bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study
Authors: Escuriola-Ettingshausen Carmen , Klamroth Robert , Escobar Miguel , Stasyshyn Oleksandra , Tangada Srilatha , Engl Werner , Honauer Ivan , Lee Hye-Youn , Chowdary Pratima , Windyga Jerzy 
Published: July 2023

Background: The phase 3, prospective PROPEL study demonstrated that pharmacokinetic (PK)-guided prophylaxis targeting elevated factor VIII (FVIII) troughs in patients with hemophilia A resulted in lower annualized bleeding rates (ABRs) and a higher proportion of patients experiencing zero bleeds in the second 6 months of treatment when targeting a FVIII trough of 8–12% versus 1–3%. Objective: To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a post hoc analysis using data from PROPEL. Design: This is a post hoc analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously. Methods: This post hoc analysis reports data stratified by FVIII half-life ( t1/2), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry. Results: Targeting an elevated FVIII trough of 8–12% was associated with higher average FVIII levels over time, regardless of FVIII t1/2 at baseline. The decrease in total ABR between the 8–12% and 1–3% arms was greatest in patients with a FVIII t1/2 of 6 to <12 h (0.7 versus 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 versus 1.6); the presence of arthropathy (0.1 versus 1.7); and those previously treated on-demand (0.3 versus 1.8). Conclusion: These results support the feasibility of targeting elevated FVIII levels using personalized rurioctocog alfa pegol prophylaxis. These benefits may be especially important in patients with a short FVIII t1/2 and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints. Registration: ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960
Generalizing factors of COVID-19 vaccine attitudes in different regions: A summary generation and topic modeling approach
Authors: Liu Yang , Shi Jiale , Zhao Chenxu , Zhang Chengzhi 
Published: July 2023

Objective The goal of this study is to use summary generation and topic modeling to identify factors contributing to vaccine attitudes for three different vaccine brands, with the aim of generalizing these factors across different regions. Methods A total of 5562 tweets about three vaccine brands (Sinovac, AstraZeneca, and Pfizer) were collected from 14 December 2020 to 30 December 2021. BERTopic clustering is used to group the tweets into topics, and then contrastive learning (CL) is adopted to generate summaries of each topic. The main content of each topic is generalized into three factors that contribute to vaccine attitudes: vaccine-related factors, health system-related factors, and individual social attributes. Results BERTopic clustering outperforms Latent Dirichlet Allocation clustering in our analysis. It can also be found that using CL for summary generation helped to better model the topics, particularly at the center-point of the clustering. Our model identifies three main factors contributing to vaccine attitudes that are consistent across different regions. Conclusions Our study demonstrates the effectiveness of deep learning methods for identifying factors contributing to vaccine attitudes in different regions. By determining these factors, policymakers and medical institutions can develop more effective strategies for addressing concerns related to the vaccination process.
The Hybrid Transtibial Technique Using the LARS Device in Primary Anterior Cruciate Ligament Reconstruction
Authors: Huang Xian-Cheng , Wang Shuang , Li Jia-Tong , Lu Wen-Qian , Luo Yong , Yang Qing-Jun , Zhang Xin-Tao , You Tian 
Published: July 2023

Background: The recently published hybrid transtibial technique (HTT) using the Pathfinder Guide with a flexible transtibial technique (TT) guide wire may represent a beneficial combination of both the anteromedial portal and TT technique. The HTT has been described as especially suitable for anterior cruciate ligament (ACL) reconstruction in adolescents or ACL revision. However, we also found that the HTT worked for primary ACL reconstruction in adults also using the Ligament Advanced Reinforcement System (LARS). Indications: Acute ACL rupture in active patients who are eager to return to sports quickly. Technique Description: The HTT combined with the conventional LARS reconstruction procedure improves the placement of the femoral tunnel, which involves a guiding vessel clamp through the anteromedial portal combined with a 2.0 mm Kirschner wire via the tibial tunnel. Finally, we used a metal screw for fixation of the ligament. Results: The patient experienced satisfactory reconstruction of his ACL and regained active range of motion in 1 month and a full return to sports in 6 months. Discussion/Conclusion: The HTT using the LARS for primary ACL reconstruction is easy, safe, and reproducible. This combined technique has not yet been published and it may provide good functional results that allow patients to recover quickly and return to sports as soon as possible. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
MYD88L265P augments proximal B-cell receptor signaling in large B-cell lymphomas via an interaction with DOCK8
Authors: Mandato Elisa , Yan Qingsheng , Ouyang Jing , Paczkowska Julia , Qin Yan , Hao Yansheng , Bojarczuk Kamil , Hansen Julia , Chapuy Björn , Rodig Scott J. , Khan Sumbul Jawed , Redd Robert A. , Shipp Margaret A. 
Published: July 2023

