bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering and targeting potential of CAR NK cells in colorectal cancer
Authors: Khawar Muhammad Babar , Afzal Ali , Dong Shuangshuang , Si Yue , Sun Haibo 
Published: November 2024

Abstract
Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promise, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Synchronous Pulmonary Langerhans Cell Histiocytosis and Multiple Cutaneous Reticulohistiocytomas With a Common BRAF-V600E/D Mutation Driver
Authors: Parra Ourania , Georgantzoglou Natalia , Green Donald , Wilson Jessica G. , Linos Konstantinos 
Published: November 2024

Abstract:
Histiocytoses constitute a group of heterogeneous disorders characterized by involvement of variable organs by neoplastic macrophage or dendritic cells. They may affect both adults and children with a predilection to the skin, bone, lungs, lymph nodes, and CNS. The coexistence of different types of histiocytoses in the same patient is an extremely rare phenomenon. We describe a very rare case of co-occurring pulmonary Langerhans cell histiocytosis with multiple cutaneous reticulohistiocytomas with a common BRAF-V600E mutation as the driver genetic event in both the lung and skin lesions. The presence of a common BRAF-V600E mutation provides evidence of their clonal relation and contributes to our understanding in the pathogenesis of multiple, co-occurring histiocytic proliferations.
The Ubiquitin Ligase HERC2 Promotes Ang II-Induced Cardiac Hypertrophy Through Destabilization of MeCP2 to Enhance Lin28a Expression
Authors: Zhou Bin , Fu Hui-fan , Niu Jiang-feng , Deng Wei , Deng Fu-mou , Zhou Zhi-dong , Zhou Wei , Xiong Qinggen , Li Chang 
Published: November 2024

Abstract:
Homologous to the E6-AP carboxy terminus-type E3 ubiquitin ligases participate in the progression of cardiovascular diseases. HERC2 has been reported to play critical roles in many pathologic processes, but its role in cardiac hypertrophy remains unclear. In this study, we observed that the expression and activity of HERC2 were significantly upregulated in hypertrophic hearts and angiotensin II (Ang II)-stimulated primary cardiomyocytes. Knockdown of HERC2 in cardiomyocytes significantly alleviated the myocardial hypertrophy induced by Ang II. Conversely, cardiac-specific overexpression of HERC2 aggravated Ang II-induced cardiac hypertrophy in vitro and in vivo. Furthermore, we demonstrated that HERC2 promoted cardiac hypertrophy through increasing the expression of lin-28 homologue A (Lin28a), an RNA-binding protein that regulates pathologic cardiac hypertrophic. Knocking down Lin28a attenuated Ang II-induced myocardial hypertrophy and abolished the increase in myocardial hypertrophy by overexpression of HERC2. Further investigation indicated that HERC2 promoted the expression level of Lin28a by reducing methyl-CpG binding protein 2 (MeCP2), a transcriptional suppressor of Lin28a. We also showed that the prohypertrophic effect of HERC2 was partially dependent on MeCP2 inhibition. Mechanistically, HERC2 directly bound with MeCP2, and promotes its K48-linked polyubiquitination and degradation. Combined, these findings demonstrate that HERC2 plays a crucial role in pathologic cardiac hypertrophy, thereby indicating that targeting the HERC2/MeCP2/Lin28a axis is a potential strategy for heart failure therapy.
Genetic Estimates of Correlation and Causality Between Keratoconus and Osteoarthritis
Authors: Han Tian , Han Xiaosong , Liu Liu , Wang Yuliang , Peng Xiaoliao , Zhou Xingtao 
Published: November 2024

Purpose:
The relationship between keratoconus (KC) and osteoarthritis (OA) has been hypothesized, yet the causal link remained obscure. We aimed to evaluate the genetic correlation and causality between KC and OA through a genetic perspective.

Methods:
Linkage Disequilibrium Score Regression and bidirectional 2-sample Mendelian randomization (MR) analysis were conducted. Data were used from genome-wide association study on KC (4669 cases and 116,547 controls), OA (encompassing 24,955 patients with knee OA, 15,704 patients with hip OA, 39,427 patients with knee or hip OA, and 378,169 control participants), and KC data in the FinnGen consortium for replication and meta-analysis. Simple model, weighted model, inverse-variance weighted, weighted median, and MR-Egger regression were employed to assess the causal effects. MR pleiotropy residual sum and outlier method, MR-Egger method, and leave-one-out analysis were also applied to detect pleiotropy.

