bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cabozantinib for brain metastases in renal cell carcinoma: a single-institution retrospective analysis
Authors: Tokura Yuumi , Kijima Toshiki , Kokubun Hidetoshi , Uematsu Toshitaka , Takei Kohei , Betsunoh Hironori , Yashi Masahiro , Kamai Takao 
Published: February 2025

Abstract

Objective
Brain metastases from renal cell carcinoma (RCC) present considerable treatment challenges and poor prognoses. In this study, we evaluated the efficacy of cabozantinib, a multi- tyrosine kinase inhibitors (TKIs), in improving the progression-free survival (PFS) and overall survival (OS) of patients with RCC with brain metastases.

Methods
This retrospective study included 30 patients with RCC and brain metastases treated at a single institution between 2010 and 2024. Patient demographics, treatment modalities, and survival outcomes were analyzed. Systemic therapies included cabozantinib, TKIs, and immune checkpoint inhibitors (ICIs). Local therapies included Gamma Knife surgery (GKS) and whole-brain radiation therapy (WBRT). Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models.

Results
Cabozantinib-treated patients (n = 12) exhibited significantly longer median PFS (21.6 vs. 4.1 months; P &lt; .001) and OS (25.7 vs. 8.3 months; P = .019) compared to non-cabozantinib patients (n = 18). In patients treated with GKS, cabozantinib further improved PFS (29.6 vs. 3.9 months; P &lt; .001) and OS (25.7 vs. 12.8 months; P &lt; .001). Cox regression analysis identified cabozantinib as the sole independent predictor of improved PFS (hazard ratio [HR], 0.09; P = .004) and OS (HR, 0.17; P = .009).

Conclusion
Cabozantinib significantly improved survival outcomes in RCC patients with brain metastases, underscoring its role as an effective systemic therapy. However, potential risks such as brain hemorrhage highlight the importance of careful patient selection and close monitoring. Further prospective studies are warranted to explore optimal combination strategies.
New Kids on the Block: Estimating Use of Next Generation Gram-negative Antibiotics Across Greater than 700 Hospitals in the United States
Authors: Harris Anthony D , Goodman Katherine E , Pineles Lisa , Walker Morgan , Bork Jacqueline T , Heil Emily L , Claeys Kimberly C , Brooks Justin , Kadri Sameer , Maron Bradley A , Baghdadi Jonathan D 
Published: February 2025

Abstract

Background
In recent years, new broad-spectrum antibiotics targeting Gram-negative organisms have been introduced, including cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, eravacycline, imipenem-relebactam, omadacycline and meropenem-vaborbactam. This study aimed to describe new antibiotic use across a large national cohort.

Methods
We performed a retrospective cohort study of hospital discharges from June 2022-May 2023 using the PINC-AI Database. Antibiotic utilization was ascertained from daily charges. Clinical indication(s) were inferred from ICD-10 diagnosis codes. Antibiotic therapy was considered definitive if continued &gt;3 days. Piperacillin-tazobactam was used as a comparator.

Results
Across 832 hospitals, 3,890,557 admissions (61.9% of all admissions) included an antibiotic prescription. New antibiotics were prescribed in 9,768 admissions (0.25% of antibiotic-prescribing admissions) across 537 hospitals. Ceftolozane-tazobactam was prescribed in 4,157 admissions (42.6% of 9,768), ceftazidime-avibactam in 3,660 (37.5%), eravacycline in 1,213 (12.4%), cefiderocol in 1,060 (10.9%), meropenem-vaborbactam) in 456 (4.7%), omadacycline in 104 (1.1%), and imipenem-relebactam in 99 (1.0%). In contrast, piperacillin-tazobactam was prescribed in 731,719 (18.8%) and colistin in 570 (0.01%) admissions. 46% (n=4,647/9,768) of new antibiotics were started in the first 3 days of hospital admission, and 70% (n=6,799/9,768) were used as definitive therapy. Sepsis (76%), pneumonia (46%), and urinary tract infection (39%) were the most common clinical indications. On average, patients treated with new antibiotics had 8 more comorbid conditions than patients receiving piperacillin-tazobactam.

