bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do final-year medical students in Scotland have the knowledge and confidence to deliver the physical activity guidelines? A cross-sectional online survey to evaluate changes over a decade
Authors: Schlegel Isabelle , Ryde Gemma C 
Published: January 2025

ObjectivesThis study assessed knowledge of physical activity (PA) guidelines and confidence to deliver PA advice, across current final-year medical students in Scotland. This follows a 2013 survey finding that this cohort lacked this knowledge and confidence; thus, authors recommended improvements to undergraduate medical PA education and re-evaluation of these measures thereafter.DesignA cross-sectional online survey.SettingThe survey was distributed across four Scottish universities.ParticipantsFinal-year undergraduate medical students; n=166 completed the survey. 69% women, 23.3±1.8 years old and 69% met the PA guidelines.Results27% correctly identified the UK PA guidelines, despite 52% stating awareness of these. While 80% reported receiving PA education, only 20% felt adequately trained to give PA advice to the general population. This study highlights that compared with 2013, more students were aware of PA guidelines and had received training, but fewer could identify the guidelines, and they felt less adequately trained to give PA advice.ConclusionThis study highlights the ongoing need to improve PA in the undergraduate medical curriculum. Future studies should continue to evaluate students' confidence and ability to deliver PA advice to patients as PA training is implemented across UK universities.
The Cambridge Knee Injury Tool (CamKIT): a clinical prediction tool for acute soft tissue knee injuries
Authors: Molloy Thomas , Gompels Benjamin , Castagno Simone , McDonnell Stephen 
Published: January 2025

Background/aimThis study focuses on the development of the Cambridge Knee Injury Tool (CamKIT), a clinical prediction tool developed as a 12-point scoring tool based on a modified e-Delphi study.MethodsA retrospective cohort evaluation was conducted involving 229 patients presenting to a Major Trauma Centre with acute knee pain over 3 months. The evaluation extracted data on the 12 scoring tool variables as well as diagnostic and management pathway outcomes. CamKIT scores for the injured and non-injured cohorts were then calculated and evaluated.ResultsThe CamKIT yielded a median score of 7.5 (IQR: 6–9) in the injured cohort, compared with a median score of 2 (IQR: 1–4) in the non-injured cohort, with a statistically significant difference (p<0.0001). When constructed as a three-tier risk stratification tool, the CamKIT produces a sensitivity of 100%, a specificity of 94.3%, a positive predictive value of 89% and a negative predictive value of 100% for diagnosing clinically significant soft tissue knee injuries.ConclusionThe CamKIT provides a non-invasive tool that has the potential to streamline the diagnostic process and empower healthcare workers in resource-stretched settings by instilling confidence and promoting accuracy in clinical decision-making. The CamKIT also has the potential to support efficiency in the secondary healthcare setting by enabling more targeted and timely use of specialist resources. This research contributes to the ongoing efforts to enhance patient outcomes and the overall quality of care in managing acute knee injuries.
Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma
Authors: Chung Shin-Yi , Yeh Yi-Chen , Huang Chien-Jung , Chiang Nai-Jung , Hsu Dennis Shin-Shian , Chan Ming-Hsien , Lu Meng-Lun , Hsu Tzu-Sheng , Hung Yi-Ping , Yeh Chun-Nan , Hsiao Michael , Chang Yu-Chan , Wang Yu-Chao , Chen Ming-Huang 
Published: January 2025

BackgroundCholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear. This study elucidates their contributions to the TME.MethodsWe examined 16 tumor samples from a single-arm, phase II trial of nivolumab plus modified gemcitabine and S-1 and various datasets. Immunohistochemistry and RNA sequencing were employed to assess TLSs and TILs presence and activity. Differential gene expression and signature of immune cell composition were examined by GeoMx Digital Spatial Profiler and Cancer Transcriptome Altas analysis.ResultsTLS-positive (N=7) patients demonstrated significantly better immunotherapy outcomes compared with TLS-negative (N=9) patients, including higher objective response rates (71% vs 0%) and disease control rates (100% vs 67%). The presence of TLSs correlated with improved progression-free and overall survival (p=0.03). TLSs were associated with “inflamed” tumors characterized by substantial immune infiltration, particularly involving T and B cells. Gene expression analyses identified significant upregulation of B cell-related genes in TLSs. Additionally, TLSs exhibited higher properties of memory B cells and myeloid dendritic cells but lower levels of innate immune cells compared with TILs. T cells within TLSs showed elevated expression of precursor-exhausted-related genes and lower cytotoxicity signature. Furthermore, TILs in TLS-positive tumors had higher levels of exhaustion signatures compared with TILs in TLS-negative tumors. Clinical data corroborated these findings, with higher PD-L1 and LAG-3 expression in TLS-positive tumors.ConclusionOur findings revealed that TILs in TLS-positive tumors have more exhausted T cell signature and PD-1 and LAG-3 protein expression in CCA which support our clinical finding. TLSs can predict favorable immunotherapy responses in patients with cholangiocarcinoma, highlighting their potential as a biomarker and therapeutic target to enhance treatment efficacy.
Combined PARP14 inhibition and PD-1 blockade promotes cytotoxic T cell quiescence and modulates macrophage polarization in relapsed melanoma
Authors: Leshem Rotem , Sefton Kieran Neil , Wong Chun Wai , Lin I-Hsuan , Isaac Dervla Tamara , Niepel Mario , Hurlstone Adam 
Published: January 2025

BackgroundProgrammed cell death 1 (PD-1) signaling blockade by immune checkpoint inhibitors (ICI) effectively restores immune surveillance to treat melanoma. However, chronic interferon-gamma (IFNγ)-induced immune homeostatic responses in melanoma cells contribute to immune evasion and acquired resistance to ICI. Poly ADP ribosyl polymerase 14 (PARP14), an IFNγ-responsive gene product, partially mediates IFNγ-driven resistance. PARP14 inhibition prolongs PD-1 blockade responses in preclinical models, but fails to achieve full tumor clearance, suggesting the involvement of additional resistance mechanisms.MethodsWe identified a robust PARP14 catalytic inhibitor gene signature and evaluated its association with patient survival. Using preclinical models and single-cell RNA sequencing, we investigated immune and tumor cell adaptations to PARP14 inhibition combined with PD-1 blockade.ResultsCombining PARP14 inhibition and PD-1 blockade suppressed tumor-associated macrophages while increasing proinflammatory memory macrophages. Moreover, this combination mitigated the terminal exhaustion of cytotoxic T cells by inducing a quiescent state, thereby preserving functionality. Despite the enhanced immune responses, tumor cells developed adaptive resistance by engaging alternative immune evasion pathways.ConclusionsAlthough adaptive resistance mechanisms re-emerge, PARP14 inhibition combined with PD-1 blockade offers a promising strategy to enhance treatment outcomes and overcome ICI resistance in melanoma, as immune cells are primed for further therapeutic interventions that leverage the quiescent state.
The effects of L-thyroxine and its association with physical exercise decrease the inflammation in an acute lung injury model
Authors: Martha Bianca Andrade , Tonial Giovana Vivan , Luft Carolina , Costa Bruna Pasqualotto , Antunes Géssica Luana , Costa Mariana Severo da , Matzenbacher Lucas Strassburger , Garcia Maria Cláudia Rosa , Oliveira Jarbas Rodrigues de 
Published: January 2025

Acute lung injury (ALI) is an inflammatory disease with a high incidence and prevalence that can lead to death. While L-thyroxine is widely used as a synthetic hormone in the treatment of hypothyroidism, its effects on inflammatory processes are not fully understood. Physical exercise, recommended for the general population, serves as an ally in treating various pathologies. Due to this and the lack of understanding of how L-thyroxine affects the immune response, coupled with the well-known benefits of exercise, this study aimed to evaluate L-thyroxine’s effects on lipopolysaccharide-induced inflammation and its combination with exercise in ALI. We assessed L-thyroxine’s effects on RAW 264.7 cells exposed to LPS and its association with exercise in a mouse ALI model. Pre-treatment with L-thyroxine demonstrated a decrease in the production of reactive oxygen species ( P < 0.01) and the expression of pro-inflammatory genes and proteins ( P < 0.05). In ALI, pre-treatment with L-thyroxine, either alone or combined with exercise, reduced the cell influx ( P < 0.01) and the release of inflammatory cytokines ( P < 0.05), in addition to mitigating lung damage caused by LPS ( P < 0.01). However, combining L-thyroxine with exercise did not enhance its anti-inflammatory effect.
Empowering canine genomics: design and validation of a high-density SNP array for Indian dogs
Authors: Nachiappan Raja Kolandanoor , Arora Reena , Vijh Ramesh Kumar , Sharma Upasna , Raheja Meenal , Sharma Manisha , Maggon Mehak , Ahlawat Sonika 
Published: January 2025

