bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesogens: a unifying theory for the global rise in obesity
Authors: Heindel Jerrold J. , Lustig Robert H. , Howard Sarah , Corkey Barbara E. 
Published: January 2024

AbstractDespite varied treatment, mitigation, and prevention efforts, the global prevalence and severity of obesity continue to worsen. Here we propose a combined model of obesity, a unifying paradigm that links four general models: the energy balance model (EBM), based on calories as the driver of weight gain; the carbohydrate-insulin model (CIM), based on insulin as a driver of energy storage; the oxidation-reduction model (REDOX), based on reactive oxygen species (ROS) as a driver of altered metabolic signaling; and the obesogens model (OBS), which proposes that environmental chemicals interfere with hormonal signaling leading to adiposity. We propose a combined OBS/REDOX model in which environmental chemicals (in air, food, food packaging, and household products) generate false autocrine and endocrine metabolic signals, including ROS, that subvert standard regulatory energy mechanisms, increase basal and stimulated insulin secretion, disrupt energy efficiency, and influence appetite and energy expenditure leading to weight gain. This combined model incorporates the data supporting the EBM and CIM models, thus creating one integrated model that covers significant aspects of all the mechanisms potentially contributing to the obesity pandemic. Importantly, the OBS/REDOX model provides a rationale and approach for future preventative efforts based on environmental chemical exposure reduction.
The effect of fertility treatment and socioeconomic status on neonatal and post-neonatal mortality in the United States
Authors: Sharma Meesha , Fineman David C. , Keller Roberta L. , Maltepe Emin , Rinaudo Paolo F. , Steurer Martina A. 
Published: January 2024

Abstract
Objective
To determine the association between fertility treatment, socioeconomic status (SES), and neonatal and post-neonatal mortality.

Study design
Retrospective cohort study of all births (19,350,344) and infant deaths from 2014–2018 in the United States. The exposure was mode of conception—spontaneous vs fertility treatment. The outcome was neonatal (<28d), and post-neonatal (28d–1y) mortality. Multivariable logistic models were stratified by SES.

Result
The fertility treatment group had statistically significantly higher odds of neonatal mortality (high SES OR 1.59; CI [1.5, 1.68], low SES OR 2.11; CI [1.79, 2.48]) and lower odds of post-neonatal mortality (high SES OR 0.87, CI [0.76, 0.996], low SES OR 0.6, CI [0.38, 0.95]). SES significantly modified the effect of ART/NIFT on neonatal and post-neonatal mortality.

Conclusions
Fertility treatment is associated with higher neonatal and lower post-neonatal mortality and SES modifies this effect. Socioeconomic policies and support for vulnerable families may help reduce rates of infant mortality.
Glioblastoma biomarkers in urinary extracellular vesicles reveal the potential for a ‘liquid gold’ biopsy
Authors: Hallal Susannah M. , Tűzesi Ágota , Sida Liam A. , Xian Elissa , Madani Daniel , Muralidharan Krishna , Shivalingam Brindha , Buckland Michael E. , Satgunaseelan Laveniya , Alexander Kimberley L. 
Published: January 2024

Abstract
Background
Biomarkers that reflect glioblastoma tumour activity and treatment response are urgently needed to help guide clinical management, particularly for recurrent disease. As the urinary system is a major clearance route of circulating extracellular vesicles (EVs; 30–1000 nm nanoparticles) we explored whether sampling urinary-EVs could serve as a simple and non-invasive liquid biopsy approach for measuring glioblastoma-associated biomarkers.

Methods
Fifty urine specimens (15–60 ml) were collected from 24 catheterised glioblastoma patients immediately prior to primary (n = 17) and recurrence (n = 7) surgeries, following gross total resection (n = 9), and from age/gender-matched healthy participants (n = 14). EVs isolated by differential ultracentrifugation were characterised and extracted proteomes were analysed by high-resolution data-independent acquisition liquid chromatography tandem mass spectrometry (DIA-LC-MS/MS).

Results
Overall, 6857 proteins were confidently identified in urinary-EVs (q-value ≤ 0.01), including 94 EV marker proteins. Glioblastoma-specific proteomic signatures were determined, and putative urinary-EV biomarkers corresponding to tumour burden and recurrence were identified (FC ≥ | 2 | , adjust p-val≤0.05, AUC > 0.9).

