bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated High-dose Fentanyl Administration in Rats Reveals Minimal Tolerance to Unconsciousness, Bradycardia, Muscle Rigidity, and Respiratory Depression
Authors: Obert David P. , Park Gwi H. , Strong Kaitlyn , Schreier David R. , Korn Elizabeth , Troyas Carla , Vincent Kathleen F. , Solt Ken 
Published: December 2024

Background:
Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses, fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity.

Methods:
Male and female Sprague–Dawley rats were studied (n = 40). A bolus of 100 µg/kg fentanyl was administered intravenously twice a week for 5 consecutive weeks. Time to return of righting reflex after fentanyl injection and changes in electromyography/electroencephalography activity as well as heart rate were analyzed. Additionally, arterial blood gas analysis for evaluation of ventilation was performed. Mixed-effect models with Dunnett test and effect sizes were used for statistical analysis.

Results:
Repeated injections resulted in a U-shaped change in time to return of righting reflex with the longest latency after the first exposure (median, 50 [first to third quartile, 36 to 56] min) and the shortest after the fifth exposure (16 [13 to 33] min). After fentanyl administration, heart rate dropped immediately by 225 beats/min (95% CI, 179 to 271; F = 3,952.16; P < 0.001), while electromyography activity increased by 291% (95% CI, 212 to 370; F = 27.51; P < 0.001) and partial pressure of arterial carbon dioxide increased by 49.4 mmHg (95% CI, 40.6 to 58.2; F = 75.97; P < 0.001) within 5 min after injection. Additionally, pH decreased by 0.48 (95% CI, 0.41 to 0.54; F = 142.00; P < 0.01), and partial pressure of arterial oxygen decreased by 50.4 mmHg (40.8 to 60.0; F = 57.90; P < 0.001). Repeated fentanyl exposures did not significantly affect the extent of these changes (EMG, F = 1.63, P = 0.237; partial pressure of arterial carbon dioxide, F = 1.23, P = 0.312; heart rate, F = 1.05, P = 0.400; pH, F = 3.05, P = 0.066; arterial partial pressure of oxygen, F = 3.35, P = 0.052). Electroencephalography analysis revealed that repeated fentanyl exposures elicited significantly higher absolute power in frequencies greater than 20 Hz as indicated by an area under the receiver operator characteristics curve greater than 0.7.

Conclusions:
The authors established a rodent model of repeated high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after 10 exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.
Platelet Glycoprotein Ⅵ: A Novel Target for Antithrombotic Therapy in Cardiovascular Disease
Authors: Liu Menglu , Zhao Xueyan 
Published: December 2024

Abstract
Platelets play an important role in thrombosis caused by acute coronary syndrome and stroke. As the main platelet collagen receptor, platelet glycoprotein Ⅵ (GPⅥ) is an important modulator in the activation and aggregation of platelets at vascular injury sites. Recently, GPⅥ has been identified as a potent antithrombotic target. The structure, properties, functions, and downstream signaling of GPⅥ are reviewed; its relationship with bleeding, thrombosis, and other diseases are discussed; and potential of GPⅥ as a future antiplatelet therapeutic target is summarized in this article.
Win Ratio approach for the composite outcome of postoperative pulmonary complications
Authors: Serpa Neto Ary , Campos Niklas S. , Bluth Thomas , Hemmes Sabrine N.T. , Ferrando Carlos , Librero Julian , Soro Marina , Ball Lorenzo , Mazzinari Guido , de Abreu Marcelo Gama , Schultz Marcus J. 
Published: December 2024

BACKGROUND
The win ratio analysis method might provide new insight on the impact of positive end-expiratory pressure (PEEP) on clinical outcomes.

OBJECTIVE
The aim is to re-analyse the results of the ’Re-evaluation of the effects of high PEEP with recruitment manoeuvres vs. low PEEP without recruitment manoeuvres during general anaesthesia for surgery’ (REPEAT) study using the win ratio analysis.

DESIGN
Individual patient data meta-analysis.

SETTING
Three international multicentre randomised trials.

PARTICIPANTS
Patients undergoing general anaesthesia for surgery.

INTERVENTION
High vs. low PEEP.

MAIN OUTCOME MEASURE
Hierarchical composite endpoint of: all-cause hospital mortality; hospital length of stay; need for postoperative mechanical ventilation; severe pulmonary complications; and mild pulmonary complications.

