bluuebunny/crossref_metadata_2025_split huggingface dataset:
Healthcare needs, expectations, utilization, and experienced treatment effects in patients with hereditary spastic paraplegia: a web-based survey in the Netherlands
Authors: Kerstens Hans C. J. W. , Van Lith Bas J. H. , Nijkrake Maarten J. , De Swart Bert J. M. , Van den Bemd Laura A. C. , Smeets Rob J. E. M. , Klemens Fheodoroff , Van de Warrenburg Bart P. C. , Van der Wees Philip J. , Geurts Alexander C. H. 
Published: June 2021

Abstract
Background
We aimed to identify healthcare needs, expectations, utilization, and the experienced treatment effects in a population of Dutch patients with hereditary spastic paraplegia (HSP).

Methods
We distributed an online questionnaire among 194 adult persons with HSP in the Netherlands, of which 166 returned a fully completed version. After applying predefined exclusion criteria, 109 questionnaires from persons with pure HSP were analysed.

Results
Healthcare needs and expectations were primarily focused on the relief of muscle stiffness and reduction of balance and gait impairments (65–80%), but many participants also expressed needs regarding relief of non-motor symptoms (e.g. pain, fatigue), emotional problems, impaired sleep and self-care capacity, and participation problems (> 60%). Remarkably, despite these frequent needs, relatively few participants (< 33%) expected to be able to improve in these additional domains. Rehabilitation physicians and physiotherapists were more frequently consulted than neurologists and occupational therapists, respectively. Physiotherapy was the most often proposed non-pharmacological intervention (85%), followed by orthopedic footwear (55%) and splints (28%). Approximately one third of the participants was never offered any pharmacological (spasmolytic) treatment. Spasmolytic oral drugs, injections, and intrathecal baclofen were given to 41%, 26%, and 5% of the participants, respectively. Independent of the type of pharmacological intervention, 35–46% of these participants experienced decreased spastiticy and improved general fitness. Other experienced effects differed per type of intervention.

Conclusions
Based on this web-based survey in the Netherlands, there seems to be ample room for improvement to meet and attune the healthcare needs and expectations of people with HSP concerning both their motor and non-motor symptoms and functional limitations. In addition, the provision of adequate information about non-pharmacological and pharmacological interventions seems to be insufficient for many patients to allow shared decision making. These conclusions warrant a more pro-active attitude of healthcare providers as well as an interdisciplinary approach for a substantial proportion of the HSP population, also involving professionals with a primary occupational and/or psychosocial orientation.
Causative variant profile of collagen VI-related dystrophy in Japan
Authors: Inoue Michio , Saito Yoshihiko , Yonekawa Takahiro , Ogawa Megumu , Iida Aritoshi , Nishino Ichizo , Noguchi Satoru 
Published: June 2021

Abstract
Background
Collagen VI-related dystrophy spans a clinical continuum from severe Ullrich congenital muscular dystrophy to milder Bethlem myopathy. This disease is caused by causative variants in COL6A1, COL6A2, or COL6A3. Most reported causative variants are de novo; therefore, to identify possible associated causative variants, comprehensive large cohort studies are required for different ethnicities.

Methods
We retrospectively reviewed clinical information, muscle histology, and genetic analyses from 147 Japanese patients representing 130 families, whose samples were sent for diagnosis to the National Center of Neurology and Psychiatry between July 1979 and January 2020. Genetic analyses were conducted by gene-based resequencing, targeted panel resequencing, and whole exome sequencing, in combination with cDNA analysis.

Results
Of a total of 130 families with 1–5 members with collagen VI-related dystrophy, 120 had mono-allelic and 10 had bi-allelic variants in COL6A1, COL6A2, or COL6A3. Among them, 60 variants were in COL6A1, 57 in COL6A2, and 23 in COL6A3, including 37 novel variants. Mono-allelic variants were classified into four groups: missense (69, 58%), splicing (40, 33%), small in-frame deletion (7, 6%), and large genomic deletion (4, 3%). Variants in the triple helical domains accounted for 88% (105/120) of all mono-allelic variants.

