bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial fibrillation
Authors: Dan Gheorghe-Andrei , Steffel Jan 
Published: November 2024

Abstract
Atrial fibrillation (AF) is the commonest cardiac arrhythmia in hospitalized patients, with an increasing incidence with age and an epidemic increase projected for the next 10 years. Therapy of AF has several goals: to decrease mortality (mainly due to cardiovascular diseases), stroke rate, ventricular deterioration, and heart failure, cognitive impairment, and dementia, as well as to increase quality of life. The recent European AF guidelines specify the management strategies for each of the above-mentioned goals. For stroke prevention, treatment with a non-vitamin K antagonist oral anticoagulant (NOAC) has emerged as the therapy of choice for the majority of patients with AF in the absence of rheumatic mitral disease and mechanical valve prostheses. However, in daily use of these drugs, many challenges remain that healthcare providers need to be aware of. Regarding treatment of the arrhythmia itself, it remains a therapy addressing the quality of life. Catheter ablation has emerged as a valid alternative for a variety of patients. Nevertheless, pharmacological antiarrhythmic drug therapy remains an important pillar for the majority of patients, and effective and safe use implies an important skill for every cardiologist.
Associations of social vulnerability index with patient-reported outcomes in women treated with chemotherapy for early-stage breast cancer
Authors: Almond Natalie , Deal Allison M , Page Annie , Nyrop Kirsten A , Muss Hyman B 
Published: November 2024

Abstract

Background
In a convenience sample of women scheduled for chemotherapy for early-stage breast cancer, we investigated associations of the Center for Disease Control and Prevention’s neighborhood-level social vulnerability index (SVI) with pretreatment demographics and patient-reported outcome (PRO) measures (health behavior, function and quality of life, treatment toxicities during chemotherapy).

Methods
The SVI Overall score is comprised of 4 themes: socioeconomic, household composition, minority status/language, and household type/transportation, with scores ranging from 0 = lowest to 1 = highest vulnerability neighborhoods. Participant SVI scores were derived from zip codes listed in the patient’s address within the electronic medical record (EMR). Associations of study variables with SVI were evaluated using Spearman correlation for continuous variables and Kruskal–Wallis tests for categorical variables.

Results
In a sample of 309 women, the mean age was 56 years (range 23-83) and 75% White. Greater vulnerability SVI Overall score was associated with lower education (P =.02), nonmarriage (P ≤.0001), higher body mass index (P =.03), and prechemotherapy PRO measures such as fewer self-reported walking minutes/week (P ≤.001), history of smoking (P =.02) and alcohol use (P &lt; .001), depression (P =.01), and lower emotional social support (P =.008). During chemotherapy, moderate, severe, or very severe symptoms were associated with greater vulnerability SVI Overall scores for hot flashes (P =.03), arthralgia (P =.02), myalgia (P =.02), peripheral neuropathy (P =.01), edema of limbs (P =.04), and nausea (P &lt;.001).

Conclusions
SVI scores derived from addresses in the patient’s EMR can be used to generate information that adds to the patient’s social history in ways that are informative for anticipating and monitoring chemotherapy-related toxicities.
Molecular dynamics and machine learning stratify motion-dependent activity profiles of S-layer destabilizing nanobodies
Authors: Cecil Adam J , Sogues Adrià , Gurumurthi Mukund , Lane Kaylee S , Remaut Han , Pak Alexander J 
Published: November 2024

