed digital infrastructure in Thailand over the past two decades, with the widespread use of e-commerce, digital money and online services becoming a daily norm for all ages. The COVID-19 restrictions, which limited in-person business operations, boosted demand for takeout and delivery services and fueled the expected steady growth of the online food delivery market in Thailand. The pandemic also resulted in a shift towards online ordering and delivery, reflecting changes in customer behavior. This study focuses on exploring the factors that have driven Bangkokians to use online food delivery services after the COVID-19 restrictions were lifted in June 2022.Design/methodology/approachData were collected from 398 participants who had ordered food delivery services after the announcement.FindingsThe findings showed that perceived usefulness, time saving benefit and price saving benefit have a significant impact on the intention of customers to use online food delivery services, while food safety risk perception had no effect.Practical implicationsBangkokians favor online food delivery services due to convenience and time-saving, indicating high demand post-pandemic. Businesses should invest in improving their platforms to meet evolving consumer behavior.Originality/valueThe result of this study offers valuable insights into the attitudes and behaviors of Bangkokians towards online food delivery services and could be beneficial for businesses in the industry to improve their services, enhance customer satisfaction as well as increase their competitiveness.
Emotional intelligence and analytical skill as human capital factors influencing competitiveness through analysis of Toyota Kata, Kaizen and Quality 4.0: empirical study conducted during COVID-19
Authors: Ríos-Hernández Alejandro , Mendoza-Gómez Joel , Valdez–de la Rosa Luz María 
Published: December 2023

PurposeThis study empirically tests a model of human capital (HC) factors affecting the organisational competitiveness (OC) of automotive parts suppliers in the Industry 4.0 framework, including concepts such as Toyota Kata (TK), Kaizen and Quality 4.0, during the coronavirus disease 2019 pandemic.Design/methodology/approachAn instrument was created to measure emotional intelligence (EI) and analytical skill (AS) as input variables and OC as the output variable. The instrument was distributed electronically to Tier 1 non-technical employees in Nuevo León and Querétaro, México. A total of 195 surveys were obtained. The instrument used stepwise multiple linear regression.FindingsThis study proposes a model to strengthen the OC of Tier 1 automotive parts supply industry from the perspective of HC factors. Furthermore, it is shown that EI and AS have a positive and significant impact on OC.Practical implicationsFrom an HC perspective, this study provides a useful basis to improve OC for researchers, industry experts and managers at different levels of the automotive industry, including the triple helix (academia, industry and the government).Originality/valueNo studies simultaneously test the relationship of EI and AS to OC; therefore, this study fills a gap in the literature. Furthermore, the study explored the literature on individual Kaizen (IK) and TK, leading to a contrast between the definitions of EI and AS. Finally, for EI, a reference to motivation was found in the IK. In the case of AS, an orientation to ability of problem solving was found in TK.
Caring about bequest, so caring for parents? Evidence from China's housing sector
Authors: He Jia , Wu Jing , Zhang Qi , Zhang Rongjie 
Published: December 2023

AbstractThis article reveals an informal eldercare arrangement in China by focusing on how the value of housing owned by aging parents affects adult children's caregiving behavior. Using three waves of national survey data in 2011–2015, we find that when the potential housing‐bequest value increases, adult children from multi‐child households provide more emotional support for their parents, demonstrating the role of the intergenerational‐exchange mechanism in China's current eldercare arrangement. However, such an informal mechanism is weakened by the prevalent social norms of son preference and is also less effective among emerging only‐child households. Therefore, we call for more market‐oriented arrangements.
Peritoneal dialysis in Herzegovina, Federation of Bosnia and Herzegovina: 18 years of experience from our center
Authors: Raguž Fila , Tomić Monika , Stojčić Andrea , Tipurić Manuel , Volarić Mile , Bevanda Sanja 
Published: December 2023

AbstractIntroductionDue to treatment of end‐stage‐renal‐disease (ESRD), continuous peritoneal dialysis (CAPD) is used in 11% of cases and is associated with several PD‐associated infections.MethodsClinical data on 71 patients with CAPD were evaluated in addition to exit site infections and episodes of acute peritonitis (AP).ResultsThere were 39 men and 32 women. Average age was 61 years when we began CAPD and average time spent on CAPD program was 3.35 years. Illness that dominantly caused ESRD was diabetes (23 patients). Exit site infection was mostly caused by S epidermidis‐MRSE and AP was most commonly caused by Staphylococcus sp. group. Most common cause of death was cardiovascular disease. At the end of this study, 9 patients were alive and still on CAPD, 10 were transplanted, 15 switched to HD and 36 died.ConclusionOptimal prevention measures and treatment of infectious complications in CAPD is necessary for better treatment possibilities.
Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub‐study of the PLOT‐ICU cohort
Authors: Anthon Carl Thomas , Pène Frédéric , Perner Anders , Azoulay Elie , Puxty Kathryn , Van De Louw Andry , Chawla Sanjay , Castro Pedro , Povoa Pedro , Coelho Luis , Metaxa Victoria , Kochanek Matthias , Liebregts Tobias , Kander Thomas , Sivula Mirka , Møller Morten Hylander , Russell Lene 
Published: December 2023

AbstractIntroductionPlatelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia.MethodsThis is a protocol and statistical analysis plan for a post hoc sub‐study of 504 thrombocytopenic patients from the ‘Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT‐ICU)’. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis‐derived versus pooled whole‐blood‐derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight‐based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell‐ and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow‐up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively.ConclusionsThe outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT‐ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.
A revision of the Australian endemic genus Labroma Sharp, 1873 (Coleoptera: Scarabaeidae)
Authors: Reid Chris A. M. , Tees Natalie A. 
Published: December 2023

AbstractThe Australian endemic dung beetle Labroma Sharp, 1873 is redescribed and revised. Five species are recognised, two new: L. horrens Sharp, 1873, L. monteithi sp. nov., L. toonumbar sp. nov., L. tuberculata (Waterhouse, 1874) and L. umbratilis Matthews, 1974. The genus, hitherto only known from southwest Western Australia, is newly recorded from New South Wales. Systematics of the genus and conservation status of its species are discussed.
Mechanics of vaginal breech birth: Factors influencing obstetric maneuver rate, duration of active second stage of labor, and neonatal outcome
Authors: Lia Massimiliano , Martin Mireille , Költzsch Elisabeth , Stepan Holger , Dathan‐Stumpf Anne 
Published: December 2023

AbstractBackgroundWe investigated possible parameters that could predict the need for obstetric maneuvers, the duration of the active second stage of labor (i.e., the duration of active pushing), and short‐term neonatal outcome in vaginal breech births.Materials and MethodsWe performed a retrospective analysis of 268 successful singleton vaginal breech births in women without previous vaginal births from January 2015 to August 2022. Multivariable regression was used to investigate associations between maternal and fetal characteristics (including antepartum magnetic resonance (MR) pelvimetry) with obstetric maneuvers, the duration of active second stage of labor, pH values, and admission to the neonatal unit. Models for the prediction of obstetric maneuvers were built and internally validated.ResultsObstetric maneuvers were performed in a total of 130 women (48.5%). A total of 32 neonates (11.9%) had to be admitted to the neonatal unit. The intertuberous distance (ITD) (p < 0.001), epidural analgesia (p < 0.001), and birthweight (p = 0.026) were associated with the duration of active second stage of labor. ITD (p = 0.028) and birthweight (p = 0.011) were also independently associated with admission to the neonatal unit, while pH values below 7.10 dropped significantly (p = 0.0034) if ITD was ≥13 cm. Furthermore, ITD (p < 0.001) and biparietal diameter (p = 0.002) were independent predictors for obstetric maneuvers.ConclusionsITD is independently associated with the duration of active second stage of labor. Thus, it can predict suboptimal birth mechanics in the last stage of birth, which may lead to the need for obstetric maneuvers, lower arterial pH values, and admission to the neonatal unit. Consequently, MR pelvimetry gives additional information for practitioners and birthing people preferring a vaginal breech birth.
Tumor suppressive function of IGF2BP1 in gastric cancer through decreasing MYC
Authors: Ding Ning , Cao Guodong , Wang Zhuo , Xu Shengjun , Chen Wenwen 
Published: December 2023

AbstractGastric cancer is one of the most common causes of cancer‐related death worldwide. The N6‐methyladenosine (m6A) reader IGF2BP1 (insulin‐like growth factor‐2 mRNA binding protein 1) has been reported to promote cancer progression by stabilizing oncogenic mRNAs through its m6A‐binding activity in some tumors. However, the role of IGF2BP1 in gastric carcinogenesis remains unclear. In this study, we found that IGF2BP1 is significantly downregulated in tumor tissues from patients with gastric cancer. Lower expression of IGF2BP1 is associated with poor prognosis. Gastric cancer cell proliferation is suppressed by IGF2BP1 in an m6A‐dependent manner. Additionally, IGF2BP1 is able to significantly attenuate tumor growth of gastric cancer cells. Further m6A sequencing and m6A‐RNA immunoprecipitation assays show that MYC (c‐myc proto‐oncogene) mRNA is a target transcript of IGF2BP1 in gastric cancer cells. IGF2BP1 inhibits gastric cancer cell proliferation by reducing the mRNA and protein expression of MYC. Mechanistically, IGF2BP1 promotes the degradation of MYC mRNA and inhibits its translation efficiency. Taken together, these data suggest that IGF2BP1 plays a tumor‐suppressive role in gastric carcinogenesis by downregulating MYC in an m6A‐dependent manner, thereby making the IGF2BP1‐MYC axis a potential target for gastric cancer treatment.