bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ex Vivo Efficacy of SAR442257 Anti-CD38 Trispecific T-cell Engager in Multiple Myeloma Relapsed After Daratumumab and BCMA-targeted Therapies
Authors: Keller Alana L. , Reiman Lauren T. , Perez de Acha Olivia , Parzych Sarah E. , Forsberg Peter A. , Kim Peter S. , Bisht Kamlesh , Wang Hongfang , van de Velde Helgi , Sherbenou Daniel W. 
Published: February 2024

Abstract

T cell–engaging antibodies (TCEs) are showing promising efficacy in relapsed/refractory multiple myeloma, even in patients that relapsed after B-cell maturation antigen (BCMA)-targeted therapy. Patients with multiple myeloma may have compromised T-cell health unaccounted for by preclinical models. Here, we use Myeloma Drug Sensitivity Testing (My-DST) for ex vivo measurement of anti-multiple myeloma cytotoxicity for the trispecific CD38/CD28xCD3 TCE SAR442257 through activation of the patients’ own endogenous T cells to inform clinical development of the compound in multiple myeloma. My-DST incubates primary mononuclear cells in humanized media for 48 hours followed by flow cytometry for multiple myeloma cell viability with or without drug treatment. SAR442257 was tested on 34 samples from patients with multiple myeloma across disease settings. Potential biomarkers, T-cell dependence, and degranulation were assessed. SAR442257 was effective at low dose in My-DST cultures. High ex vivo response rates were observed in primary aspirates taken from patients with multiple myeloma at diagnosis, with modestly reduced response in multiple myeloma recently treated with anti-CD38 mAbs. SAR442257 was highly effective in patients relapsing after BCMA therapy. The CD38/CD28xCD3 trispecific format was substantially more effective than a conventional bispecific CD38/CD3 antibody format and CD38 mAbs. Anti-multiple myeloma cell cytotoxicity was dependent on the presence of endogenous T cells. Surface CD38 expression was the strongest biomarker of TCE response. My-DST is capable of measuring T cell–dependent killing using the multiple myeloma patient's own bone marrow–derived T cells. SAR442257 shows promise for multiple myeloma and may be best suited for patients declared resistant to both CD38 mAbs and BCMA-targeted therapy.

Significance:
This study introduces the use of My-DST to measure and characterize sensitivity to anti-CD38 T-cell engager SAR442257 in primary samples using matched endogenous T cells. Preclinical testing in samples from patients with diverse treatment history supports further testing in post-chimeric antigen receptor T-cell multiple myeloma.
Academic Challenges and Coping Mechanisms among Senior High School Students with Overseas Filipino Worker Parents
Authors: Taola Mica , Sagdi Lorence James , Millado Erwina , Harun Nurul Ain , Alviar Jayson 
Published: February 2024

Students with Overseas Filipino Worker (OFW) parents face a wide array of challenges that affect their well-being. The consequences of parent’s absence directly affect their child’s psychological state which can result to poor academic performance. This study aimed to determine the academic challenges and coping mechanisms of the Senior High School students with Overseas Filipino Workers (OFWs) parents through analysis of their lived experience. This study employed a phenomenological research design. In this study a purposive sampling technique was employed to select the six (6) respondents with OFW parents in Senior High School. These students were selected using the following criteria: (1) a senior high school student at Tairan National High School; (2) whose mother is working abroad; and (3) willingness of the respondents to participate in the study. The data collected from the interview were analyzed using thematic analysis. Three (3) subthemes emerged in the senior high school students’ academic challenges: (1) school-related problem; (2) lack of parent’s attention and guidance; and (3) communication. On the other hand, the coping mechanisms of the students include (1) reciprocating parent’s efforts; (2) understanding the parents’ reasons for working abroad; (3) building a circle of friends and family support system. Results showed that the parents’ absence affects the academic performances of the students. However, the students displayed strong commitment to do well in school to reciprocate parents’ sacrifices. Thus, this phenomenological study establishes the baseline in developing programs and support system to the students with OFW parents.
Heterogeneity in the Prevalence of Cardiovascular Risk Factors by Ethnicity and Birthplace Among Asian Subgroups: Evidence From the 2010 to 2018 National Health Interview Survey
Authors: Lim Arum , Elias Sabrina , Benjasirisan Chitchanok , Byiringiro Samuel , Chen Yuling , Turkson‐Ocran Ruth‐Alma , Dennison Himmelfarb Cheryl R. , Commodore‐Mensah Yvonne , Koirala Binu 
Published: February 2024

Background
Asian people in the United States have different sociodemographic and health‐related characteristics that might affect cardiovascular disease (CVD) risk by ethnicity and birthplace. However, they are often studied as a monolithic group in health care research. This study aimed to examine heterogeneity in CVD risk factors on the basis of birthplace among the 3 largest Asian subgroups (Chinese, Asian Indian, and Filipino) compared with US‐born non‐Hispanic White (NHW) adults.

