bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Obesity Care Among US Adults, 2010–2021
Authors: Podolsky Meghan I. , Raquib Rafeya , Hempstead Katherine , Stokes Andrew C. 
Published: January 2025

Background:
Obesity is a major contributor to mortality in the United States. Clinical guidelines emphasize the need for multimodal treatment, but novel treatments may be changing care-seeking behavior.

Objective:
To characterize obesity treatment access patterns and factors associated with obesity care from 2010 to 2021 in the United States.

Research Design:
This multiyear cross-sectional study was conducted using Medical Expenditure Panel Survey data, covering respondents from 2010 to 2021.

Subjects:
We defined individuals with a body mass index ≥30 or those with any health care event linked to a diagnosis of obesity as being clinically eligible for obesity treatment.

Measure(s):
The primary outcome was the proportion of individuals assumed eligible for obesity treatment who accessed obesity treatment or were prescribed medication to treat obesity in each calendar year from 2010 to 2021.

Results:
The population of individuals eligible for obesity treatment was 82,729. In total, 1311 (1.6%) reported receiving treatment for obesity. The proportion of participants receiving a prescription for obesity increased from 0.3% (0.2%, 0.6%) in 2010 to 1.8% (1.3%, 2.5%) in 2021. Multivariable l﻿ogistic regression found that female individuals, older individuals, and those with higher levels of education had higher odds of ﻿accessing obesity medication or any obesity treatment.

Conclusions:
Utilization of pharmaceutical and nonpharmaceutical obesity treatment has increased from 2010 to 2021 but remains low. The likelihood of receiving treatment was lower for groups with lower socioeconomic status. As more effective obesity therapies become available, efforts should be made to ensure equitable access.
Is there a role for neoadjuvant therapies followed by radical cystectomy in oligometastatic bladder cancer?
Authors: Cadenar Anna , Mancon Stefano , Shariat Shahrokh F. , D’Andrea David 
Published: January 2025

Purpose of review
This review explores the potential role of neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for oligometastatic bladder cancer (OMBC) treatment. We focused on extrapolating evidence from studies including lymph node-positive only and metastatic bladder cancer to address the key challenges and therapeutic strategies for OMBC.

Recent findings
Current evidence for NAC and RC in OMBC is limited, with most data derived from studies in locally advanced bladder cancer. NAC has shown efficacy in downstaging and improving survival in patients with locally advanced disease, but its benefits in OMBC remain speculative. Additionally, diagnostic uncertainties, particularly regarding the inclusion of pelvic lymph nodes and the role of FDG-PET/CT, pose significant challenges to accurate staging and treatment decisions. Recent studies highlight the potential of metastasis-directed therapy, but uncertainties remain on patient selection and treatment protocols for OMBC.

Summary
There is need for prospective studies to evaluate neoadjuvant systemic treatments and RC specifically in OMBC. Moreover, resolving current diagnostic challenges is crucial to avoid undertreatment due to inaccurate staging. Until more concrete evidence emerges, changes to standard treatment protocols should be approached with caution and offered only within trials.
Intestinal stem cell marker MEX3A regulates PPARγ expression with functional impact in colorectal carcinogenesis
Authors: Silva Ana R. , Coelho Alexandre , Machado Vanessa , Russel Morgana , Mexieiro Dalila , Amaral Ana L. , Cavadas Bruno , Carvalho-Maia Carina , Gigliano Davide , Jerónimo Carmen , Almeida Raquel , Pereira Bruno 
Published: January 2025

