bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein S antibody as an adjunct therapy for hemophilia B
Authors: Wilson Hope P. , Pierre Aliyah , Paysse Ashley L. , Kumar Narender , Cooley Brian C. , Rudra Pratyadipta , Dorsey Adrianne W. , Polania-Villanueva Diana , Chatterjee Sabyasachi , Janbain Maissaa , Velez Maria C. , Majumder Rinku 
Published: September 2023

Abstract
Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (&lt;1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.
VWF–ADAMTS13 axis dysfunction in children with sickle cell disease treated with hydroxycarbamide vs blood transfusion
Authors: Fogarty Helen , Ahmad Azaz , Atiq Ferdows , Doherty Dearbhla , Ward Soracha , Karampini Ellie , Rehill Aisling , Leon Gemma , Byrne Ciara , Geoghegan Rosena , Conroy Helena , Byrne Mary , Budde Ulrich , Schneppenheim Sonja , Sheehan Ciara , Ngwenya Noel , Baker Ross I. , Preston Roger J. S. , Tuohy Emma , McMahon Corrina , O’Donnell James S. 
Published: September 2023

Abstract
Previous studies have reported elevated von Willebrand factor (VWF) levels in patients with sickle cell disease (SCD) and demonstrated a key role for the VWF-ADAMTS13 axis in the pathobiology of SCD vaso-occlusion. Although blood transfusion is the gold standard for stroke prevention in SCD, the biological mechanisms underpinning its improved efficacy compared with hydroxycarbamide are not fully understood. We hypothesized that the improved efficacy of blood transfusion might relate to differences in VWF–ADAMTS13 axis dysfunction. In total, 180 children with a confirmed diagnosis of SCD (hemoglobin SS) on hydroxycarbamide (n = 96) or blood transfusion (n = 84) were included. Despite disease-modifying treatment, plasma VWF and VWF propeptide were elevated in a significant proportion of children with SCD (33% and 47%, respectively). Crucially, all VWF parameters were significantly higher in the hydroxycarbamide compared with the blood transfusion cohort (P &lt; .05). Additionally, increased levels of other Weibel-Palade body–stored proteins, including factor VIII (FVIII), angiopoietin-2, and osteoprotegerin were observed, indicated ongoing endothelial cell activation. Children treated with hydroxycarbamide also had higher FVIII activity and enhanced thrombin generation compared with those in the blood transfusion cohort (P &lt; .001). Finally, hemolysis markers strongly correlated with VWF levels (P &lt; .001) and were significantly reduced in the blood transfusion cohort (P &lt; .001). Cumulatively, to our knowledge, our findings demonstrate for the first time that despite treatment, ongoing dysfunction of the VWF–ADAMTS13 axis is present in a significant subgroup of pediatric patients with SCD, especially those treated with hydroxycarbamide.
LARAI portal provides a safe method for lateral meniscus repair: three-dimensional computed tomography and cadaveric assessment
Authors: Long Yi , Zhang Zhengzheng , Zhou Min , Hou Jingyi , Zhou Yunfeng , Jiang Liang , Xu Xiaoding , Yang Rui 
Published: September 2023

Abstract
Background
Lateral, All-Round and All-Inside (LARAI) portal is a viewing or working portal for observing and repairing the lesions of the lateral meniscus. However, there are safety concerns about popliteal artery (PA) injuries during the procedure. This study aimed to assess the safe distance between the trajectory of the LARAI portal and PA.

Materials and methods
Both three-dimensional computed tomography (3D-CT) and cadavers were used to simulate the LARAI portal trajectory. In the 3D-CT study, between January 2020 and September 2020, 45 participants who underwent computed tomography angiography were included in the study. The shortest distance from the PA to the simulated trajectory needle (PS) was measured using 3D-CT. Mean −3SD −2 was calculated to assess the safety of the LARAI portal trajectory. If this value was more than zero, the trajectory was considered “safe.” In the cadaveric study, lower limbs from seven fresh-frozen cadavers were used to establish the “safe” trajectories of the LARAI portal, and the PS was measured.