Methods and Results
A cross‐sectional analysis was conducted using the 2010 to 2018 National Health Interview Survey data from 125 008 US‐born and foreign‐born Chinese, Asian Indian, Filipino, and US‐born NHW adults. Generalized linear models with Poisson distribution were used to examine the prevalence and prevalence ratios of self‐reported hypertension, diabetes, high cholesterol, physical inactivity, smoking, and overweight/obesity among Asian subgroups compared with US‐born NHW adults. The study included 118 979 US‐born NHW and 6029 Asian adults who self‐identified as Chinese (29%), Asian Indian (33%), and Filipino (38%). Participants' mean (±SD) age was 49±0.1 years, and 53% were females. In an adjusted analysis, foreign‐born Asian Indians had significantly higher prevalence of diabetes, physical inactivity, and overweight/obesity; foreign‐born Chinese had higher prevalence of physical inactivity, and foreign‐born Filipinos had higher prevalence of all 5 CVD risk factors except smoking compared with NHW adults.

Conclusions
This study revealed significant heterogeneity in the prevalence of CVD risk factors among Asian subgroups by ethnicity and birthplace, stressing the necessity of disaggregating Asian subgroup data. Providers should consider this heterogeneity in CVD risk factors and establish tailored CVD prevention plans for Asian subgroups.
Traversing Uncharted Territory? The Legislative and Regulatory Landscape of Heritable Human Genome Editing in Australia
Authors: Pandos Olga C 
Published: February 2024

AbstractIn 2018, the birth of the world’s first ‘CRISPR Babies’ rendered the global community in disbelief. This was the catalyst for an international moratorium on Heritable Human Genome Editing (‘HHGE’). For the first time, the international community was prompted to consider a pathway forward to regulate HHGE. In light of the evolving maturity of Clustered Regularly Interspaced Short Palindromic Repeats (‘CRISPR’) as a biotechnology, it is timely to evaluate Australian federal legal and regulatory frameworks governing human genome editing. The response to HHGE must carefully balance the need to prevent unethical applications, against the progress of research to improve and refine the technology. This article argues Australia’s federal legislative regime must be reviewed to ensure it has the necessary capabilities to effectively regulate HHGE. It applies three schools of thought which offer an instructive theoretical lens to understand how Australian law has responded to advancements in technology. In addition, an analysis of the governing federal legislation reveals three regulatory gaps — complexity, operational ambiguity and inconsistent legislative objectives. Together, these gaps may be indicative of a legislative and regulatory landscape that is no longer fit for purpose.
Development of a Job Retention Vocational Rehabilitation Intervention for People with Multiple Sclerosis Following the Person-Based Approach
Authors: De Dios Pérez Blanca , das Nair Roshan , Radford Kathryn 
Published: February 2024

Objective To describe the process of developing a job retention vocational rehabilitation intervention for people with multiple sclerosis. Design We used the person-based approach, to develop interventions through an iterative process incorporating stakeholders’ views, resulting in an intervention that is likely to be more acceptable, contextually relevant, and implementable for end-users. Phase 1 combined the results of a systematic review and interview study to develop the guiding principles and intervention logic model. Phase 2 involved conceptual testing and refining the intervention with stakeholder feedback. We present the final intervention following the template for intervention description and replication. Participants We recruited 20 participants for Phase 1 (10 people with multiple sclerosis, four employers, six healthcare professionals), and 10 stakeholders (three people with multiple sclerosis, seven healthcare professionals) for Phase 2 to contribute to the intervention refinement process. Results Stakeholders described the need for an individually tailored intervention to support people with multiple sclerosis to manage symptoms and workplace relationships. A stepped-care approach and remote support were deemed essential. The resulting intervention involves an initial assessment of employment needs, vocational goal setting, up to 10 h of tailored support (e.g., reasonable adjustments, employer engagement, legal rights), and a final review to discuss future steps. People with multiple sclerosis can include their employer for advice to optimise the management of the employee with multiple sclerosis at work. Conclusion The person-based approach provided a rigorous framework to systematically understand the vocational needs of people with multiple sclerosis and develop a vocational rehabilitation intervention.
Passaged Articular Chondrocytes From the Superficial Zone and Deep Zone Can Regain Zone-Specific Properties After Redifferentiation
Authors: Davis Elizabeth E.R. , Manzoni Thomas J. , Bianchi Vanessa J. , Weber Joanna F. , Wu Po Han , Regmi Suresh C. , Waldman Stephen D. , Schmidt Tannin A. , Su Alvin W. , Kandel Rita A. , Parreno Justin 
Published: February 2024

