bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurocognitive deficits in survivors of childhood acute myeloid leukemia
Authors: Takahashi Satoko , Sato Satomi , Igarashi Shunji , Dairoku Hitoshi , Takiguchi Yuichi , Takimoto Tetsuya 
Published: May 2022

Abstract
Background
Although treatment of acute myeloid leukemia (AML) contains neurotoxic agents, studies investigating neurocognitive outcomes in children with AML are sparse. We evaluated late cognitive effects in children treated with a high-dose cytarabine based regimen, focusing on general intellectual ability and specific neurocognitive domains.

Methods
We evaluated 12 survivors of childhood AML who were treated between 2006 and 2016 and completed the Wechsler Intelligence Scales. One-sample t-tests were used to compare full-scale intelligence quotient (FSIQ) and primary index scores to norms. The overall effect of index scores and subtests was examined with one-way ANOVA. Univariate analyses and multiple regression models examined demographic and clinical characteristics associated with FSIQ.

Results
Participants who underwent the Wechsler Intelligence Scale for Children demonstrated impairment on working memory index and participants who underwent the Wechsler Adult Intelligence Scale showed low score in the subtests that reflect working memory, whereas they exhibited no statistical differences versus the population means for FSIQ. There were no significant differences in the overall effect of index scores and subtests. On univariate analysis, FSIQ were related to time since diagnosis and age at assessment, and both were significant predictors of FSIQ on multiple linear regression.

Conclusions
Survivors of childhood AML exhibited impairment of working memory, even if their FSIQ was within the normal range. Difficulties in specific cognitive domains are associated with reduced quality of life. It is important to identify survivors who are at risk and provide tailored interventions.
A study protocol of the adaptation and evaluation by means of a cluster-RCT of an integrated workplace health promotion program based on a European good practice
Authors: Smit Denise J. M. , van Oostrom Sandra H. , Engels Josephine A. , van der Beek Allard J. , Proper Karin I. 
Published: May 2022

AbstractBackgroundAn integrated workplace health promotion program (WHPP) which targets multiple lifestyle factors at different levels (individual and organizational) is potentially more effective than a single component WHPP. The aim of this study is to describe the protocol of a study to tailor a European good practice of such an integral approach to the Dutch context and to evaluate its effectiveness and implementation.MethodsThis study consists of two components. First, the five steps of the Map of Adaptation Process (MAP) will be followed to tailor the Lombardy WHP to the Dutch context. Both the employers and employees will be actively involved in this process. Second, the effectiveness of the integrated Dutch WHPP will be evaluated in a clustered randomized controlled trial (C-RCT) with measurements at baseline, 6 months and 12 months. Clusters will be composed based on working locations or units - dependent on the organization’s structure and randomization within each organization takes place after baseline measurements. Primary outcome will be a combined lifestyle score. Secondary outcomes will be the separate lifestyle behaviors targeted, stress, work-life balance, need for recovery, general health, and well-being. Simultaneously, a process evaluation will be conducted. The study population will consist of employees from multiple organizations in different industry sectors. Organizations in the intervention condition will receive the integrated Dutch WHPP during 12 months, consisting of an implementation plan and a catalogue with activities for multiple lifestyle themes on various domains: 1) screening and support; 2) information and education; 3) adjustments in the social, digital or physical environment; and 4) policy.DiscussionThe MAP approach provides an appropriate framework to systematically adapt an existing WHPP to the Dutch context, involving both employers and employees and retaining the core elements, i.e. the catalogue with evidence-based activities on multiple lifestyle themes and domains enabling an integrated approach. The following process and effect evaluation will contribute to further insight in the actual implementation and effectiveness of the integrated WHP approach.Trial registrationNTR (trialregister.nl), NL9526. Registered on 3 June 2021.
Healthcare and treatment experiences among people diagnosed with HIV before and after a province-wide treatment as prevention initiative in British Columbia, Canada
Authors: Tattersall Tessa , Tam Clara , Moore David , Wesseling Tim , Grieve Sean , Wang Lu , Bacani Nic , Montaner Julio S. G. , Hogg Robert S. , Barrios Rolando , Salters Kate 
Published: May 2022

