bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models
Authors: Talbot Lindsay J. , Chabot Ashley , Ross Aaron B. , Beckett Alexandra , Nguyen Phuong , Fleming Andrew , Chockley Peter J. , Shepphard Heather , Wang Jian , Gottschalk Stephen , DeRenzo Christopher 
Published: August 2024

Abstract

Purpose:
Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.CAR T cells expressing the cognate receptors.

Experimental Design:
We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokine protein detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T-cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2- and CXCR6.B7-H3.CAR T cells in vitro and in vivo.

Results:
T cells transgenically expressing CXCR2 or CXCR6 exhibited ligand-specific enhanced migration over T cells modified with nonfunctional control receptors. Differential homing kinetics were observed, with CXCR2.T-cell homing quickly and plateauing early, whereas CXCR6.T cells took longer to home but achieved a similar plateau. When expressed in B7-H3.CAR T cells, CXCR2- and CXCR6 modification conferred enhanced homing toward OS in vitro and in vivo. CXCR2- and CXCR6-B7-H3.CAR-treated mice experienced prolonged survival in a metastatic model compared with B7-H3.CAR T-cell-treated mice.

Conclusions:
Our patient-based pipeline identified targets for chemokine receptor modification of CAR T cells targeting OS. CXCR2 and CXCR6 expression enhanced the homing and anti-OS activity of B7-H3.CAR T cells. These findings support clinical evaluation of CXCR-modified CAR T cells to improve adoptive cell therapy for patients with OS.
Long-Term Incidence of Bradycardia and Pacemaker Implantations Among Cross-Country Skiers: A Cohort Study
Authors: Svedberg Niclas , Sundström Johan , James Stefan , Hållmarker Ulf , Hambraeus Kristina , Andersen Kasper 
Published: August 2024

BACKGROUND:
Bradycardia is more common among well-trained athletes than in the general population, but the association with pacemaker implantations is less known. We investigated associations of endurance training with incidence of bradycardia and pacemaker implantations, including sex differences and long-term outcome, in a cohort of endurance trained individuals.

METHODS:
All Swedish skiers who completed >1 race in the cross-country skiing event Vasaloppet between 1989 and 2011 (n=209 108) and a sample of 532 290 nonskiers were followed until first event of bradycardia, pacemaker implantation, or death, depending on end point. The Swedish National Patient Register was used to obtain diagnoses. Cox regression was used to investigate associations of number of completed races and finishing time in Vasaloppet with incidence of bradycardia and pacemaker implantations. In addition, Cox regression was used to investigate associations of pacemaker implantations with death in skiers and nonskiers.

RESULTS:
Male skiers had a higher incidence of bradycardia (adjusted hazard ratio [aHR], 1.19 [95% CI, 1.05–1.34]) and pacemaker implantations (aHR, 1.17 [95% CI, 1.04–1.31]) compared with male nonskiers. Those who completed the most races and had the best performances exhibited the highest incidence. For female skiers in Vasaloppet, the incidence of bradycardia (aHR, 0.98 [95% CI, 0.75–1.30]) and pacemaker implantations (aHR, 0.98 [95% CI, 0.75–1.29]) was not different from that of female nonskiers. The indication for pacemaker differed between skiers and nonskiers, with sick sinus syndrome more common in the former and third-degree atrioventricular block in the latter. Skiers had lower overall mortality rates than nonskiers (aHR, 0.16 [95% CI, 0.15–0.17]). There were no differences in mortality rates by pacemaker status among skiers.

CONCLUSIONS:
In this study, male endurance skiers had a higher incidence of bradycardia and pacemaker implantations compared with nonskiers, a pattern not seen in women. Among male skiers, those who completed the most races and had the fastest finishing times had the highest incidence of bradycardia and pacemaker implantations. Within each group, mortality rates did not differ in relation to pacemaker status. These findings suggest that bradycardia associated with training leads to a higher risk for pacemaker implantation without a detrimental effect on mortality risk.
Association Between Hospital Policy on Local Versus General Anesthesia, and Outcomes of Carotid Endarterectomy
Authors: Kirchhoff Felix , Knappich Christoph , Kallmayer Michael , Bohmann Bianca , Lohe Vanessa , Tsantilas Pavlos , Naher Shamsun , Eckstein Hans‐Henning , Kuehnl Andreas 
Published: August 2024

Background
Carotid endarterectomy (CEA) is an established procedure for the treatment of extracranial internal carotid artery stenosis. However, the type of anesthesia during elective CEA is still under debate. This study analyzes the association between the hospital policy on local anesthesia (LA) versus general anesthesia, and the outcome of elective CEA in German hospitals.