Background: Bioengineered cartilage is a developing therapeutic to repair cartilage defects. The matrix must be rich in collagen type II and aggrecan and mechanically competent, withstanding compressive and shearing loads. Biomechanical properties in native articular cartilage depend on the zonal architecture consisting of 3 zones: superficial, middle, and deep. The superficial zone chondrocytes produce lubricating proteoglycan-4, whereas the deep zone chondrocytes produce collagen type X, which allows for integration into the subchondral bone. Zonal and chondrogenic expression is lost after cell number expansion. Current cell-based therapies have limited capacity to regenerate the zonal structure of native cartilage. Hypothesis: Both passaged superficial and deep zone chondrocytes at high density can form bioengineered cartilage that is rich in collagen type II and aggrecan; however, only passaged superficial zone–derived chondrocytes will express superficial zone–specific proteoglycan-4, and only passaged deep zone–derived chondrocytes will express deep zone–specific collagen type X. Study Design: Controlled laboratory study. Methods: Superficial and deep zone chondrocytes were isolated from bovine joints, and zonal subpopulations were separately expanded in 2-dimensional culture. At passage 2, superficial and deep zone chondrocytes were seeded, separately, in scaffold-free 3-dimensional culture within agarose wells and cultured in redifferentiation media. Results: Monolayer expansion resulted in loss of expression for proteoglycan-4 and collagen type X in passaged superficial and deep zone chondrocytes, respectively. By passage 2, superficial and deep zone chondrocytes had similar expression for dedifferentiated molecules collagen type I and tenascin C. Redifferentiation of both superficial and deep zone chondrocytes led to the expression of collagen type II and aggrecan in both passaged chondrocyte populations. However, only redifferentiated deep zone chondrocytes expressed collagen type X, and only redifferentiated superficial zone chondrocytes expressed and secreted proteoglycan-4. Additionally, redifferentiated deep zone chondrocytes produced a thicker and more robust tissue compared with superficial zone chondrocytes. Conclusion: The recapitulation of the primary phenotype from passaged zonal chondrocytes introduces a novel method of functional bioengineering of cartilage that resembles the zone-specific biological properties of native cartilage. Clinical Relevance: The recapitulation of the primary phenotype in zonal chondrocytes could be a possible method to tailor bioengineered cartilage to have zone-specific expression.
Competitive Analysis of the Binding Affinity of Montelukast, Zafirlukast and Gemilukast to CysLTR1, P2Y12 and PPAR-γ and their Possible Cardioprotective Effect: Using in silico Methods
Authors: Roy Matrika Saha , Sarkar Bidduth Kumar , Nadvi Md Rohan , Sarkar Arghya Prosun , Kundu Sukalyan Kumar , Ahmed Hossain , Islam Md Jahirul , Sarkar Barno Kumar , Singh Peter , Maitra Tanushree , Hasan Maruf 
Published: February 2024