Results
In the 3D-CT study, the longest PS (P < 0.001) was found 20 mm lateral to the edge of the patellar tendon trajectory at 0 mm from the posterior cruciate ligament (PCL). Safe trajectories were also found 10 mm, 15 mm, and 20 mm lateral to the edge of the patellar tendon at 0 mm from the PCL, as well as the 20 mm lateral to the edge of the patellar tendon at 3 mm from the PCL. The cadaveric study showed that the average PS of all safe trajectories closely adjoined to PCL was greater than 14 mm.

Conclusions
The LARAI portal trajectory in the “figure of four” is safe, and the optimal insertion point is 10–20 mm lateral to the edge of the patellar tendon and closely adjoined to the posterolateral margin of the PCL at knee joint line level.

Level of evidence
Level IV.
Multimodal imaging and photothermal/chemodynamic therapy of cervical cancer using GSH-responsive MoS2@MnO2 theranostic nanoparticles
Authors: Shao Runrun , Qiao Xiaofang , Cao Linlin , Man Jianliang , Guo Lingyun , Li Lanlan , Liu Wen , Li Lihong , Wang Bin , Guo Lixia , Ma Sufang , Zhang Boye , Wang Haojiang , Yan Lili 
Published: September 2023

AbstractThe development of nanoparticles capable of inducing reactive oxygen species (ROS) formation has become an important strategy for cancer therapy. Simultaneously, the preparation of multifunctional nanoparticles that respond to the tumor microenvironment is crucial for the diagnosis and treatment of tumors. In this study, we designed a Molybdenum disulfide (MoS2) core coated with Manganese dioxide (MnO2), which possessed a good photothermal effect and could produce Fenton-like Mn2+ in response to highly expressed glutathione (GSH) in the tumor microenvironment, thereby generating a chemodynamic therapy (CDT). The nanoparticles were further modified with Methoxypoly(Ethylene Glycol) 2000 (mPEG-NH2) to improve their biocompatibility, resulting in the formation of MoS2@MnO2-PEG. These nanoparticles were shown to possess significant Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging capabilities, making them useful in tumor diagnosis. In vitro and in vivo experiments demonstrated the antitumor ability of MoS2@MnO2-PEG, with a significant killing effect on tumor cells under combined treatment. These nanoparticles hold great potential for CDT/photothermal therapy (PTT) combined antitumor therapy and could be further explored in biomedical research.
Current status and influencing factors of self-management in knee joint discomfort among middle-aged and elderly people: a cross-sectional study
Authors: Guo Yabin , Zhao Peipei , Zeng Biyun , Su Manman , Zhou Yang , Liu Xiaotong , Zhou Yang 
Published: September 2023

Abstract
Background
This study aims to identify the current status and factors influencing self-management of knee discomfort in middle-aged and elderly people in China.

Methods
A stratified multistage cluster sampling method was used to select participants from communities in China from January 15 to May 31, 2020. A cross-sectional survey was conducted using the general information questionnaire and the Knee Joint Discomfort Self-management Scale. Univariate analysis and a generalized linear model were used to analyze the factors influencing self-management.

Results
The prevalence of knee discomfort was 77%. Moderate to severe discomfort accounted for 30.5%. The average item score of self-management in 9640 participants was 1.98 ± 0.76. The highest and lowest levels were: ‘daily life management’ and ‘information management’. Gender, ethnicity, education level, economic source, chronic disease, knee pain in the past month, and the degree of self-reported knee discomfort were significant predictors of self-management.

