bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic Association and Risk Prediction With Heart Failure in Older Adults
Authors: Liu Guning , Nguyen Ngoc Quynh H. , Wong Kari E. , Agarwal Sunil K. , Boerwinkle Eric , Chang Patricia P. , Claggett Brian L. , Loehr Laura R. , Ma Jianzhong , Matsushita Kunihiro , Rodriguez Carlos J. , Rossi Joseph S. , Russell Stuart D. , Stacey R. Brandon , Shah Amil M. , Yu Bing 
Published: March 2024

BACKGROUND:
Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

METHODS:
Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication.

RESULTS:

Sixty metabolites (hazard ratios range, 0.79–1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19–1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017–0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (
P
<0.05).

CONCLUSIONS:
Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.
MBNL1 Regulates Programmed Postnatal Switching Between Regenerative and Differentiated Cardiac States
Authors: Bailey Logan R.J. , Bugg Darrian , Reichardt Isabella M. , Ortaç C. Dessirée , Nagle Abigail , Gunaje Jagadambika , Martinson Amy , Johnson Richard , MacCoss Michael J. , Sakamoto Tomoya , Kelly Daniel P. , Regnier Michael , Davis Jennifer 
Published: March 2024

BACKGROUND:
Discovering determinants of cardiomyocyte maturity is critical for deeply understanding the maintenance of differentiated states and potentially reawakening endogenous regenerative programs in adult mammalian hearts as a therapeutic strategy. Forced dedifferentiation paired with oncogene expression is sufficient to drive cardiac regeneration, but elucidation of endogenous developmental regulators of the switch between regenerative and mature cardiomyocyte cell states is necessary for optimal design of regenerative approaches for heart disease. MBNL1 (muscleblind-like 1) regulates fibroblast, thymocyte, and erythroid differentiation and proliferation. Hence, we examined whether MBNL1 promotes and maintains mature cardiomyocyte states while antagonizing cardiomyocyte proliferation.

METHODS:
MBNL1 gain- and loss-of-function mouse models were studied at several developmental time points and in surgical models of heart regeneration. Multi-omics approaches were combined with biochemical, histological, and in vitro assays to determine the mechanisms through which MBNL1 exerts its effects.

RESULTS:
MBNL1 is coexpressed with a maturation-association genetic program in the heart and is regulated by the MEIS1/calcineurin signaling axis. Targeted MBNL1 overexpression early in development prematurely transitioned cardiomyocytes to hypertrophic growth, hypoplasia, and dysfunction, whereas loss of MBNL1 function increased cardiomyocyte cell cycle entry and proliferation through altered cell cycle inhibitor transcript stability. Moreover, MBNL1-dependent stabilization of estrogen-related receptor signaling was essential for maintaining cardiomyocyte maturity in adult myocytes. In accordance with these data, modulating MBNL1 dose tuned the temporal window of neonatal cardiac regeneration, where increased MBNL1 expression arrested myocyte proliferation and regeneration and MBNL1 deletion promoted regenerative states with prolonged myocyte proliferation. However, MBNL1 deficiency was insufficient to promote regeneration in the adult heart because of cell cycle checkpoint activation.

CONCLUSIONS:
Here, MBNL1 was identified as an essential regulator of cardiomyocyte differentiated states, their developmental switch from hyperplastic to hypertrophic growth, and their regenerative potential through controlling an entire maturation program by stabilizing adult myocyte mRNAs during postnatal development and throughout adulthood. Targeting loss of cardiomyocyte maturity and downregulation of cell cycle inhibitors through MBNL1 deletion was not sufficient to promote adult regeneration.
From the Religious Field to the Alternative Field
Authors: Bawidamann Loïc 
Published: March 2024

Abstract
This article examines the link between religion and conspiracy theories by focusing on religious agents operating two alternative media outlets in Switzerland, opposing perceived mainstream opinions. Informed by Bourdieu’s field theory, the article elaborates on the agents’ surpassing of field boundaries, spawning an alternative field that accommodates all agents expelled from their initial fields. Through web scraping and qualitative interviews with the content creators, the analysis elucidates the particular significance of religious agents in the production and distribution of conspiracy theories, as they inherently oppose social differentiation, enabling them to contend with dominant authorities convincingly. The article concludes by offering an understanding of the alternative field and, by extension, of conspiracy theories as a process of dedifferentiation, striving for a realignment of the current structure of society.
Increases in the Local Eddy Energetics of the Extratropical Atmosphere over the Last Four Decades
Authors: Battalio J. Michael , Lora Juan M. 
Published: March 2024