ABSTRACTRNA-binding proteins (RBPs) are major effectors of post-transcriptional regulation. Recently, we described the role of MEX3A in maintaining intestinal stem cell identity and epithelial renewal by repressing the PPARγ pathway. This work aimed to study MEX3A functional impact in colorectal cancer (CRC). MEX3A and PPARγ expression profiles were characterized in murine and human models. CRISPR/Cas9-mediated MEX3A knockout was performed in patient-derived CRC tumoroids (PDCTs) and MEX3A RNA targets identified through the HyperTRIBE technique.Apc+/fl;Mex3a+/−mice presented a significant reduction in tumor burden.Apc+/fl;Kras+/G12D;Mex3a+/−mice presented a reduced tumor area, while corresponding tumoroids exhibited reduced growth and enhanced differentiation potential mediated by PPARγ signalling. MEX3A overexpression (85% of human CRC cases) was inversely correlated with PPARγ downregulation (72% of cases). Accordingly, MEX3A-depleted PDCTs showed decreasedLGR5expression, accompanied by increased PPARγ expression and higher sensitivity to 5-Fluorouracil/Oxaliplatin (FOLFOX)-based chemotherapy. The HyperTRIBE results revealed a direct interaction between MEX3A andPPARGtranscripts.STATEMENT OF SIGNIFICANCEThese results emphasize that MEX3A plays a crucial role in colorectal carcinogenesis, partially through regulation of the PPARG pathway, mediating tumour development and response to therapy, thus constituting a potential therapeutic target.
Label-free Detection and Characterization of Metabolism in Fresh and Cryopreserved Macrophages
Authors: Canales Daniela De Hoyos , Hu Linghao , Walsh Alex J. 
Published: January 2025

AbstractCryopreservation is a widely used technique to preserve biological samples for extended periods of time at low temperatures. Even though it is known to have significant effects on cell viability, its effect on their metabolism remains unexplored. Studying how cryopreservation influences the metabolism of cells is important to guarantee the reliability of samples transported between sites for analysis. Optical metabolic imaging allows for the study of cellular metabolism in a label-free manner by using the autofluorescence properties of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), two metabolic coenzymes. The goal of this research is to study the metabolic changes in macrophages after cryopreservation and compare these results with freshly isolated macrophage samples to evaluate if the metabolic data is retained after cryopreservation. The metabolism of macrophages was analyzed with fluorescence lifetime imaging microscopy (FLIM) using a multiphoton microscope. Monocytes were isolated from human whole blood and separated into two groups. In Group 1, freshly isolated monocytes were differentiated into macrophages using macrophage-colony stimulating factor (M-CSF) over 8 days. In Group 2, isolated monocytes were cryopreserved after separation from whole blood and then thawed and stimulated with M-CSF for 8 days. Single-cell analysis showed there are significant changes in FLIM parameters between the groups suggesting that the metabolic data of macrophages is altered after a cryopreservation and cell thawing cycle. Our research bridges the current gap by studying the metabolic changes of cells after cryopreservation using a non-invasive and label-free imaging technique.
spEMO: Exploring the Capacity of Foundation Models for Analyzing Spatial Multi-Omic Data
Authors: Liu Tianyu , Huang Tinglin , Ying Rex , Zhao Hongyu 
Published: January 2025

AbstractSeveral pathology foundation models have been designed by pre-training a model with pathology information for disease-centered downstream applications. These models have been treated as a breakthrough for pathology research. Along with pathology images, we can also measure spatial multi-omic expression levels for each spot, which provide additional information for understanding the spatial context. However, we still lack an effective tool to leverage the contributions of these technologies. Here, we present a novel artificial intelligence system, named as spEMO, to incorporate the embeddings from pathology foundation models and large language models to analyze spatial multi-omic data. Overall, spEMO outperforms foundation models trained only with single-modality data through introducing better representations. Our method also explores different approaches to combining information from various sources and shows the contributions of integrating external embedding information to handle different novel downstream applications, including spatial domain identification, spot-type prediction, whole-slide disease-state prediction and interpretation, multi-cellular interaction inference, and medical report generation. Furthermore, we define a new task of multi-modal alignment to assess the information retrieval ability of pathology foundation models. This task offers a new direction to evaluate the quality of foundation models and gain insights for model development.
Binding Kinetics, Bias, Receptor Internalization and Effects on Insulin Secretionin vitroandin vivoof a Novel GLP-1R/GIPR Dual Agonist, HISHS-2001
Authors: Manchanda Yusman , Jones Ben , Carrat Gaelle , Ramchunder Zenouska , Marchetti Piero , Leclerc Isabelle , Thennati Rajamannar , Burade Vinod , Natarajan Muthukumaran , Shahi Pradeep , Tomas Alejandra , Rutter Guy A. 
Published: January 2025