Abstract
Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease with at least 5 recognized molecular subtypes. Cluster 5 (C5)/MCD tumors frequently exhibit concurrent alterations in the toll-like receptor (TLR) and B-cell receptor (BCR) pathway members, MYD88L265P and CD79B, and have a less favorable prognosis. In healthy B cells, the synergy between TLR and BCR signaling pathways integrates innate and adaptive immune responses and augments downstream NF-κB activation. In addition, physiologic TLR9 pathway engagement via MYD88, protein tyrosine kinase 2 (PYK2), and dedicator of cytokinesis 8 (DOCK8) increases proximal BCR signaling in healthy murine B cells. Although C5/MCD DLBCLs are selectively sensitive to Bruton tyrosine kinase (BTK) inhibition in in vitro studies and certain clinical trials, the role of mutated MYD88 in proximal BCR signaling remains undefined. Using engineered DLBCL cell line models, we found that concurrent MYD88L265P and CD79B alterations significantly increased the magnitude and duration of proximal BCR signaling, at the level of spleen tyrosine kinase and BTK, and augmented PYK2-dependent DOCK8 phosphorylation. MYD88L265P DLBCLs have significantly increased colocalization of DOCK8 with both MYD88 and the proximal BCR-associated Src kinase, LYN, in comparison with MYD88WT DLBCLs, implicating DOCK8 in MYD88L265P/proximal BCR cross talk. Additionally, DOCK8 depletion selectively decreased proximal BCR signaling, cellular proliferation, and viability of DLBCLs with endogenous MYD88L265P/CD79BY196F alterations and increased the efficacy of BTK blockade in these lymphomas. Therefore, MYD88L265P/DOCK8-enhanced proximal BCR signaling is a likely mechanism for the increased sensitivity of C5/MCD DLBCLs to BTK blockade.
The role of the MDM2/p53 axis in antitumor immune responses
Authors: Brummer Tilman , Zeiser Robert 
Published: July 2023

Abstract
Mouse double minute 2 homolog (MDM2) is a negative regulator of the tumor suppressor p53 and is often highly expressed in acute myeloid leukemia (AML) and other solid tumors. Inactivating mutations in TP53, the gene encoding p53, confers an unfavorable prognosis in AML and increases the risk for relapse after allogeneic hematopoietic cell transplantation. We review the concept that manipulation of MDM2 and p53 could enhance immunogenicity of AML and solid tumor cells. Additionally, we discuss the mechanisms by which MDM2 and p53 regulate the expression of major histocompatibility complex class I and II, transcription of double stranded RNA of endogenous retroviruses, responses of interferons, production of interleukin-15, and expression of tumor necrosis factor–related apoptosis–inducing ligand receptor 1 and 2 on malignant cells. The direct effects of MDM2 inhibition or MDM2 deletion in effector T cells are discussed in the context of cancer immunotherapy. The preclinical findings are connected to clinical studies using MDM2 inhibition to enhance antitumor immunity in patients. This review summarizes current evidence supporting the use of MDM2 inhibition to restore p53 as well as the direct effects of MDM2 inhibition on T cells as an emerging concept for combined antitumor immunotherapy against hematological malignancies and beyond.
Chemical restraint as behavioural euthanasia: case studies from the Royal Commission into Aged Care Quality and Safety
Authors: Cain Patricia , Chejor Pelden , Porock Davina 
Published: July 2023