India harbors a substantial population of 9.43 million dogs, showcasing diverse phenotypes and utility. Initiatives focusing on awareness, conservation, and informed breeding can greatly enhance the recognition and welfare of the unique Indian canine heritage. This study describes the design and development of a high-density SNP array for genomic characterization of Indian dogs. Paired-end (150 bp) DNA sequences of 48 samples from four diverse dog populations were generated with 10× coverage, following the standard pipeline of Axiom Array technology for chip design. More than 23 million raw SNPs were initially identified, with 629 597 SNP markers ultimately tiled on the Indian canine array ( Axiom_Shwaan) after stringent filtering and processing. With an inter-marker distance of 3.8 kb the Axiom_Shwaan greatly increases the canine genome coverage. The array was validated by genotyping 186 samples representing 11 dog breeds/populations from India. The high call rate (99%) of SNPs on the designed chip indicates its suitability for use in Indian dog populations, reflecting sufficient genetic diversity. The principal component and phylogenetic analyses delineated the native dog breeds into discrete groups. This high-density SNP array will empower future applications in population genetics, breed/selection signature identification, development of trait-specific biomarkers, and genome-wide data mining for various canine abilities.
Robust integration of dual quaternion approaches, magnetic offsets and screw motion
Authors: Çalışkan Abdussamet 
Published: January 2025

Abstract
In this study, the dual magnetic curves of the corresponding flux surfaces are determined, and the use of these dual curves enables the definition of magnetic offsets. The kinematic properties of these curves are explored, emphasizing their role in describing the motion and transformations of the flux surfaces. The integral invariants of the flux surfaces and developable are investigated by the utilization of the dual magnetic angle between dual magnetic curves. Additionally, we identify connections between Mannheim offsets and spherical images associated with dual quaternions. Furthermore, the study utilizes dual quaternions to perform a geometric and kinematic analysis of magnetic curves and screw motion, providing a comprehensive framework to link magnetic geometry and kinematic motion.
The Effects of Previous Amenorrhea on Endothelial and Vascular Function
Authors: Williford Katherine T. , Frye Emma V. , Kappus Rebecca M. 
Published: January 2025

Introduction: Endogenous estrogen has a protective cardiovascular effect. Estrogen loss, such as during menopause and amenorrhea, results in stiffer vessels and endothelial dysfunction. It is unknown if reversing amenorrhea and regaining a regular menstrual cycle leads to the restoration of cardiovascular function.Methods: Sixteen women were divided into groups: eumenorrheic (n = 10; 23 ± 3 years) women who had a consistent menstrual cycle and amenorrheic (n = 6; 22 ± 1 year) women who previously were without their menstrual cycle for at least 6 consecutive months. Endothelial function, arterial stiffness, and brachial and aortic blood pressure were assessed.Results: There were no differences between groups in endothelial function or arterial stiffness measures. The previously amenorrheic group displayed lower brachial systolic and mean pressures and aortic systolic, diastolic, and mean pressures. When controlling for physical activity, only central pressure remained significantly lower in the amenorrheic group.Conclusions: Previous amenorrhea in young women does not result in long‐term cardiovascular consequences in arterial and endothelial function measures assuming regular menstruation resumes. Physical activity shows a blood pressure–lowering effect in the peripheral arteries, while the previously amenorrheic group demonstrated lower central pressures, independent of physical activity.
Switching to Tumescent Dissection in Mastectomy
Authors: Bakillah Emna , Brooks Ari D. , Adekeye Seye 
Published: January 2025