Conclusions
We report the causative variant profile of a large set of Japanese cases of collagen VI-related dystrophy. This dataset can be used as a reference to support genetic diagnosis and variant-specific treatment.
The parabrachial-to-amygdala pathway provides aversive information to induce avoidance behavior in mice
Authors: Ito Mariko , Nagase Masashi , Tohyama Suguru , Mikami Kaori , Kato Fusao , Watabe Ayako M. 
Published: June 2021

AbstractThe neuronal circuitry for pain signals has been intensively studied for decades. The external lateral parabrachial nucleus (PB) was shown to play a crucial role in nociceptive information processing. Previous work, including ours, has demonstrated that stimulating the neuronal pathway from the PB to the central region of the amygdala (CeA) can substitute for an actual pain signal to drive an associative form of threat/fear memory formation. However, it is still unknown whether activation of the PB–CeA pathway can directly drive avoidance behavior, escape behavior, or only acts as strategic freezing behavior for later memory retrieval. To directly address this issue, we have developed a real-time Y-maze conditioning behavioral paradigm to examine avoidance behavior induced by optogenetic stimulation of the PB–CeA pathway. In this current study, we have demonstrated that the PB–CeA pathway carries aversive information that can directly trigger avoidance behavior and thereby serve as an alarm signal to induce adaptive behaviors for later decision-making.
C4b-binding protein α-chain enhances antitumor immunity by facilitating the accumulation of tumor-infiltrating lymphocytes in the tumor microenvironment in pancreatic cancer
Authors: Sasaki Kosuke , Takano Shigetsugu , Tomizawa Satoshi , Miyahara Yoji , Furukawa Katsunori , Takayashiki Tsukasa , Kuboki Satoshi , Takada Mamoru , Ohtsuka Masayuki 
Published: June 2021

Abstract
Background
Recent studies indicate that complement plays pivotal roles in promoting or suppressing cancer progression. We have previously identified C4b-binding protein α-chain (C4BPA) as a serum biomarker for the early detection of pancreatic ductal adenocarcinoma (PDAC). However, its mechanism of action remains unclear. Here, we elucidated the functional roles of C4BPA in PDAC cells and the tumor microenvironment.

Methods
We assessed stromal C4BPA, the C4BPA binding partner CD40, and the number of CD8+ tumor-infiltrating lymphocytes in resected human PDAC tissues via immunohistochemical staining. The biological functions of C4BPA were investigated in peripheral blood mononuclear cells (PBMCs) and human PDAC cell lines. Mouse C4BPA (mC4BPA) peptide, which is composed of 30 amino acids from the C-terminus and binds to CD40, was designed for further in vitro and in vivo experiments. In a preclinical experiment, we assessed the efficacy of gemcitabine plus nab-paclitaxel (GnP), dual immune checkpoint blockades (ICBs), and mC4BPA peptide in a mouse orthotopic transplantation model.

Results
Immunohistochemical analysis revealed that high stromal C4BPA and CD40 was associated with favorable PDAC prognosis (P=0.0005). Stromal C4BPA strongly correlated with the number of CD8+ tumor-infiltrating lymphocytes (P=0.001). In in vitro experiments, flow cytometry revealed that recombinant human C4BPA (rhC4BPA) stimulation increased CD4+ and CD8+ T cell numbers in PBMCs. rhC4BPA also promoted the proliferation of CD40-expressing PDAC cells. By contrast, combined treatment with gemcitabine and rhC4BPA increased PDAC cell apoptosis rate. mC4BPA peptide increased the number of murine T lymphocytes in vitro and the number of CD8+ tumor-infiltrating lymphocytes surrounding PDAC tumors in vivo. In a preclinical study, GnP/ICBs/mC4BPA peptide treatment, but not GnP treatment, led to the accumulation of a greater number of CD8+ T cells in the periphery of PDAC tumors and to greater tumor regression than did control treatment.

Conclusions
These findings demonstrate that the combination of GnP therapy with C4BPA inhibits PDAC progression by promoting antitumor T cell accumulation in the tumor microenvironment.
Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial
Authors: Ajlan Aziza , Aleid Hassan , Ali Tariq Zulfiquar , Joharji Hala , Almeshari Khalid , Nazmi Ahmed Mohammed , Shah Yaser , Devol Edward , Alkortas Dalal , Alabdulkarim Zinah , Broering Dieter , Alahmadi Ibrahim , Ullah Asad , Alotaibi Anwar , Aljedai Ahmed 
Published: June 2021

Abstract
Background
Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated.

Aims
To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol.