Abstract
Changes in the vertical and meridional temperature gradients of the atmosphere drive competing influences on storm-track activity. We apply local eddy energetics to the ERA5, JRA-55, MERRA-2, and NCEP-2 reanalyses during 1980–2020 to determine the locations, magnitudes, and trends of the energy transfer mechanisms for synoptic-scale eddies. Eddy kinetic energy (EKE) increases more rapidly in the Southern Hemisphere at all altitudes and seasons, with larger increases during austral winter and spring. In the Northern Hemisphere, increases occur within the Atlantic and Pacific storm tracks at pressures below 300 hPa but only during boreal winter and spring and confined within a narrow zonal band; EKE decreases during boreal summer and fall. Most EKE changes correspond with trends in baroclinic energy conversion upstream of storm tracks and appear to align with increases in the growth rate of the most unstable baroclinic mode. Barotropic energy conversion of EKE to the mean flow becomes locally more intense downstream of the storm tracks. Conversion of EKE to long-period eddies plays a minor role averaged over a hemisphere but can be important locally. The primary strengthening pathway for removal of EKE is a combination of surface friction and viscous dissipation. The increased baroclinic conversion in the Southern Hemisphere appears related to upper-level tropical temperature increases. In the Northern Hemisphere, increased baroclinic conversion is enabled by a combination of increased vertical heat fluxes and a region of temperature increases within 30°–60°N.

Significance Statement
Traveling atmospheric disturbances arrange into storm tracks that determine the weather in the midlatitudes. Storm tracks are evolving in time due to anthropogenic warming; however, the location and strength of temperature changes compete for influence on the storm tracks. A framework to quantify the mechanisms of generation of kinetic energy contained by eddies pinpoints the extent of storm-track evolution. Storm tracks generally strengthen across the planet but have increased the most in the Southern Hemisphere. Strengthening in the Northern Hemisphere is limited to the winter in a narrow latitudinal band, because of warming in the Arctic that reduces the primary instability that drives eddies. The locations of northern warming and storm-track strengthening suggest a role for tropical dynamics.
On the Importance of Regime-Specific Evaluations for Numerical Weather Prediction Models as Demonstrated Using the High-Resolution Rapid Refresh (HRRR) Model
Authors: Lee Temple R. , Pal Sandip , Leeper Ronald D. , Wilson Tim , Diamond Howard J. , Meyers Tilden P. , Turner David D. 
Published: March 2024

Abstract
The scientific literature has many studies evaluating numerical weather prediction (NWP) models. However, many of those studies averaged across a myriad of different atmospheric conditions and surface forcings that can obfuscate the atmospheric conditions when NWP models perform well versus when they perform inadequately. To help isolate these different weather conditions, we used observations from the U.S. Climate Reference Network (USCRN) obtained between 1 January and 31 December 2021 to distinguish among different near-surface atmospheric conditions [i.e., different near-surface heating rates (), incoming shortwave radiation (SWd) regimes, and 5-cm soil moisture (SM05)] to evaluate the High-Resolution Rapid Refresh (HRRR) Model, which is a 3-km model used for operational weather forecasting in the United States. On days with small (large) , we found afternoon T biases of about 2°C (−1°C) and afternoon SWd biases of up to 170 W m−2 (100 W m−2), but negligible impacts on SM05 biases. On days with small (large) SWd, we found daytime temperature biases of about 3°C (−2.5°C) and daytime SWd biases of up to 190 W m−2 (80 W m−2). Whereas different SM05 had little impact on T and SWd biases, dry (wet) conditions had positive (negative) SM05 biases. We argue that the proper evaluation of weather forecasting models requires careful consideration of different near-surface atmospheric conditions and is critical to better identify model deficiencies in order to support improvements to the parameterization schemes used therein. A similar, regime-specific verification approach may also be used to help evaluate other geophysical models.

Significance Statement
Improving weather forecasting models requires careful evaluations against high-quality observations. We used observations from the U.S. Climate Reference Network (USCRN) and found that the performance of the High-Resolution Rapid Refresh (HRRR) Model varies as a function of differences in near-surface heating and solar radiation. This finding indicates that model evaluations need to be conducted under varying near-surface weather conditions rather than averaging across multiple weather types. This new approach will allow for model developers to better identify model deficiencies and is a useful step to helping improve weather forecasts.
Relationship Factors in the Longitudinal Spillover of Stress Between Parents and Children During COVID-19
Authors: Hu Yuyang , Russell Beth S. , Wu Rui , Adamsons Kari , Horton Abagail L. , Tambling Rachel R. 
Published: March 2024