Abstract
Nanobody (Nb)-induced disassembly of surface array protein (Sap) S-layers, a two-dimensional paracrystalline protein lattice from Bacillus anthracis, has been presented as a therapeutic intervention for lethal anthrax infections. However, only a subset of existing Nbs with affinity to Sap exhibit depolymerization activity, suggesting that affinity and epitope recognition are not enough to explain inhibitory activity. In this study, we performed all-atom molecular dynamics simulations of each Nb bound to the Sap binding site and trained a collection of machine learning classifiers to predict whether each Nb induces depolymerization. We used feature importance analysis to filter out unnecessary features and engineered remaining features to regularize the feature landscape and encourage learning of the depolymerization mechanism. We find that, while not enforced in training, a gradient-boosting decision tree is able to reproduce the experimental activities of inhibitory Nbs while maintaining high classification accuracy, whereas neural networks were only able to discriminate between classes. Further feature analysis revealed that inhibitory Nbs restrain Sap motions toward an inhibitory conformational state described by domain–domain clamping and induced twisting of domains normal to the lattice plane. We believe these motions drive Sap lattice depolymerization and can be used as design targets for improved Sap-inhibitory Nbs. Finally, we expect our method of study to apply to S-layers that serve as virulence factors in other pathogens, paving the way forward for Nb therapeutics that target depolymerization mechanisms.
Spatial organization and stochastic fluctuations of immune cells impact clinical responsiveness to immunotherapy in melanoma patients
Authors: Giuliani Giuseppe , Stewart William , Li Zihai , Jayaprakash Ciriyam , Das Jayajit 
Published: November 2024

Abstract
High-dimensional, spatial single-cell technologies, such as CyTOF imaging mass cytometry (IMC), provide detailed information regarding locations of a large variety of cancer and immune cells in microscopic scales in tumor microarray slides obtained from patients prior to immune checkpoint inhibitor (ICI) therapy. An important question is how the initial spatial organization of these cells in the tumor microenvironment (TME) changes with time and regulates tumor growth and eventually outcomes as patients undergo ICI therapy. Utilizing IMC data of melanomas of patients who later underwent ICI therapy, we develop a spatially resolved interacting cell system model that is calibrated against patient response data to address the above question. We find that the tumor fate in these patients is determined by the spatial organization of activated CD8+ T cells, macrophages, and melanoma cells and the interplay between these cells that regulate exhaustion of CD8+ T cells. We find that fencing of tumor cell boundaries by exhausted CD8+ T cells is dynamically generated from the initial conditions that can play a protumor role. Furthermore, we find that specific spatial features such as co-clustering of activated CD8+ T cells and macrophages in the pretreatment samples determine the fate of the tumor progression, despite stochastic fluctuations and changes over the treatment course. Our framework enables the determination of mechanisms of interplay between a key subset of tumor and immune cells in the TME that regulate clinical response to ICIs.
Outpatient Physical Therapy Attendance by Older Adults After Emergency Department Discharge was a Predictor for Lower 30-Day Revisits—But Demographic Factors Affected Attendance
Authors: Ryer Suzanne V , Simpson Michelle , Singh Maharaj 
Published: November 2024

Abstract

Objective
Given the high risk of functional loss and revisits among older adults presenting to the emergency department (ED), there is a need to understand how post-ED discharge outpatient physical therapy affects outcomes. This study sought to examine patient demographics and their association with outpatient physical therapy utilization after ED discharge and physical therapy attendance with 30-day ED revisits among older adults discharged to home.

Methods
In this retrospective cohort study, we analyzed data from 1395 older adults (65 years old and older) who had a referral to outpatient physical therapy upon discharge from 15 EDs between January 2021 and December 2022. Descriptive statistics and multivariate logistic regression were used to evaluate the likelihood of attending outpatient physical therapy and the odds of a 30-day ED revisit.

Results
Of the sample, 39.3% attended outpatient physical therapy. Older adults in the first and second neighborhood income quintile had a 51% lower odds of attending outpatient physical therapy than those in the fourth quintile. Patients with a diagnosis of vertigo had a 67% higher odds of attending outpatient physical therapy (OR = 1.67; 95% CI = 1.21–2.29) than those with back pain. Older adults who did not attend outpatient physical therapy within 30 days of ED visit had a 88% higher odds of returning to the ED than those who did attend (OR = 1.88; 95% CI = 1.34–2.64). Older adults in the first and second income quintile had a 66% higher odds of revisiting the ED than those in the fourth quintile.

Conclusion
Outpatient physical therapy attendance after ED discharge was a predictor of revisit within 30 days. Patient diagnosis of vertigo and higher median household income were predictors of higher outpatient physical therapy attendance. However, a diagnosis of falls or mobility concerns and a lower household income status were associated with lower attendance.