Background Asthma is a very common respiratory disorder, affecting more than 360 million people worldwide. It is a chronic inflammatory disorder of the airways with the symptoms of shortness of breath, coughing, chest tightness, wheezing, and sometimes chest pain. Leukotrienes play an important role in bronchoconstriction during the allergen or exercise-induced acute asthma attack. Aim The study aims to predict the interactions between leukotriene antagonist drugs and CysLT receptor-1 (CysLTR1), P2Y12 and peroxisome proliferator-activated receptor gamma (PPAR-γ) on a competitive basis. The study also has the objective of understanding the cardioprotective roles of the drugs. Introduction Asthma is strongly linked to the development of acute coronary syndrome by the leukotriene-induced activation of CysLTR1, platelet aggregation and thrombosis by activating P2Y12. PPAR-γ is considered to show benefits against atherosclerosis, diabetes, hypertension, obesity and dyslipidaemia, which are risk factors for the development of cardiovascular disorders. Leukotriene receptor inhibitors act with these three types of receptors to show therapeutic effects. Materials and Methods To predict the possible interactions between the drugs and the receptors, the study has used in silico methods. Results and Discussion Montelukast, Zafirlukast and Gemilukast are potential antagonists of CysLTR1 and P2Y12. They are also responsible for the upregulation of PPAR-γ. Thus, these drugs show a cardioprotective role in asthma-induced cardiac disorders. Conclusion A competitive in silico study of Montelukast, Zafirlukast and Gemilukast to predict their binding to CysLTR1, P2Y12 & PPAR-γ revealed that Montelukast is more effective than the other two drugs for showing a cardioprotective role.
Limited utility of adding 3T cervical spinal cord MRI to monitor disease activity in multiple sclerosis
Authors: Lim Timothy Reynold U , Kumaran Sunitha P , Suthiphosuwan Suradech , Espiritu Adrian I , Jones Ashley , Lin Amy Wei , Oh Jiwon , Bharatha Aditya 
Published: February 2024

Background: Performing routine brain magnetic resonance imaging (MRI) is widely accepted as the standard of care for disease monitoring in multiple sclerosis (MS), but the utility of performing routine spinal cord (SC) MRI for this purpose is still debatable. Objective: This study aimed to measure the frequency of new isolated cervical spinal cord lesions (CSLs) in people with MS (pwMS) undergoing routine brain and cervical SC-MRI for disease monitoring and determine the factors associated with the development of new CSLs and their prognostic value. Methods: We retrospectively identified 1576 pwMS who underwent follow-up 3T brain and cervical SC-MRI over a 9-month period. MRI was reviewed for the presence of new brain lesions (BLs) and CSLs. Clinical records were reviewed for interval relapses between sequential scans and subsequent clinical relapse and disability worsening after the follow-up MRI. Results: In 1285 pwMS (median interval: 13–14 months) who were clinically stable with respect to relapses, 73 (5.7%) had new CSLs, of which 49 (3.8%) had concomitant new BLs and 24 (1.9%) had new isolated CSLs only. New asymptomatic CSLs were associated with ⩾ 3 prior relapses ( p = 0.04), no disease-modifying therapy (DMT) use ( p = 0.048), and ⩾ 3 new BLs ( p < 0.001); ⩾ 3 new BLs (OR: 7.11, 95% CI: 4.3–11.7, p < 0.001) remained independently associated with new CSLs on multivariable analysis. Having new asymptomatic CSLs was not independently associated with subsequent relapse or disability worsening after the follow-up MRI (median follow-up time of 26 months). Conclusion: Routine brain and cervical SC-MRI detected new isolated CSLs in only < 2% of clinically stable pwMS. Developing new asymptomatic CSLs was associated with concomitant new BLs and did not confer an independent increased risk of relapse or disability worsening. Performing SC-MRI may not be warranted for routine monitoring in most pwMS, and performing only brain MRI may be sufficient to capture the vast majority of clinically silent disease activity.
A study on the risk stratification for patients within 24 hours of admission for risk of hospital-acquired urinary tract infection using Bayesian network models
Authors: Jakobsen Rune Sejer , Nielsen Thomas Dyhre , Leutscher Peter , Koch Kristoffer 
Published: February 2024

Early identification of patients at risk of hospital-acquired urinary tract infections (HA-UTI) enables the initiation of timely targeted preventive and therapeutic strategies. Machine learning (ML) models have shown great potential for this purpose. However, existing ML models in infection control have demonstrated poor ability to support explainability, which challenges the interpretation of the result in clinical practice, limiting the adaption of the ML models into a daily clinical routine. In this study, we developed Bayesian Network (BN) models to enable explainable assessment within 24 h of admission for risk of HA-UTI. Our dataset contained 138,250 unique hospital admissions. We included data on admission details, demographics, lifestyle factors, comorbidities, vital parameters, laboratory results, and urinary catheter. Models developed from a reduced set of five features were characterized by transparency compared to models developed from a full set of 50 features. The expert-based clinical BN model over the reduced feature space showed the highest performance (area under the curve = 0.746) compared to the naïve- and tree-augmented-naïve BN models. Moreover, models developed from expert-based knowledge were characterized by enhanced explainability.
The Utilization of Forced-Rate Cycling to Facilitate Motor Recovery Following Stroke: A Randomized Clinical Trial
Authors: Linder Susan M. , Bischof-Bockbrader Andrea , Davidson Sara , Li Yadi , Lapin Brittany , Singh Tamanna , Lee John , Bethoux Francois , Alberts Jay L. 
Published: February 2024