Methods
This retrospective analysis is based on the nationwide German statutory carotid quality assurance database for the years 2012 to 2016. Research was funded by Germany's Federal Joint Committee Innovation Fund (funding reference number 01VSF19016). Emergency CEA and carotid stenting procedures were excluded from the analysis. A total of 119 800 patients remained in the analysis. Hospitals were classified on a yearly basis as routine general anesthesia (<10% LA), selective LA (10%–90% LA), or routine LA centers (>90% LA). The primary outcome event was the combined in‐hospital rate of stroke or death. Secondary outcome events were in‐hospital stroke, major stroke or death, death, myocardial infarction, and major adverse cardiovascular events. Univariate and multivariable regression analyses were performed to analyze associations between the primary outcome event and the hospital policy on LA versus general anesthesia as well as clinical or procedural variables.

Results

Patient characteristics did not differ significantly between the groups (age, degree of stenosis, and rate of symptomatic patients). Raw primary outcome event rates were 1.9%, 2.1%, and 1.6% in routine general anesthesia, selective LA, and routine LA centers, respectively. Multivariable analysis revealed a significant lower rate of the primary outcome event for CEA operated under LA (adjusted odds ratio, 0.47 [95% CI, 0.33–0.67];
P
<0.001). Stratified multivariable analysis revealed that the beneficial effect of LA was only present in routine LA centers.

Conclusion
LA is associated with a lower risk of in‐hospital stroke or death after CEA in centers that use LA routinely.
The Transformation of Islamic Property and Evidentiary Law in Colonial-era Morocco: The Case of Shufʿa as Préemption
Authors: Schriber Ari 
Published: August 2024

Abstract
A cornerstone of French land policy in colonial Protectorate Morocco (1912–56) was to restrict jurisdiction of sharīʿa courts while maintaining sharīʿa-based property laws in French courts. This article examines the Islamic property concept of shufʿa (the right of “preemption” or “first-refusal” for co-owned land) as adjudicated in sharīʿa courts and French courts of colonial-era Morocco. Both jurisdictions claimed to uphold the provisions of shufʿa stipulated by the Mālikī legal school of Islamic law; however, the French courts used a codified version—le droit de préemption—while relying on property facts established by the new colonial institution of land registration (Fr., immatriculation foncière; Ar., taḥfīẓ ʿaqārī). By analyzing paradigmatic shufʿa disputes in each jurisdiction, the article argues that evidence and procedure are critical to understanding Islamic law’s encounter with the colonial state. Most importantly, French courts implemented a hybrid version of Islamic property law in which immatriculation supplanted Islamic legal modes of proof making. The French hybrid approach thus constituted a competing version of state sharīʿa that was mutually exclusive with the sharīʿa courts and persisted into the post-colonial period. This discussion more broadly seeks to center property, evidence, and judicial procedure in scholarly narratives concerning twentieth-century Islamic legal history.
Transnational and Decolonial Feminist Insights Into the Neoliberalization of Estonian Academia
Authors: Koobak Redi , Marling Raili 
Published: August 2024

Since the 1990s Estonia has been characterized by the acceptance of neoliberal values, as an antidote to the Soviet past. Neoliberal practices, like quantification and market- orientation, have permeated most spheres of society, including academia. There has been very little critical reflection on the epistemic inequalities created by this academic model for Estonia as a semi-peripheral country. In this article, the authors aim to place the neoliberalization of academia within a broader framework of colonial practices within global knowledge production, continuing their previous work on the blind spots of transnational feminism and intersections of feminisms and neoliberalism. Building on insights developed within transnational and decolonial feminism, the authors propose three interventions into neoliberal academic culture: telling better stories, practicing slow scholarship to tease apart complex colonial entanglements and using creative writing practices.
Knee Arthroscopic Surgery in Middle-Aged Patients With Meniscal Symptoms: A 10-Year Follow-up of a Prospective, Randomized Controlled Trial
Authors: Sonesson Sofi , Springer Ingo , Yakob Jafar , Hedevik Henrik , Gauffin Håkan , Kvist Joanna 
Published: August 2024