Methods
Prospective, randomized, double blind, non-inferiority, controlled clinical trial

Expected outcomes
1. Primary outcomes:
Biopsy-proven acute rejection within first year following transplant
2. Secondary outcomes:
a. Patient and graft survival at 1 year
b. eGFR at 6 months and at 12 months
c. Emergence of de novo donor-specific antibodies (DSAs)

Trial registration
The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.
The effect of the mobile “blood pressure management application” on hypertension self-management enhancement: a randomized controlled trial
Authors: Bozorgi Ali , Hosseini Hamed , Eftekhar Hassan , Majdzadeh Reza , Yoonessi Ali , Ramezankhani Ali , Mansouri Mehdi , Ashoorkhani Mahnaz 
Published: June 2021

Abstract
Background
Self-management of hypertension is of great significance given its increasing incidence and its associated disabilities. In view of the increased use of mobile health in medicine, the present study evaluated the effect of a self-management application on patient adherence to hypertension treatment.

Methods
This clinical trial was performed on 120 hypertensive patients who were provided with a mobile intervention for 8 weeks and followed up until the 24th week. Data on the primary outcome (adherence to treatment) and secondary outcomes (adherence to the DASH diet, regular monitoring of blood pressure, and physical activity) were collected using a questionnaire and a mobile application, respectively. The inter-group change difference over time was analyzed using repeated measures ANOVA (general linear model).

Results
The treatment adherence score increased by an average of 5.9 (95% CI 5.0–6.7) in the intervention group compared to the control group. The scores of “adherence to the low-fat and low-salt diet plans” were 1.7 (95% CI 1.3–2.1) and 1.5 (95% CI 1.2–1.9), respectively. Moreover, moderate physical activity increased to 100.0 min (95% CI 61.7–138.3) per week in the intervention group.

Conclusion
The treatment and control of blood pressure require a multifaceted approach given its complexity and multifactorial nature. Considering the widespread use of smartphones, mHealth interventions can be effective in self-management and better patient adherence to treatments. Our results showed that this application can be used as a successful tool for hypertension self-management in patients attending public hospitals in developing countries.

Trial registration
Iran Randomized Clinical Trial Center IRCT2015111712211N2. Registered on 1 January 2016
A GH89 human α-N-acetylglucosaminidase (hNAGLU) homologue from gut microbe Bacteroides thetaiotaomicron capable of hydrolyzing heparosan oligosaccharides
Authors: Yang Xiaohong , Yang Xiaoxiao , Yu Hai , Na Lan , Ghosh Tamashree , McArthur John B. , Chou Tsui-Fen , Dickson Patricia , Chen Xi 
Published: June 2021

AbstractCarbohydrate-Active enZYme (CAZY) GH89 family enzymes catalyze the cleavage of terminal α-N-acetylglucosamine from glycans and glycoconjugates. Although structurally and mechanistically similar to the human lysosomal α-N-acetylglucosaminidase (hNAGLU) in GH89 which is involved in the degradation of heparan sulfate in the lysosome, the reported bacterial GH89 enzymes characterized so far have no or low activity toward α-N-acetylglucosamine-terminated heparosan oligosaccharides, the preferred substrates of hNAGLU. We cloned and expressed several soluble and active recombinant bacterial GH89 enzymes in Escherichia coli. Among these enzymes, a truncated recombinant α-N-acetylglucosaminidase from gut symbiotic bacterium Bacteroides thetaiotaomicron ∆22Bt3590 was found to catalyze the cleavage of the terminal α1–4-linked N-acetylglucosamine (GlcNAc) from a heparosan disaccharide with high efficiency. Heparosan oligosaccharides with lengths up to decasaccharide were also suitable substrates. This bacterial α-N-acetylglucosaminidase could be a useful catalyst for heparan sulfate analysis.
Rapid-flow expulsion maneuver in subglottic secretion clearance to prevent ventilator-associated pneumonia: a randomized controlled study
Authors: Li Ying , Yuan Xue , Sun Bing , Li Hai-chao , Chu Hui-wen , Wang Li , Zhao Yu , Tang Xiao , Wang Rui , Li Xu-yan , Tong Zhao-hui , Wang Chen 
Published: June 2021

Abstract
Background
Following endotracheal intubation, clearing secretions above the endotracheal tube cuff decreases the incidence of ventilator-associated pneumonia (VAP); therefore, subglottic secretion drainage (SSD) is widely advocated. Our group developed a novel technique to remove the subglottic secretions, the rapid-flow expulsion maneuver (RFEM). The objective of this study was to explore the effectiveness and safety of RFEM compared with SSD.