Background The potential for aerobic exercise (AE) to enhance neuroplasticity post-stroke has been theorized but not systematically investigated. Our aim was to determine the effects of forced-rate AE (FE) paired with upper extremity (UE) repetitive task practice (FE + RTP) compared to time-matched UE RTP (RTP only) on motor recovery. Methods A single center randomized clinical trial was conducted from April 2019 to December 2022. Sixty individuals ≥6 months post-stroke with UE hemiparesis were randomized to FE + RTP (N = 30) or RTP only (N = 30), completing 90-minute sessions, 3×/week for 8 weeks. The FE + RTP group underwent 45-minute of FE (5-minute warm-up, 35-minute main set, and 5-minute cool down) followed by 45-minute of UE RTP. The RTP only group completed 90-minute of RTP. Primary outcomes were the Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). The 6-minute Walk Test (6MWT, secondary outcome) assessed walking capacity. Results Sixty individuals enrolled and 56 completed the study. The RTP only group completed more RTP in terms of repetitions (411.8 ± 44.4 vs 222.8 ± 28.4, P < .001) and time (72.7 ± 6.7 vs 37.8 ± 2.4 minutes, P < .001) versus FE + RTP. There was no significant difference between groups on the FMA (FE + RTP, 36.2 ± 10.1-44.0 ± 11.8 and RTP only, 34.4 ± 11.0-41.2 ± 13.4, P = .43) or ARAT (FE + RTP, 32.5 ± 16.6-37.7 ± 17.9 and RTP only, 32.8 ± 18.6-36.4 ± 18.5, P = .88). The FE + RTP group demonstrated greater improvements on the 6MWT (274.9 ± 122.0-327.1 ± 141.2 m) versus RTP only (285.5 ± 160.3-316.9 ± 170.0, P = .003). Conclusions There was no significant difference between groups in the primary outcomes. The FE + RTP improved more on the 6MWT, a secondary outcome. Trial Registration: ClinicalTrials.gov : NCT03819764.
Cause of Extensor Pollicis Longus Ruptures After Distal Radius Fracture Fixation Using a Volar Plate
Authors: Laane Charlotte L. E. , Dijkmans Anjuli L. , Messinger Chelsea J. , Wijffels Mathieu M. E. , Bhashyam Abhiram R. , Chen Neal C. 
Published: February 2024

Background: This research sought to analyze a cohort of patients with extensor pollicis longus (EPL) ruptures after volar locked plating of a distal radius fracture (DRF) to characterize the incidence of ruptures that are unlikely to be related to dorsal screw prominence. Methods: This is a retrospective, observational, descriptive cohort study of adults with operative fixation of a closed DRF and an EPL rupture between 2002 and 2022. Eighteen patients with operative fixation using a volar plate of a closed DRF had an EPL rupture. The cohort consisted of 66% women with an average age of 57.5 years. Median follow-up was 14.5 months. Results: The incidence of EPL rupture was 0.4% (18/4768). The average time from DRF and DRF fixation to EPL rupture was 3.7 and 3.4 months, respectively. Based on the operative record, in 2 of the 18 patients (11%), the rupture was directly attributable to prominent hardware; however, in 4 of the 18 patients (22%), the rupture was not related to prominent hardware, and the cause was indeterminate in 12 patients (67%). Radiologic analysis of those in the indeterminate group demonstrated that 5 of the 12 patients had screws that had a high probability of being prominent. Conclusions: The incidence of EPL rupture after volar plating of DRF is between 0% and 1% and usually occurs about 3 months after fixation. Approximately 50% of EPL ruptures are attributable to prominent dorsal screws. Although screw prominence is an important cause of EPL rupture, it is not the sole cause of rupture.