Results:
No statistically significant genetic correlation between KC and OA (all P > 0.05) were observed. MR estimates obtained from all 5 methods after meta-analysis revealed nonsignificant odds ratio values of KC-related traits to knee OA, hip OA, and OA (all adjusted P > 0.05). No evidence of causal relationships of knee and hip OA with KC-related traits was detected after meta-analysis of all 5 MR methods (all adjusted P > 0.05).

Conclusions:
The large MR analysis indicated that KC may not be causally associated with a risk of OA.
Femtosecond Laser-Assisted Graft Preparation and Implantation of Corneal Allogeneic Intrastromal Ring Segments for Corneal Ectasia: 1-Year Results
Authors: Bteich Yara , Assaf Jad F. , Müller Fabian , Gendy Jeremiah E. , Jacob Soosan , Hafezi Farhad , Awwad Shady T. 
Published: November 2024

Purpose:
To evaluate the outcomes of patients treated with corneal allogeneic intrastromal ring segments cut with femtosecond laser (Femto-CAIRS) without concomitant corneal crosslinking.

Methods:
Patients with keratoconus treated with Femto-CAIRS at the American University of Beirut Medical Center were included (May 2022–January 2023). A proprietary software program was developed on the femtosecond laser to cut allogeneic segments. Visual, refractive, tomographic, aberrometric, and epithelial data by anterior segment optical coherence tomography were measured at baseline and 1, 3, 6, and 12 months postoperatively.

Results:
20 eyes of 15 patients were included and followed up for 12 months. The manifest refraction spherical equivalent and cylinder improved from −6.79 ± 4.9 diopter (D) and −4.25 ± 1.8 D to −1.88 ± 2.9 D (P < 0.001) and −2.64 ± 1.4 D (P = 0.01) 12 months postoperatively, respectively. 75% of eyes gained 3 or more corrected distance visual acuity lines, most of which (65%) gained 4 lines or more 12 months postoperatively. The maximum keratometry and vertical coma decreased by 5.2 D (P < 0.001) and 1 μm (P = 0.001), respectively, 3 months postoperatively and remained stable until 12 months. The largest anterior stromal elevation over the central 5-mm diameter decreased from 36.0 ± 18.2 μm preoperatively to 19.9 ± 9.25 μm at 1 week postoperatively (P < 0.001) and remained relatively stable. Epithelial thickness over the cone increased relative to baseline starting 1 month postoperatively and becoming stable after 6 months while the mean epithelial thickness central to the ring peaked at 1 month after which it decreased to reach a plateau at 6 months.

Conclusions:
The Femto-CAIRS procedure improves visual and tomographic parameters and allows repeatable and safe results with the possibility of customization for individualized management.
Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study
Authors: Farrar John T. , Locke Kenneth T. , Clemens J. Quentin , Griffith James W. , Harte Steven E. , Kirkali Ziya , Kreder Karl J. , Krieger John N. , Lai H. Henry , Moldwin Robert M. , Mullins Chris , Naliboff Bruce D. , Pontari Michel A. , Rodríguez Larissa V. , Schaeffer Anthony J. , Schrepf Andrew , Stephens-Shields Alisa , Sutcliffe Siobhan , Taple Bayley J. , Williams David A. , Landis J. Richard 
Published: November 2024

Abstract
Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.
Childhood maltreatment and chronic “all over” body pain in adulthood: a counterfactual analysis using UK Biobank
Authors: Timmins Kate A. , Hales Tim G. , Macfarlane Gary J. ,   on behalf of the Consortium Against Pain InEquality (CAPE) investigators and Chronic Pain Advisory Group
Published: November 2024