This study took a family systems perspective and tested spillover theory to examine the transmission of stress from parents to children during COVID-19. Using a longitudinal design with a 1-year interval, we tested the association between parent perceived stress and perceived child stress, and the sequential mediating effects of poor family functioning and parent–child closeness. The data comprised 134 parents residing in the US who were assessed from the initial first peak of COVID-19 infections in 2020 to 2021, 1 year later. Results indicated that when controlling for covariates, there was a significant association between parent perceived stress and perceived child stress. What is more, poor family functioning and parent–child closeness fully mediated the former link in sequence. These findings highlighted the need for improving family relationship quality when providing interventions that target families suffering in stressful contexts.
Adjunctive Brexpiprazole for Patient Life Engagement in Major Depressive Disorder: A Canadian, Phase 4, Open-Label, Interventional Study: Brexpiprazole d'appoint pour l'engagement dans la vie des patients souffrant de trouble dépressif majeur: une étude interventionnelle canadienne ouverte de phase 4
Authors: Therrien François , Ward Caroline , Chokka Pratap , Habert Jeffrey , Ismail Zahinoor , McIntyre Roger S. , MacKenzie Erin M. 
Published: March 2024

Objectives To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. Methods An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1–2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5–2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. Results Of 122 enrolled patients, 120 (98.4%) were treated (mean [ SD] dose: 1.2 [0.4] mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR10 Life Engagement subscale score (baseline mean [ SD]: 16.1 [4.7]; change [95% confidence interval]: −8.11 [−9.34, −6.88]; p < 0.001) and IDS-SR total score (baseline mean [ SD]: 41.3 [9.8]; change [95% confidence interval]: −17.38 [−20.08, −14.68]; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue ( n = 13, 10.8%), headache ( n = 13, 10.8%), insomnia ( n = 12, 10.0%), nausea ( n = 9, 7.5%), tremor ( n = 8, 6.7%), and weight increase ( n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean ( SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. Conclusions Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. Clinical Trial Registration ClinicalTrials.gov identifier: NCT04830215.
Family-friendly work conditions and well-being among Malaysian women
Authors: Mat Pozian Nadirah , Miller Yvette D , Mays Jenni 
Published: March 2024

Background: Although participation in paid work improves women’s quality of life and well-being, the health benefits decline for women with young children. Implementing family-friendly work conditions is one strategy for improving working women’s well-being, especially those with competing unpaid work responsibilities. Objective: This study investigated the extent to which accessibility and use of 11 specific family-friendly work conditions were associated with physical health, anxiety and depression in Malaysian women with young children. Design: A cross-sectional design using a retrospective self-complete, anonymous, online survey was conducted between March and October 2021. Methods: Women with a child aged 5 years or less ( N = 190) completed an online survey measuring their exposure (availability and use) to 11 specific family-friendly work conditions, and their physical health, anxiety, and depression. The sample included women who were currently and recently working and with both formal and informal employment. Results: After accounting for potential confounders, women who used paid maternity leave have a lower likelihood of having anxiety symptoms. Conclusion: Future research is needed to extend the findings from this study by over-sampling women who are informally employed and not currently working. Policy creation and development processes, including research and decision-making, should be led by and inclusive of women. For example, research funding could be allocated to ‘lived experience’ research that privileges the co-design of research with consumers. Based on these findings, the extent to which family-friendly work conditions fulfill their intent to improve the well-being for working women requires further critique.
Expanding the repertoire reveals recurrent, cryptic, and hematopoietic HLA class I minor histocompatibility antigens
Authors: Fuchs Kyra J. , van de Meent Marian , Honders M. Willy , Khatri Indu , Kester Michel G. D. , Koster Eva A. S. , Koutsoumpli Georgia , de Ru Arnoud H. , van Bergen Cornelis A. M. , van Veelen Peter A. , ’t Hoen Peter A. C. , van Balen Peter , van den Akker Erik B. , Veelken J. Hendrik , Halkes Constantijn J. M. , Falkenburg J. H. Frederik , Griffioen Marieke 
Published: March 2024