Conclusion
In-depth DIA-LC-MS/MS characterisation of urinary-EVs substantiates urine as a viable source of glioblastoma biomarkers. The promising ‘liquid gold’ biomarker panels described here warrant further investigation.
Integrative score based on CDK6, PD-L1 and TMB predicts response to platinum-based chemotherapy and PD-1/PD-L1 blockade in muscle-invasive bladder cancer
Authors: Su Xiaohe , Jin Kaifeng , Guo Qiji , Xu Ziyue , Liu Zhaopei , Zeng Han , Wang Yiwei , Zhu Yu , Xu Le , Wang Zewei , Chang Yuan , Xu Jiejie 
Published: January 2024

Abstract
Background
Cyclin-dependent kinase 6 (CDK6) was proved to be an important regulator in the progression of cell cycle and has been a promising therapeutic target in cancer treatment. However, the clinical significance of CDK6 in muscle-invasive bladder cancer (MIBC) remains obscure. Herein, we attempt to explore the clinical relevance of CDK6 and assess the feasibility of the integrative model to predict immune checkpoint blockade (ICB) response.

Methods
This study enrolled 933 patients with muscle-invasive bladder cancer (MIBC) from Zhongshan Hospital (ZSHS), The Cancer Genome Atlas (TCGA), Chemo, IMvigor210 and UC-GENOME cohorts. Kaplan-Meier survival and Cox regression analyses were performed to assess clinical outcomes based on CDK6 expression.

Results
High CDK6 expression conferred poor prognosis and superior response to platinum-based chemotherapy but inferior response to ICB in MIBC. Furthermore, the integrative model named response score based on CDK6, PD-L1 and TMB could better predict the response to ICB and chemotherapy. Patients with higher response scores were characterised by inflamed immune microenvironment and genomic instability.

Conclusions
CDK6 expression was correlated with prognosis and therapy response in MIBC. Integration of CDK6, PD-L1 and TMB could better identify patients who were most likely to benefit from ICB and chemotherapy.
Unveiling the mechanistic link between extracellular amyloid fibrils, mechano-signaling and YAP activation in cancer
Authors: Farris Francesco , Elhagh Alice , Vigorito Ilaria , Alongi Nicoletta , Pisati Federica , Giannattasio Michele , Casagrande Francesca , Veghini Lisa , Corbo Vincenzo , Tripodo Claudio , Di Napoli Arianna , Matafora Vittoria , Bachi Angela 
Published: January 2024

AbstractThe tumor microenvironment is a complex ecosystem that plays a critical role in cancer progression and treatment response. Recently, extracellular amyloid fibrils have emerged as novel components of the tumor microenvironment; however, their function remains elusive. In this study, we establish a direct connection between the presence of amyloid fibrils in the secretome and the activation of YAP, a transcriptional co-activator involved in cancer proliferation and drug resistance. Furthermore, we uncover a shared mechano-signaling mechanism triggered by amyloid fibrils in both melanoma and pancreatic ductal adenocarcinoma cells. Our findings highlight the crucial role of the glycocalyx protein Agrin which binds to extracellular amyloid fibrils and acts as a necessary factor in driving amyloid-dependent YAP activation. Additionally, we reveal the involvement of the HIPPO pathway core kinase LATS1 in this signaling cascade. Finally, we demonstrate that extracellular amyloid fibrils enhance cancer cell migration and invasion. In conclusion, our research expands our knowledge of the tumor microenvironment by uncovering the role of extracellular amyloid fibrils in driving mechano-signaling and YAP activation. This knowledge opens up new avenues for developing innovative strategies to modulate YAP activation and mitigate its detrimental effects during cancer progression.
Effect of glucagon like peptide-1 receptor agonist exenatide, used as an intracranial pressure lowering agent, on cognition in Idiopathic Intracranial Hypertension
Authors: Grech Olivia , Mitchell James L. , Lyons Hannah S. , Yiangou Andreas , Thaller Mark , Tsermoulas Georgios , Brock Kristian , Mollan Susan P. , Sinclair Alexandra J. 
Published: January 2024

Abstract
Background
Cognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Peptide-1 (GLP-1) receptor agonist, exenatide, has been shown to significantly reduce ICP in IIH, therefore this study aimed to determine the effects of exenatide on cognition in IIH.