AbstractBackgroundThe prescription of psychotropic medication to older people living with dementia in residential aged care has become an increasing concern. The use of prescription medication is often prefaced as a way of preventing harm to self and others. However, the use of such medications has been considered a way of managing some of the behavioural and psychological symptoms of dementia. Using a large secondary data set, this study aimed to identify the precursors and mediating factors that influence the use of chemical restraint of older people in residential aged care.MethodsPublicly available documents from the Australian Royal Commission into Aged Care Quality and Safety were used as the data corpus for this study. Keywords were used to search over 7000 documents to extract a set of topic-related content. We identified the cases of seven people in respite or permanent residential aged care who had been prescribed or administered psychotropic medication under circumstances that appeared to demonstrate chemical restraint. All documents relating to the cases were collated for our data set. A descriptive case study approach to analysis was taken.ResultsFour key descriptive patterns were identified: labelling and limits to tolerance, pushing prescription as a solution, coverups and avoiding consent, and family’s fight for liberty. Triangulation across the data and academic literature supports the findings.ConclusionOur findings provide some insight into how chemical restrain happens. Featuring throughout the cases were reports of a lack of workforce capacity to care for and support residents exhibiting dementia behaviours. Prescription of psychotropic medications featured as a “first resort” care solution. Family and friends found such approaches to care unacceptable and frequently challenged the practice. Where consent for prescription was explicitly denied, more covert approaches are demonstrated. Family awareness, presence, and advocacy were key to challenging the practice of chemical restraint. Shortfalls in the capacity of the current workforce come into play here. However, workforce shortcomings can no longer mask this ubiquitous practice. Just as importantly the spotlight needs to be turned on the prescribers and the providers.
The global prevalence of sexual dysfunction in obese and overweight women: a systematic review and meta-analysis
Authors: Salari Nader , Hasheminezhad Razie , Sedighi Tabassom , Zarei Hosna , Shohaimi Shamarina , Mohammadi Masoud 
Published: July 2023

Abstract
Background
Obesity is a pressing public health risk issue worldwide. Women, in particular, face a higher risk of obesity. Recent research has highlighted the association between obesity and female sexual dysfunction. Therefore, the objective of this study is to investigate the global prevalence of sexual dysfunction in obese and overweight women through a systematic review and meta-analysis.

Methods
In this study, a systematic search was conducted across electronic databases, including PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar. The search aimed to identify studies published between December 2000 and August 2022 that reported metabolic syndrome's impact on female sexual dysfunction.

Results
The review included nine studies with a sample size of 1508 obese women. The I2 heterogeneity index indicated high heterogeneity (I2: 97.5). As a result, the random effects method was used to analyze the data. Based on this meta-analysis, the prevalence of sexual dysfunction in women with obesity was reported as 49.7% (95%CI: 35.8–63.5). Furthermore, the review comprised five studies involving 1411 overweight women. The I2 heterogeneity test demonstrated high heterogeneity (I2: 96.6). Consequently, the random effects model was used to analyze the results. According to the meta-analysis, the prevalence of sexual dysfunction in overweight women was 26.9% (95% CI: 13.5–46.5).

Conclusion
Based on the results of this study, it has been reported that being overweight and particularly obese is an important factor affecting women's sexual dysfunction. Therefore, health policymakers must acknowledge the significance of this issue in order to raise awareness in society about its detrimental effect on the female population.
Knowledge, behaviours, and training related to 2SLGBTQIA+ health education amongst entry-level physiotherapy students in Canada: results of a nationwide, cross-sectional survey
Authors: Primeau Codie A. , Philpott Holly T. , Vader Kyle , Unger Janelle , Le Christina Y. , Birmingham Trevor B. , MacDermid Joy C. 
Published: July 2023

