bluuebunny/crossref_metadata_2025_split huggingface dataset:
Level of Expression of MHCI-Presented Neoepitopes Influences Tumor Rejection by Neoantigen-Specific CD8+ T Cells
Authors: Deng Li , Walsh Scott R. , Nguyen Andrew , Inkol Jordon M. , Westerveld Michael J. , Chen Lan , El-Sayes Nader , Mossman Karen L. , Workenhe Samuel T. , Wan Yonghong 
Published: October 2024

Abstract
Neoantigen-targeted therapy holds an array of benefits for cancer immunotherapy, but the identification of peptide targets with tumor rejection capacity remains a limitation. To better define the criteria dictating tumor rejection potential, we examined the capacity of high-magnitude T-cell responses induced toward several distinct neoantigen targets to regress MC38 tumors. Despite their demonstrated immunogenicity, vaccine-induced T-cell responses were unable to regress established MC38 tumors or prevent tumor engraftment in a prophylactic setting. Although unable to kill tumor cells, T cells showed robust killing capacity toward neoantigen peptide–loaded cells. Tumor-cell killing was rescued by saturation of target peptide–loaded MHCs on the cell surface. Overall, this study demonstrates a pivotal role for target protein expression levels in modulating the tumor rejection capacity of neoantigens. Thus, inclusion of this metric, in addition to immunogenicity analysis, may benefit antigen prediction techniques to ensure the full antitumor effect of cancer vaccines.
Defining Cardiomyocyte Repolarization Response to Pharmacotherapy in Long‐QT Syndrome Type 3
Authors: Ge Ning , Li Rui , Liu Min , Xia Wenxin , O'Brien Stephen T. , McInerney Veronica , Galvin Joseph , Ward Deirdre , McGorrian Catherine , O'Brien Timothy , Shen Sanbing , Prendiville Terence W. 
Published: October 2024

Background
Long‐QT syndrome is a primary cardiac ion channelopathy predisposing a patient to ventricular arrhythmia through delayed repolarization on the resting ECG. We aimed to establish a patient‐specific, human induced pluripotent stem cell (hiPSC)‐derived cardiomyocytes model of long‐QT syndrome type 3 (LQT3) using clustered regularly interspaced palindromic repeats (CRISPR/Cas9), for disease modeling and drug challenge.

Methods and Results

HiPSCs were generated from a patient with LQT3 harboring an
SCN5A
pathogenic variant (c.1231G>A; p.Val411Met), and an unrelated healthy control. The same
SCN5A
pathogenic variant was engineered into the background healthy control hiPSCs via CRISPR/Cas9 gene editing to generate a second disease model of LQT3 for comparison with an isogenic control. All 3 hiPSC lines were differentiated into cardiomyocytes. Both the patient‐derived LQT3 (
SCN5A
+/−
) and genetically engineered LQT3 (
SCN5A
+/−
) hiPSC‐derived cardiomyocytes showed significantly prolonged cardiomyocyte repolarization compared with the healthy control. Mexiletine, a cardiac voltage‐gated sodium channel (Na
V
1.5) blocker, shortened repolarization in both patient‐derived LQT3 and genetically engineered LQT3 hiPSC‐derived cardiomyocytes, but had no effect in the control. Notably, calcium channel blockers nifedipine and verapamil showed a dose‐dependent shortening of repolarization, rescuing the phenotype. Additionally, therapeutic drugs known to prolong the corrected QT in humans (ondansetron, clarithromycin, and sotalol) demonstrated this effect in vitro, but the LQT3 clones were not more disproportionately affected compared with the control.

Conclusions
We demonstrated that patient‐derived and genetically engineered LQT3 hiPSC‐derived cardiomyocytes faithfully recapitulate pathologic characteristics of LQT3. The clinical significance of such an in vitro model is in the exploration of novel therapeutic strategies, stratifying drug adverse reaction risk and potentially facilitating a more targeted, patient‐specific approach in high‐risk patients with LQT3.
[18F]PI-2620 Tau PET signal across the aging and Alzheimer’s disease clinical spectrum
Authors: Young Christina B. , Vossler Hillary , Romero America , Smith Viktorija , Park Jennifer , Trelle Alexandra N. , Winer Joseph R. , Wilson Edward N. , Zeineh Michael M. , Sha Sharon J. , Khalighi Mehdi , Yutsis Maya V. , Morales Aimara P. , Anders David , Zaharchuk Greg , Henderson Victor W. , Andreasson Katrin I. , Wagner Anthony D. , Poston Kathleen L. , Davidzon Guido A. , Mormino Elizabeth C. 
Published: October 2024