Abstract
Evidence linking adverse childhood experiences and chronic pain in adulthood is largely cross-sectional, potentially subject to recall bias and does not allow exploration of mediating pathways. We analysed a large population-based cohort (UK Biobank) using a causal framework, to determine if childhood maltreatment is related to chronic “all over” body pain in adulthood. We used doubly robust estimation with inverse probability weights to estimate the difference in risk of chronic pain “all over” between those exposed/not exposed to childhood maltreatment (abuse or neglect). In addition, we looked at interaction with adult stressful life events and examined mediation using inverse odds weighting in a generalized linear model. Using cases with complete data (n = 118,347), the risk of chronic “all over” body pain was higher in the exposed (6.3%, 95% confidence interval [CI] 6.0%-6.5%) than in the unexposed (4.0%; 95% CI 3.8%-4.2%). This difference remained in analyses stratified by sex. Conversely, when analyses were repeated with a negative control exposure, childhood sunburn, risk differences were 0.8% in women (95% CI 0.3%-1.3%) and 0.5% in men (95% CI 0.1%-0.9%). Childhood maltreatment and adult life events had similar effects, and there was a supra-additive risk (1.2%; 95% CI 0.6-1.7) when experiencing both. In mediation analyses, the total effect was a relative risk of 1.57 (95% CI 1.49-1.66), while the estimated indirect effect via all mediators was relative risk 1.16 (95% CI 1.14-1.18). Reducing childhood maltreatment would likely prevent cases of chronic widespread pain in adulthood. Stressful adult events and mediators may offer opportunities for intervention.
Evolving indications and management patterns in heart – kidney transplantation
Authors: Lang Frederick M. , Topkara Veli K. 
Published: November 2024

Purpose of review
Dual heart–kidney transplantation (HKT) is an increasingly utilized option for patients with end-stage heart failure and impaired renal function. In 2023, the United Network for Organ Sharing (UNOS) formalized indications for simultaneous heart–kidney transplantation (SHKT) and kidney-after-heart transplantation (KAHT). In light of this landmark effort, we review the evolution in HKT indications, outcomes after SHKT and KAHT in various patient populations, novel considerations in pre and posttransplant management, and areas for future research.

Recent findings
The UNOS policy was borne out of retrospective outcome studies suggesting that SHKT is superior to single-organ heart transplantation (HT) in select patients with sufficiently severe renal impairment. KAHT utilization continues to evolve, providing a helpful safety net for HT recipients with irreversible worsening of renal function. Time-limited pretransplant device trials are useful for identifying optimal candidates for HKT, and calcineurin inhibitor-sparing regimens can preserve posttransplant renal function. Explorations into artificial intelligence algorithms and biomarker technology represent interesting future opportunities.

Summary
Recent studies have refined selection and management of dual HKT recipients. The new UNOS policies now provide helpful standardization to the field. Rapid innovation to date has made dual HKT an exciting therapeutic strategy for patients with few options left.
Prehospital Restraint Use in Pediatric Patients With Mental and Behavioral Health Emergencies
Authors: Cummings Caroline , Babcock Lynn , Zhang Yin , Lee Sang Hoon , Schwartz Hamilton , Semenova Olga , Pomerantz Wendy J. ,   the Cincinnati Children's Prehospital Care Committee
Published: November 2024

Objectives
The aims of the study are to characterize children with mental and behavioral health conditions (MBH) transported by emergency medical services (EMS) and examine differences in patient, emergency department (ED), and EMS transport characteristics based on restraint interventions during EMS transport.

Methods
This is a retrospective cohort study of EMS patients with MBH crises, aged 5–18, transported to 2 pediatric EDs over 9 years. Demographic and ED data were collected electronically; EMS data were extracted manually from prehospital care records. Field interventions studied included pharmacologic and mechanical restraints by EMS clinicians. Univariate analysis compared variables between patients who received EMS restraints and those who did not and multivariable logistic regression identified patient factors independently associated with EMS restraint use.