Conclusions
Ceftazidime-avibactam and ceftolozane-tazobactam remain the most frequently prescribed new antibiotics, with uptake of subsequently approved agents trailing. New antibiotics are most commonly used as treatment for sepsis among patients with multiple comorbidities.
Citizen preferences for online hate speech regulation
Authors: Munzert Simon , Traunmüller Richard , Barberá Pablo , Guess Andrew , Yang JungHwan 
Published: February 2025

Abstract
The shift of public discourse to online platforms has intensified the debate over content moderation by platforms and the regulation of online speech. Designing rules that are met with wide acceptance requires learning about public preferences. We present a visual vignette study using a sample (n=2,622) of German and US citizens that were exposed to 20,976 synthetic social media vignettes mimicking actual cases of hateful speech. We find people’s evaluations to be primarily shaped by message type and severity, and less by contextual factors. While focused measures like deleting hateful content are popular, more extreme sanctions like job loss find little support even in cases of extreme hate. Further evidence suggests in-group favoritism among political partisans. Experimental evidence shows that exposure to hateful speech reduces tolerance of unpopular opinions.
Comparative safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs for cardiovascular outcomes in rheumatoid arthritis
Authors: Sendaydiego Xavier , Gold Laura S , Dubreuil Maureen , Andrews James S , Reid Pankti , Liew David F L , Goulabchand Radjiv , Hughes Grant C , Sparks Jeffrey A , Jarvik Jeffrey G , Singh Siddharth , Liew Jean W , Singh Namrata 
Published: February 2025

Abstract

Objectives
To assess the comparative safety of tumor necrosis factor inhibitor (TNFi), non-TNFi, and Janus kinase inhibitor (JAKi) biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) for the risk of major adverse cardiovascular events (MACE) using US administrative claims data.

Methods
We performed a cohort study using MerativeTM Marketscan® Research Databases (2012–2021) of individuals aged 18–64 years with RA initiating b/tsDMARD treatment. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for developing MACE within 2 years of b/tsDMARD initiation, adjusting for potential confounders.

Results
We included a total of 34 375 treatment exposures: 71% TNFi, 10% JAKi, 8% abatacept, 5% rituximab, and 5% IL-6i. Most individuals were female (77–84%) with a median (interquartile range) of 50 (42, 56) years. Rituximab had the highest incidence rate of MACE (196/10 000 person-years; 95% CI 126, 291), followed by IL-6i (111/10 000 person-years; 95% CI 57, 193). Multivariable analyses showed non-statistically significantly higher MACE risk with rituximab (HR 1.5; 95% CI 0.9, 2.4) and IL-6i (HR 1.3; 95% CI 0.7, 2.4) exposures but no increased risk with JAKi relative to TNFi use.

Conclusion
In this large nationwide study, rituximab and IL-6i users had numerically higher, but not statistically significant, MACE risk. Our data support the safety of b/tsDMARD use for RA treatment. This study was limited by short follow-up time and confounding by indication; further studies that can overcome these limitations are needed.
Heart rate variability responses of horses and veterans with post-traumatic stress disorder to ground-based adaptive horsemanship lessons: a pilot study
Authors: Rankins Ellen M , Faremi Boluwatife E , Hartmann Kyle , Quinn Andrea , Posada-Quintero Hugo F , McKeever Kenneth H , Malinowski Karyn 
Published: February 2025