Abstract
[18F]PI-2620 is a second generation tracer that has shown high binding affinity for tau aggregation in Alzheimer’s disease (AD). However, [18F]PI-2620 signal in a large sample spanning the healthy aging and AD clinical spectrum as well as the stability of signal across different acquisition time windows has not yet been examined. Here, amyloid negative (Aβ-) cognitively unimpaired (CU; n = 49), amyloid positive (Aβ+) CU (n = 37), CU individuals with unknown amyloid status (n = 5), mild cognitive impairment (MCI; n = 14), dementia due to AD (n = 19), and non-AD neurodegenerative disorder (n = 54) participants were scanned with [18F]PI-2620 using a 45–75 min and/or 60–90 min acquisition time window. The impact of acquisition time on standardized uptake value ratio (SUVR) magnitude was first quantified with linear mixed models, and in participants and regions with high [18F]PI-2620 signal, SUVRs increased linearly up to 0.04 SUVR with each additional 5 min past injection time. We then accounted for differences in acquisition time using a voxel-wise correction approach and showed high correlations (all r’s ≥ 0.986) between SUVRs calculated from 45–75 min data and SUVRs from 60–90 min data that were interpolated to the 45–75 min scale in 15 participants who were scanned across both time windows. Using real and interpolated 45–75 min data, we next examined [18F]PI-2620 signal in Braak regions of interest and an off-target binding region (putamen) in Aβ- and Aβ+ CU, Aβ+ MCI, and Aβ+ AD dementia (n = 115) and showed that SUVRs in all Braak regions increased with greater disease severity. Within CU, higher Braak I SUVR was significantly associated with greater CSF pTau-181 (n = 35), and higher SUVRs were significantly associated with worse memory and language (n = 57). Thus, voxel-wise acquisition time corrections can be applied to combine [18F]PI-2620 datasets collected at different post-injection times, and once acquisition time is accounted for, [18F]PI-2620 signal shows the expected increases across the AD spectrum and can be used for detection of early tau elevations.
Crashworthiness study of polyamide bi-tubular thin-walled tubes using hybrid lattice filling
Authors: Kandasamy Mohan Kumar , Ganesan Arumaikkannu 
Published: October 2024

Thin-Walled Tubes (TWT) are widely used as crashworthiness elements to absorb and dissipate kinetic energy during collision through plastic deformation. Various design strategies, including nested tubes, triggers, and filling with lattices, are commonly used to enhance the crashworthiness of TWT. Additive Manufacturing (AM) offers unique opportunities to produce complex lattice-filled TWT with higher precision, but challenges persist in the design and fabrication of bi-tubular TWT to enhance crashworthiness. The aim of this study is to propose an approach for hybrid lattice filling in bi-tubular structures. In the preliminary phase, the parametric study was conducted to understand the influence of tube cross-section geometry, thickness, and trigger hole diameter on the crashworthiness of empty TWT using Taguchi’s L9 orthogonal array. Empty TWTs were fabricated using Selective Laser Sintering (SLS) with PA12 material and compressed uni-axially at 8 mm/min speed. In the second phase, bi-tubular TWT was filled with three different unit cells such as Cube, Kelvin, and Octet Truss (OT) having 30% relative density. In the lattice filling approach, two different strategies were followed such as uniform and hybrid lattice filling. Designed TWTs were fabricated and tested under uni-axial compression at two different speeds such as 8 mm/min and 8 mm/sec. Based on the results of the preliminary study, it has been observed that cross-section geometry and tube thickness significantly enhance SEA through an increase in the stiffness and number of folding. With the help of the Signal to Noise (S/N) ratio graph, appropriate levels were selected as input for the hybrid lattice-filling approach. The results of the second phase revealed that hybrid lattice filling significantly enhances the deformation modes, energy absorption, and crashworthiness properties of TWTs. Hybrid lattice-filled TWT offers better Specific Energy Absorption (SEA) as 18.32 kJ/kg at 8 mm/sec compression speed, which is 113.9% higher than empty and 42.8% higher than uniform lattice-filled TWT. This work demonstrated that adopting the hybrid lattice-filling approach is one of the potential ways to enhance the crashworthiness of protective equipment such as crash boxes and frames.
Development of in situ forming autologous fibrin scaffold incorporating synthetic teriparatide peptide for bone tissue engineering
Authors: Khalili Mohammad Reza , Molafilabi Azam , Mousazadeh Sepideh , Mehrabi Arezou , Kiani Jafar , Brouki Milan Peiman , Ghasemi Faezeh 
Published: October 2024