AbstractThe use of incretin analogues has emerged in recent years as an effective approach to achieve both enhanced insulin secretion and weight loss in type 2 diabetes (T2D) patients. Agonists which bind and stimulate multiple receptors have shown particular promise. However, off target effects, including nausea and diarrhoea, remain a complication of using these agents, and modified versions with optimized pharmacological profiles and/or biased signaling at the cognate receptors are increasingly sought. Here, we describe the synthesis and properties of a molecule which binds to both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors (GLP-1R and GIPR) to enhance insulin secretion. HISHS-2001 shows increased affinity at the GLP-1R, as well as a tendency towards reduced internalization and recycling at this receptorversusFDA-approved dual GLP-1R/GIPR agonist tirzepatide. HISHS-2001 also displayed significantly greater bias towards cAMP generationversusβ-arrestin 2 recruitment compared to tirzepatide. In contrast, Gαsrecruitment was lowerversustirzepatide at the GLP-1R, but higher at the GIPR. Administered to obese hyperglycaemicdb/dbmice, HISHS-2001 increased circulating insulin whilst lowering body weight and HbA1c with similar efficacy to tirzepatide at substantially lower doses. Thus, HISHS-2001 represents a novel dual receptor agonist with an improved pharmacological profile.
ntSynt-viz: Visualizing synteny patterns across multiple genomes
Authors: Coombe Lauren , Warren René L. , Birol Inanc 
Published: January 2025

AbstractWith the explosion of chromosome-scale genome assemblies being generated in recent years, there is vast potential for comparative genomics analyses through detecting multi-genome synteny. While existing tools can detect synteny blocks between multiple genomes, their text-based outputs make it challenging to intuitively explore large-scale synteny patterns. Interpretable, information-rich and easy-to-use synteny visualization tools are imperative to enable important biological insights from the synteny block data output by the aforementioned utilities. Here, we present ntSynt-viz, a command-line tool for automated sorting, normalization and plotting of multi-genome synteny blocks. We show how ntSynt-viz provides clearer and more easily interpretable chromosome-painting ribbon plots compared to the state-of-the-art tool NGenomeSyn when evaluating synteny between 14 human genomes and 9 hoverfly genomes. We expect that ntSynt-viz will provide crucial insights into large-scale synteny patterns between divergent genomes, thereby advancing research into key evolutionary questions. ntSynt-viz is freely available on GitHub (https://github.com/bcgsc/ntsynt-viz).
Sense of coherence and self-care in people with diabetes: systematic review
Authors: Vega-Martínez María del Carmen , López-Martínez Catalina , del-Pino-Casado Rafael 
Published: January 2025

AbstractIntroductionDiabetes mellitus is one of the diseases with the greatest social and health impact. Self-care in people with diabetes requires constant physical and emotional effort, which is one of the barriers to adherence to the care plan. Sense of coherence can play an important role in self-care.AimsTo examine the relationship between sense of coherence and self-care in individuals with diabetes mellitus.MethodA systematic review with narrative synthesis for all included studies and with meta-analysis in those with adequate statistical data. We searched PubMed, CINAHL, PsychInfo and Scopus up to July 2024. We included original studies that reported effect sizes on the association between sense of coherence and self-management of care plans in individuals with diabetes. Methodological quality of the studies was independently assessed by two researchers by evaluating the risk of selection bias, classification bias and confounding bias. Meta-analysis was performed using a random-effects model and various sensitivity and subgroup analyses were performed to assess the robustness of the meta-analysis result.ResultsThirteen articles were included in the review (six were included in the meta-analysis), whose participants (9,800) were people with type 1 or 2 diabetes. In the studies analyzing the relationship between sense of coherence and adherence to self-care (diet, exercise, and medication), a positive association was observed between these variables. In addition, sense of coherence may have a protective effect against negative perceptions of self-care. In the meta-analysis, a positive and moderate association between sense of coherence and adherence to self-care was found, with no heterogeneity and possible publication bias that does not affect the results of the meta-analysis.LimitationsSmall number of studies; all were cross-sectional.ConclusionsSense of coherence may play a relevant role in improving adherence to the self-care plan in people with type 1 or 2 diabetes.PROSPERO idCRD42023390705
Cortical Manifolds in Cognitive Recovery following Supratentorial Neurosurgery
Authors: Poologaindran A , Romero-Garcia R , Luppi AI , Hart MG , Santarius T , Price S , Sughrue ME , Bethlehem RAI , Sonkusare S , Erez Y , Suckling J 
Published: January 2025

