bluuebunny/crossref_metadata_2025_split huggingface dataset:
From hyperinsulinemia to cancer progression: how diminishing glucose storage capacity fuels insulin resistance
Authors: Kareva Irina 
Published: May 2024

AbstractType 2 diabetes (T2D) is a complex metabolic disorder characterized by insulin resistance, hyperglycemia and hyperinsulinemia, with a quarter to half of people with T2D unaware of their diagnosis until the disease has reached advanced stages. T2D is associated with increased risk and worse prognosis of cardiovascular disease, cognitive decline, and cancer. Here we propose an updated framework for describing emergence of insulin resistance that precedes development of T2D. We show that diminishing capacity to store excess glucose can qualitatively capture the transition from normal to diabetic phenotype as captured by responses to oral glucose tolerance tests (OGTTs). We then show that an emerging tumor can either progress or regress depending on the metabolic environment of the host, consistent with experimental results of Hopkins et al. (2018), who showed that drug-induced transient diabetic phenotype, and specifically hyperinsulinemia, resulted in loss of therapeutic efficacy, and its reversal restored drug sensitivity and response to therapy. Given the prevalence of hyperinsulinemia in individuals with normoglycemia, addressing this condition emerges as a promising avenue to augment cancer therapy outcomes.
Non-invasive detection of bilirubin concentrations during the first week of life in a low-resource setting along the Thailand-Myanmar border
Authors: Bancone Germana , Gilder Mary Ellen , Win Elsie , Gornsawun Gornpan , Moo Paw Khu , Archasuksan Laypaw , Wai Nan San , Win Sylverine , Hanboonkunupakarn Borimas , Nosten Francois , Carrara Verena I , McGready Rose 
Published: May 2024

AbstractBackgroundNeonatal hyperbilirubinaemia (NH) is a common problem worldwide and causes morbidity and mortality especially in low-resource settings.MethodsA study was carried out at Shoklo Malaria Research Unit clinics along the Thailand-Myanmar border to evaluate a non-invasive test for diagnosis of NH in a low-resource setting. Performance of transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine capillary serum bilirubin testing before phototherapy during neonatal care in the first week of life. Results were analysed by direct agreement and by various bilirubin thresholds used in clinical practice. Total serum bilirubin was also measured in cord blood at birth and tested for prediction of hyperbilirubinaemia requiring phototherapy in the first week of life.ResultsBetween April 2020 and May 2023, 742 neonates born at SMRU facilities were included in the study. A total of 695 neonates provided 1 to 9 capillary blood samples for analysis of serum bilirubin (total 1244 tests) during the first week of life and performance of the transcutaneous bilirubinometer was assessed in 307 neonates who provided 687 paired transcutaneous-capillary blood tests. Bilirubin levels were also measured in 738 cord blood samples.Adjusted values of the transcutaneous bilirubinometer showed excellent agreement with capillary serum bilirubin concentration (intraclass correlation coefficient=0.923) and high sensitivity (>98%) at all clinical thresholds analysed across three years of sampling and multiple users. Concentrations of bilirubin detected in cord blood were not useful in identifying neonates at risk of hyperbilirubinaemia requiring treatment.ConclusionsThe transcutaneous bilirubinometer is a reliable tool to screen neonates and identify those needing confirmatory blood testing. Bilirubin concentrations in cord blood are not predictive of hyperbilirubinemia in neonates.Summary boxWhat is already known on this topicNon-invasive detection of bilirubin levels in cord blood and transcutaneously can support better clinical care of neonates at risk of hyperbilirubinaemia, especially in low resources settings.What this study addsThis study was the first carried out in neonates of Karen and Burman ethnicity born at the Thailand-Myanmar border. The study provides new data on the performance of a transcutaneous bilirubinometer used by locally trained birth attendants. The results show that cord blood bilirubin levels are not predictive of hyperbilirubinaemia risk in the first days of life.How this study might affect research, practice or policyThis study adds to the growing body of knowledge about performance and utility of non-invasive screening tools and diagnostics to improve neonatal health in low-resource settings and LMIC countries.
Feasibility of time-restricted eating during pregnancy and effect on glycemic control in people with increased risk of gestational diabetes – a randomized controlled trial
Authors: Skarstad HS , Haganes KL , Sujan MAJ , Gellein TM , Johansen MK , Salvesen KÅ , Hawley JA , Moholdt T. 
Published: May 2024

