bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting aldosterone to improve cardiorenal outcomes: from nonsteroidal mineralocorticoid receptor antagonists to aldosterone synthase inhibitors
Authors: Helmeczi Wryan , Hundemer Gregory L. 
Published: February 2025

Purpose of review
Aldosterone dysregulation plays a major role in the pathogenesis of hypertension, cardiovascular disease, and kidney disease. Traditionally, steroidal mineralocorticoid receptor (MR) antagonists, namely spironolactone and eplerenone, have been the only available options to target aldosterone. Over recent years, a host of promising novel aldosterone-targeted pharmacologic agents have been developed thereby providing new options to mitigate aldosterone-mediated cardiovascular and kidney disease.

Recent findings
Recently, a number of nonsteroidal MR antagonists (finerenone, esaxerenone, and ocedurenone) and highly specific aldosterone synthase inhibitors (baxdrostat, lorundrostat, dexfadrostat, and vicadrostat) have been developed. The early clinical data for these novel medications looks promising regarding their efficacy in improving blood pressure control, preventing adverse cardiovascular outcomes, and slowing chronic kidney disease progression. Moreover, they appear to be generally safe and well tolerated.

Summary
In the coming years, nonsteroidal MR antagonists and aldosterone synthase inhibitors are likely to play an increasingly large role in routine medical practice to help improve cardiovascular and kidney outcomes.
Environmental factors trigger pubertal development
Authors: Malave-Ortiz Sofia , Grant Cameron , Shaw Natalie D. 
Published: February 2025

Purpose of review
We provide an overview of the secular trend of earlier pubertal development, why there is a growing concern that environmental factors may be to blame, and how these factors may influence the developing reproductive axis.

Recent findings
We highlight recent work suggesting that, in addition to activating sex steroid receptors, environmental compounds may influence neuropeptide receptors and/or epigenetic regulators. We describe recent studies linking air pollution, metals, endocrine disrupting compounds (EDCs), short sleep duration, early life adversity, and stress to pubertal timing.

Summary
Pubertal timing is tightly controlled by genetic, epigenetic, and environmental factors. While animal and epidemiological studies have pointed to several potential environmental factors, additional work is necessary to identify the critical levels and developmental windows of exposure as well as the mechanistic underpinnings.
Acute Care Management of Brief Resolved Unexplained Events
Authors: DeLaroche Amy M. , Nama Nassr , Tieder Joel S. 
Published: February 2025

Abstract
A brief resolved unexplained event was defined in 2016 by the American Academy of Pediatrics in their clinical practice guideline. Since introduction of this term, research has characterized the epidemiology, clinical outcomes, and management of patients following a brief resolved unexplained event. Pediatric health care providers should be familiar with the current brief resolved unexplained event literature to minimize unnecessary health care utilization and guide shared decision-making discussions with caregivers.
Impact of Bowel Diary Completion and Education on Fecal Incontinence Severity
Authors: Andy Uduak U. , Carper Benjamin , Zyczynski Halina , Sripad Abhishek , Dyer Keisha Y. , Schaffer Joseph , Mazloomdoost Donna , Gantz Marie G. ,   for the NICHD Pelvic Floor Disorders Network
Published: February 2025

Objective
This study aimed to determine the effect of a run-in period on fecal incontinence (FI) symptom severity.

Study Design
This study conducted a planned secondary analysis of the run-in period to a study evaluating the effect of 12-week treatment with percutaneous tibial nerve stimulation versus sham in reducing FI severity in women. All participants completed a 4-week run-in period designed to exclude from randomization women whose symptoms reduced below the eligibility threshold after receiving education on FI and completing bowel diaries. Change in St Mark's (Vaizey) score and weekly FI episodes during the run-in period (week 1 vs week 4) was assessed.

Results
One hundred and eighty-five women completed the run-in period. The mean St Mark's (Vaizey) score was 17.8 ± 2.6 and 16.9 ± 3.5 at week 1 and week 4, respectively. There was no significant change in the St Mark's (Vaizey) score from week 1 to week 4 (mean change, −0.93 [95% CI, −1.56 to −0.31]). The average number of FI episodes per week did not change significantly between week 1 and week 4, nor did other bowel diary measures. Only 11 (6%) women became ineligible for the trial following the run-in period, all of whom had baseline St Mark's (Vaizey) scores of 18 or lower.