Abstract
Introduction
In 2010, the Canadian province of British Columbia (BC) initiated the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) program to improve HIV testing, linkage to care, and treatment uptake, thereby operationalizing the HIV Treatment as Prevention (TasP) framework at the population-level. In this analysis, we evaluated self-reported HIV care experiences and therapeutic outcomes among people diagnosed with HIV prior to and after implementation of this provincial program.

Methods
A cross-sectional analysis was performed on the baseline data of a cohort of people living with HIV (PLWH) (19 years and older) in the province of BC sampled from July 2016 to September 2018. All participants consented to linking their survey data to the provincial HIV treatment registry. Individuals diagnosed with HIV from January 1 2000—December 31 2009 were classified as pre-intervention and those diagnosed January 1 2010—December 31 2018 as post-intervention cohorts. Bivariate analyses were run using Chi-square and Wilcoxon Rank Sum tests. Cox proportional hazards regression model demonstrates time to antiretroviral therapy (ART) initiation (from HIV baseline) and virological suppression (2 consecutive plasma viral load measurements < 200 copies/ml).

Results
Of the 325 participants included in this analysis, 198 (61%) were diagnosed with HIV in the pre-intervention era and 127 (39%) in the post-intervention era. A higher proportion of participants in post-intervention era were diagnosed at walk-in clinics (45% vs. 39%) and hospitals (21% vs. 11%) (vs pre-intervention) (p = 0.042). Post-intervention participants had initiated ART with less advanced HIV disease (CD4 count 410 vs. 270 cells/ul; p = 0.001) and were less likely to experience treatment interruptions at any point in the 5 years after HIV diagnosis (17% vs. 48%; p < 0.001). The post-intervention cohort had significantly more timely ART initiation (aHR: 5.97, 95%CI 4.47, 7.97) and virologic suppression (aHR: 2.03, 95%CI 1.58, 2.60) following diagnosis, after controlling for confounders.

Conclusions
We found favourable treatment experiences and more timely ART initiation and virologic suppression after a targeted TasP provincial program. Our results illustrate the importance of accessible low-barrier HIV testing and treatment in tackling the HIV epidemic.
Exposure to job-related violence among young female sex workers in urban slums of Southwest Nigeria
Authors: Ikuteyijo Olutoyin Opeyemi , Akinyemi Akanni Ibukun , Merten Sonja 
Published: May 2022

Abstract
Background
In Nigeria, many young girls are engaged in commercial sex work as a means of livelihood and support of dependent relatives. Although studies have documented some of the violence related issues among commercial sex workers, the plight of adolescent and young sex workers particularly in urban slums may be different in context and depth.

Objective
This study explored the lived experiences of violence and health related harm among vulnerable young female sex workers in urban slums in Ibadan and Lagos, Southwest Nigeria. It also analyzed their coping strategies and survival mechanisms.

Design
The study is cross-sectional and applied an interpretive phenomenological approach to this qualitative study through in-depth interviews.

Participants
Young female sex workers ages (15–24 years) who reported having experienced violence were recruited for the study. Twelve participants completed the interviews out the 20 initially contacted.

Data collection and analysis
Primary data were collected using in-depth interviews (IDIs). Data were transcribed using a phenomenological framework analysis. Participants’ reports based on life experiences were identified: lived experience “daily brothel life experience”; sources of violence such as law enforcement agents’ intermittent raids; violence experience with clients who often demanded sexual acts beyond the agreed scope; and coping strategies employed to mitigate the challenges.

Settings
The study was conducted in brothels of two selected slum areas in Ibadan and Lagos, Southwest Nigeria.