AbstractTime-restricted eating (TRE) is a nutritional intervention that confines the daily time-window for energy intake. TRE reduces fasting glucose concentrations in non-pregnant individuals, but whether this eating protocol is feasible and effective for glycemic control in pregnancy is unknown. The aim of this randomized controlled trial was to investigate the feasibility and effect of a 5-week TRE intervention among pregnant individuals at risk of gestational diabetes mellitus (GDM), compared with a usual-care control group. Participants underwent 2-h oral glucose tolerance tests and estimation of body composition, before and after the intervention. Interstitial glucose levels were continuously measured, and adherence rates and ratings of hunger were recorded daily. Thirty of 32 participants completed the trial. Participants allocated to TRE reduced their daily eating window from 12.3 (SD 1.3) to 9.9 (SD 1.0) h, but TRE did not affect glycemic measures, blood pressure, or body composition, compared with the control group. TRE increased hunger levels in the evening, but not in the morning, and induced only small changes in dietary intake. A 5-week TRE intervention was feasible for pregnant individuals with increased risk of GDM but had no effect on cardiometabolic outcomes.
The impact of behavioral interventions on respiratory viruses in a two-cohort study
Authors: Nikparvar Behnam , Exten Cara , Bharti Nita 
Published: May 2024

AbstractBehavioral interventions are a critical tool for managing novel and emerging pathogens. However, the dynamics of behavioral interventions have been difficult to measure and are poorly understood. In this study, we investigate the uptake, persistence, and waning, of behavioral interventions among two cohorts in Centre County, PA, focusing on the three years following the emergence of SARS-CoV-2. We detected clusters of behaviors that followed similar patterns of engagement and variations over time and identified some novel COVID-19 behavioral interventions that may have severely disrupted non-COVID-19 respiratory disease incidence. Additionally, we detected links between changes in risk perception and changes in behaviors over time. These findings can inform recommendations around behavioral interventions during outbreak management, including information dissemination and behavioral guidelines.
Toward personalized skin cancer care: multiple skin cancer development in five cohorts
Authors: Wheless Lee , Liao Kai-Ping , Zheng Siwei , Li Yao , Yao Lydia , Xu Yaomin , Madden Christopher , Ike Jacqueline , Smith Isabelle T , Mosley Dominique , Grossarth Sarah , Hartman Rebecca I , Wilson Otis , Hung Adriana , Wehner Mackenzie R 
Published: May 2024

ABSTRACTImportanceMany patients will develop more than one skin cancer, however most research to date has examined only case status.ObjectiveDescribe the frequency and timing of the treatment of multiple skin cancers in individual patients over timeDesignLongitudinal claims and electronic health record-based cohort studySettingVanderbilt University Medical Center database called the Synthetic Derivative, VA, Medicare, Optum Clinformatics® Data Mart Database, IBM MarketscanParticipantsAll patients with a Current Procedural Terminology code for the surgical management of a skin cancer in each of five cohorts.ExposuresNone.Main Outcomes and MeasuresThe number of CPT codes for skin cancer treatment in each individual occurring on the same day as an ICD code for skin cancer over timeResultsOur cohort included 5,508,374 patients and 13,102,123 total skin cancers treated.Conclusions and RelevanceNearly half of patients treated for skin cancer were treated for more than one skin cancer. Patients who have not developed a second skin cancer by 2 years after the first are unlikely to develop multiple skin cancers within the following 5 years. Better data formatting will allow for improved granularity in identifying individuals at high risk for multiple skin cancers and those unlikely to benefit from continued annual surveillance. Resource planning should take into account not just the number of skin cancer cases, but the individual burden of disease.Key pointsQuestion: How many skin cancer patients are treated for more than one skin cancer and how soon after the first skin cancer do they occur?Findings: 43% of patients were treated for more than one skin cancer, the majority of which occurred within two years after the initial skin cancer. Just 3% of patients were treated for 10 or more skin cancers, but these patients accounted for 22% of all of the skin cancer treatments in the cohort Meaning: Nearly half of all skin cancer patients were treated for multiple skin cancers, while those without a second skin cancer after two years were less likely to be treated for a subsequent skin cancer within the next five years.
KREH2 helicase represses ND7 mRNA editing in procyclic-stageTrypanosoma bruceiby opposite modulation of canonical and “moonlighting” gRNA utilization creating a proposed mRNA structure
Authors: Meehan Joshua , Ivens Alasdair , Grote Scott , Rodshagen Tyler , Chen Zihao , Goode Cody , Sharma Sunil K. , Kumar Vikas , Frese Addison , Goodall Zachary , McCleskey Laura , Sechrist Rebecca , Zeng Lanying , Savill Nicholas J. , Rouskin Silvi , Schnaufer Achim , McDermott Suzanne M. , Cruz-Reyes Jorge 
Published: May 2024