Results
Among 10,264 patients transported by EMS for MBH crises, 1400 encounters were randomly selected, with 768 records available. EMS restraint interventions were used in 73 (9.5%) patients: 5 (0.7%) received only pharmacologic restraints, 58 (7.6%) received only physical restraints, and 10 (1.3%) received both. Those who received EMS restraints were more likely to be younger (35.6% vs 19.6%, P = 0.001), male (71.2% vs 44.6%, P < 0.0001), and had longer scene times (13 vs 9 min). Restraint use was more common when patients were picked up from schools (30.1% vs 14.8%, P = 0.007). EMS-restrained patients were also more likely to receive physical (12.3% vs 2.3%, P < 0.0001), mechanical (15.1% vs 1.0%, P < 0.0001), or pharmacologic (24.7% vs 3.9%, P < 0.0001) restraints in the ED. Predictors of EMS restraint use were male sex (odds ratio, 3.00; 95% confidence interval, 1.74–5.17) and being picked up from schools (odds ratio, 2.08; 95% confidence interval, 1.13–3.81), whereas age group, race, and insurance type were not independent predictors.

Conclusions
Nearly 1 in 10 pediatric patients experiencing mental health crises and transported by EMS required restraint interventions in the field. Male patients, younger aged children, and those picked up from school represent a distinct and vulnerable population that could benefit from specialized prehospital care to manage agitation.
Respiratory Vaccination Rates in People Living With Spinal Cord Injury/Disorder in Switzerland
Authors: Mueller Gabi , Eriks-Hoogland Inge , Hund-Georgiadis Margret , Jordan Xavier , Schubert Martin , Bertschy Sue , Wenk Christian , Brinkhof Martin WG 
Published: November 2024

Objective
The aim of the study is to provide a population-based evaluation of vaccination coverage to prevent respiratory complications from SARS-COV-2, influenza, and pneumococcus, among community-dwelling persons with spinal cord injury/disease.

Design
This is a cross-sectional survey conducted in 2022, utilizing questionnaires administered to persons with spinal cord injury/disease living in Switzerland. Main outcomes were ever-vaccination rates for SARS-COV-2, influenza, and pneumococcus. Secondary outcomes included demographics, lesion and education levels, as well as respiratory and cardiovascular conditions. Vaccine hesitancy was additionally assessed for all three vaccines in nonvaccinated persons through questions on reasons for not getting vaccinated.

Results
A total of 1158 persons participated in this survey. Overall vaccination rates were highest for SARS-COV-2 86.5% (95% CI = 84.4–88.3), followed by influenza 44.6 (41.7–47.6) and pneumococcus: 7.5% (6.0–9.3). The most prominent reasons for not being vaccinated were doubt on effectiveness (72.7%) and potential side effects (60%) for SARS-COV-2, patients did not feel at risk for influenza (57%) and insufficient information from the physician (52.4%) for pneumococcus vaccination.

Conclusions
In individuals with spinal cord injury/disease, vaccination coverage is notably low for influenza and especially pneumococcus. Vaccine hesitancy varies between vaccination types and is associated with vaccine-specific reasons. These findings underscore the imperative for updated clinical vaccination guidelines, improved public health information, and targeted intervention programs for specific patient groups.
Adherence to Physical Activity Guidelines in Manual Wheelchair Users With Spinal Cord Injury and the Association With Shoulder Pain
Authors: de Vries Wiebe H.K. , Arnet Ursina , Bossuyt Fransiska M. , de Groot Sonja , Eriks-Hoogland Inge , Perret Claudio 
Published: November 2024

Objective
The aim of the study is to investigate the association between adherence to spinal cord injury–specific physical activity guidelines in manual wheelchair users with spinal cord injury and shoulder pain prevalence.

Design
This is a cross-sectional analysis of the SwiSCI Community Survey 2022 data, assessing aerobic activity and muscle strength training adherence in manual wheelchair users with spinal cord injury and shoulder pain prevalence. Logistic regression analysis was used to identify the association between meeting the physical activity guidelines and shoulder pain.

Results
Low adherence to aerobic activity and strength training guidelines are observed, with 46% and 64% of the study sample not meeting the respective guidelines. The low adherence to physical activity guidelines contrasts with the general Swiss population from which around 75% is physically active for more than 2.5 hrs a week. Manual wheelchair users present a high prevalence of shoulder pain (40%) and nonadherence to aerobic guidelines in the study sample correlates with 1.55–1.97 higher odds of having shoulder pain.