Introduction: This study investigates the potential of an in-situ forming scaffold using a fibrin-based scaffold derived from autologous plasma combined with Synthetic Teriparatide (TP) for bone regeneration application. TP is known for its bone formation stimulation but has limited clinical use due to side effects. This autologous delivery system aims to provide precise, controlled, localized, and long-term release of TP for accelerating bone regeneration. Methods: Fibrinogen from autologous plasma was extracted using ethanol, and thrombin was precipitated with ammonium sulfate to create the fibrin scaffold. Characterization of fibrinogen was done through FTIR, SDS-Page, porosity, SEM, degradation, and rheology tests. Viability was assessed by MTT in five groups with different concentrations of TP in fibrin scaffold (50, 100, and 150 µl/ml), fibrin alone, and a control group against HEK and Wharton’s jelly cells. The release profile of different concentrations of TP in the fibrin scaffold was also examined. Results: The formation time of the fibrin scaffold was 4 ± 0.2 s. The highest Infrared absorption for fibrinogen was confirmed. Rheology assessment revealed a higher elastic modulus than the viscous modulus. The created fibrin scaffold displayed a consistent three-dimensional microstructure with an interconnected porous network. Cytotoxicity assays demonstrated good biocompatibility and enhanced cell growth with different concentrations of TP in the fibrin scaffold. The TP release increased with higher concentrations, peaking at an average of 61% over 54 h. Conclusion: Autologous plasma-derived fibrin scaffolds incorporating TP exhibit satisfactory release within the scaffold and hold promise as a versatile bone filler for clinical use, facilitating osteoregeneration.
Sarcoma or haematoma? If only it was that simple! Part 2
Authors: Berry Catharine , Charnock Mark 
Published: October 2024

Introduction: Imaging appearances and clinical presentation of soft tissue sarcoma and soft tissue haematomas are similar. It is imperative that sarcoma is differentiated from benign soft tissue lesions due to the poor outcomes and high morbidity associated with sarcoma. Topic Description: Part 2 of this pictorial review summarises the key ultrasound appearances of soft tissue sarcoma and soft tissue haematomas and some differential diagnoses. Discussion: Ultrasound is the first line test in the investigation of soft tissue masses. With the overlapping ultrasound appearances of soft tissue sarcoma and soft tissue haematomas, it is essential that practitioners are aware of key ultrasound appearances and understand when to escalate cases for further investigation. Conclusion: Sound knowledge of the clinical and sonographic features of soft tissue haematomas and soft tissue sarcoma as well as recognising potential differential diagnoses is fundamental to ensuring an accurate diagnosis, timely management and improved patient outcomes.
Amputation versus circular external fixation in the treatment of diabetic foot with osteomyelitis: a cost and quality-of-life analysis
Authors: López Capdevilla Laia , Santamaría Fumas Alejandro , Sales Pérez José Miguel , Domínguez Sevilla Alejandro , del Corral Cuervo Julio , Varela-Quintana Carlos , Rabanal Rubio María , Roza Miguel Pablo 
Published: October 2024