ABSTRACTUnknown factors regulate mitochondrial U-insertion/deletion (U-indel) RNA editing in procyclic-form (PCF) and bloodstream-form (BSF)T. brucei. This editing, directed by anti-sense gRNAs, creates canonical protein-encoding mRNAs and may developmentally control respiration. Canonical editing by gRNAs that specify protein-encoding mRNA sequences occurs amid massive non-canonical editing of unclear sources and biological significance. We found PCF-specific repression at a major early checkpoint in mRNA ND7, involving helicase KREH2-dependent opposite modulation of canonical and non-canonical “terminator” gRNA utilization. Terminator-programmed editing derails canonical editing and installs proposed repressive structure in 30% of the ND7 transcriptome. BSF-to-PCF differentiationin vitrorecreated this negative control. Remarkably, KREH2-RNAi knockdown relieved repression and increased editing progression by reverting canonical/terminator gRNA utilization. ND7 transcripts lacking early terminator-directed editing in PCF exhibited similar negative editing control along the mRNA sequence, suggesting global modulation of gRNA utilization fidelity. The terminator is a “moonlighting” gRNA also associated with mRNA COX3 canonical editing, so the gRNA transcriptome seems multifunctional. Thus, KREH2 is the first identified repressor in developmental editing control. This and our prior work support a model whereby KREH2 activates or represses editing in a stage and substrate-specific manner. KREH2’s novel dual role tunes mitochondrial gene expression in either direction during development.
The carnivoran adaptive landscape reveals functional trade-offs among the skull, appendicular, and axial skeleton
Authors: Law Chris J. , Hlusko Leslea J. , Tseng Z. Jack 
Published: May 2024

AbstractAnalyses of form-function relationships are widely used to understand links between morphology, ecology, and adaptation across macroevolutionary scales. However, few have investigated functional trade-offs and covariance within and between the skull, limbs, and vertebral column simultaneously. In this study, we investigated the adaptive landscape of skeletal form and function in carnivorans to test how functional trade-offs between these skeletal regions contribute to ecological adaptations and the topology of the landscape. We found that morphological proxies of function derived from carnivoran skeletal regions exhibit trade-offs and covariation across their performance surfaces, particularly in the appendicular and axial skeletons. These functional trade-offs and covariation correspond as adaptations to different adaptive landscapes when optimized by various factors including phylogeny, dietary ecology, and, in particular, locomotor mode. Lastly, we found that the topologies of the optimized adaptive landscapes and underlying performance surfaces are largely characterized as a single gradual gradient rather than as rugged, multipeak landscapes with distinct zones. Our results suggest that carnivorans may already occupy a broad adaptive zone as part of a larger mammalian adaptive landscape that masks the form and function relationships of skeletal traits.
Cdc25A phosphatase is activated and mediates neuronal cell death by PUMA via pRB/E2F1 pathway in a model of Parkinson’s disease
Authors: Das Anoy Kumar , Biswas Subhas C 
Published: May 2024