Conclusion
The self-management of knee discomfort in middle-aged and elderly people is poor, and the degree of discomfort is a significant predictor. Healthcare providers should consider socioeconomic demographic and clinical characteristics to help these individuals improve their self-management skills. Attention should also be given to improving their ability to access health information and making them aware of disease risks.
Online decision tools for personalized survival prediction and treatment optimization in elderly patients with lung squamous cell carcinoma: a retrospective cohort study
Authors: Shao Chen-ye , Luo Jing , Ju Sheng , Li Chu-ling , Ding Cheng , Chen Jun , Liu Xiao-long , Zhao Jun , Yang Li-qin 
Published: September 2023

Abstract
Background
Despite major advances in cancer therapeutics, the therapeutic options of Lung Squamous Cell Carcinoma (LSCC)-specific remain limited. Furthermore, the current staging system is imperfect for defining a prognosis and guiding treatment due to its simplicity and heterogeneity. We sought to develop prognostic decision tools for individualized survival prediction and treatment optimization in elderly patients with LSCC.

Methods
Clinical data of 4564 patients (stageIB-IIIB) diagnosed from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for prognostic nomograms development. The proposed models were externally validated using a separate group consisting of 1299 patients (stage IB-IIIB) diagnosed from 2012–2015 in China. The prognostic performance was measured using the concordance index (C-index), calibration curves, the average time-dependent area under the receiver operator characteristic curves (AUC), and decision curve analysis.

Results
Eleven candidate prognostic variables were identified by the univariable and multivariable Cox regression analysis. The calibration curves showed satisfactory agreement between the actual and nomogram-estimated Lung Cancer-Specific Survival (LCSS) rates. By calculating the c-indices and average AUC, our nomograms presented a higher prognostic accuracy than the current staging system. Clinical usefulness was revealed by the decision curve analysis. User-friendly online decision tools integrating proposed nomograms were created to estimate survival for patients with different treatment regimens.

Conclusions
The decision tools for individualized survival prediction and treatment optimization might facilitate clinicians with decision-making, medical teaching, and experimental design. Online tools are expected to be integrated into clinical practice by using the freely available website (https://loyal-brand-611803.framer.app/).
Spatio-temporal analysis of childhood vaccine uptake in Nigeria: a hierarchical Bayesian Zero-inflated Poisson approach
Authors: Lawal Temitayo Victor , Atoloye Kehinde Adebola , Adebowale Ayo Stephen , Fagbamigbe Adeniyi Francis 
Published: September 2023

Abstract
Background
Globally, child mortality and morbidity remain a serious health challenge and infectious diseases are the leading causes. The use of count models together with spatial analysis of the number of doses of childhood vaccines taken is limited in the literature. We used a Bayesian zero-inflated Poisson regression model with spatio-temporal components to assess the number of doses of childhood vaccines taken among children aged 12–23 months and their associated factors.

Methods
Data of 19,564 children from 2003, 2008, 2013 and 2018 population-based cross-sectional Nigeria Demographic and Health Survey were used. The childhood vaccines include one dose of Bacillus-Calmette-Guérin; three doses of Diphtheria-Pertussis-Tetanus; three doses of Polio and one dose of Measles. Uptake of all nine vaccines was regarded as full vaccination. We examined the multilevel factors associated with the number of doses of childhood vaccines taken using descriptive, bivariable and multivariable Bayesian models. Analysis was conducted in Stata version 16 and R statistical packages, and visualization in ArcGIS.

Results
The prevalence of full vaccination was 6.5% in 2003, 14.8% in 2008, 21.8% in 2013 and 23.3% in 2018. Full vaccination coverage ranged from 1.7% in Sokoto to 51.9% in Anambra. Factors associated with the number of doses of childhood vaccines taken include maternal age (adjusted Incidence “risk” Ratio (aIRR) = 1.05; 95% Credible Interval (CrI) = 1.03–1.07) for 25–34 years and (aIRR = 1.07; 95% CrI = 1.05–1.10) for 35–49 years and education: (aIRR = 1.11, 95% CrI = 1.09–1.14) for primary and (aIRR = 1.16; 95% CrI = 1.13–1.19) for secondary/tertiary education. Other significant factors are wealth status, antenatal care attendance, working status, use of skilled birth attendants, religion, mother’s desire for the child, community poverty rate, community illiteracy, and community unemployment.