Methods
This study was a single-center, prospective, randomized and controlled trial, conducted at Respiratory Intensive Care Unit (ICU) of Beijing Chao-Yang Hospital, a university-affiliated tertiary hospital. The primary outcome was the incidence of VAP, assessed for non-inferiority.

Results
Patients with an endotracheal tube allowing drainage of subglottic secretions (n = 241) were randomly assigned to either the RFEM group (n = 120) or SSD group (n = 121). Eleven patients (9.17%) in the RFEM group and 13 (10.74%) in the SSD group developed VAP (difference, − 1.59; 95% confidence interval [CI] [− 9.20 6.03]), as the upper limit of 95% CI was not greater than the pre-defined non-inferiority limit (10%), RFEM was declared non-inferior to SSD. There were no statistically significant differences in the duration of mechanical ventilation, ICU mortality, or ICU length of stay and costs between groups. In terms of safety, no accidental extubation or maneuver-related barotrauma occurred in the RFEM group. The incidence of post-extubation laryngeal edema and reintubation was similar in both groups.

Conclusions
RFEM is effective and safe, with non-inferiority compared to SSD in terms of the incidence of VAP. RFEM could be an alternative method in first-line treatment of respiratory ICU patients.
Trial registration This study has been registered on ClinicalTrials.gov (Registration Number: NCT02032849, https://clinicaltrials.gov/ct2/show/NCT02032849); registered on January 2014
Low birth weight as a predictor of adverse health outcomes during adulthood in twins: a systematic review and meta-analysis
Authors: Hassan Sapha , Jahanfar Shayesteh , Inungu Joseph , Craig Jeffrey M. 
Published: June 2021

Abstract
Background
Low birth weight might affect adverse health outcomes during a lifetime. Our study analyzes the association between low birth weight and negative health outcomes during adulthood in twin populations.

Methods
Searches were conducted using databases inclusive of MEDLINE, CINAHL, Web of Science, and EBSCO. Observational studies on twins with low birth weight and adverse health outcomes during adulthood were included. Two reviewers independently screened the papers, and a third reviewer resolved the conflicts between the two reviewers. Following abstract and title screening, full-texts were screened to obtain eligibility. Eligible full-text articles were then assessed for quality using a modified Downs and Black checklist. Studies with a score within one standard deviation of the mean were included in the analysis. A fixed-effect model was used for analysis.

Results
3987 studies were screened describing low birth weight as a risk factor for adverse health outcomes during adulthood for all twelve-body systems (circulatory, digestive, endocrine, lymphatic, muscular, nervous, reproductive, respiratory, skeletal, urinary, and integumentary systems). One hundred fourteen articles made it through full-text screening, and 14 of those articles were assessed for quality. Five papers were selected to perform two meta-analyses for two outcomes: asthma and cerebral palsy. For asthma, the meta-analyses of three studies suggested a higher odds of low birth weight twins developing asthma (OR 1.33, 95% CI 1.24-1.44, I2 = 77%). Meta-analysis for cerebral palsy included two studies and suggested a 4.88 times higher odds of low birth weight twins developing cerebral palsy compared to normal birth weight twins (OR 4.88, 95% CI 2.34-10.19, I2 = 79%). We could not find enough studies for other adverse health outcomes to pool data for a Forest plot.

Conclusions
The odds of low birth weight were found to be high in both asthma and cerebral palsy. There are not enough studies of similar nature (study types, similar body systems) to ensure a meaningful meta-analysis. We recommend that future research considers following up on twins to obtain data about adverse health outcomes during their adult lives.
The health impacts of preventive cardiovascular medication reduction on older populations: protocol for a systematic review and meta-analysis
Authors: van der Veen Rik S. , Lee Joseph J. , McManus Richard J. , Hobbs Richard F. D. , Mahtani Kamal R. , Koshiaris Constantinos , Sheppard James P. 
Published: June 2021

Abstract
Background
Polypharmacy is inevitable and appropriate for many conditions, but in some cases, it can be problematic resulting in an increased risk of harm and reduced quality of life. There has been an increasing interest to reduce cardioprotective medications in older adults to potentially reduce the risk of harm due to treatment; however, there is no evidence on safety and efficacy to support this practice currently. This paper describes a protocol for a systematic review on the safety and efficacy of reducing cardioprotective medication in older populations.