AbstractBackgroundIndividuals who identify as 2SLGBTQIA+ report worse health outcomes than heterosexual/cisgender counterparts, in part due to poor experiences with healthcare professionals. This may stem from inadequate 2SLGBTQIA+ health and inclusiveness training in health professional student education. The purpose of the study was to evaluate knowledge, behaviours, and training related to 2SLGBTQIA+ health education and inclusiveness for entry-level physiotherapy students in Canada.MethodsWe conducted a nationwide, cross-sectional survey with physiotherapy students from accredited Canadian physiotherapy programs. We administered the survey through Qualtrics and recruited students through targeted recruitment emails and social media posts on Twitter and Instagram between August and December 2021. Survey responses are reported as frequencies (percentage). We also completed multivariable logistic regressions to evaluate associations among question responses related to working with 2SLGBTQIA+ individuals (i.e., communication, feeling prepared and assessment competency). Covariates included training hours (< 10/10 + hours) and 2SLGBTQIA+ identity (yes/no).ResultsA total of 150 students responded to the survey, with 35 (23%) identifying as 2SLGBTQIA+ . Many students felt confident in communicating effectively with clients who identify as 2SLGBTQIA+ (69%). However, only half (47%) felt comfortable assessing clients who identify as 2SLGBTQIA+ . Routine practice of inclusive behaviours such as using pronouns, considering identities are fluid and a patient’s gender identity and/or sexual orientation may shift from one visit to the next, and considering trauma-informed care practices were reported from less than half of the students (< 45%). Around 29% of students reported no 2SLGBTQIA+ training in their physiotherapy program, while 47% reported 0–10 hours, and 24% reported 10 + hours of training. Students with 10 + hours of training had 92% higher odds of feeling competent in assessing 2SLGBTQIA+ clients, compared to those with < 10 hours of training.ConclusionsEntry-level physiotherapy students in Canada show a lack of understanding and awareness for 2SLGBTQIA+ health and inclusive behaviours which can meaningfully impact patient experience. Students report feeling incompetent when working with 2SLGBTQIA+ patients, which may be associated with lack of 2SLGBTQIA+ training in their programs. Greater efforts and attention towards increasing 2SLGBTQIA+ health education and inclusivity in Canadian entry-level physiotherapy programs is critically needed.
Feasibility and reproducibility of semi-automated longitudinal strain analysis: a comparative study with conventional manual strain analysis
Authors: Peng Gui-juan , Luo Shu-yu , Zhong Xiao-fang , Lin Xiao-xuan , Zheng Ying-qi , Xu Jin-feng , Liu Ying-ying , Chen Li-xin 
Published: July 2023

Abstract
Background
Conventional approach to myocardial strain analysis relies on a software designed for the left ventricle (LV) which is complex and time-consuming and is not specific for right ventricular (RV) and left atrial (LA) assessment. This study compared this conventional manual approach to strain evaluation with a novel semi-automatic analysis of myocardial strain, which is also chamber-specific.

Methods
Two experienced observers used the AutoStrain software and manual QLab analysis to measure the LV, RV and LA strains in 152 healthy volunteers. Fifty cases were randomly selected for timing evaluation.

Results
No significant differences in LV global longitudinal strain (LVGLS) were observed between the two methods (-21.0% ± 2.5% vs. -20.8% ± 2.4%, p = 0.230). Conversely, RV longitudinal free wall strain (RVFWS) and LA longitudinal strain during the reservoir phase (LASr) measured by the semi-automatic software differed from the manual analysis (RVFWS: -26.4% ± 4.8% vs. -31.3% ± 5.8%, p < 0.001; LAS: 48.0% ± 10.0% vs. 37.6% ± 9.9%, p < 0.001). Bland–Altman analysis showed a mean error of 0.1%, 4.9%, and 10.5% for LVGLS, RVFWS, and LASr, respectively, with limits of agreement of -2.9,2.6%, -8.1,17.9%, and -12.3,33.3%, respectively. The semi-automatic method had a significantly shorter strain analysis time compared with the manual method.

Conclusions
The novel semi-automatic strain analysis has the potential to improve efficiency in measurement of longitudinal myocardial strain. It shows good agreement with manual analysis for LV strain measurement.