Results
The results showed that the major motivation for engaging in commercial sex work was for economic reasons. However, there are inherent risks involved particularly for the vulnerable young people. Stigmatization from the community, clients’ uncontrolled-aggressive behavior and harassment from law enforcement agents are some of the frequent violence experiences reported. Self-help coping strategies are usually employed to prevent or mitigate the challenges.

Conclusion
The plight of this young people required policy and program attention towards alternative economic empowerment to rehabilitate those willing to leave the profession. Also the need to develop arm reduction interventions towards protection of young sex workers against violence.
Efficacy of adjuvant treatment for fracture nonunion/delayed union: a network meta-analysis of randomized controlled trials
Authors: Yang Jun , Zhang Xiangmin , Liang Wangbo , Chen Guo , Ma Yanbo , Zhou Yonghua , Fen Rong , Jiang Kaichang 
Published: May 2022

Abstract
Background
Fracture nonunion/delayed union seriously affects physical and mental health and quality of life. The aim of this study was to evaluate the relative efficacy of different adjuvant treatments for nonunion/delayed union by network meta-analysis.

Methods
A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating adjuvant treatment in the management of nonunion/delayed union. A network meta-analysis reporting on healing rate, healing time, and adverse effect (AE) outcomes was conducted to assess and compare different interventions.

Results
Thirty studies were included in the analysis. For the healing rate outcome, bone marrow aspirate (BMA) + autologous cancellous bone (ACB) was found to be significantly better than ACB alone (odds ratio: 0.12; 95% confidence interval: 0.03, 0.59). In the ranking results, BMA+ platelet-rich plasma (PRP) (96%), BMA + ACB (90%), and BMA alone (82%) showed relative advantages in the healing rate. Low-intensity pulsed ultrasonography (LIUS) intervention significantly shortened the healing time compared with ACB (SMD: -9.26; 95% CI: − 14.64, − 3.87). LIUS (100%), BMA + PRP (74%), and bone morphogenetic proteins (BMPs) (69%) have relative advantages. Compared with the control, electromagnetic field (EMF) (OR: 13.21; 95% CI: 1.58, 110.40) and extracorporeal shock wave (ESWT) (OR: 4.90; 95% CI: 1.38, 17.43) had a higher AE risk.

Conclusions
Among the current intervention strategies, BMA in combination with PRP and ACB can improve the healing rate of nonunion/delayed union. LIUS can significantly shorten the healing time. EMF and ESWT may have a high risk of AE. However, large-scale, well-designed studies are still needed to confirm the results.

Trial registration
Retrospectively registered.
Association of bone-related biomarkers with femoral neck bone strength
Authors: Xia Ning , Cai Yun , Wang Wei , Bao Chen , Li Yunming , Xie Qingyun , Xu Wei , Liu Da 
Published: May 2022

Abstract
Background
Femoral neck fractures are the worst consequence of osteoporosis (OP), and its early prevention and treatment have become a public health problem. This study aims to investigate the relationship of bone-related biomarkers, femoral neck bone mineral density (BMD) and maximum load (Lmax), selecting the indicator which can reflect femoral neck bone loss and reduced bone strength.

Methods
A total of 108 patients were recruited from January 2017 to December 2019. Venous blood samples were collected from patients before total hip replacement, and femoral neck samples were collected during the surgery. Femoral neck BMD, femoral neck Lmax, bone-related markers (serum levels of bone turnover markers, protein expression of type I collagen (COL-I) and osteopontin (OPN) in femoral neck) were all measured and analyzed.

Results
The expression of COL-I in femoral neck were significantly decreased, whereas other markers were all significantly increased with the decreasing of femoral neck BMD and Lmax (P < 0.05). Among them, serum C-terminal telopeptide of type I collagen (CTX) levels and OPN expression of femoral neck were increased in osteopenia. In multiple linear regression analysis, CTX and OPN were both negatively correlated with femoral neck BMD and Lmax, and they were independent factors of femoral neck BMD and Lmax, whereas COL-I was independent factor affecting Lmax (P < 0.05). Besides, CTX was negatively correlated with COL-I (β = -0.275, P = 0.012) and positively correlated with OPN (β = 0.295, P = 0.003).