Background: Charcot foot is a severe complication of diabetes mellitus. Amputation is associated with 5-year mortality rates as high as 70%, and the overall treatment cost for diabetic foot surpasses that of conditions such as cancer or depression. Objectives: To compare clinical, quality-of-life, and cost outcomes related to Charcot foot management through two distinct treatments: amputation and resection with stabilization using circular external fixation (CEF). Methods: This retrospective study included all adult patients treated at our unit between 2008 and 2022 for acute diabetic foot with infected ulcers. The allocation to treatment groups was based on the timing of patient enrollment. We gathered anthropometric, diagnostic, and surgical data, documenting individualized costs for preoperative, postoperative, and rehabilitation phases. Health status was assessed using the EQ-5D-3L questionnaire, and recorded data included mortality. Results: A total of 31 patients (18 amputations; 13 CEF) were included. Amputees exhibited significantly higher mortality compared to those with a CEF (44.8% vs 7.7%, p = 0.045). The estimated 3-year survival was 60.8% for amputees and 90% for the CEF group (log-rank test, p = 0.096). In terms of quality of life (EQ-5D-3L), amputees reported a reduction of 14.67 points while CEF patients reported an increase of 40.39 points ( p < 0.001). The EQ-5D-3L index improved by 1.8 points for amputees, as compared with 62.3 points in the CEF group ( p < 0.001). The total mean cost of managing an amputated patient was €222,864, practically identical to the €224,438 incurred in the CEF group ( p = 0.767). No statistically significant differences were found in the time distribution of costs. However, some specific expense items demonstrated statistical significance. Conclusion: In treating infected diabetic foot ulcers, external fixation leads to a better quality of life compared to amputation. There’s also a trend suggesting higher survival rates with external fixation, and both approaches have similar costs.
The quality and reliability of short videos about thyroid nodules on BiliBili and TikTok: Cross-sectional study
Authors: Chen Yuying , Wang Qianyu , Huang Xuanwei , Zhang Yu , Li Yuanhui , Ni Tianyu , Pan Gang , Luo Dingcun , Ni Yeqin 
Published: October 2024

Background The detection rate of thyroid nodules has witnessed a significant surge in recent years, triggering heightened public apprehension. Short video platforms such as TikTok and BiliBili have showed tremendous potential in the dissemination of health information. There is a plethora of videos about thyroid nodules on TikTok and BiliBili, but the quality and reliability of videos concerning thyroid nodules remains unknown. Methods On December 3rd, 2023, the top 100 short videos related to thyroid nodules on BiliBili and TikTok were collected through a comprehensive search in Chinese. After extracting the basic information, the quality and reliability of each video was assessed by using the global quality score (GQS) and DISCERN score. Further, Spearman correlation analyses were applied to examine the correlation among video variables, GQS and DISCERN score. Results Compared to BiliBili, TikTok exhibits greater popularity, as evidenced by higher counts of likes ( P = 0.021), comments ( P = 0.008) and shares ( P = 0.017). The median (interquartile range) scores of GQS and DISCERN score were 3 (2–3) on TikTok while 2 (2–3) on BiliBili. Both reviewers exhibited good consistency in GQS and DISCERN score. Moreover, it was observed that the videos shared by thyroid specialists demonstrated higher scores both in GQS ( P = 0.014) and DISCERN score ( P = 0.022) than others on TikTok. Spearman correlation analysis revealed no significant correlation between video variables and the scores of GQS and DISCERN score. Conclusions The quality and reliability of thyroid nodules videos on BiliBili and TikTok were unsatisfactory. Notably, videos shared by thyroid specialists are more likely to exhibit superior quality and reliability. People should exercise caution when perusing short videos.
Piloting the Impact of an e-Learning on Knowledge About HIV Prevention and Prophylaxis Among General Practitioners in Belgium
Authors: Van Oost Niels , Van Raemdonck Annelies , Schoenmakers Birgitte 
Published: October 2024

INTRODUCTION The Joint United Nations Program on HIV/AIDS (UNAIDS) has set a goal to eliminate AIDS as a public health threat by 2030 and the World Health Organization emphasized pre-exposure prophylaxis (PrEP) as a crucial element. Despite the lack of a specific role for general practitioners (GPs) in PrEP care, GPs could play a crucial role in the follow-up but this is still uncommon. Above, GPs estimate their knowledge about PrEP as low. OBJECTIVES This study seeks to understand the knowledge of GPs regarding PrEP care. Through online e-learning, we aimed to enhance our knowledge of PrEP care. METHODS Firstly, we assessed general knowledge about the PrEP of GPs. Secondly, we investigated the impact of e-learning on knowledge of PrEP care among GPs. We developed a multiple-choice questionnaire to evaluate self-assessed knowledge and knowledge about PrEP. One group of participants completed an e-learning module and took a pre- and post-test to assess changes in knowledge. Another group completed the questionnaire without e-learning. RESULTS Seventy-two participants completed the survey. Finally, 18 participants successfully completed the e-learning module. Nineteen percent ( n = 14) of all GPs considered their general knowledge of PrEP to be “good,” while 68% ( n = 49) of the GPs felt confident in identifying patients at risk, rating their ability as “good.” Participants achieved an average score of 4.7 (test group) and 4.6 (e-learning group) out of 10 on the knowledge test. After completion of the e-learning, the overall average score of the e-learning group significantly increased by 33% ( p-value < .03). CONCLUSIONS GP generally scored low on knowledge covering different aspects of PrEP. However, after completing an e-learning module, there was a significant increase in the average test scores. These findings highlight the potential efficacy of targeted educational interventions in enhancing the understanding of PrEP among GPs.
Where are the values in evaluating palliative care? Learning from community-based palliative care provision
Authors: Whitelaw Sandy , Vijay Devi , Clark David 
Published: October 2024