Graphical Abstract
The anchor design of anchor-based method to determine the minimal clinically important difference: a systematic review
Authors: Zhang Yu , Xi Xiaoyu , Huang Yuankai 
Published: July 2023

Abstract
Background
Positive results for clinical outcomes should be not only statistically significant, but also clinically significant. The minimum clinically important difference (MCID) is used to define the minimum threshold of clinical significance. The anchor-based method is a classical method for ascertaining MCID. This study aimed to summarise the design of the anchors of the anchor-based method by reviewing the existing research and providing references and suggestions.

Method
This study was mainly based on literature research. We performed a systematic search using Web of Science, PubMed, CNKI, Wanfang, and VIP databases. Two reviewers independently screened titles and abstracts to identify relevant articles. Data were extracted from eligible articles using a predefined data collection form. Discrepancies were resolved by discussion and the involvement of a third reviewer.

Result
Three hundred and forty articles were retained for final analysis. For the design of anchors, Subjective anchors (99.12%) were the most common type of anchor used, mainly the Patient’s rating of change or patient satisfaction (66.47%) and related scale health status evaluation items or scores (39.41%). Almost half of the studies (48.53%) did not assess the correlation test between the anchor and the research indicator or scale. The cut-off values and grouping were usually based on the choice of the anchor types. In addition, due to the large number of included studies, this study selected the most calculated SF-36 (28 articles) for an in-depth analysis. The results showed that the overall design of the anchor and the cut-off value were the same as above. The statistical methods used were mostly traditional (mean change, ROC). The MCID thresholds of these studies had a wide range (SF-36 PCS: 2–17.4, SF-36 MCS: 1.46–10.28), and different anchors or statistical methods lead to different results.

Conclusion
It is of great importance to select several types of anchors and to use more reliable statistical methods to calculate the MCID. It is suggested that the order of selection of anchors should be: objective anchors > anchors with established MCID in subjective anchors (specific scale > generic scale) > ranked anchors in subjective anchors. The selection of internal anchors should be avoided, and anchors should be evaluated by a correlation test.
Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): a feasibility study for a randomized controlled trial
Authors: Sirevåg Kristine , Stavestrand S. H. , Sjøbø T. , Endal T. B. , Nordahl H. M. , Andersson E. , Nordhus I. H. , Rekdal Å. , Specht K. , Hammar Å. , Halmøy A. , Mohlman J. , Hjelmervik H. , Thayer J. F. , Hovland A. 
Published: July 2023

Abstract
Background
Generalised anxiety disorder (GAD) is a frequent and severe disorder among older adults. For older adults with GAD the effect of the recommended treatment, cognitive behaviour therapy (CBT), is reduced. Physical exercise (PE) may enhance the effect of CBT by improving cognitive function and increasing levels of brain-derived neurotrophic factor (BDNF), a predictor of the effect of CBT in patients with anxiety. The aim of the study was to assess the feasibility of a randomized controlled trial (RCT) investigating treatment effect of the combination of CBT and PE for GAD in a sample of older adults, including procedures for assessment and treatment.

Methods
Four participants aged 62–70 years (M = 65.5, SD = 3.2) with a primary diagnosis of GAD were included. Participants received 15 weeks of PE in combination with 10 weeks of CBT. Participants completed self-report measures, and clinical, biological, physiological and neuropsychological tests at pre-, interim- and post-treatment.

Results
Procedures, protocols, and results are presented. One participant dropped out during treatment. For the three participants completing, the total adherence to PE and CBT was 80% and 100%, respectively. An independent assessor concluded that the completers no longer fulfilled the criteria for GAD after treatment. Changes in self-report measures suggest symptom reduction related to anxiety and worry. The sample is considered representative for the target population.

Conclusions
The results indicate that combining CBT and PE for older adults with GAD is feasible, and that the procedures and tests are suitable and manageable for the current sample.

Trial registration
ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016, https://clinicaltrials.gov/ct2/show/NCT02690441.