AbstractParkinson’s disease (PD) is a predominant movement disorder caused mainly due to selective loss of the dopaminergic neurons in the substantia nigra pars compacta of the mid brain. There is currently no cure for PD barring treatments to manage symptoms. The reasons might be due to lack of precise understanding of molecular mechanisms leading to neurodegeneration. Aberrant cell cycle activation has been implicated in neuronal death pathways of various neurodegenerative diseases including PD. This study investigates the role of cell cycle regulator Cell division cycle 25A (Cdc25A) in a PD-relevant neuron death model induced by 6-OHDA treatment. We find Cdc25A is rapidly elevated, activated and is playing a key role in neuron death by regulating Rb phosphorylation and E2F1 activity. Knockdown of Cdc25A via shRNA downregulates the levels of pro-apoptotic PUMA, an E2F1 target and cleaved Caspase-3 levels, suggesting Cdc25A may regulate neuronal apoptosis through these effectors. Our work sheds light on the intricate signaling networks involved in neurodegeneration and highlights Cdc25A as a potential therapeutic target for mitigating aberrant cell cycle re-entry underlying PD pathogenesis. These novel insights into molecular mechanisms provide a foundation for future development of neuroprotective strategies to slow or prevent progression of this debilitating disease.
Exploring operational requirements of mixtures for insecticide resistance management in public health using a mathematical model assuming polygenic resistance
Authors: Hobbs Neil Philip , Hastings Ian Michael 
Published: May 2024

AbstractLong-lasting insecticide treated nets (LLINs) have been developed which contain two active ingredients. Mixture products for vector control are now an available insecticide resistance management (IRM) strategy. There is a theoretical concern around the use mixtures pertaining to dosing, insecticide decay, initial resistance, and cross resistance. Mixture LLINs all currently have a pyrethroid as one of the partner insecticides. Using previously described mathematical models of polygenic insecticide resistance evolution, which implement selection either by truncation (“polytrucate) or as a probabilistic process (“polysmooth”) mixtures are evaluated for their IRM potential. Scenarios are developed to explore the impact of the initial levels of resistance to the pyrethroid insecticide, insecticide decay rates, and insecticide doses, and cross resistance. Results from our simulations indicate that mixtures should be deployed at full doses. As the initial level of resistance to the pyrethroid increases the benefit of mixture decreases. Insecticide decay was found to be less important than might be thought, with other variables having a greater impact. The mechanism of selection demonstrated consistent results, diverging only at very high levels of resistance to the pyrethroid. Our simulations demonstrate that the impact of positive cross resistance is best mitigated using full-dose mixtures. Insecticide decay less important than previously considered, and opens up the opportunity to mix a wider variety of insecticides. However, as mixtures remain a challenge to develop and therefore strategies which could generate an effect of a “temporal” mixture should be evaluated.
Monitoring of the invasive round goby in an estuarine seascape based on eDNA
Authors: Green Leon , Dahlgren Thomas G. , Axberg Alizz , Panova Marina , Obst Matthias , Sundberg Per 
Published: May 2024

0.0AbstractNon-indigenous species (NIS) is one of the five most global concerns when it comes to ecosystem services and threats to native biodiversity. This is especially true in aquatic environments which are harder to monitor than terrestrial environments, and NIS are often found first when they are fully established and basically impossible to eradicate. In marine environments, this is further complicated due to the connectivity and difficulty of eradication. The development and implementation of effective monitoring methods for marine NIS are therefore crucial to enable early detection useful for management strategies. In this study, we develop and evaluate environmental DNA monitoring using quantitative (q)PCR as a means to assess presence of the euryhaline round goby fish (Neogobius melanostomus) in a seascape environment close to Scandinavia’s largest shipping port. We developed a dPCR assay for the species, targeting a region of 12S gene, and verified its specificity compared to other common species from the gobiid-family in the region. We also experimentally determined the decaying rate of round goby DNA in water to a half-life of 9.8 hours in 15 PSU and 15°C with live fish in captivity. Finally, we sampled 10 sites within a 400 km2area for eDNA and presence of the species using fyke-nets and baited remote video to validate the accuracy of the water samples to predict presence, and abundance. We found that the number of DNA copies extracted from the water samples varied strongly at sites where round gobies were caught in nets or on video, but that the average value from four water samples significantly correlated with an average value from four video samples, and also with the total catch at each site. The eDNA assay also detected signals from the species at sites where no fish were caught by fishing or on video. These results show that this method is highly sensitive for the species even in low abundance, and with sufficient amounts of replicates, it can be possible to determine the relative abundance between sites.
Identification of Candidate Diagnostic gene CDC25C for Trametinib-induced Cardiotoxicity by Integrating Bioinformatics and Machine Learning
Authors: Pei Jixiang , Yan Xiong , Guo Qingming , Wang Zhimei , Liu Yukun 
Published: May 2024