Conclusion
Although full vaccination has remained low, there have been improvements over the years with wide disparities across the states. Improving the uptake of vaccines by educating women on the benefits of hospital delivery and vaccines through radio jingles and posters should be embraced, and state-specific efforts should be made to address inequality in access to routine vaccination in Nigeria.
Clinicians’ views of prescribing oral and intravenous bisphosphonates for osteoporosis: a qualitative study
Authors: Bishop Simon , Narayanasamy Melanie Jay , Paskins Zoe , Corp Nadia , Bastounis Anastasios , Griffin Jill , Gittoes Neil , Leonardi-Bee Jo , Langley Tessa , Sahota Opinder 
Published: September 2023

Abstract
Background
Bisphosphonate medications, including alendronate, ibandronate and risedronate administered orally and zoledronate, administered intravenously, are commonly prescribed for the treatment of osteoporosis based on evidence that, correctly taken, bisphosphonates can improve bone strength and lead to a reduction in the risk of fragility fractures. However, it is currently unclear how decisions to select between bisphosphonate regimens, including intravenous regimen, are made in practice and how clinicians support patients with different treatments.

Methods
This was an interpretivist qualitative study. 23 semi-structured telephone interviews were conducted with a sample of general practitioners (GPs), secondary care clinicians, specialist experts as well as those providing and leading novel treatments including participants from a community intravenous (IV) zoledronate service. Data analysis was undertaken through a process of iterative categorisation.

Results
The results report clinicians varying experiences of making treatment choices, as well as wider aspects of osteoporosis care. Secondary care and specialist clinicians conveyed some confidence in making treatment choices including on selecting IV treatment. This was aided by access to diagnostic testing and medication expertise. In contrast GPs reported a number of challenges in prescribing bisphosphonate medications for osteoporosis and uncertainty about treatment choice. Results also highlight how administering IV zoledronate was seen as an opportunity to engage in broader care practices.

Conclusion
Approaches to making treatment decisions and supporting patients when prescribing bisphosphonates for osteoporosis vary in practice. This study points to the need to co-ordinate osteoporosis treatment and care across different care providers.
Physicians’ attitudes and experiences about withholding/withdrawing life-sustaining treatments in pediatrics: a systematic review of quantitative evidence
Authors: Zhong Yajing , Cavolo Alice , Labarque Veerle , Gastmans Chris 
Published: September 2023

Abstract
Background
One of the most important and ethically challenging decisions made for children with life-limiting conditions is withholding/withdrawing life-sustaining treatments (LST). As important (co-)decision-makers in this process, physicians are expected to have deeply and broadly developed views. However, their attitudes and experiences in this area remain difficult to understand because of the diversity of the studies. Hence, the aim of this paper is to describe physicians’ attitudes and experiences about withholding/withdrawing LST in pediatrics and to identify the influencing factors.

Methods
We systematically searched Pubmed, Cinahl®, Embase®, Scopus®, and Web of Science™ in early 2021 and updated the search results in late 2021. Eligible articles were published in English, reported on investigations of physicians’ attitudes and experiences about withholding/withdrawing LST for children, and were quantitative.

Results
In 23 included articles, overall, physicians stated that withholding/withdrawing LST can be ethically legitimate for children with life-limiting conditions. Physicians tended to follow parents’ and parents-patient’s wishes about withholding/withdrawing or continuing LST when they specified treatment preferences. Although most physicians agreed to share decision-making with parents and/or children, they nonetheless reported experiencing both negative and positive feelings during the decision-making process. Moderating factors were identified, including barriers to and facilitators of withholding/withdrawing LST. In general, there was only a limited number of quantitative studies to support the hypothesis that some factors can influence physicians’ attitudes and experiences toward LST.