Conclusions
Completion of a bowel diary and receiving education on FI during the 4-week run-in period did not significantly affect symptom severity in women with FI. Only 6% of women became ineligible for participation following the run-in period, suggesting that, in a refractory population, a run-in period may have minimal effect.
An introduction to clinical prediction models using logistic regression in acute care surgery research: Methodologic considerations and common pitfalls
Authors: Garwe Tabitha , Choi Jeff 
Published: February 2025

ABSTRACT
Clinical prediction models can enhance timely clinical decision-making when appropriately developed and integrated within clinical workflows. A risk prediction model is typically a regression equation that uses patient risk factor data to estimate the probability of the presence of disease (diagnostic) or its future occurrence (prognostic). Risk prediction models are widely studied in the surgical literature and commonly developed using logistic regression. For a risk prediction model to be useful, it must balance statistical performance and clinical usefulness. This article provides a brief overview of the various methodologic issues to consider when developing or validating a risk prediction model and common pitfalls.
Obesity and Work in Abdominal Surgery
Authors: Childers Christopher P , Petty Abigail M , Selzer Don J , Senkowski Christopher K 
Published: February 2025

Background:
Recent analyses have shown that Modifier 22 does not reimburse surgeons for the increased work required to care for the most complex patients. New strategies are needed to identify patients that require additional work to create a financial system that ensures equitable access. Obesity has been identified as a growing and potentially reliable patient risk factor that could be used to identify cases that require additional work.

Study Design:
Using 2022 ACS NSQIP data, this study evaluated 10 common general surgery operations (appendectomy, cholecystectomy, colon/rectal operations, hernia repairs). The primary predictor was BMI category (Normal: 18.5-25, overweight: 25-29.9, class I obesity: 30-34.9, class II obesity: 35-39.9, class III obesity 40-49.9, extreme obesity >=50). Primary outcomes were operative time and composite measures of complications.

Results:
The final sample included 158,692 operations. Across the entire cohort, 22.2% were normal weight and 76.3% were overweight or obese. Overall, operative time was increased by 5.6% (95% CI 4.8-6.3%) for overweight, by 10.6% (CI 9.8-11.5%) for class I obesity, by 14.7% (CI 13.6-15.8%) for class II obesity, by 18.9% (CI 17.6-20.2%) for class III obesity, and by 26.8% (CI 14.1-29.6%) for extreme obesity compared to those with normal BMI. Obesity was associated with higher odds of any complication or serious complication, driven by wound complications, pulmonary emboli, and renal insufficiency.

Conclusion:
Obesity is a growing challenge in abdominal surgery and is associated with increase operative time and risk of complications. The consistency of the magnitude of effect makes it an ideal target for a modifier or add-on code that could identify cases requiring additional work.
Dust production through collisions between small bodies: an application to the G-ring arc
Authors: Lattari V. , Sfair R. , Siqueira P. B. , Schäfer C. M. 
Published: February 2025

The G-ring arc of Saturn, confined by the 7:6 corotation eccentric resonance with Mimas, is primarily composed of micrometric particles. These particles, significantly influenced by the solar radiation pressure, are subject to rapid depletion. This study investigates a mechanism for dust replenishment in the arc, specifically analysing collisions between macroscopic bodies and the satellite Aegaeon. Utilizing N-body and smoothed particle hydrodynamics simulations, we assess the dust generation from these impacts, with a focus on the most likely collision parameters derived from the N-body simulations. Our findings indicate that, while collisions among macroscopic bodies are inefficient for dust production, impacts involving Aegaeon are substantially more effective, providing conservative lower limits for dust generation. This mechanism, in conjunction with the natural decay processes and continuous dust generation from impacts, potentially keeps the arc population over thousands of years with a possible variation in brightness.
This article is part of the theme issue ‘Major advances in planetary sciences thanks to stellar occultations’.
Evaluating the Impact of Over-the-Counter Aspirin on the Growth of Selected Intestinal Microbial Strains
Authors: Srinivasan Shivaneesri , Ratnasingam Shalini 
Published: February 2025