Methods
MEDLINE (PubMed), Embase (Ovid), and CENTRAL (Cochrane Central Register of Controlled Trials) will be searched from their inception onwards for relevant studies. Randomised controlled trials and non-randomised studies on interventions (prospective, retrospective cohort, case-control) conducted in older adults (75 years or older) examining reduction of cardioprotective medications will be included. The primary outcome of this study will be all-cause hospitalisation. Secondary outcome variables of interest are all-cause hospitalisation, mortality, quality of life, serious adverse events, major adverse cardiovascular events, falls, fractures, cognitive functioning, bleeding events, renal functioning, medication burden, drug reinstatement, time-in-hospital, and frailty status. Two reviewers will independently screen all citations, full-text articles, and extract data. Confidence in cumulative evidence will be assessed using the GRADE approach; the risk of bias will be assessed by the RoB-II tool for randomised controlled studies and ROBINS-I for non-randomised studies. Where sufficient data are available, we will conduct a random effects meta-analysis by combining the outcomes of the included studies. Sub-group analysis and meta-regression are planned to assess the potential harms and risks of different drug classes and the impacts in different patient populations (e.g. sex, cognitive status, renal status, and age).

Discussion
The study will be a comprehensive review on all published articles identified using our search strategy on the safety and efficacy of cardioprotective medication reduction in the older population. The findings will be crucial to inform clinicians on potential health outcomes of reducing cardiovascular medication in the elderly.

Systematic review registration
PROSPERO CRD42020208223
Exploring the socio-economic determinants of educational inequalities in diarrhoea among under-five children in low- and middle-income countries: a Fairlie decomposition analysis
Authors: Fagbamigbe Adeniyi Francis , Adebola Olukemi Grace , Dukhi Natisha , Fagbamigbe Omon Stellamaris , Uthman Olalekan A. 
Published: June 2021

Abstract
Background
What explains the underlying causes of educational inequalities in diarrhoea among under-five children in low- and middle-income countries (LMIC) is poorly exploited, operationalized, studied and understood. This paper aims to assess the magnitude of educational-related inequalities in the development of diarrhoea and decompose risk factors that contribute to these inequalities among under-five children (U5C) in LMIC.

Methods
Secondary data of 796,150 U5C from 63,378 neighbourhoods in 57 LMIC was pooled from the Demographic and Health Surveys (DHS) conducted between 2010 and 2019. The main determinate variable in this decomposition study was mothers’ literacy levels. Descriptive and inferential statistics comprising of bivariable analysis and binary logistic multivariable Fairlie decomposition techniques were employed at p = 0.05.

Results
Of the 57 countries, we found a statistically significant pro-illiterate odds ratio in 6 countries, 14 showed pro-literate inequality while the remaining 37 countries had no statistically significant educational-related inequality. The countries with pro-illiterate inequalities are Burundi (OR = 1.11; 95% CI: 1.01–1.21), Cameroon (OR = 1.84; 95% CI: 1.66–2.05), Egypt (OR = 1.26; 95% CI: 1.12–1.43), Ghana (OR = 1.24; 95% CI: 1.06–1.47), Nigeria (OR = 1.80; 95% CI: 1.68–1.93), and Togo (OR = 1.21; 95% CI: 1.06–1.38). Although there are variations in factors that contribute to pro-illiterate inequality across the 6 countries, the overall largest contributors to the inequality are household wealth status, maternal age, neighbourhood SES, birth order, toilet type, birth interval and place of residence. The widest pro-illiterate risk difference (RD) was in Cameroon (118.44/1000) while the pro-literate risk difference was widest in Albania (− 61.90/1000).

Conclusions
The study identified educational inequalities in the prevalence of diarrhoea in children with wide variations in magnitude and contributions of the risk factors to pro-illiterate inequalities. This suggests that diarrhoea prevention strategies is a must in the pro-illiterate inequality countries and should be extended to educated mothers as well, especially in the pro-educated countries. There is a need for further studies to examine the contributions of structural and compositional factors associated with pro-educated inequalities in the prevalence of diarrhoea among U5C in LMIC.