Background: The World Health Organization Astana Declaration of 2018 sees primary healthcare as key to universal health coverage and gives further support to the goal of building sustainable models of community palliative care. Yet evaluating the benefits of such models continues to pose methodological and conceptual challenges. Objective: To explore evaluation issues associated with a community-based palliative care approach in Kerala, India. Design: An illuminative case study using a rapid evaluation methodology. Methodology: Qualitative interviews, documentary analysis and observations of home care and community organising. Results: We appraise a community palliative care programme in Kerala, India, using three linked ‘canvases’ of enquiry: (1) ‘complex’ multi-factorial community-based interventions and implications for evaluation; (2) ‘axiological’ orientations that foreground values in any evaluation process and (3) the status of evaluative evidence in postcolonial contexts. Three values underpinning the care process were significant: heterogeneity, voice and decentralisation. We identify ‘objects of interest’ related to first-, second- and third-order outcomes: (1) individuals and organisations; (2) unintended targets outside the core domain and (3) indirect, distal effects within and outside the domain. Conclusion: We show how evaluation of palliative care in complex community circumstances can be successfully accomplished when attending to the significance of community care values.
The effect of Oleoylethanolamide supplementation on lipid profile, fasting blood sugar and dietary habits in obese people: a randomized double-blind placebo-control trial
Authors: Ostadrahimi Alireza , Khajebishak Yaser , Moradi Fardin , Payahoo Laleh 
Published: October 2024

Abstract
Background
Abnormalities in biochemical parameters and changes in eating habits are considered complications of obesity. Oleoylethanolamide (OEA), an endocannabinoid-like compound, has been shown to have protective effects on many metabolic disorders. Given this evidence, the present study aimed to assess the effects of OEA on lipid profile parameters, fasting blood sugar (FBS), and dietary habits in healthy obese people.

Methods
In this randomized, double-blind, placebo-controlled clinical trial, which was carried out in 2016 in Tabriz, Iran, 60 obese people were enrolled in the study based on inclusion criteria. The intervention group consumed 125 mg of OEA capsules, and the placebo group received the same amount of starch twice for 8 weeks. Blood samples (5 mL) were taken at baseline and the end of the study in a fasting state. Serum concentrations of FBS, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC) were measured by enzymatic methods using commercial kits. The low-density lipoprotein cholesterol (LDL-C) concentration was obtained using the Friede-Wald formula. To assess dietary habits, a food frequency questionnaire (147 items) was used at baseline and the end of the study. A value less than < 0.05 was considered to indicate statistical significance.

Results
The TG concentration decreased significantly in the intervention group (mean (SD): 166.29 (70.01) mg/dL to 142.22 (48.05) mg/dL, p = 0.047). Changes in the placebo group were not significant (p > 0.05). After adjusting for baseline values and demographic characteristics, the difference in TG between groups remained significant (p = 0.044). Changes in other biochemical parameters were not significant. There was no significant difference between or within groups in terms of food groups.

Conclusion
OEA, as a complementary agent, plays a protective role in TG regulation. However, future studies with longer durations are needed to explore the impact of OEA on regulating dietary habits and to identify the mechanisms related to metabolic abnormalities in obese people.

Trial Registration
The study was registered in the Iranian Registry of Clinical Trials (IRCT) center as IRCT201607132017N30 with URL. www.IRCT.IR in date 03/10/2016.