ABSTRACTTrametinib is a MEK inhibitor that has been shown to have considerable efficacy in retarding melanoma progression. However, the exact mechanism of cardiotoxicity induced by trametinib remains unclear. Our study was designed to investigate the underlying mechanisms by which trametinib-induced cardiotoxicity (TIC) might exist, offering novel perspectives and guidance for potential prediction, diagnosis, and treatment of TIC. The GSE217421 dataset indicated 574 up-regulated and 705 down-regulated DEGs. According to the KEGG analysis, these genes were implicated in several pathways and functions, including Cell Cycle, Axon Guidance, Cellular Senescence, and Dilated Cardiomyopathy. The GO analysis suggested their association with Mitotic Cell Cycle, Microtubule Cytoskeleton and Adenyl Nucleotide Binding. The hub genes (CDC25C) for TIC were screened through Multiple machine learning algorithms. Next, The expression level of CDC25C was verified using the GSE217423 validation set. Nomogram model based on CDC25C demonstrated excellent diagnostic capability according to three different evaluation measures. To further explore the regulatory mechanism of CDC25C in TIC, we constructed a multi-regulatory network using miRNAs-lncRNAs-TFs-CDC25C and conducted an immunoinfiltration analysis. Our study suggests that CDC25C may be a candidate diagnostic gene and a potential therapeutic target for the early occurrence and development of TIC. This provides new ideas for the prediction, diagnosis and treatment strategies for TIC.
Native Korean wild mice (Mus musculus): molecular phylogeny and morphometrics
Authors: Kim Daewoo , Oh Jooseong , Oh Jang Geun , Yang Hee-Young , Kim Geun-Joong , Lee Tae-Hoon , Lee Bae-Geun , Park Chungoo , Nam Dong-Ha 
Published: May 2024

AbstractTaxonomic status of house mice in the Korean Peninsula remains poorly understood. Here, we analyze genetic and morphological characteristics of mice from Korea and evaluate their phylogenetic relationships to the well-known primary subspecies. Using a comprehensive set of publicly available genetic data (mtDNAcytbgene), Korean mice including our specimens from islands, mountains, and agricultural fields were identified toMus mus musculus. External morphology, such as tail ratios of our specimens, resembled previously assigned subspecies (e.g.,M. m. molossinus,M. m. utsuryonis, andM. m. yamashinai), suggesting a single subspecific group withinM. m. musculus. Korean mice displayed a distinctive landmark configuration around the snout, with a relatively short and slender premaxillary tooth-patch width (PMXW) and a larger maxillary tooth-row length (MXTL) compared to laboratory strains derived fromM. m. domesticus. Our investigation provides insights into the phylogenetic relationships and taxonomic status of Korean mice relative to the primary lineages ofM. musculussubspecies. Understanding the evolutionary history of KoreanM. m. musculussheds new light on how their spatiotemporal dynamics led to diversification, with the Korean Peninsula serving as an ecological bridge between East Eurasia and neighboring regions.
A synthetic method to assay polycystin channel biophysics
Authors: Larmore Megan , Esarte Palomero Orhi , Kamat Neha P. , DeCaen Paul G. 
Published: May 2024

ABSTRACTIon channels are biological transistors that control ionic flux across cell membranes to regulate electrical transmission and signal transduction. They are found in all biological membranes and their conductive state kinetics are frequently disrupted in human diseases. Organelle ion channels are among the most resistant to functional and pharmacological interrogation. Traditional channel protein reconstitution methods rely upon exogenous expression and/or purification from endogenous cellular sources which are frequently contaminated by resident ionophores. Here we describe a fully synthetic method to assay functional properties of polycystin channels that natively traffic to primary cilia and endoplasmic reticulum organelles. Using this method, we characterize their oligomeric assembly, membrane integration, orientation and conductance while comparing these results to their endogenous channel properties. Outcomes define a novel synthetic approach that can be applied broadly to investigate channels resistant to biophysical analysis and pharmacological characterization.