Abstract
Heart rate variability (HRV) can be measured as an indicator of autonomic nervous system (ANS) balance and thus, stress and affective arousal. Mixed results have been reported in the limited literature addressing the effects of equine-assisted services (EAS) on HRV in the human and horse participants. The aims of the present study were to determine the effects of ground-based adaptive horsemanship (AH) lessons on veterans’ and horses’ HRV during weekly lessons as well as veterans’ resting HRV outside of lessons. Veterans with post-traumatic stress disorder (PTSD) were randomly assigned to 8 weeks of AH or control (CON, no changes in treatments or activities) conditions. Horses were assigned to AH or control (CON, stall in arena) conditions based on previous experience (EAS or recreational riding). Electrocardiogram traces from the veteran and AH and CON horses were recorded during the 30-min lessons. Traces were recorded during resting conditions before (PRE) and after (POST) the 8-week period from AH and CON veterans and healthy, non-veterans. Heart rate (HR), root mean square of successive differences (RMSSD) and low frequency to high frequency ratios (LF/HF) were calculated after identification of peaks with the Pan-Tompkins algorithm and manual correction during 5-min epochs. Data were analyzed with repeated measures, mixed model ANOVAs (SAS v9.4). HR was lowest (p ≤ 0.0323) in the horses and veterans during the first 10 min of the lessons. Veterans’ RMSSD was higher (p ≤ 0.0496) in weeks 4 and 6 than week 2. LF/HF was greater in veterans with PTSD than healthy, non-veterans across PRE and POST time points. Increased HR later in the lessons is likely a result of increased movement in the horses and veterans. An interval of decreased stress and increased resiliency might be present in veterans participating in multi-day AH sessions. Increased sympathetic arousal measured via LF/HF was not mitigated by 8 weeks of AH. Horses appeared unstressed by the interactions as no changes in HRV were observed
Adapalene potentiates the cytotoxicity of anti-cancer drugs by enhancing cell cycle dysregulation and apoptosis in MKN-45 cells
Authors: Yuan Tein-Ming , Liu Bang-Hung , Huang Yi-Ching , Chuang Show-Mei 
Published: February 2025

Abstract
Adapalene is a third-generation synthetic retinoid that has been approved by the FDA as a dermatological drug was recently repurposed for its potential anti-cancer effects. Here, its anti-cancer potential was determined in human gastric adenocarcinoma cell lines. Adapalene did not show significant cytotoxicity toward AGS and MKN-45 cells, but displayed synergistic or additive effects in inhibiting cell growth and increasing apoptosis in MKN-45 cells, but not AGS cells, when combined with 5-FU, cisplatin, docetaxel, or doxorubicin. Co-treatment with adapalene plus docetaxel or doxorubicin increased DNA damage and S-phase arrest without affecting the expression levels of HR23A/B, XPC, or Rad51. In MKN-45 cells exposed to docetaxel or doxorubicin, adapalene co-treatment downregulated Aurora A and upregulated p21, potentially contributing to its ability to enhance DNA damage and cell cycle dysregulation, and increased reactive oxygen species (ROS) accumulation, which may potentiate the cytotoxicity of the anti-cancer agents. Our present results reveal that adapalene is not cytotoxic towards MKN-45 gastric cancer cells when applied alone, but can synergistically enhance the sensitivity of these cells to conventional chemotherapeutic drugs. Further investigations are warranted to fully elucidate the mechanisms underlying the synergistic effects of adapalene and identify markers that could, given the heterogeneity of gastric cancers, identify patients who are likely to benefit from adapalene co-treatment.
PTPN9 promotes melanoma progression by regulating the ferroptosis pathway
Authors: Wang Hongmei , Qiao Sen , Huang Lingyan , Zhang Zhengping , Wang Jiao , Tian Wenxiu 
Published: February 2025

AbstractIn recent years, there has been a gradual increase in the incidence and mortality rates of melanoma, posing a significant threat to human health and life. Protein tyrosine phosphatases (PTPNs) have been implicated in the progression of various human cancers, including breast, lung, and cervical cancer. To investigate PTPN9 expression in melanoma, impacting the disease's survival and prognosis. Our study, which involved an analysis of The Cancer Genome Atlas database and immunohistochemical staining of pathological sections, identified an upregulation of PTPN9 expression in melanoma, impacting the disease's survival and prognosis. At the cellular level, we investigated the effects of PTPN9 on the proliferation, invasion, and metastasis of A375 and SK‐MEL‐28 cells. Through various experimental techniques such as Western blot protein detection, electron microscopy, and oil red O staining, we observed that PTPN9 potentially contributes to the development of skin cutaneous melanoma (SKCM) by regulating ferroptosis‐related proteins ACSL4, FTH1, and P53, thereby influencing lipid metabolism. The results of this study highlight the unique role of PTPN9 in SKCM and suggest its potential as a biomarker for the disease.
REBOA for remote damage control resuscitation and the race against time
Authors: Marsden Max , Lendrum Robert , Perkins Zane , Davenport Ross A. 
Published: February 2025