Background: Short- and midterm evaluations of arthroscopic meniscal surgery have shown little or no effect in favor of surgery, although long-term effects, including radiographic changes, are unknown. Purpose: To compare the 10-year outcomes in middle-aged patients with meniscal symptoms between a group that received an exercise program alone and a group that received knee arthroscopy in addition to the exercise program with respect to the prevalence of radiographic and symptomatic osteoarthritis (OA), patient-reported outcomes, and clinical status. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Of 179 eligible patients aged 45 to 64 years, 150 were randomized to undergo either 3 months of exercise therapy (nonsurgery group) or knee arthroscopy in addition to the exercise therapy (surgery group). Surgery usually consisted of partial meniscectomy (n = 56) or diagnostic arthroscopy (n = 8). Radiographs were assessed according to the Kellgren-Lawrence score at the baseline and 5- and 10-year follow-ups. Patient-reported outcome measures were reported at the baseline and 1-, 3-, 5-, and 10-year follow-ups. Clinical status was assessed at a 10-year follow-up. The primary outcomes were radiographic OA and changes in the Knee injury and Osteoarthritis Outcome Score Pain subscale (KOOSPAIN) from the baseline to the 10-year follow-up. The primary analysis was performed using the intention-to-treat approach. Results: At the time of the 10-year follow-up, eight patients had died, leaving 142 eligible patients. Radiographic OA was assessed for 95 patients (67%), questionnaires were answered by 110 (77%), and the clinical status was evaluated for 95 (67%). Radiographic OA was present in 67% of the patients in each group ( P≥ .999); symptomatic OA was present in 47% of the nonsurgery group and 57% of the surgery group ( P = .301). There were no differences between groups regarding changes from baseline to 10 years in any of the KOOS subscales. Conclusion: Knee arthroscopic surgery, in most cases consisting of partial meniscectomy or diagnostic arthroscopy, in addition to exercise therapy in middle-aged patients with meniscal symptoms, did not increase the rates of radiographic or symptomatic OA and resulted in similar patient-reported outcomes at the 10-year follow-up compared with exercise therapy alone. Considering the short-term benefit and no long-term harm from knee arthroscopic surgery, the treatment may be recommended when first-line treatment—including exercise therapy for ≥3 months—does not relieve patient’s symptoms. Registration: Clinical Trials NCT01288768 (ClinicalTrials.gov identifier).
The Association Between the Development of Cam Morphology During Skeletal Growth in High-Impact Athletes and the Presence of Cartilage Loss and Labral Damage in Adulthood: A Prospective Cohort Study With a 12-Year Follow-up
Authors: Claes Paula A.M. , Hanff David F. , Weir Adam , Riedstra Noortje S. , Weinans Harrie , Eygendaal Denise , Heerey Josh , Oei Edwin H.G. , van Klij Pim , Agricola Rintje 
Published: August 2024