Conclusions
Aerobic activity adherence is associated with lower shoulder pain prevalence, emphasizing its potential for injury prevention. Overall, the presented findings necessitate further longitudinal studies and interventions for a comprehensive understanding and effective management of shoulder pain in manual wheelchair users with spinal cord injury.
Labor Market Participation of Persons With Spinal Cord Injury Living in Switzerland Between 2012 and 2022
Authors: Schwegler Urban , Galvis Aparicio Mayra , Staubli Stefan , Austin-Cliff George , Brinkhof Martin W.G. 
Published: November 2024

Objectives
The aim of the study is to examine labor market participation of individuals with spinal cord injury living in Switzerland over the past decade and in relation to the general population.

Design
This is a descriptive study, using longitudinal panel data from the 2012, 2017, and 2022 community surveys of the Swiss Spinal Cord Injury Cohort Study and general population data from the Swiss Labor Force Survey.

Results
Employment rates among spinal cord injury responders were 56% in 2012, 61% in 2017, and 64.6% in 2022. Employment gaps between the spinal cord injury and the Swiss general population samples decreased from 22.5% (2012) to 15.4% (2022). This decrease was particularly evident for females, middle-aged individuals, and people with tetraplegia but contrasted with increased employment gaps in Southwestern Switzerland.

Conclusions
By identifying increased employment rates among spinal cord injury responders along with decreased employment gaps in relation to the general population, our study indicates improved opportunities for persons with impairments in the Swiss labor market over the past decade. While there is still room to improve the labor market participation prospects among the Swiss spinal cord injury population, particular efforts at the regional level are required to ensure equal labor market participation opportunities for all individuals with spinal cord injury living in Switzerland.
Medical mistrust and vaccine-hesitant attitudes explain SARS-CoV-2 vaccination disparities in a mixed serostatus cohort
Authors: Friedman M. Reuel , Wingood Gina , Krause Kristen D. , Krier Sarah , D'Souza Gypsyamber , Kempf Mirjam-Colette , Mimiaga Matthew J. , Kwait Jenn , Jones Deborah L. , Martinson Jeremy , Marques Ernesto T. , Tien Phyllis , Anastos Kathryn , Ramirez Catalina , Cohen Mardge , Camacho-Rivera Marlene , Goparaju Lakshmi , Rinaldo Charles R. 
Published: November 2024

Objectives:
To understand the extent of racial disparities in SARS-CoV-2 vaccination among PWH and those vulnerable to HIV infection and to estimate the contributions of medical mistrust and vaccine-hesitant attitudes to these disparities.

Design:
Quantitative data analyses in a racially and gender-diverse, mixed-serostatus prospective cohort, the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study.

Methods:
Interviewer-assisted questionnaires assessed SARS-CoV-2 vaccination, medical mistrust, and vaccine-hesitant attitudes from March 2021 to September 2022 (n = 3948). Longitudinal analyses assessed effects of sociodemographics on medical mistrust and vaccine-hesitant attitudes. A hierarchical multivariable logistic regression assessed effects of these co-factors on SARS-CoV-2 vaccination. Causal mediation models assessed whether medical mistrust mediated the relationship between Black identity and vaccine-hesitant attitudes, and vaccine-hesitant attitudes mediated the relationship between Black identity and SARS-CoV-2 nonvaccination.

Results:
Participants’ mean age was 56.7; 55.3% were Black, 52.6% cisgender female, 62.6% PWH. 10.1% reported never receiving SARS-CoV-2 vaccinations (13.4% of Black and 4.5% of White participants). Black-identified participants had higher odds of nonvaccination than White participants [aOR = 1.72; 95% confidence interval (CI) 1.08–2.72]. Medical mistrust mediated the relationship between Black identity and vaccine-hesitant attitudes, accounting for 46% of the effect (P < 0.0001). Vaccine-hesitant attitudes mediated the relationship between Black identity and SARS-CoV-2 nonvaccination to the extent that 57.7% (95% CI 25.3–90.1%) of the disparity would be eliminated if vaccine-hesitant attitudes among Black respondents were reduced to levels reported among other racial groups.

Conclusion:
Findings indicate a profound need to build trustworthy healthcare environments to combat medical mistrust and vaccine-hesitant attitudes in Black communities in the United States, including those affected by HIV.