Purpose of review
The management of noncompressible haemorrhage (NCH) remains a critical challenge in trauma care, with early mortality rates persistently high despite advances in trauma systems. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has emerged as a potential intervention to address severe haemorrhage in prehospital and hospital settings. This review examines the role of REBOA in remote damage control resuscitation, focusing on the ‘golden hour’ and the ‘platinum 5 minutes’ concepts that underscore the urgency of timely interventions.

Recent findings
Evidence from the UK-REBOA trial and related studies highlights the complexity of implementing REBOA in prehospital settings, emphasising the importance of early deployment, appropriate patient selection, and minimisation of delays. Technological innovations, including AI-assisted decision-making and automated partial REBOA systems, offer promising avenues for optimising REBOA’s application. Furthermore, the concept of damage control prehospital care prioritises essential interventions tailored to individual patient needs, advocating for a streamlined approach to reduce on-scene time.

Summary
The integration of REBOA with advanced prehospital strategies holds the potential for reducing preventable deaths from traumatic haemorrhage, but further research is needed to refine protocols and enhance outcomes in this high-stakes domain.
Is the heart rate dipping pattern associated with sleep quality during an ambulatory blood pressure monitoring? A cross-sectional study
Authors: Leiva Sisnieguez Carlos E. , Olano Ricardo D. , Stavile Rodolfo N. , Minetto Julián , Cerri Gustavo , Espeche Walter G. , Carbajal Horacio A. , Salazar Martín R. 
Published: February 2025

Objective:
The aim of this study was to characterize individuals with nondipping heart rate (HR) and to assess the association between that pattern and sleep quality during the night of an ambulatory blood pressure monitoring (ABPM).

Methods:
Individuals who attended our Unit to perform an ABPM, from February 2022 to May 2024, were asked about clinical and epidemiological antecedents and responded two validated surveys, about sleep quality during the night of the ABPM and in the prior 30 days. Then, they were categorized according to the presence of a dipping in nocturnal HR (defined as a decline in average HR at night equal or higher than 10% compared with daytime values) as HR dippers or HR nondippers (drop in mean nighttime HR lower than 10% of diurnal mean) in order to compare the mentioned variables.

Results:
One thousand two hundred and nine individuals were included. They were predominantly female (61.8%), middle-aged (median 50 years, IQR 36–60), overweight (median BMI 29, IQR 25.3–33.5) and had median ABPM estimates within normal ranges. In individuals without beta-blockers (n = 1107), HR nondippers had an adverse cardiovascular disease (CVD) risk profile, and no differences were found between HR dippers and HR nondippers concerning perceived good rest during the ABPM night (63.5 vs. 59.7%, P = 0.211) and usual sleep quality. The sensitivity analysis including beta-blockers’ users (n = 102) was consistent.

Conclusion:
A blunted dipping in mean nighttime HR identifies individuals with a high CVD risk profile and is not associated with bad sleep quality during the night of an ABPM.
Radiation Communication: Thoughts and Considerations
Authors: Sugarman Steve , Hardin Holly 
Published: February 2025