Methods
This was an exploratory study of the IIH:Pressure trial (ISTCRN 12678718). Women with IIH and telemetric ICP monitors (n = 15) were treated with exenatide (n = 7) or placebo (n = 8) for 12 weeks. Cognitive function was tested using the National Institute of Health Toolbox Cognitive Battery at baseline and 12 weeks.

Results
Cognitive performance was impaired in fluid intelligence ((T-score of 50 = population mean), mean (SD) 37.20 (9.87)), attention (33.93 (7.15)) and executive function (38.07 (14.61)). After 12-weeks there was no evidence that exenatide compromised cognition (no differences between exenatide and placebo). Cognition improved in exenatide treated patients in fluid intelligence (baseline 38.4 (8.2), 12 weeks 52.9 (6.6), p = 0.0005), processing speed (baseline 43.7 (9.4), 12 weeks 58.4 (10.4), p = 0.0058) and episodic memory (baseline 49.4 (5.3), 12 weeks 62.1 (13.2), p = 0.0315).

Conclusions
In patients with raised ICP due to IIH, exenatide, a drug emerging as an ICP lowering agent, does not adversely impact cognition. This is encouraging and has potential to be relevant when considering prescribing choices to lower ICP.
Exploratory study on the relationship between urinary sodium/potassium ratio, salt intake, and the antihypertensive effect of esaxerenone: the ENaK Study
Authors: Katsuya Tomohiro , Inobe Yoshito , Uchiyama Kazuaki , Nishikawa Tetsuo , Hirano Kunio , Kato Mitsutoshi , Fukui Toshiki , Hatta Tsuguru , Iwasaki Arata , Ishii Hajime , Sugiura Toshiyuki , Taguchi Takashi , Tanabe Ayumi , Sugimoto Kotaro , Shimosawa Tatsuo ,   on behalf of the ENaK investigators
Published: January 2024

AbstractExcessive salt intake is one of the causes of hypertension, and reducing salt intake is important for managing the risk of hypertension and subsequent cardiovascular events. Esaxerenone, a mineralocorticoid receptor blocker, has the potential to exert an antihypertensive effect in hypertensive patients with excessive salt intake, but evidence is still lacking, especially in clinical settings. We aimed to determine if baseline sodium/potassium ratio and baseline estimated 24-h urinary sodium excretion can predict the antihypertensive effect of esaxerenone in patients with essential hypertension inadequately controlled with an angiotensin receptor blocker (ARB) or a calcium channel blocker (CCB). This was an exploratory, open-label, interventional study with a 4-week observation period and a 12-week treatment period. Esaxerenone was orally administered once daily in accordance with the Japanese package insert. In total, 126 patients met the eligibility criteria and were enrolled (ARB subcohort, 67; CCB subcohort, 59); all were included in the full analysis set (FAS) and safety analysis. In the FAS, morning home systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from baseline to end of treatment (primary efficacy endpoint) (−11.9 ± 10.9/ − 6.4 ± 6.8 mmHg, both p < 0.001); a similar trend was observed in both subcohorts. Significant reductions were also shown in bedtime home and office SBP/DBP (all p < 0.001). Each BP change was consistent regardless of the urinary sodium/potassium ratio or estimated 24-h urinary sodium excretion at baseline. The urinary albumin-creatinine ratio (UACR) and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased from baseline to Week 12 in the total population and both subcohorts. No new safety concerns were raised. Esaxerenone significantly decreased morning home, bedtime home, and office BP; UACR; and NT-proBNP in this patient population, regardless of concomitant ARB or CCB use. The antihypertensive effect of esaxerenone was independent of the urinary sodium/potassium ratio and estimated 24-h urinary sodium excretion at baseline.
Self-perceptions as mechanisms of achievement inequality: evidence across 70 countries
Authors: Hofer Sarah I. , Heine Jörg-Henrik , Besharati Sahba , Yip Jason C. , Reinhold Frank , Brummelman Eddie 
Published: January 2024