Background: Cam morphology develops during skeletal growth, but its influence on cartilage and the labrum in high-impact athletes later in life is unknown. Purpose: To (1) explore the association between the presence and duration of cam morphology during adolescence and the cartilage and labral status 7 to 12 years later and (2) report the prevalence of cartilage loss and labral damage in a population of young male athletes (<32 years old) who played professional soccer during skeletal growth. Study Design: Cohort study (Prognosis); Level of evidence, 2. Methods: A total of 89 healthy male academy soccer players from the Dutch soccer club Feyenoord (aged 12-19 years) were included at baseline. At baseline and 2.5- and 5-year follow-ups, standardized supine anteroposterior pelvis and frog-leg lateral radiographs of each hip were obtained. At 12-year follow-up, magnetic resonance imaging of both hips was performed. Cam morphology was defined by a validated alpha angle ≥60° on radiographs at baseline or 2.5- or 5-year follow-up when the growth plates were closed. Hips with the presence of cam morphology at baseline or at 2.5-year follow-up were classified as having a “longer duration” of cam morphology. Hips with cam morphology only present since 5-year follow-up were classified as having a “shorter duration” of cam morphology. At 12-year follow-up, cartilage loss and labral abnormalities were assessed semiquantitatively. Associations were estimated using logistic regression, adjusted for age and body mass index. Results: Overall, 35 patients (70 hips) with a mean age of 28.0 ± 2.0 years and mean body mass index of 24.1 ± 1.8 participated at 12-year follow-up. Cam morphology was present in 56 of 70 hips (80%). The prevalence of cartilage loss was 52% in hips with cam morphology and 21% in hips without cam morphology (adjusted odds ratio, 4.52 [95% CI, 1.16-17.61]; P = .03). A labral abnormality was present in 77% of hips with cam morphology and in 64% of hips without cam morphology (adjusted odds ratio, 1.99 [95% CI, 0.59-6.73]; P = .27). The duration of cam morphology did not influence these associations. Conclusion: The development of cam morphology during skeletal growth was associated with future magnetic resonance imaging findings consistent with cartilage loss in young adults but not with labral abnormalities.
Microscopic Magnetic Resonance Imaging Comparing Asymptomatic and Symptomatic Ulnar Collateral Ligament Injuries in Baseball Players
Authors: Hoshika Shota , Matsuki Keisuke , Takeuchi Yasutaka , Takahashi Norimasa , Sugaya Hiroyuki 
Published: August 2024

Background: The relationship between abnormalities of the ulnar collateral ligament (UCL) on magnetic resonance imaging (MRI) and elbow symptoms in baseball players remains unclear. Purpose/Hypothesis: This study aimed to compare findings of the UCL on microscopic MRI between asymptomatic and symptomatic elbows in baseball players. We hypothesized that the MRI grade of UCL injuries would exhibit no correlation with medial elbow symptoms in baseball players. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The study participants were skeletally mature baseball players who underwent high-resolution microscopic MRI of the medial elbow including for medical checkups. Elbows with previous surgical treatment or traumatic UCL injuries were excluded. The patients were divided into symptomatic and asymptomatic groups. The UCL appearance on microscopic MRI was categorized into 4 grades and compared between the groups. Abnormal findings in the medial elbow including bony fragments at the medial epicondyle, osteophytes or bony fragments in the sublime tubercle, and bone marrow edema (BME) in the sublime tubercle were also evaluated. Results: A total of 426 baseball players (426 elbows) with a mean age of 20 years (range, 14-41 years) were included. The asymptomatic and symptomatic groups included 158 and 268 elbows, respectively. In the asymptomatic group, based on MRI grading of the UCL, 46 (29%) elbows were rated as grade I, 64 (41%) as grade II, 40 (25%) as grade III, and 8 (5%) as grade IV. In the symptomatic group, 75 (28%) elbows were rated as grade I, 118 (44%) as grade II, 61 (23%) as grade III, and 14 (5%) as grade IV. There was no significant difference in the MRI grades between the groups ( P = .9). BME in the sublime tubercle was more frequently seen in the symptomatic group than in the asymptomatic group ( P < .001). Conclusion: There was no difference in MRI grades of the UCL between symptomatic and asymptomatic elbows in baseball players; approximately 30% of elbows demonstrated high-grade UCL injuries in both groups. BME in the sublime tubercle was more frequently seen in symptomatic elbows than in asymptomatic elbows. BME in the sublime tubercle was a better indicator of symptoms than was MRI grading of the UCL.
Transparency Matters: Assessing Harms Reporting Compliance in Randomized Controlled Trials Underpinning the AAOS Clinical Practice Guideline for Anterior Cruciate Ligament Injuries
Authors: Brown Jim , DiCicco Luke , Shepard Samuel , Hughes Griffin , Bennett Steven , Anderson J. Michael , Hanson Chad , Heckler Matt 
Published: August 2024