Abstract
The importance of effective communication cannot be overstated. What you say and how you say it matters, and this is a basic truth of effective communication. A misunderstanding of radiation effects can lead people to make decisions they may not have otherwise made had they been more aware of the true nature of the potential hazard. When addressing topics that may cause anxiety in people, it is important to communicate in understandable terms while still relaying factual and useful information. It can be difficult to take a complicated topic and simplify it into terms that are easily understood, all while maintaining factual integrity. However, communication is more than simply the words we say. Most people understand the roles body language and physical appearance have on message reception. Additionally, many people overlook other considerations that may help to motivate behavior change, such as emotion, social networks, and group identity. While the communicator may not have a firm grasp on all communication complexities, one characteristic that should be embraced by all communicators is empathy. The word “radiation” can be a scary—or otherwise anxiety-inducing—word. It can cause stress and fear in many audiences, including first responder audiences. We must understand and address that people may be afraid or otherwise anxious before we tell them what to do. Whether helping an individual who has radiation-related concerns about an upcoming medical procedure or influencing the public’s willingness to accept protective action recommendations during a radiation emergency, the consequences of effective communications can be far reaching and significantly affect both small-scale and large-scale responses to radiological incidents.
Health Phys. 127(0):000-000; 2024
Clinical trials and real-world studies examining faricimab and high-dose aflibercept for wet age-related macular degeneration and diabetic macular edema
Authors: Kalavar Meghana , Sridhar Jayanth 
Published: February 2025

Purpose of review
The goal of this review is to summarize emerging clinical trial and real world evidence for faricimab and high dose aflibercept (8 mg), two recently approved treatments for wet age-related macular degeneration and diabetic macular edema.

Recent findings
Faricimab, a bispecific monoclonal antibody targeting vascular endothelial growth factor (VEGF) and angiopoietin-2, and high-dose aflibercept have demonstrated significant potential for extending treatment intervals while maintaining efficacy. Pivotal clinical trials such as YOSEMITE, and RHINE established faricimab to be noninferior to standard anti-VEGF therapy with superior durability. Real-world data corroborated these results, demonstrating improved anatomic outcomes with extended treatment intervals, though improvements in best corrected visual acuity (BCVA) remains varied. High-dose aflibercept has similarly demonstrated noninferiority in landmark clinical trials such as PHOTON and PULSAR, with extended dosing intervals. However, comprehensive real-world data for high dose aflibercept remains limited and warrants further investigation.

Summary
Both faricimab and high-dose aflibercept show promise in reducing treatment burden for wet age-related macular degeneration and diabetic macular edema through extended dosing intervals while maintaining or improving clinical outcomes compared to standard anti-VEGF therapy. Faricimab has demonstrated this both in clinical trials as well as real-world studies, while high-dose aflibercept has demonstrated similar durability in trials but requires additional real-world evidence.
Associations Between Suicidal Ideation and Behaviors, Sexual Violence Victimization, and Sexual Orientation in Youth
Authors: Allen Larissa , Zelazny Jamie , Sereika Susan 
Published: February 2025

ABSTRACT

Introduction
The relationship between sexual violence victimization (SVV) and suicidal thoughts and behaviors (STBs) has been established. However, when applied to LGBTQ+ (i.e., lesbian, gay, bisexual, transgender, and queer) populations, the impact of SVV on the severity of STBs experienced requires further exploration. Suicide is a major public health problem, with youth aged 10–24 years accounting for 14% of all suicides seen in the United States. The association between SVV, STBs, and other psychopathologies, such as anxiety and depression, is stronger in sexual minorities (LGBQT+) than in the heterosexual population. A cross-sectional secondary analysis of the 2021 Youth Risk Behavior Survey (YRBS) was completed to investigate the association between SVV and STBs in LGBTQ+ youth populations when compared with their heterosexual peers and to determine if sexual orientation is a potential moderator in this relationship.

Methods
Sexual orientation, questions related to STBs, and sexual assault/rape and intimate partner violence experiences were extracted from the 2021 YRBS. Binary logistic regression considering the complex sample survey design of the YRBS was utilized to assess associations of SVV with STBs while controlling for sexual orientation.

Results
Sexual minority youth exhibit higher odds of both experiencing SVV and exhibiting STBs compared with their heterosexual peers. Some aspects of STBs in the presence of SVV are moderated by sexual orientation.

Conclusion
Further investigation is needed into this association in LGBTQ+ youth populations who have experienced sexual violence to better understand this relationship.