Impact
Physical therapy after ED discharge has the potential to reduce 30-day ED revisit but requires strategies to improve access equity across diagnostic groups and household income levels.
Identifying diagnosed major chronic diseases associated with recent housing instability among aging adults: data from the ‘All of Us’ research program
Authors: Beydoun Hind A , Mayno Vieytes Christian A , Beydoun May A , Lampros Austin , Tsai Jack 
Published: November 2024

Abstract

Background
Housing instability is a known barrier to healthcare utilization potentially affecting the prevention, diagnosis and treatment of chronic diseases among diverse groups of adults. We examined the intersection of recent housing instability with prevalent cardiovascular disease, diabetes, cancer and psychiatric diagnoses among aging adults.

Methods
Cross-sectional data on 147 465 participants of the ‘All of Us’ Research Program (6 May 2018–1 July 2022), ≥50 years of age at enrollment, were analyzed. Self-reported housing instability over the past 6 months was examined in relation to diagnosed conditions at age ≥50 years based on electronic health records. Multivariable logistic regression models sequentially adjusting for demographic and socioeconomic characteristics were constructed to estimate odds ratios (OR) with their 95% confidence intervals (CI).

Results
After adjusting for confounders, past 6 months housing instability was associated with lower odds of diagnosed cardiovascular disease (OR = 0.89, 95% CI: 0.87, 0.93) and cancer (OR = 0.82, 95% CI: 0.78, 0.86), higher odds of diagnosed psychiatric (OR = 1.35, 95% CI: 1.30, 1.40) conditions, but was unrelated to diagnosed diabetes (OR = 0.98, 95% CI: 0.94, 1.01).

Conclusions
Recent housing instability among aging adults is positively associated with psychiatric diagnoses, but negatively associated with cardiovascular and cancer diagnoses, with implications for chronic disease prevention.
Unsettling research quality
Authors: Franssen Thomas , Brorstad Borlaug Siri , Langfeldt Liv 
Published: November 2024

Abstract
This special section foregrounds the notion of research quality. In the introduction we contextualize the papers of this special section by, first, introducing the history of studies of research quality in the field of research evaluation. We then consider the what the six papers of the special section contribute to the study of research quality. We end our introduction by highlighting three interesting avenues for further research.
Toward a mission-oriented framework for funding public research institutions: a multi-case study approach
Authors: Alizadeh Parisa 
Published: November 2024

Abstract
This study proposes a mission-oriented framework for funding public research institutions (PRIs). Using a multi-case study approach and focus group interviews, a comprehensive framework was developed and refined. The framework encompasses three main dimensions: funding mechanisms, the amount of government funding, and organizational arrangements for resource allocation. It introduces diversified funding mechanisms for PRIs, including block grants, performance-based contracts, competitive funding, targeted allocations for specific missions, and excellence budgets. The proportion of each mechanism in the funding portfolio can vary depending on the mission types of PRIs. The framework recommends estimating government funding amounts using per capita formulas based on relevant input/output indicators tailored to the mission types of PRIs. Clear organizational arrangements are essential, including establishing a national research agency to oversee the estimation, steering, and monitoring of financial resource allocation and utilization.
Evaluation of the Electroconvulsive Therapy’s Impact on Retinal Structures in First-Episode Psychosis Patients Using Optical Coherence Tomography
Authors: Kurhan Faruk , Yıldız Veysi , Kamış Gülsüm Zuhal , Karataş Kübra , Batur Muhammed 
Published: November 2024

Abstract

Background and Hypothesis
Schizophrenia is a complex disorder thought to have neurodevelopmental and neurodegenerative aspects. Optical coherence tomography (OCT) measurements of schizophrenia patients revealed that the retinal layers of these patients were thinner than those of healthy controls. This study aimed to examine retinal changes in first-episode psychosis patients treated with electroconvulsive therapy (ECT) via OCT.