Background: The American Academy of Orthopaedic Surgeons (AAOS) has developed a clinical practice guideline (CPG) for management of anterior cruciate ligament (ACL) injuries. Primary studies such as randomized controlled trials (RCTs) are cited as evidence for the guidelines. Given the influence that these trials have on patient care, adherence to standardized protocols for conducting and reporting RCTs is essential. Purpose: To evaluate the CONSORT (Consolidated Standards of Reporting Trials) Extension for Harms–related reporting of RCTs cited as supporting evidence for the AAOS CPG on the management of ACL tears. Study Design: Cross-sectional study. Methods: The reference section of the AAOS guideline for ACL tears was first screened for RCTs cited in the CPG. Next, each RCT was evaluated for adherence to the CONSORT Extension for Harms checklist. Both identification of RCTs and assessment of adherence were performed in a masked and duplicate process. Descriptive statistics were used to summarize adherence to CONSORT Extension for Harms items. A Pearson correlation test was conducted to assess the relationship between the year of publication and adherence to CONSORT harms reporting. Results: The sample included 113 RCTs, of which 16 (14.2%) were published before the CONSORT Extension for Harms was implemented in 2004. Sample sizes ranged from 24 to 4564 participants, with a mean of 228. None of the included RCTs included all 18 items in the CONSORT Extension for Harms checklist. The mean number of checklist items reported was 4 (of 18; 22.2%). A moderate, positive, and statistically significant correlation was found between the RCT publication year and the adherence with reporting of the CONSORT Extension for Harms ( t111 = 3.54; P < .001) ( r = 0.32; 95% CI, 0.14-0.47). Conclusion: Harms were infrequently reported in RCTs cited as supporting evidence in the AAOS CPG for the management of ACL tears. One encouraging finding was the positive correlation between the year when RCTs were published and how well they adhered to reporting harms. Efforts to improve adverse event reporting are warranted, as RCTs are commonly used to make clinical decisions in orthopaedic surgery.
Identification of CGNL1 as a diagnostic marker in fibroblasts of diabetic foot ulcers: Insights from single cell RNA sequencing and bulk sequencing data
Authors: Wang Li , Tang Lulu , Zhou Lingna , Lai Yingtao , Li Hui , Wang Xiaojun , Liu Xiaoyi 
Published: August 2024

Objectives This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and the role of ferroptosis in diabetic foot ulcers (DFUs). Methods The GEO (Gene Expression Omnibus) was searched to obtain the DFUs single-cell and transcriptional datasets. After identifying cell types by classic marker genes, the integrated single-cell dataset was used to run trajectory inference, RNA velocity, and ligand-receptor interaction analysis. Next, bulk RNA-seq datasets of DFUs were analyzed to the key ferroptosis genes. Results Here, we profile 83529 single transcriptomes from the foot samples utilizing single-cell sequencing (scRNA-seq) data of DFU from GEO database and identified 12 cell types, with fibroblasts exhibiting elevated levels of ferroptosis activity and substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, and healing-enriched functional annotations. Trajectory inference and cell-cell communication analysis revealed two major cell fates with subpopulations of fibroblasts and altered ligand-receptor interactions. Bulk RNA sequencing data identified CGNL1 as a distinctive diagnostic signature in fibroblasts. Notably, CGNL1 positively correlated with pro-inflammatory fibroblasts. Conclusions Overall, our analysis delineated the heterogeneity present in cell populations of DFUs, showing distinct fibroblast subtypes characterized by their own unique transcriptional features and enrichment functions. Our study will help us better understand DFUs pathogenesis and identifies CGNL1 as a potential target for DFUs therapies.
Volume Progression and Price–Volume Relationship of Commodity Futures: Case of Bullion and Base Metals
Authors: Kumar M. Ajoy , Swathi J  , Pallavi T. A.  , Bavana S.  
Published: August 2024

Purpose: The purpose of this study is to examine the behaviour of trading volumes in commodity futures markets over the life of the contract and to analyse the relationship between changes in price, volume and open interest. Methodology: The volume progression is examined by dividing the life of a futures contract to six phases and analysing how the volumes picked up during each phase. The relationship between price, volume and open interest was examined using the Pearson correlation and the vector autoregression (VAR) model. Findings: It is found that the volumes in commodity futures are clustered around the last phase of the contract’s life. As far as the relationship between price, volume and open interest is concerned, there is a very low correlation between the variables. Price is not influenced by volume or open interest. The volume changes are found to be influenced by open interest, and the open interest is influenced by its own past values. Practical Implications: The findings of the study have implications for traders in the commodity futures market as well as policymakers as it throws light on the crucial issue of lack of volumes in the futures market. Contribution/Originality: The study contributes to the literature in terms of analysis of volume progression, which is not researched extensively in the Indian market. The findings of the study, which contradict the findings of other similar studies, open up scope for further research.