Introduction: Tumescent dissection (TUM) combines the use of crystalloid, local anesthetic, and epinephrine to create a bloodless plane to raise skin flaps. We aim to compare outcomes of TUM versus standard electrocautery dissection in mastectomies with and without reconstruction.Methods: We conducted a retrospective cohort study of patients who underwent mastectomy by a single surgeon between January 2016 and October 2020 utilizing the electronic medical record. The primary outcome was complication rate, and the secondary outcome was operative time. Chi‐squared analysis and two‐sample t‐tests were used to examine outcomes.Results: Among 242 patients, 141 patients underwent TUM and 101 patients underwent electrocautery. 44.68% of TUM patients experienced one or more complications compared to 59.41% of electrocautery patients (p = 0.024). There were fewer cases of wound healing complications in the TUM group with reconstruction compared to the electrocautery group with reconstruction (6.1% vs. 21%, p = 0.005). Infection rate was higher in the TUM group with reconstruction compared to the electrocautery group with reconstruction (14.3% vs. 3.2%, p = 0.023). There was no significant difference in rates of hematoma, seroma, skin flap necrosis, nipple areolar complex necrosis, or re‐exploration by dissection technique. The mean operative time was shorter with TUM compared to electrocautery (216.09 min vs. 250.16 min, p = 0.016).Conclusion: TUM yields comparable results with decreased overall complication rates compared to electrocautery dissection. Electrocautery thermal effect may account for skin‐related complications. Additionally, tumescent mastectomies have shorter length of operative time which could reduce the risk of complications associated with increased time under general anesthesia.
Cardiovascular Disease Multimorbidity and Decreased Health‐Related Quality of Life in Haiti: A Cross‐Sectional Study
Authors: Sabwa Shalom , Rouzier Vanessa , Sufra Rodney , St. Sauveur Reichling , Mourra Nour , Rasul Rehana , Inddy Joseph , Yan Lily D. , Sterling Madeline , Pinheiro Laura , Deschamps Marie , Pape Jean William , McNairy Margaret L. 
Published: January 2025

Background
Multimorbidity is increasingly prevalent in lower‐ and middle‐income countries. Health‐related quality of life (HRQOL) has been inversely associated with multimorbidity but is understudied in lower‐ and middle‐income countries. We report cardiovascular disease (CVD) multimorbidity in Haiti and its association with HRQOL.

Methods and Results
We used data from the Haiti CVD Cohort, a population‐based longitudinal cohort of adults. CVD multimorbidity was 2+ CVD risk factors/diseases at enrollment. HRQOL was measured using the Short Form‐12, yielding physical component summary/mental component summary scores between 0 and 100, with higher scores indicating better HRQOL. We used linear regressions to assess the association between CVD multimorbidity and HRQOL and individual CVD comorbidities and HRQOL. Additionally, we examined sex and education as potential effect modifiers. Among 2,996 participants, the median age was 40 years (interquartile range [IQR], 27–55), 58.0% were women, and 70.3% earned <1 US dollar per day. CVD multimorbidity prevalence was 24.1%; compared with those without CVD multimorbidity, those with CVD multimorbidity were older (median age, 56.0 years [IQR, 47.0–53.0]) and women (70.5%). Adjusted models revealed CVD multimorbidity was inversely related to physical component summary (−2.7 [95% CI, −3.8 to −1.6]) and mental component summary (−1.0 [95% CI, −1.8 to −0.2]). Heart failure and hypertension showed the strongest CVD morbidities associated with poor HRQOL. In the interaction analysis, among men, CVD multimorbidity was associated with a 4.3‐point lower physical component summary score. Among those with less education, CVD multimorbidity was associated with a 4.6‐point lower physical component summary score than no CVD multimorbidity.

Conclusions
Our data are among the first to describe HRQOL data with high CVD multimorbidity in a young population in urban Haiti, and CVD multimorbidity was associated with decreased HRQOL.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03892265.
Insights Into Causal Effects of Genetically Proxied Lipids and Lipid‐Modifying Drug Targets on Cardiometabolic Diseases
Authors: Fu Liwan , Liu Qin , Cheng Hong , Zhao Xiaoyuan , Xiong Jingfan , Mi Jie 
Published: January 2025

Background
The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships and underlying mechanisms.

Methods
Genetic variants related to lipid profiles and targets for lipid modification were sourced from the Global Lipids Genetics Consortium. Summary data for 10 cardiometabolic diseases were compiled from both discovery and replication data sets. Expression quantitative trait loci data from relevant tissues were employed to evaluate significant lipid‐modifying drug targets. Comprehensive analyses including colocalization, mediation, and bioinformatics were conducted to validate the results and investigate potential mediators and mechanisms.