The human intestinal microbiota varies in composition among individuals and is largely influenced by external factors such as diet, drugs and environment. While it is well-known to play a pivotal role in maintaining gut health, its interactions with non-antibiotic pharmaceuticals remain understudied. This in vitro study evaluates the effects of over-the-counter (OTC) aspirin (Cardiprin) on the growth dynamics of three commensal gut bacterial strains, Escherichia coli, Klebsiella pneumoniae and Enterococcus faecalis. Employing a dual-method approach of disk diffusion assay (DDA) and colony-forming unit (CFU) analysis, the study evaluates aspirin’s effects at physiologically relevant (300 µg/mL) and high (1000 µg/mL) concentrations. DDA demonstrated consistent inhibition zones across all strains and highlighted aspirin’s weak antibacterial potency, while CFU analyses revealed strain-specific responses. At 300 µg/mL of aspirin, E. coli and E. faecalis exhibited growth comparable to baseline while K. pneumoniae uniquely showed enhanced growth. However, at a higher concentration of 1000 µg/mL, growth of all strains were inhibited to different extents. These results underscore the need for further investigation into the therapeutic and unintended effects of oral aspirin on gut microbial growth.
Boosting Hyperalignment Performance with Age-specific Templates
Authors: Zhang Yuqi , Gobbini Maria Ida , Haxby James V. , Feilong Ma 
Published: February 2025

AbstractHyperalignment aligns individual brain activity and functional connectivity patterns to a common, high-dimensional model space, resolving idiosyncrasies in functional–anatomical correspondence and revealing shared information encoded in fine-grained spatial patterns. Given that the brain undergoes significant developmental and functional changes over the lifespan, it is likely that certain features in brain functional organization are more prominent in certain age groups than others. In this study, we examined whether age-specific functional templates, as compared to a canonical template, could enhance alignment accuracy across diverse age groups. We used the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) dataset (18 to 87 yo) to build age-specific templates and tested their performance for analyzing data in young and old brains in both the Cam-CAN dataset and the Dallas Lifespan Brain Study (DLBS) dataset (20 to 90 yo). We found the congruent age-specific template outperforms the incongruent template for various analyses, including inter-subject correlation of hyperaligned connectivity profiles and predicting individualized connectomes using the template. The results are consistent across both datasets. This work enhances our understanding of age-related differences in brain function, highlights the benefits of creating age-specific templates to refine hyperalignment model performance, and may contribute to the development of age-sensitive diagnostic tools and interventions for neurological disorders.
Subgenome dominance ofALStarget site mutations impacts herbicide resistance in allohexaploidEchinochloa crus-galli
Authors: Cutti Luan , Turra Guilherme Menegol , Machado Filipi Mesquita , Sulzbach Estéfani , Angonese Paula Sinigaglia , Markus Catarine , Gaines Todd Adam , Merotto Aldo 
Published: February 2025

AbstractHerbicide target site resistance in polyploid species is more complex than diploids due to potential subgenome interactions and gene dosage of mutations. The objective of this study was to identify the level of resistance and cross-resistance patterns ofALSmutations located in the different subgenomes of allohexaploidEchinochloa crus-galli.E. crus-gallipopulations were screened and dose-response curves were performed with ALS-inhibitors from different chemical groups. TheALSgenes of each subgenome (A, B, and C) were sequenced. Copy number variation, global relative expression, and the specific relative expression ofALSgene from each subgenome were performed. Out of 100 populations, 32% were resistant only to imazethapyr, and 48% were cross-resistant to all ALS-inhibitors. The mutations Ala122Thr, Ala205Asn, and Ser653Asn confer resistance only to imazethapyr, while Trp574Leu confers resistance to all four herbicides tested.ALSmutations were most frequent in subgenome A, butALSfrom subgenome C had the highest expression. The biotype SAOJER-01 had Trp574Leu mutation in subgenome C and was 22 times more resistant to imazethapyr and penoxsulam than CAMAQ-01, which had the same Trp574Leu mutation in subgenome A with no differences in herbicide metabolism rate. TheALSgenes from subgenomes A and C contribute approximately 13% and 50% respectively to the totalALStranscripts. The higher contribution of subgenome C to the totalALStranscripts pool combined with the Trp574Leu resistance mutation makes the biotype SAOJER-01 more resistant to herbicides than CAMAQ-01. This is the first study showing the effect of subgenome gene expression level on the herbicide resistance level in a polyploid weed species. In addition, while imazethapyr did not control any biotype with anALSmutation, the other ALS-inhibitor herbicides were able to control biotypes carrying Ala122Thr, Ala205Asn, and Ser653Asn, which reinforces the utility of these herbicides in weed and resistance management.
Comparative Molecular, Innate, and Adaptive Impacts of Chemically Diverse STING Agonists
Authors: Mizuno Nobuyo , Boehm Dylan , Jimenez-Perez Kevin , Abraham Jinu , Springgay Laura , Rose Ian , DeFilippis Victor R. 
Published: February 2025