RESULTS
A total of 3774 patients undergoing general anaesthesia for surgery were included in this analysis. The median (interquartile range [IQR]) age was 57 [45 to 68] years and 2077 (55%) were women. A total of 3 560 720 comparison pairs were produced. The high PEEP group had a higher percentage of losses than wins in hospital mortality (1.1 vs. 0.9%) and hospital length of stay (33.8 vs. 33.2%), comparable percentages of losses and wins in postoperative invasive mechanical ventilation (0.2 vs. 0.2%), a higher percentage of wins in severe complications (2.5 vs. 2.1%) and a higher percentage of ties in mild complications (18.7 vs. 3.9% wins vs. 3.3% losses). The win ratio for high PEEP compared with low PEEP group was 1.00 (95% CI 0.92 to 1.09).

CONCLUSION
No beneficial effects of high PEEP compared with low PEEP were found in this win ratio analysis.

REGISTRATION
Clinicaltrials.gov (study identifier NCT03937375).
Surgeon adoption of immediate sequential bilateral cataract surgery in the United States from 2018 to 2022
Authors: Ali Muhammad , Dun Chen , Chang David F. , Son Hyeck-Soo , Woreta Fasika A. , Soiberman Uri S. , Prescott Christina R. , Makary Martin A. , Srikumaran Divya 
Published: December 2024

Purpose:
To assess 5-year trends in the rate of immediate sequential bilateral cataract surgery (ISBCS) and surgeon characteristics associated with performing ISBCS.

Setting:
100% Medicare Fee-For-Service beneficiaries from 2018 to 2022.

Design:
Cross-sectional study.

Methods:
ISBCS cases were identified among patients aged 65 years or older undergoing bilaterally performed cataract surgery (BPCS). Cochrane Armitage trend test was used to assess patient and surgeon characteristics over time. Multivariate logistic regression was used to evaluate surgeon characteristics associated with performing ISBCS.

Results:
Among 1 190 169 BPCS, 3954 (0.33%) were ISBCS. Quarterly ISBCS rate increased from 2.12 to 5.5 per 1000 BPCS (P < .001). Among 10 290 surgeons, 1119 (10.87%) performed ISBCS on some patients. Proportion of surgeons performing ISBCS per 1000 cataract surgeons increased from 15.63 during the first quarter of 2018 to 26.55 during the last quarter of 2022 (P < .001). Among the ISBCS surgeons, the proportion of ISBCS cases per 1000 BPCS doubled from 17.20 in 2018 to 35.50 in 2022 (P < .001). On multivariate analysis, surgeons in the highest surgical volume quartile (odds ratio [OR], 1.21; 95% CI, 1.01-1.45; Ref: lowest quartile), recent graduates (0 to 10 years: OR, 2.43; 95% CI, 1.87-3.15; Ref: ≥ 31 years), and surgeons in the West (OR, 2.408; 95% CI, 2.052-2.826; Ref: South) had higher odds of performing ISBCS.

Conclusions:
There was an increased rate of ISBCS possibly suggesting greater interest among patients and surgeons. Although the overall ISBCS rate remained low, the number of surgeons performing ISBCS increased. Higher volume surgeons, recent graduates, and those practicing in the West were more likely to perform ISBCS.
The Effect of Reflexology Socks in the Management of Opioid-Induced Constipation
Authors: Ozdemir Ferda Akyuz , Can Gulbeyaz 
Published: December 2024

Background
Constipation is an important symptom that is common in patients using opioids and leads to major health problems among patients. Reflexology is one of the approaches utilized to manage constipation.

Objective
To examine the effect of reflexology socks on constipation in patients with opioid-induced constipation.

Methods
This study was designed as a single-blind, randomized, controlled experimental trial. The study was conducted with the participation of a total of 101 patients who were suffering from cancer and other noncancer diseases, using opioids, and complaining of constipation. The patients in the intervention group (n = 51) were advised to walk with reflexology socks for 4 weeks, whereas the patients in the control group (n = 50) were advised to walk only.

Results
It was found that the severity of opioid-induced constipation was lower in the intervention group than in the control group at the end of the fifth week (P < .05). Additionally, after the application, the quality-of-life mean score was lower in the intervention group (mean, 48.46 ± 24.66) compared with control group (mean, 109.88 ± 10.62), and reflexology socks were effective in enhancing quality of life in the intervention group (P < .05).

Conclusions
This study concluded that reflexology socks were an effective approach to the management of constipation.