Study Design
Thirty first-episode psychosis patients (13 men, 17 women) aged 18 to 65 years who had no comorbidities and no smoking, alcohol, or substance use disorders and who were treated with ECT were included in the study. The patients were evaluated using OCT before treatment and after an average of 7.4 sessions of ECT in remission, and the results were compared.

Study Results
Statistically significant increases were observed in retinal layer thickness, inner plexiform layer, outer plexiform layer, and total retinal thickness within the 1 mm ring (P = .015, P = .045, and P = .025, respectively). The inner nuclear layer thickness significantly increased within the 6 mm ring (P = .037).

Conclusions
In conclusion, ECT noticeably affected retinal structures, particularly according to similar measurements, indicating potential improvements in and the ability to reverse neuronal degeneration after one month of treatment. This study highlights the potential impact of ECT on retinal structures in individuals experiencing first-episode psychosis, as it can enhance specific retinal layers and reverse neuronal degeneration.
Why are Latin American countries in the limbo of open-access scientific publications?
Authors: Chavarría Max , Lomonte Bruno , Gutiérrez José María , Moreno Edgardo , Pérez Alice L 
Published: November 2024

Abstract
Open Access (OA) model in scientific journals has brought about a range of benefits in terms of information accessibility. However, the high costs associated with Article Processing Charges (APCs) have posed a significant challenge for many scientists, leaving them in a ‘limbo’, where their ability to publish in reputable journals is contingent upon their financial capacity. Here, we intend to highlight the challenges faced by Latin American scientists that have arisen as a direct consequence of the implementation of the OA, specifically: (i) difficulties in disseminating our scientific work due to the impossibility of covering the high APCs imposed by journals, and (ii) the strong emergence and consolidation in our region of publishers with predatory practices. We urge the scientific community to establish policies that contribute to equity in OA models and to defend the right of Latin American scientists not only to read science freely but also to be read.
A randomized dose finding study of combination dronabinol and acetazolamide for the treatment of obstructive sleep apnea
Authors: Walsh Jennifer , Rankin Timothy , Mehra Sumit , Naughton Matthew T , Roebuck Teanau , McDermott Elizabeth , Pattichis Andreas , Smith Rafael , Walsh Rosemarie , Bleackley Mark , Maddison Kathleen , O’Brien Terence J 
Published: November 2024

Abstract

Study Objectives
Current treatments for obstructive sleep apnea (OSA) are ineffective or not tolerated in a proportion of patients. Other therapeutic options are needed and pharmaceuticals may provide an alternative. This randomized, double-blind, placebo-controlled, crossover study examined the effect of a combination of acetazolamide and dronabinol (IHL-42X) at low, medium, and high doses on OSA severity.

Methods
Participants with OSA (apnea–hypopnea index; AHI ≥15 events/hour) received 1 week of IHL-42X at each of three doses and placebo, each separated by a 1-week washout. The change from baseline in AHI, oxygen desaturation index (ODI), Epworth sleepiness score (ESS), and mood (profile of mood states) on the final night of each treatment arm relative to the change from baseline to placebo were the major endpoints. Adverse events (AEs) were monitored throughout.

Results
Ten of 11 participants completed the final night of at least one treatment arm. IHL-42X demonstrated a greater reduction in AHI from baseline compared with placebo (low, −19.7 ± 27.1; medium, −17.5 ± 23.3; high, −16.4 ± 23.8 vs. placebo, −2.8 ± 21.0 events/hour; all p &lt; .05). The change from baseline in ODI3% was greater for the medium IHL-42X dose when compared with placebo (−15.4 ± 19.0 vs. placebo, −2.8 ± 21.0 events/hour; p &lt; .05) but not the low or high doses (low, −15.2 ± 24.8; high, −8.3 ± 13.2 events/hour). IHL-42X did not change ESS or mood. No serious AEs occurred; however, 35 mild–moderate possibly, probably, or treatment-related AEs occurred during IHL-42X dosing and 5 occurred during placebo.