ABSTRACTPharmacologic activation of the innate immune response is being actively being pursued for numerous clinical purposes including enhancement of vaccine potency and potentiation of anti-cancer immunotherapy. Pattern recognition receptors (PRRs) represent especially useful targets for these efforts as their engagement by agonists can trigger signaling pathways that associate with phenotypes desirable for specific immune outcomes. Stimulator of interferon genes (STING) is an ER-resident PRR reactive to cyclic dinucleotides such as those synthesized endogenously in response to cytosolic dsDNA. STING activation leads to transient generation of type I interferon (IFN-I) and proinflammatory responses that augment immunologically relevant effects including antiviral responses, antigen presentation, immune cell trafficking, and immunogenic cell death. In recent years engineered cyclic dinucleotides and small molecules have been discovered that induce STING and safely confer clinically useful outcomes in animal models such as adjuvanticity of anti-microbial vaccines and tumor clearance. Unfortunately, clinical trials examining the efficacy of STING agonists have thus far failed to satisfactorily recapitulate these positive outcomes and this has prevented their translational advancement. A likely relevant yet perplexingly under investigated aspect of pharmacologic STING activation is the diversity of molecular and immune responses that associate with chemical properties of the agonist. Based on this, a comparative survey of these was undertaken using unrelated STING-activating molecules to characterize the molecular, innate, cellular, and immune outcomes they elicit. This was done to inform and direct future studies aimed at designing and selecting agonists appropriate for desired clinical goals. This revealed demonstrable differences between the agonists in potency, transcriptomes, cytokine secretion profiles, immune cell trafficking, and antigen-directed humoral and cell mediated immune responses. As such, this work illustrates that phenotypes deriving from activation of a protein target can be linked to chemical properties of the engaging agonist and thus heightened scrutiny is necessary when selecting molecules to generate specificin vivoeffects.
Sphingolipid metabolism drives mitochondria remodeling during aging and oxidative stress
Authors: Ebert Adam C. , Hepowit Nathaniel L. , Martinez Thyandra A. , Vollmer Henrik , Singkhek Hayley L. , Frazier Kyrie D. , Kantejeva Sophia A. , Patel Maulik R. , MacGurn Jason A. 
Published: February 2025

AbstractOne of the hallmarks of aging is a decline in the function of mitochondria, which is often accompanied by altered morphology and dynamics. In some cases, these changes may reflect macromolecular damage to mitochondria that occurs with aging and stress, while in other cases they may be part of a programmed, adaptive response. In this study, we report that mitochondria undergo dramatic morphological changes in chronologically aged yeast cells. These changes are characterized by a large, rounded morphology, decreased co-localization of outer membrane and matrix markers, and decreased mitochondrial membrane potential. Notably, these transitions are prevented by pharmacological or genetic interventions that perturb sphingolipid biosynthesis, indicating that sphingolipids are required for these mitochondrial transitions in aging cells. Consistent with these findings, we observe that overexpression of inositol phospholipid phospholipase (Isc1) prevents these alterations to mitochondria morphology in aging cells. We also report that mitochondria exhibit similar sphingolipid-dependent morphological transitions following acute exposure to oxidative stress. These findings suggest that sphingolipid metabolism contributes to mitochondrial remodeling in aging cells and during oxidative stress, perhaps as a result of damaged sphingolipids that localize to mitochondrial membranes. These findings underscore the complex relationship between mitochondria function and sphingolipid metabolism, particularly in the context of aging and stress.
Two-pion exchange for coupled-channel scattering of two heavy mesons
Authors: Chacko J. T. , Baru V. , Hanhart C. , Krug S. L. 
Published: February 2025