Results

Significant causal associations were identified between lipids, lipid‐modifying drug targets, and various cardiometabolic diseases. Notably, genetic enhancement of LPL (lipoprotein lipase) was linked to reduced risks of myocardial infarction (odds ratio [OR]
1
, 0.65 [95% CI, 0.57–0.75],
P
1
=2.60×10
−9
; OR
2
, 0.59 [95% CI, 0.49–0.72],
P
2
=1.52×10
−7
), ischemic heart disease (OR
1
, 0.968 [95% CI, 0.962–0.975],
P
1
=5.50×10
−23
; OR
2
, 0.64 [95% CI, 0.55–0.73],
P
2
=1.72×10
−10
), and coronary heart disease (OR
1
, 0.980 [95% CI, 0.975–0.985],
P
1
=3.63×10
−14
; OR
2
, 0.64 [95% CI, 0.54–0.75],
P
2
=6.62×10
−8
) across 2 data sets. Moreover, significant Mendelian randomization and strong colocalization associations for the expression of LPL in blood and subcutaneous adipose tissue were linked with myocardial infarction (OR, 0.918 [95% CI, 0.872–0.967],
P
=1.24×10
−3
; PP.H4, 0.99) and coronary heart disease (OR, 0.991 [95% CI, 0.983–0.999],
P
=0.041; PP.H4=0.92). Glucose levels and blood pressure were identified as mediators in the total effect of LPL on cardiometabolic outcomes.

Conclusions
The study substantiates the causal role of lipids in specific cardiometabolic diseases, highlighting LPL as a potent drug target. The effects of LPL are suggested to be influenced by changes in glucose and blood pressure, providing insights into its mechanism of action.
Poor Olfaction and Risk of Stroke in Older Adults: The Atherosclerosis Risk in Communities Study
Authors: Chamberlin Keran W. , Li Chenxi , Kucharska-Newton Anna , Luo Zhehui , Reeves Mathew , Shrestha Srishti , Pinto Jayant M. , Deal Jennifer A. , Kamath Vidyulata , Palta Priya , Couper David , Mosley Thomas H. , Chen Honglei 
Published: January 2025

BACKGROUND:
Poor olfaction may be associated with adverse cerebrovascular events, but empirical evidence is limited. We aimed to investigate the association of olfaction with the risk of stroke in the Atherosclerosis Risk in Communities Study.

METHODS:
We included 5799 older adults with no history of stroke at baseline from 2011 to 2013 (75.5±5.1 years, 59.0% female and 22.2% Black). Olfaction was assessed by the 12-item Sniffin’ Sticks odor identification test and defined as poor (number correct ≤8), moderate (9–10), or good (11–12). Participants were followed from baseline to the date of the first stroke, death, last contact, or December 31, 2020, whichever occurred first. We used the discrete-time subdistribution hazard model to estimate the marginal cumulative incidence of stroke across olfactory statuses and adjusted risk ratios, accounting for covariates and competing risk of death.

RESULTS:
After up to 9.6 years of follow-up, we identified 332 incident stroke events. The adjusted marginal cumulative incidence of stroke at 9.6-year follow-up was 5.3% (95% CI, 4.2%–6.3%), 5.9% (95% CI, 4.8%–7.1%), and 7.7% (95% CI, 6.5%–9.1%) for good, moderate, and poor olfaction, respectively. Compared with good olfaction, poor olfaction was significantly associated with higher stroke risk throughout follow-up, albeit the association modestly attenuated after 6 years. Specifically, the adjusted risk ratios were 2.14 (95% CI, 1.22–3.94) at year 2, 1.98 (95% CI, 1.43–3.02) at year 4, 1.91 (95% CI, 1.43–2.77) at year 6, 1.49 (95% CI, 1.17–2.00) at year 8, and 1.45 (95% CI, 1.16–1.95) at year 9.6. Results were robust in multiple subgroup and sensitivity analyses.

CONCLUSIONS:
In older adults, poor olfaction assessed by a single olfaction test was associated with the higher risk of stroke in the next 10 years.