Conclusions
One week of nightly IHL-42X at low, medium, and high doses was well tolerated, safe, and associated with significant reductions in OSA severity.
Liver–gut axis signaling regulates circadian energy metabolism in shift workers
Authors: Yang Zhenning , Zarbl Helmut , Kong Bo , Taylor Rulaiha , Black Kathleen , Kipen Howard , Basaly Veronia , Fang Mingzhu , Guo Grace L. 
Published: November 2024

AbstractCircadian rhythm is critical to maintaining the whole‐body metabolic homeostasis of an organism. Chronic disruption of circadian rhythm by shift work is an important risk factor for metabolic diseases. Fibroblast growth factor 15/19 (FGF15/19), a key component in the liver–gut axis, potently suppresses bile acid (BA) synthesis and improves insulin sensitivity. FGF15/19 emerges as a novel pharmaceutical target for prevention and treatment of metabolic diseases. The nicotinamide adenine dinucleotide (NAD+)‐dependent sirtuin 1 (SIRT1) deacetylase plays an important role in the maintenance of hepatic homeostasis by linking hepatic metabolism to circadian rhythm. Here, our clinical study identified that circadian rhythmicity and levels of plasma FGF19 and BA profiling, and cellular NAD+‐dependent SIRT1 signaling were disturbed in night shift (NS, n = 10) compared to day shift (DS, n = 12) nurses. Our in vitro data showed that recombinant FGF19 protein rescued cellular circadian rhythm disrupted by SIRT1 inhibitors. Furthermore, we determined the effect of FGF15 on circadian rhythm and hepatic metabolism in wild‐type (WT), Fgf15 knockout (KO), and Fgf15 transgenic (TG) mice. The expressions of circadian‐controlled genes (CCGs) involved in SIRT1 signaling, BA and lipid metabolism, and inflammation were disrupted in Fgf15 KO compared to WT and/or Fgf15 TG mice. Moreover, systemic FGF15 deficiency led to the circadian disturbance of NAD+‐dependent SIRT1 signaling and significant reduction during nighttime in mice. These findings suggest that FGF15/19 regulates the circadian energy metabolism, which warrants further studies as a putative prognostic biomarker and pharmaceutical target for preventing against metabolic diseases associated with chronic shift work.
Statewide Trends in Medications for Opioid Use Disorder Utilization in Rhode Island, United States, 2017–2023
Authors: Shaw Leah C. , Hallowell Benjamin D. , Paiva Taylor , Schulz Christina T. , Daly Mackenzie , Borden Samantha K. , Goulet Jamieson , Samuels Elizabeth A. , Cerdá Magdalena , Marshall Brandon D. L. 
Published: November 2024

Background
Buprenorphine and methadone are US Food and Drug Administration-approved medications for opioid use disorder (MOUD). Although utilization of MOUD was increasing pre-COVID-19, it is not well understood how this trend shifted during and “after” the COVID-19 pandemic in Rhode Island. This analysis will consider the differential utilization of MOUD over time and by key demographic factors.

Methods
We utilized two of Rhode Island’s statewide databases to examine aggregate counts of dispensed buprenorphine and methadone from January 1, 2017, to December 31, 2023. Data were stratified by age group, sex assigned at birth, and race/ethnicity (where available). Counts were stratified into pre-COVID-19 (Q1 2017–Q1 2020), COVID-19 (Q2 2020–Q4 2022), and endemic COVID-19 (2023) eras. Averages and annualized percent change for each period were calculated to understand how utilization changed over time.

Results
Before COVID-19, buprenorphine and methadone utilization were increasing annually. During COVID-19, utilization declined annually by 0.40% and 0.43%, respectively. In the endemic COVID-19 time period, buprenorphine and methadone utilization declined more rapidly at 2.59% and 1.77%, respectively. Declines were more dramatic for adults aged 18–34.

Conclusions
We observed a decline in MOUD utilization during and after COVID-19 in Rhode Island, primarily driven by substantial decreases in MOUD use among the youngest group of adult residents. Interventions specifically tailored to youth, such as school-based or primary healthcare-based programs, may be particularly effective in engaging with youth in substance use disorder treatment.