To improve the theoretical understanding of multiquark states like Zb(10610) and Zb(10650), we calculate the heavy-meson heavy-(anti)meson scattering potential up to next-to-leading order, O(Q2), within chiral effective field theory (χEFT) employing a power counting scheme that explicitly keeps track with the large momentum scale Q∼2μδ (where δ=mV−mP is the vector-pseudoscalar mass difference and μ their reduced mass) introduced by the coupled channel dynamics. We provide expressions for the two-pion exchange (TPE) terms up to O(Q2) and their partial-wave decomposition. We show that these potentials are well approximated by contact terms at O(Q2), with minor residual nonanalytic TPE contributions, supporting χEFT convergence in the theoretical predictions for Zb(10610) and Zb(10650), as well as their spin partners. These findings are also relevant for D(*)D(*) scattering, especially for the Tcc state, for both physical and lattice quantum chromodynamics (QCD) data with moderately larger pion masses. We further demonstrate that the differences between isovector and isoscalar potentials for heavy mesons are naturally explained by the TPE contributions.

Published by the American Physical Society
2025
Addendum to “Testing meson portal dark sector solutions to the MiniBooNE anomaly at CCM”
Authors: Aguilar-Arevalo A. A. , Biedron S. , Boissevain J. , Borrego M. , Bugel L. , Chavez-Estrada M. , Conrad J. M. , Cooper R. L. , Diaz A. , Distel J. R. , D’Olivo J. C. , Dunton E. , Dutta B. , Fields D. , Gochanour J. R. , Gold M. , Guardincerri E. , Huang E. C. , Kamp N. , Kim D. , Knickerbocker K. , Louis W. C. , Lyles J. T. M. , Mahapatra R. , Maludze S. , Mirabal J. , Newmark D. , deNiverville P. , Pandey V. , Poulson D. , Ray H. , Renner E. , Schaub T. J. , Schneider A. , Shaevitz M. H. , Smith D. , Sondheim W. , Szelc A. M. , Taylor C. , Thompson A. , Thompson W. H. , Tripathi M. , Thornton R. T. , Van Berg R. , Van de Water R. G. ,   CCM Collaboration
Published: February 2025

In Aguilar-Arevalo [], we explored various effective field theories that could explain the MiniBooNE excess involving long-lived particles produced from charged meson decays and the sensitivity of the Coherent CAPTAIN Mills experiment to these models. In this addendum, we extend the analysis to project sensitivity of upcoming MicroBooNE data to the long-lived particle models considered in the previous work. We find that a dedicated MicroBooNE analysis of the single photon final state with longer exposure and improved signal efficiency will be sensitive to these new physics explanations of the MiniBooNE excess, and could rule them out with a null observation at the 95% confidence level.

Published by the American Physical Society
2025
Renormalized Classical Spin Liquid on the Ruby Lattice
Authors: Wang Zhenjiu , Pollet Lode 
Published: February 2025

The recent experimental detection of the onset of a dynamically prepared, gapped Z2 quantum spin liquid on the ruby lattice brought the physics of frustrated magnetism and lattice gauge theory to Rydberg tweezer arrays [Semeghini , Probing topological spin liquids on a programmable quantum simulator, ]. The thermodynamic properties of such models remain inadequately addressed, yet knowledge thereof is indispensable if one wants to prepare large, robust, and long-lived quantum spin liquids. Using large scale quantum Monte Carlo simulations we find in the model a renormalized classical spin liquid with constant entropy density S/N approaching ln(2)/6 in the thermodynamic limit for all moderate and large values of the detuning δ and starting from T/Ω∼0.5 (in units of the Rabi frequency Ω) down to the lowest temperatures we could simulate, T/Ω∼0.01. With van der Waals interactions, constant entropy plateaus are still found but its value shifts with δ. We comment on the implications of the adiabatic approximation to the dynamical ramps for the electric degrees of freedom, which leads to a reinterpretation of the experimental observations.

Published by the American Physical Society
2025