Implications for Practice
Reflexology socks may be more useful for patients to manage constipation because it is difficult to find a reflexologist, and reflexology sessions are charged and expensive. In this way, patients will wear reflexology socks comfortably and easily at home, and the severity of constipation will be alleviated.
Prevention of Maternal Rh D Alloimmunization: A Comparative Review of Guidelines
Authors: Boureka Eirini , Tsakiridis Ioannis , Giouleka Sonia , Liberis Anastasios , Michos Georgios , Kalogiannidis Ioannis , Mamopoulos Apostolos , Athanasiadis Apostolos , Dagklis Themistoklis 
Published: December 2024

Importance
Rhesus alloimmunization refers to the sensitization of an Rh D–negative mother after exposure to D-positive fetal red blood cells, which can lead to significant fetal and neonatal morbidity and mortality.

Objective
The aim of this study was to review and compare the most recently published international guidelines on the prevention of maternal alloimmunization.

Evidence Acquisition
A comparative review of guidelines from the American College of Obstetricians and Gynecologists, the British Committee for Standards in Hematology, the International Federation of Gynecology and Obstetrics, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, and the Society of Obstetricians and Gynecologists of Canada regarding the prevention of maternal Rh D alloimmunization was conducted.

Results
There is consensus among the reviewed guidelines regarding the timing of antenatal antibody screening; the management of an already sensitized pregnancy; the administration and timing of postnatal prophylaxis with a D-positive neonate; and the need for prophylaxis after invasive procedures, abdominal trauma, and external cephalic version. Controversies exist regarding the management of women expressing weak D blood type and the optimal dose and regimen for routine antenatal prophylaxis, with recommendations suggesting administration between 28 and 34 weeks, versus specifically at 28 weeks. Moreover, significant discrepancies exist regarding the need for prophylaxis after some sensitizing events such as threatened, spontaneous, or surgical miscarriage; termination of pregnancy; and molar and ectopic pregnancy, as well as the optimal dose of anti-D globulin after invasive antenatal procedures, abdominal trauma, external cephalic version, and postnatal prophylaxis.

Conclusions
Anti-D globulin remains an important tool for the prevention of maternal alloimmunization, thus contributing to a significant improvement in fetal and neonatal outcomes. However, due to lack of evidence, discrepancies exist between relevant guidelines. Hence, further studies and the development of consistent evidence-based protocols and algorithms are pivotal to safely guide through pregnancy and subsequently reduce fetal and neonatal morbidity, without subjecting women to unnecessary treatment.

Target Audience
Obstetricians and gynecologists, family physicians.

Learning Objectives
After participating in this activity, the learner should be better able to explain the mechanism of maternal Rh alloimmunization; identify all the potential Rh-related sensitizing events; and assess the appropriate management strategies for Rh prophylaxis, both antenatally and postnatally.
Utility of Routine Postoperative Examination for Detecting Vaginal Cuff Dehiscence After Total Laparoscopic Hysterectomy
Authors: Caskey Rachel , Niino Clarissa , Meyer Raanan , Schneyer Rebecca , Hamilton Kacey , Truong Mireille D. , Wright Kelly , Siedhoff Matthew 
Published: December 2024

(Abstracted from J Minim Invasive Gynecol 2024;31(2):147–154
Hysterectomy can be performed in a variety of ways: laparoscopic, vaginal, or open. One potential complication of the procedure is vaginal cuff dehiscence (VCD), which is a full-thickness separation of the vaginal epithelial edges.
Disparities Research for Pelvic Floor Disorders: A Systematic Review and Critique of Literature
Authors: Mou Tsung , Shinnick Julia , DeAndrade Samantha , Roselli Nicole , Andebrhan Sarah , Akanbi Tracey , Ackenbom Mary , Carter-Brooks Charelle , Beestrum Molly , Cichowski Sara , Brown Oluwateniola 
Published: December 2024

(Abstracted from Urogynecology (Phila) 2024;30(9):758–764
Pelvic floor disorders (PFDs) describe conditions inclusive of lower urinary tract symptoms (LUTSs), pelvic organ prolapse (POP), and anal incontinence (AI). The prevalence of PFDs is estimated at 1 in 4 women throughout their lifetime.
Valproate Use During Spermatogenesis and Risk to Offspring
Authors: Christensen Jakob , Trabjerg Betina B. , Dreier Julie Werenberg 
Published: December 2024