AbstractChildren from lower socioeconomic status (SES) backgrounds tend to have more negative self-perceptions. More negative self-perceptions are often related to lower academic achievement. Linking these findings, we asked: Do children’s self-perceptions help explain socioeconomic disparities in academic achievement around the world? We addressed this question using data from the 2018 Programme for International Student Assessment (PISA) survey, including n = 520,729 records of 15-year-old students from 70 countries. We studied five self-perceptions (self-perceived competency, self-efficacy, growth mindset, sense of belonging, and fear of failure) and assessed academic achievement in terms of reading achievement. As predicted, across countries, children’s self-perceptions jointly and separately partially mediated the association between socioeconomic status and reading achievement, explaining additional 11% (ΔR2 = 0.105) of the variance in reading achievement. The positive mediation effect of self-perceived competency was more pronounced in countries with higher social mobility, indicating the importance of environments that “afford” the use of beneficial self-perceptions. While the results tentatively suggest self-perceptions, in general, to be an important lever to address inequality, interventions targeting self-perceived competency might be particularly effective in counteracting educational inequalities in countries with higher social mobility.
Long-term labeling and imaging of synaptically connected neuronal networks in vivo using double-deletion-mutant rabies viruses
Authors: Jin Lei , Sullivan Heather A. , Zhu Mulangma , Lavin Thomas K. , Matsuyama Makoto , Fu Xin , Lea Nicholas E. , Xu Ran , Hou YuanYuan , Rutigliani Luca , Pruner Maxwell , Babcock Kelsey R. , Ip Jacque Pak Kan , Hu Ming , Daigle Tanya L. , Zeng Hongkui , Sur Mriganka , Feng Guoping , Wickersham Ian R. 
Published: January 2024

AbstractRabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in trans in postsynaptic source cells. Suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full 12-week course of imaging. Ex vivo whole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.
Haplotype-resolved chromosome-scale genomes of the Asian and African Savannah Elephants
Authors: Shi Minhui , Chen Fei , Sahu Sunil Kumar , Wang Qing , Yang Shangchen , Wang Zhihong , Chen Jin , Liu Huan , Hou Zhijun , Fang Sheng-Guo , Lan Tianming 
Published: January 2024

AbstractThe Proboscidea, which includes modern elephants, were once the largest terrestrial animals among extant species. They suffered mass extinction during the Ice Age. As a unique branch on the evolutionary tree, the Proboscidea are of great significance for the study of living animals. In this study, we generate chromosome-scale and haplotype-resolved genome assemblies for two extant Proboscidea species (Asian Elephant, Elephas maximus and African Savannah Elephant, Loxodonta africana) using Pacbio, Hi-C, and DNBSEQ technologies. The assembled genome sizes of the Asian and African Savannah Elephant are 3.38 Gb and 3.31 Gb, with scaffold N50 values of 130 Mb and 122 Mb, respectively. Using Hi-C technology ~97% of the scaffolds are anchored to 29 pseudochromosomes. Additionally, we identify ~9 Mb Y-linked sequences for each species. The high-quality genome assemblies in this study provide a valuable resource for future research on ecology, evolution, biology and conservation of Proboscidea species.
An ensemble of bias-adjusted CMIP6 climate simulations based on a high-resolution North American reanalysis
Authors: Lavoie Juliette , Bourgault Pascal , Smith Trevor James , Logan Travis , Leduc Martin , Caron Louis-Philippe , Gammon Sarah , Braun Marco 
Published: January 2024

AbstractESPO-G6-R2 v1.0 is a set of statistically downscaled and bias-adjusted climate simulations based on the Coupled Model Intercomparison Project 6 (CMIP6) models. The dataset is composed of daily timeseries of three variables: daily maximum temperature, daily minimum temperature and daily precipitation. Data are available from 1950 to 2100 over North America. The simulation ensemble is comprised of 14 models driven by two emissions scenarios (SSP2-4.5 and SSP3-7.0). In this paper, we describe the workflow used for the bias-adjustment, which relies on the detrended quantile mapping method and the Regional Deterministic Reforecast System (RDRS) v2.1 reference dataset. Using the framework defined in the VALUE project, we show the improvements made by the bias-adjustment on marginal, temporal and multivariate aspects of the data. We also verify that the bias-adjusted climate data have similar climate change signal to the original climate model simulations. Finally, we provide guidance to users on how to use this dataset.
A giant tyrannosaur from the Campanian–Maastrichtian of southern North America and the evolution of tyrannosaurid gigantism
Authors: Dalman Sebastian G. , Loewen Mark A. , Pyron R. Alexander , Jasinski Steven E. , Malinzak D. Edward , Lucas Spencer G. , Fiorillo Anthony R. , Currie Philip J. , Longrich Nicholas R. 
Published: January 2024