Conclusions
Compared with other indicators, serum CTX was more sensitive to differences in bone mass and bone strength of femoral neck, and could be considered as surrogate marker for OPN and COL-I.Early measurement of CTX could facilitate the diagnosis of osteopenia and provide a theoretical basis for delaying the occurrence of femoral neck OP and fragility fractures.
αvβ3-targeted sEVs for efficient intracellular delivery of proteins using MFG-E8
Authors: Mai Junxin , Wang Kai , Liu Chenxuexuan , Xiong Sheng , Xie Qiuling 
Published: May 2022

Abstract
Background
Small extracellular vesicles (sEVs) are nanometer-sized membranous particles shed by many types of cells and can transfer a multitude of cargos between cells. Recent studies of sEVs have been focusing on their potential to be novel drug carriers due to natural composition and other promising characteristics. However, there are challenges in sEVs-based drug delivery, one of which is the inefficient loading of drugs into sEVs, especially for large biomolecules.

Results
In this study, we proposed a membrane-associated protein, milk fat globule–epidermal growth factor 8 protein (MFG-E8), to produce αvβ3-targeted sEVs with high delivery efficiency of interested protein. MFG-E8 is a secreted protein with NH2-terminal epidermal growth factor (EGF)–like domains, containing an Arg-Gly-Asp(RGD) sequence that binds αvβ3 and αvβ5 integrins, and COOH terminal domains C1 and C2, which can bind to lipid membrane with strong affinity. Firstly, we transiently expressed MFG-E8 in HEK293F cells and found that this protein could be secreted and adhere to the cell membrane. The recombinant MFG-E8 is also found to locate at the outer membrane of sEVs. Then we generated engineered sEVs by expressing high levels of the EGFP fused to MFG-E8 in HEK293F cells and showed that MFG-E8 could increase the delivery efficiency of EGFP into sEVs. Further delivery of Gaussia luciferase (GL) by fusion expression with MFG-E8 in donor cells demonstrated that target proteins fused with MFG-E8 still kept their activity. Finally, we identified the sEVs’ target to integrin αvβ3 by comparing the transfection efficiency with MFG-E8 loaded sEVs (MFG-E8-sEVs) in αvβ3 positive cells and αvβ3 negative cells. Analysis showed higher target protein could transfect into αvβ3 positive cells with MFG-E8-sEVs than with EGFP loaded sEVs (EGFP-sEVs), meaning the engineered sEVs with MFG-E8 not only could increase the delivery of target protein into sEVs, but also could target the αvβ3 positive cells.

Conclusion
This study suggests that recombinant MFG-E8 is an ideal protein to increasingly deliver the drug into sEVs and give sEVs the ability to target the αvβ3 positive cells.
Developing and validating high-value patient digital follow-up services: a pilot study in cardiac surgery
Authors: Londral A. , Azevedo S. , Dias P. , Ramos C. , Santos J. , Martins F. , Silva R. , Semedo H. , Vital C. , Gualdino A. , Falcão J. , Lapão L. V. , Coelho P. , Fragata J. G. 
Published: May 2022

Abstract
Background
The existing digital healthcare solutions demand a service development approach that assesses needs, experience, and outcomes, to develop high-value digital healthcare services. The objective of this study was to develop a digital transformation of the patients’ follow-up service after cardiac surgery, based on a remote patient monitoring service that would respond to the real context challenges.

Methods
The study followed the Design Science Research methodology framework and incorporated concepts from the Lean startup method to start designing a minimal viable product (MVP) from the available resources. The service was implemented in a pilot study with 29 patients in 4 iterative develop-test-learn cycles, with the engagement of developers, researchers, clinical teams, and patients.