(Abstracted from JAMA Network Open 2024;7(6):e2414709
Valproate, an antiseizure medication, is correlated with increased risk of congenital malformations and neurodevelopmental disorders, including autism, in children when taken by pregnant women. Because valproate is commonly prescribed to epileptic men of fertile age, concerns have been raised about its potential effects on spermatogenesis.
Endometriosis Typology and Ovarian Cancer Risk
Authors: Barnard Mollie E. , Farland Leslie V. , Yan Bin , Wang Jing , Trabert Britton , Doherty Jennifer A. , Meeks Huong D. , Madsen Myke , Guinto Emily , Collin Lindsay J. , Maurer Kathryn A. , Page Jessica M. , Kiser Amber C. , Varner Michael W. , Allen-Brady Kristina , Pollack Anna Z. , Peterson Kurt R. , Peterson C. Matthew , Schliep Karen C. 
Published: December 2024

(Abstracted from JAMA 2024;332(6):482–489
Ovarian, breast, and endometrial cancers are known to be associated with endometriosis. This study was designed to assess associations between endometriosis and its subtypes with the overall incidence of ovarian cancer and the incidence of ovarian cancer by histologic type.
Cell-Free DNA Analysis of Fetal Aneuploidies in Early Pregnancy Loss
Authors: Kutteh William H. , Miller Charles E. , Park John K. , Corey Victoria , Chavez Mauro , Racicot Karen , Alagia Damian P. , Jinnett Kristine N. , Curnow Kirsten , Dalton Kristin , Bhatt Sucheta , Keefe David L. 
Published: December 2024

(Abstracted from J Clin Med 2024;13(15):4283
Approximately 10% to 20% of pregnancies end in miscarriage, or early pregnancy loss (EPL), with most losses occurring in the first trimester. An estimated half of EPLs are due to chromosomal abnormalities, including trisomies, monosomies, and sex chromosome abnormalities, with another 10% due to polyploidy, uniparental disomy, and copy-number variants.
Lateral Episiotomy or No Episiotomy in Vacuum Assisted Delivery in Nulliparous Women (EVA): Multicentre, Open Label, Randomised Controlled Trial
Authors: Bergendahl Sandra , Jonsson Maria , Hesselman Susanne , Ankarcrona Victoria , Leijonhufvud Åsa , Wihlbäck Anna-Carin , Wallström Tove , Rydström Emmie , Friberg Hannah , Kallner Helena Kopp , Wendel Sophia Brismar 
Published: December 2024

(Abstracted from BMJ 2024;385:e079014
Obstetric anal sphincter injury (OASI) is a serious complication to vaginal birth, with the primary risk factors being primiparity and instrumental birth. Rates of OASI vary across countries, affecting up to 4% of primiparous women for spontaneous births and 6% to 24% for instrumental births in the United States, Canada, and Europe.
Socioeconomic Inequities in Preemptive Kidney Transplantation and Graft Survival: An Innovative Approach to Identifying Disparities in Kidney Transplantation
Authors: Kizilbash Sarah , Wi Chung-II , Roy Madison , Ryu Euijung , Matas Arthur , Garovic Vesna , Riad Samy , Schinstock Carrie , Juhn Young 
Published: December 2024

Background.
The limitations of conventional measures of socioeconomic status (SES) limit our ability to elucidate the role of SES as a key element of social determinants of health in kidney transplantation. This study’s objective was to use an innovative SES measure, the HOUsing-based SES measure (HOUSES) index, to examine the effects of social determinants of health on access to and outcomes of kidney transplantation.

Methods.
Our study included residents of Minnesota (age older than 18 y) who underwent kidney transplantation at a single center between 2010 and 2020. SES was determined using the HOUSES index, categorized into quartiles (Q1 for lower, Q2–Q4 for higher SES). We used mixed-effects multivariable logistic and Cox models to examine the effects of HOUSES on preemptive transplants, pretransplant dialysis duration, and death-censored graft loss, adjusting for covariates.

Results.
Among 1975 eligible patients, 29.4% received preemptive transplants, 34.9% underwent pretransplant dialysis for >3 y, and 15.1% experienced death-censored graft loss for a median follow-up of 7.15 (interquartile range, 4.25–11.38) y. Lower SES recipients (Q1) demonstrated decreased preemptive transplant likelihood (adjusted odds ratio [aOR]: 0.74; 95% confidence interval [CI], 0.57-0.97; P = 0.03), longer dialysis duration (>3 y; aOR: 1.43; 95% CI, 1.01-2.03; P = 0.046), and higher death-censored graft loss (adjusted hazard ratio 1.36; 95% CI, 1.02-1.12; P = 0.036) versus higher SES recipients (Q2–Q4).