AbstractTyrannosaurid dinosaurs dominated as predators in the Late Cretaceous of Laurasia, culminating in the evolution of the giant Tyrannosaurus rex, both the last and largest tyrannosaurid. Where and when Tyrannosaurini (T. rex and kin) originated remains unclear. Competing hypotheses place tyrannosaurin origins in Asia, or western North America (Laramidia). We report a new tyrannosaurin, Tyrannosaurus mcraeensis, from the Campanian–Maastrichtian Hall Lake Formation of New Mexico, based on a fossil previously referred to T. rex. T. mcraeensis predates T. rex by ~ 6–7 million years, yet rivaled it in size. Phylogenetic analysis recovers T. mcraeensis as sister to T. rex and suggests Tyrannosaurini originated in southern Laramidia. Evolution of giant tyrannosaurs in southern North America, alongside giant ceratopsians, hadrosaurs, and titanosaurs suggests large-bodied dinosaurs evolved at low latitudes in North America.
Characterizing conformational states in GPCR structures using machine learning
Authors: Buyanov Ilya , Popov Petr 
Published: January 2024

AbstractG protein-coupled receptors (GPCRs) play a pivotal role in signal transduction and represent attractive targets for drug development. Recent advances in structural biology have provided insights into GPCR conformational states, which are critical for understanding their signaling pathways and facilitating structure-based drug discovery. In this study, we introduce a machine learning approach for conformational state annotation of GPCRs. We represent GPCR conformations as high-dimensional feature vectors, incorporating information about amino acid residue pairs involved in the activation pathway. Using a dataset of GPCR conformations in inactive and active states obtained through molecular dynamics simulations, we trained machine learning models to distinguish between inactive-like and active-like conformations. The developed model provides interpretable predictions and can be used for the large-scale analysis of molecular dynamics trajectories of GPCRs.
Facile green synthesis route for new ecofriendly photo catalyst for degradation acid red 8 dye and nitrogen recovery
Authors: Al Harby Nouf F. , Fetouh H. A. , El-Batouti Mervette 
Published: January 2024

AbstractThis study novelty is that new photo catalyst prepared from sustainability low cost precursors. Dark red color hydrogel composites have been easily prepared from gelatin biopolymer using a simple sol–gel method. Gelatin doped by cobalt chloride, and silver nanoparticles (SNPs) in the presence of traces amount of sodium dodecyl sulfate surfactant and calcium chloride. Water-insoluble Gelatin composites are thermally stable photocatalysts for the degradation of toxic anionic acid red 8 dye. Promising photodynamic activity confirmed by fluorescence emission at λmax 650 nm. Optical absorption in Vis. light enhanced photo catalytic activity. Silver nanoparticles enhanced crystallinity, and improved optical properties and porosity. Dopants by CoCl2 and silver nanoparticles increased band gap of gelatin composites from (1.82 to 1.95) indicating interfacial charge separation. Low band gaps improved photo catalytic activity. Optical band gaps (Eg) lower than 2.0 eV indicates high catalytic activity in the photo degradation acid red 8 dye using Vis. light, wavelength 650 nm. Percent removal efficiency (%Re) of the dye at 500 ppm initial concentration, pH 1, contact time 30 min., and 0.20 g L−1 dose photo catalyst reached 95%. pH not affects removal efficiency. So, gelatin composites removed AR8 dye by photodegradation mechanism rather than adsorption due to photodynamic activity. Kinetics of photodegradation followed pseudo first order kinetic with rate constant k1 5.13 × 10−2 min.−1 Good electrical conductivity and magnetic properties (effective magnetic moment (µeff 4.11 B.M) improved dye degradation into simple inorganic species. Nutrients NH4+, and NO3− degradation products recovered by using alumina silicate clay via a cation exchange mechanism.