AbstractThe cerebral cortex is topographically organized to integrate and segregate unimodal (e.g. sensorimotor) and transmodal brain networks to scaffold cognition. Cortical gradient mapping provides a framework to examine the relationship between connectivity patterns of macroscale functional brain networks within a low-dimensional (manifold) space. Using this technique, we longitudinally examine how diffuse gliomas, their neurosurgical resection, and subsequent cognitive rehabilitation impact the topographic organization of brain networks. First, using UKBioBank data (n=4000), we validate the general assembly of cortical gradients in healthy individuals. Next, using CamCan data (n=620), we found that gradient dispersion relates to executive functions (EFs) across the lifespan. Finally, in diffuse glioma patients undergoing neurosurgery (n=17), we observed that gliomas integrate into the cortical manifold by reducing gradient dispersion compared to healthy controls. This finding was replicated in an independent cohort and contrasted with meningioma patients. Finally, long-term cognitive improvement after surgery was linked to increases in gradient dispersion, while long-term deficits were associated with decreases in gradient dispersion. Overall, diffuse gliomas minimally disrupt the assembly of cortical manifolds, but the ability to reorganize the cortical manifold post-surgery is predictive of long-term cognitive outcomes. By investigating neurosurgical patients with atypical neuroanatomy, this study contributes to the expanding literature on how aging, disease, and pharmacological interventions impact cortical gradients. Future studies are warranted to further assess the utility of mapping cortical manifolds in neurosurgical patients.
Depression and incidence of inflammation-related physical health conditions: a cohort study in UK Biobank
Authors: Saha Shuvajit , Prigge Regina , Jackson Caroline A , Guthrie Bruce , Fleetwood Kelly J 
Published: January 2025

AbstractBackgroundDepression is associated with multiple physical health conditions, and inflammation is a mechanism commonly proposed to explain this association. We aimed to investigate the association between depression and the incidence of physical health conditions thought to have an inflammatory etiological component, including coronary heart disease, peripheral arterial disease, type 2 diabetes, inflammatory bowel disease, inflammatory arthritis and Parkinson’s Disease.MethodsWe conducted a cohort study using UK Biobank (UKB) data linked to primary care, hospital admission and death data. We ascertained depression at baseline using primary care and hospital records, and self-report at the UKB baseline assessment. We identified incident physical health conditions during follow-up using primary care, hospital admission and death data. We used Cox proportional hazards models to determine hazard ratios of each incident inflammation-related condition in those with versus without depression at baseline, serially adjusting for sociodemographic factors, lifestyle factors and baseline count of morbidities.ResultWe included 172,556 UKB participants who had continuous primary care records. Of these, 30,770 (17.8%) had a history of depression at baseline. After excluding participants with missing data, 168,641 (98%) were included in analysis. Median follow-up was 7.1 years (IQR: 6.3, 8.0). In the model adjusted for age and sex, depression was significantly associated with a higher hazard of all inflammation-related conditions. After additionally accounting for differences in country, ethnicity and deprivation, the association between depression and each condition generally attenuated but remained statistically significant, with effect estimates ranging from a 30% increased hazard of inflammatory bowel disease (HR 1.30, 95% CI 1.06 to 1.58) to a 53% increased hazard of Parkinson’s Disease (HR 1.53, 95% CI 1.25 to 1.87). After further adjusting for lifestyle factors and comorbidity count, the association persisted only for Parkinson’s Disease (HR 1.45, 95% CI 1.18 to 1.79).ConclusionsOur study found that depression is consistently associated with multiple inflammation-related physical health conditions, although associations did not persist after adjustment for lifestyle factors and baseline physical condition count. Further research is needed to explore underlying mechanisms, including inflammatory biomarkers and modifiable lifestyle factors on the causal pathway.
Invasive lobular carcinoma integrated multi-omics analysis reveals silencing of Arginosuccinate synthase and upregulation of nucleotide biosynthesis in tamoxifen resistance
Authors: Gupta Annapurna , Choueiry Fouad , Reardon Jesse , Pramod Nikhil , Kulkarni Anagh , Shankar Eswar , Sizemore Steven T. , Stover Daniel G. , Zhu Jiangjiang , Ramaswamy Bhuvaneswari , Majumder Sarmila 
Published: January 2025