Conclusions.
We observed significant socioeconomic disparities in kidney transplant access, dialysis duration, and graft survival. The HOUSES index may be a promising tool for individual-based targeted interventions as it identifies SES on an individual rather than an area-level basis.
Paying Attention to Attention: High Attention Sites as Indicators of Protein Family and Function in Language Models
Authors: Nayar Gowri , Tartici Alp , Altman Russ B. 
Published: December 2024

AbstractProtein Language Models (PLMs) use transformer architectures to capture patterns within protein sequences, providing a powerful computational representation of the protein sequence [1]. Through large-scale training on protein sequence data, PLMs generate vector representations that encapsulate the biochemical and structural properties of proteins [2]. At the core of PLMs is the attention mechanism, which facilitates the capture of long-range dependencies by computing pairwise importance scores across residues, thereby highlighting regions of biological interaction within the sequence [3]. The attention matrices offer an untapped opportunity to uncover specific biological properties of proteins, particularly their functions. In this work, we introduce a novel approach, using the Evolutionary Scale Model (ESM) [4], for identifying High Attention (HA) sites within protein sequences, corresponding to key residues that define protein families. By examining attention patterns across multiple layers, we pinpoint residues that contribute most to family classification and function prediction. Our contributions are as follows: (1) we propose a method for identifying HA sites at critical residues from the middle layers of the PLM; (2) we demonstrate that these HA sites provide interpretable links to biological functions; and (3) we show that HA sites improve active site predictions for functions of unannotated proteins. We make available the HA sites for the human proteome. This work offers a broadly applicable approach to protein classification and functional annotation and provides a biological interpretation of the PLM’s representation.1Author SummaryUnderstanding how proteins work is critical to advancements in biology and medicine, and protein language models (PLMs) facilitate studying protein sequences at scale. These models identify patterns within protein sequences by focusing on key regions of the sequence that are important to distinguish the protein. Our work focuses on the Evolutionary Scale Model (ESM), a state-of-the-art PLM, and we analyze the model’s internal attention mechanism to identify the significant residues.We developed a new method to identify “High Attention (HA)” sites—specific parts of a protein sequence that are essential for classifying proteins into families and predicting their functions. By analyzing how the model prioritizes certain regions of protein sequences, we discovered that these HA sites often correspond to residues critical for biological activity, such as active sites where chemical reactions occur. Our approach helps interpret how PLMs understand protein data and enhances predictions for proteins whose functions are still unknown. As part of this work, we provide HA-site information for the entire human proteome, offering researchers a resource to further study the potential functional relevance of these residues.
International Validation of Echocardiographic AI Amyloid Detection Algorithm
Authors: Duffy Grant , Oikonomou Evan , Hourmozdi Jonathan , Usuku Hiroki , Patel Jigesh , Stern Lily , Goto Shinichi , Tsujita Kenichi , Khera Rohan , Ahmad Faraz S. , Ouyang David 
Published: December 2024

ABSTRACTBackgroundDiagnosis of cardiac amyloidosis (CA) is often missed or delayed due to confusion with other causes of increased left ventricular wall thickness. Conventional transthoracic echocardiographic measurements like global longitudinal strain (GLS) has shown promise in distinguishing CA, but with limited specificity. We conducted a study to investigate the performance of a computer vision detection algorithm in across multiple international sites.MethodsEchoNet-LVH is a computer vision deep learning algorithm for the detection of cardiac amyloidosis based on parasternal long axis and apical-4-chamber view videos. We conducted a multi-site retrospective case-control study evaluating EchoNet-LVH’s ability to distinguish between the echocardiogram studies of CA patients and controls. We reported discrimination performance with area under the receiver operating characteristic curve (AUC) and associated sensitivity, specificity, and positive predictive value at the pre-specified threshold.ResultsEchoNet-LVH had an AUC of 0.896 (95% CI 0.875 – 0.916). At pre-specified model threshold, EchoNet-LVH had a sensitivity of 0.644 (95% CI 0.601 – 0.685), specificity of 0.988 (0.978 – 0.994), positive predictive value of 0.968 (95% CI 0.944 – 0.984), and negative predictive value of 0.828 (95% CI 0.804 – 0.850). There was minimal heterogeneity in performance by site, race, sex, age, BMI, CA subtype, or ultrasound manufacturer.ConclusionEchoNet-LVH can assist with earlier and accurate diagnosis of CA. As CA is a rare disease, EchoNet-LVH is highly specific in order to maximize positive predictive value. Further work will assess whether early diagnosis results in earlier initiation of treatment in this underserved population.