Results
Patients reported outcomes daily for 30 days after surgery through Internet-of-Things (IoT) devices and a mobile app. The service’s evaluation considered experience, feasibility, and effectiveness. It generated high satisfaction and high adherence among users, fewer readmissions, with an average of 7 ± 4.5 clinical actions per patient, primarily due to abnormal systolic blood pressure or wound-related issues.

Conclusions
We propose a 6-step methodology to design and validate a high-value digital health care service based on collaborative learning, real-time development, iterative testing, and value assessment.
The influence of first wave of COVID-19 outbreak on routine healthcare services, Liberia, August 2020: a mixed study approach
Authors: Babalola Obafemi J. , Sesay Himiede W. , Blebo Lily S. , Whesseh Faith K. , Umeokonkwo Chukwuma D. , Adewuyi Peter A. , Amo-Addae Maame 
Published: May 2022

Abstract
Background
The COVID-19 pandemic left countries to rapidly implement diverse and stringent public health measures without recourse to mitigate its effect on the sustenance of routine healthcare services. This study described routine health service disruption and restoration strategies at 6 months into the epidemic in Liberia.

Methods
Liberia, with 15 counties, has 839 health facilities, with one-third in Montserrado County. A cross-sectional study using a mixed approach - quantitative and qualitative research with concurrent triangulation was conducted using a structured guide for group discussions among key health workers at 42 secondary and most patronized health facilities in 14 counties and 7 Montserrado districts. Additionally, routine health data between January and June 2019 and 2020 were extracted from the source documents to the electronic checklist. We performed a descriptive analysis of quantitative data and plotted the line graph of the relative percentage change. Transcribed audio recording notes were synthesized using ATLAS ti for content analysis to identify the themes and subthemes in line with the study objectives and excerpts presented in the results.

Results
Liberia declared COVID-19 outbreak on March 16, 2020. From conducted interviews at 41 health facilities, 80% reported disruption in routine health services. From January to June 2020, scheduled routine immunization outreaches conducted decreased by 47%. Using a relative percentage change, outpatient attendance decreased by 32% in May, inpatient admission by 30% in April, malaria diagnosis and treatment by 40% in April, and routine antenatal obstetric care by 28% in April. The fear of contacting COVID-19 infection, redeployment of healthcare workers to COVID-19 response, restriction of movement due to lockdown, inadequate or lack of PPE for healthcare workers, lack of drugs and vaccine supplies for clients, and partial closure of routine healthcare services were common perceived reasons for disruptions. Massive community health education and strict compliance with COVID-19 nonpharmacological measures were some of the health facility recovery strategies.

Conclusions
The COVID-19 outbreak in Liberia caused a disruption in routine healthcare services, and strategies to redirect the restoration of routine healthcare services were implemented. During epidemics or global health emergencies, countries should sustain routine health services and plan for them.
Long-term evaluation of the safety and efficacy of recombinant human pentraxin-2 (rhPTX-2) in patients with idiopathic pulmonary fibrosis (IPF): an open-label extension study
Authors: Raghu Ganesh , Hamblin Mark J. , Brown A. Whitney , Golden Jeffrey A. , Ho Lawrence A. , Wijsenbeek Marlies S. , Vasakova Martina , Pesci Alberto , Antin-Ozerkis Danielle E. , Meyer Keith C. , Kreuter Michael , Burgess Tracy , Kamath Nikhil , Donaldson Francis , Richeldi Luca 
Published: May 2022

Abstract
Background
Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151–202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks.

Methods
Patients who completed the randomized PRM-151–202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis).

Results
All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, − 6.2% (− 7.7; − 4.6) and − 5.7% (− 8.0; − 3.3) for percent predicted FVC and − 36.3 m (− 65.8; − 6.9) and − 28.9 m (− 54.3; − 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128.

Conclusions
Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect.
Trial registration NCT02550873; EudraCT 2014-004782-24.