Abstract
Allogeneic stem cell transplantation (alloSCT) is a curative treatment for hematological malignancies. After HLA-matched alloSCT, antitumor immunity is caused by donor T cells recognizing polymorphic peptides, designated minor histocompatibility antigens (MiHAs), that are presented by HLA on malignant patient cells. However, T cells often target MiHAs on healthy nonhematopoietic tissues of patients, thereby inducing side effects known as graft-versus-host disease. Here, we aimed to identify the dominant repertoire of HLA-I-restricted MiHAs to enable strategies to predict, monitor or modulate immune responses after alloSCT. To systematically identify novel MiHAs by genome-wide association screening, T-cell clones were isolated from 39 transplanted patients and tested for reactivity against 191 Epstein-Barr virus transformed B cell lines of the 1000 Genomes Project. By discovering 81 new MiHAs, we more than doubled the antigen repertoire to 159 MiHAs and demonstrated that, despite many genetic differences between patients and donors, often the same MiHAs are targeted in multiple patients. Furthermore, we showed that one quarter of the antigens are cryptic, that is translated from unconventional open reading frames, for example long noncoding RNAs, showing that these antigen types are relevant targets in natural immune responses. Finally, using single cell RNA-seq data, we analyzed tissue expression of MiHA-encoding genes to explore their potential role in clinical outcome, and characterized 11 new hematopoietic-restricted MiHAs as potential targets for immunotherapy. In conclusion, we expanded the repertoire of HLA-I-restricted MiHAs and identified recurrent, cryptic and hematopoietic-restricted antigens, which are fundamental to predict, follow or manipulate immune responses to improve clinical outcome after alloSCT.
A potential mechanism for the cytoprotective effects of activated protein C–released endothelial extracellular vesicles
Authors: Das Kaushik , Keshava Shiva , Mukherjee Tanmoy , Rao L. Vijaya Mohan 
Published: March 2024

Abstract
Activated protein C (APC) was shown to release extracellular vesicles (EVs). APC bound to the EVs was thought to be responsible for cytoprotection. Our study demonstrates that the cytoprotective effects of APC-released EVs are independent of APC. APC-released EVs carry anti-inflammatory microRNAs in their cargo.
HormoNet: a deep learning approach for hormone-drug interaction prediction
Authors: Emami Neda , Ferdousi Reza 
Published: February 2024

AbstractSeveral experimental evidences have shown that the human endogenous hormones can interact with drugs in many ways and affect drug efficacy. The hormone drug interactions (HDI) are essential for drug treatment and precision medicine; therefore, it is essential to understand the hormone-drug associations. Here, we present HormoNet to predict the HDI pairs and their risk level by integrating features derived from hormone and drug target proteins. To the best of our knowledge, this is one of the first attempts to employ deep learning approach for prediction of HDI prediction. Amino acid composition and pseudo amino acid composition were applied to represent target information using 30 physicochemical and conformational properties of the proteins. To handle the imbalance problem in the data, we applied synthetic minority over-sampling technique technique. Additionally, we constructed novel datasets for HDI prediction and the risk level of their interaction. HormoNet achieved high performance on our constructed hormone-drug benchmark datasets. The results provide insights into the understanding of the relationship between hormone and a drug, and indicate the potential benefit of reducing risk levels of interactions in designing more effective therapies for patients in drug treatments. Our benchmark datasets and the source codes for HormoNet are available in: https://github.com/EmamiNeda/HormoNet.
Revising model for end-stage liver disease from calendar-time cross-sections with correction for selection bias
Authors: de Ferrante H. C. , van Rosmalen M. , Smeulders B. M. L. , Vogelaar S. , Spieksma F. C. R. 
Published: February 2024

Abstract
Background
Eurotransplant liver transplant candidates are prioritized by Model for End-stage Liver Disease (MELD), a 90-day waitlist survival risk score based on the INR, creatinine and bilirubin. Several studies revised the original MELD score, UNOS-MELD, with transplant candidate data by modelling 90-day waitlist mortality from waitlist registration, censoring patients at delisting or transplantation. This approach ignores biomarkers reported after registration, and ignores informative censoring by transplantation and delisting.

Methods
We study how MELD revision is affected by revision from calendar-time cross-sections and correction for informative censoring with inverse probability censoring weighting (IPCW). For this, we revised UNOS-MELD on patients with chronic liver cirrhosis on the Eurotransplant waitlist between 2007 and 2019 (n = 13,274) with Cox models with as endpoints 90-day survival (a) from registration and (b) from weekly drawn calendar-time cross-sections. We refer to the revised score from cross-section with IPCW as DynReMELD, and compare DynReMELD to UNOS-MELD and ReMELD, a prior revision of UNOS-MELD for Eurotransplant, in geographical validation.

Results
Revising MELD from calendar-time cross-sections leads to significantly different MELD coefficients. IPCW increases estimates of absolute 90-day waitlist mortality risks by approximately 10 percentage points. DynReMELD has improved discrimination over UNOS-MELD (delta c-index: 0.0040, p < 0.001) and ReMELD (delta c-index: 0.0015, p < 0.01), with differences comparable in magnitude to the addition of an extra biomarker to MELD (delta c-index: ± 0.0030).

Conclusion
Correcting for selection bias by transplantation/delisting does not improve discrimination of revised MELD scores, but substantially increases estimated absolute 90-day mortality risks. Revision from cross-section uses waitlist data more efficiently, and improves discrimination compared to revision of MELD exclusively based on information available at listing.