Conclusion
Overall, physicians agreed to withhold/withdraw LST in dying patients, followed parent-patients’ wishes, and involved them in decision-making. Barriers and facilitators relevant to the decision-making regarding withholding/withdrawing LST were identified. Future studies should explore children’s involvement in decision-making and consider barriers that hinder implementation of decisions about withholding/withdrawing LST.
Health, wealth, and medical expenditures among the elderly in rural Tanzania: experiences from Nzega and Igunga districts
Authors: Tungu Malale M. , Mujinja Phares G. , Amani Paul J. , Mwangu Mughwira A. , Kiwara Angwara D. , Lindholm Lars 
Published: September 2023

Abstract
Background
The per capita health expenditure (HE) and share of gross domestic product (GDP) spending on elderly healthcare are expected to increase. The gap between health needs and available resources for elderly healthcare is widening in many developing countries, like Tanzania, leaving the elderly in poor health. These conditions lead to catastrophic HEs for the elderly. This study aimed to analyse the association between measures of health, wealth, and medical expenditure in rural residents aged 60 years and above in Tanzania.

Methods
The data of this study were collected through a cross-sectional household survey to residents aged 60 years and above living in Nzega and Igunga districts using a standardised World Health Organization (WHO) Study on Global Ageing and Adult Health (SAGE) and European Quality of Life Five Dimension (EQ-5D) questionnaires. The quality of life (QoL) was estimated using EQ-5D weights. The wealth index was generated from principal component analysis (PCA). The linear regression analyses (outpatient/inpatient) were performed to analyse the association between measures of health, wealth, medical expenditure, and socio-demographic variables.

Results
This study found a negative and statistically significant association between QoL and HE, whereby HE increases with the decrease of QoL. We could not find any significant relationship between HE and social gradients. In addition, age influences HE such that as age increases, the HE for both outpatient and inpatient care also increases.

Conclusion
The health system in these districts allocate resources mainly according to needs, and social position is not important. We thus conclude that the elderly of lower socio-economic status (SES) was subjected to similar health expenditure as those of higher socio-economic status. Health, not wealth, determines the use of medical expenditures.
Five-year results of a treatment program for chronic hepatitis B in Ethiopia
Authors: Desalegn Hailemichael , Orlien Stian Magnus Staurung , Aberra Hanna , Mamo Eyerusalem , Grude Sine , Hommersand Kristina , Berhe Nega , Gundersen Svein Gunnar , Johannessen Asgeir 
Published: September 2023

Abstract
Background
In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) patients receive antiviral therapy. Experiences from local CHB programs are needed to inform treatment guidelines and policies on the continent. Here, we present 5-year results from one of the first large-scale CHB treatment programs in sub-Saharan Africa.

Methods
Adults with CHB were enrolled in a pilot treatment program in Addis Ababa, Ethiopia, in 2015. Liver enzymes, viral markers, and transient elastography were assessed at baseline and thereafter at 6-month intervals. Tenofovir disoproxil fumarate was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. Survival analysis was performed using the Kaplan–Meier method.

Results
In total, 1303 patients were included in the program, of whom 291 (22.3%) started antiviral therapy within the initial 5 years of follow-up. Among patients on treatment, estimated 5-year hepatocellular carcinoma-free survival was 99.0% in patients without cirrhosis at baseline, compared to 88.8% in patients with compensated cirrhosis, and 54.2% in patients with decompensated cirrhosis (p < 0.001). The risk of death was significantly higher in patients with decompensated cirrhosis at baseline (adjusted hazard ratio 44.6, 95% confidence interval 6.1–328.1) and in patients older than 40 years (adjusted hazard ratio 3.7, 95% confidence interval 1.6–8.5). Liver stiffness declined significantly after treatment initiation; the median change from baseline after 1, 3, and 5 years of treatment was − 4.0 kPa, − 5.2 kPa, and − 5.6 kPa, respectively.

Conclusions
This pilot program demonstrates the long-term benefits of CHB therapy in a resource-limited setting. The high mortality in patients with cirrhosis underscores the need for earlier detection of CHB and timely initiation of antiviral treatment in sub-Saharan Africa.

Trial registration
The study was registered at ClinicalTrials.gov (NCT02344498) on January 26, 2015.