AbstractInvasive Lobular Carcinoma (ILC), a distinct subtype of breast cancer is hallmarked by E-Cadherin loss, slow proliferation, and strong hormone receptor positivity. ILC faces significant challenges in clinical management due to advanced stage at diagnosis, late recurrence, and development of resistance to endocrine therapy - a cornerstone of ILC treatment. To elucidate the mechanisms underlying endocrine resistance in ILC, ILC cell lines (MDA-MB-134-VI, SUM44PE) were generated to be resistant to tamoxifen, a selective estrogen receptor modulator. The tamoxifen-resistant (TAMR) cells exhibit a 2-fold increase tamoxifen IC50relative to parental cells. Metabolomics and RNA-sequencing revealed deregulation of alanine, aspartate, and glutamate metabolism, purine metabolism, and arginine and proline metabolism in TAMR cells. Among the fifteen commonly dysregulated genes in these pathways, lowASS1expression was identified in the TAMR cells and was significantly correlated with poor outcome in ILC patients, specifically in the context of endocrine therapy. Our study reveals methylation mediated silencing ofASS1in TAMR cells as a likely mechanism of downregulation. Demethylation restoredASS1expression and correspondingly reduced tamoxifen IC50toward parental levels. Nucleic acid biosynthesis is augmented in TAMR cells, evidenced by increase in nucleotide intermediates. Both TAMR cell lines demonstrated increased expression of several nucleic acid biosynthesis enzymes, includingPAICS, PRPS1, ADSS2, CAD, and DHODH. Furthermore, CAD, the key multifunctional protein ofde novopyrimidine biosynthesis pathway is differentially activated in TAMR cells. Treating TAMR cell with Decitabine, a demethylating agent, or Farudodstat, a pyrimidine biosynthesis inhibitor, markedly augmented efficacy of tamoxifen. Collectively, our study unveilsASS1downregulation as a novel mechanism underlying acquired tamoxifen resistance in ILC and establishes a metabolic link between ASS1 and nucleic acid biosynthesis. RestoringASS1expression or inhibiting pyrimidine biosynthesis restored tamoxifen sensitivity.ASS1could be a potential biomarker and therapeutic target in tamoxifen resistant ILC patients, warranting further investigation.
Role of X chromosome and dosage compensation mechanisms in complex trait genetics
Authors: Fu Yu , Kenttämies Aino , Ruotsalainen Sanni , Pirinen Matti , Tukiainen Taru 
Published: January 2025

AbstractThe X chromosome (chrX) is often excluded from genome-wide association studies due to its unique biology complicating the analysis and interpretation of genetic data. Consequently, the influence of chrX to human complex traits remains debated. Here, we systematically assessed the relevance of chrX and the effect of its biology on complex traits by analyzing 48 quantitative traits in 343,695 individuals in UK Biobank with replication in 412,181 individuals from FinnGen. We show that, in the general population, chrX contributes to complex trait heritability at a rate of 3% of the autosomal heritability, consistent with the amount of genetic variation observed in chrX. We find that a pronounced male-bias in chrX heritability supports the presence of near-complete dosage compensation between sexes through X chromosome inactivation (XCI). However, we also find subtle yet plausible evidence of escape from XCI contributing to human height. Assuming full XCI, the observed chrX contribution to complex trait heritability in both sexes is greater than expected given presence of only a single active copy of chrX, mirroring potential dosage compensation between chrX and the autosomes. We find this enhanced contribution attributable to systematically larger active allele effects from chrX compared to autosomes in both sexes, independent of allele frequency and variant deleteriousness. Together these findings support a model where the two dosage compensation mechanisms work in concert to balance the influence of the chrX across the population while preserving sex-specific differences at a manageable level. Overall, our study advocates for more comprehensive locus discovery efforts in chrX.