bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fidelity of implementation of recommended care for children with malaria by community health workers in Nigeria
Authors: Adeoti Oluwatomi , Spiegelman Donna , Afonne Chinenye , Falade Catherine O. , Jegede Ayodele S. , Oshiname Frederick O. , Gomes Melba , Ajayi IkeOluwapo O. 
Published: March 2020

Abstract
Background
In the context of task shifting, a promoted approach to healthcare delivery in resource-poor settings, trained community health workers (CHWs) have been shown to be effective in delivering quality care of malaria for febrile under-5 children. While their effectiveness has been documented, the fidelity of implementation (FOI) has not been adequately studied. By understanding and measuring whether an intervention has been performed with fidelity, researchers and practitioners gain a better understanding of how and why an intervention works, and the extent to which outcomes can be improved. The objective of this study was to assess the FOI of a recommended protocol for malaria care by CHWs in a resource-poor setting in Nigeria.

Methods
Thirty-five female CHWs who participated in a 3-day training on home management of malaria among under-5 children were studied. They managed 1,646 children over the implementation period and then underwent evaluation via a one-time hospital-based observation by the trainers. During the evaluation, a pre-tested standard checklist was used to compute performance scores for CHWs; doctors and nurses were selected to serve as the gold standard for comparison. Performance scores (PS) recorded during the evaluation were used to assess adherence and compliance with the recommended treatment protocol.

Results
Of the 4 skill domains assessed, adherence was greatest for compliance with malaria treatment recommendations (94%) and lowest for post-treatment initiation counseling of home-based caregivers (69%). The average overall adherence of 83% was comparable to adherence by gold standard comparators. Mean PS was not found to be significantly associated with CHW demographics. Scores for clinical evaluation among those whose occupation was not healthcare-related were significantly lowered by 0.52 [95% CI (1.05–0.01), p = 0.05]. Compliance with the treatment protocol increased by 23% for every unit increase in total PS (p = 0.07) and doubled for every unit increase in scores for post-treatment initiation counseling of caregivers (p = 0.002).

Conclusions
Studying intervention fidelity stands to identify the shortcomings of implementation and specific areas to target for improvement in future adoption or implementation. This study concludes that future trainings should emphasize clinical evaluation and post-treatment counseling of caregivers by CHWs to ensure the best outcome for children.
Single segment of spleen autotransplantation, after splenectomy for trauma, can restore splenic functions
Authors: Toro Adriana , Parrinello Nunziatina Laura , Schembari Elena , Mannino Maurizio , Corsale Giuseppe , Triolo Anna , Palermo Filippo , Romano Alessandra , Di Raimondo Francesco , Di Carlo Isidoro 
Published: March 2020

Abstract
Background
Splenectomy is sometimes necessary after abdominal trauma, but splenectomized patients are at risk of sepsis due to impaired immunological functions.
To overcome this risk, autotransplantation of the spleen by using a new technique has been proposed, but so far, a demonstration of functionality of the transplanted tissue is lacking.

Methods
We therefore evaluated 5 patients who underwent a splenic autotransplant in comparison with 5 splenectomized patients without splenic autotransplant and 7 normal subjects.

Results
We confirmed that the patients not undergoing autotransplantation, when compared to normal subjects, had a higher platelet count, higher percentage of micronucleated reticulocytes (p = 0.002), increased levels of naive B lymphocytes (p = 0.01), a defect of class-switched memory (p = 0.001) and class-unswitched memory B cells (p = 0.002), and increased levels of PD1 on T lymphocytes CD8+ (p = 0.08). In contrast, no significant differences for any of the abovementioned parameters were recorded between patients who underwent spleen autotransplantation and normal subjects.

Conclusion
These findings suggest that splenic autotransplantation is able to restore an adequate hemocatheretic activity as well as recover the immunological deficit after splenectomy.
Ability of adhesion and biofilm formation of pathogens of periprosthetic joint infections on titanium-niobium nitride (TiNbN) ceramic coatings
Authors: Bidossi Alessandro , Bottagisio Marta , De Grandi Roberta , De Vecchi Elena 
Published: March 2020

Abstract
Background
Orthopedic metal implants are notoriously associated with release of metallic ions able to cause biological adverse reactions which might lead to implant loosening and failure. To limit any possible adverse reactions, ceramic coatings for orthopedic metal implants have been introduced. However, information regarding the interaction of these coatings with microbes responsible for periprosthetic joint infections (PJIs) is lacking. Hence, the aim of the present in vitro study is to assess the microbial affinity to a titanium-niobium nitride (TiNbN) coating.

Methods
Adhesion and biofilm formation of clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Cutibacterium acnes were assessed on TiNbN-coated titanium discs in comparison with uncoated titanium and cobalt-chrome alloys discs, with either smooth or rough surfaces. Bacterial adhesion was performed by counting adhered bacteria in the first hours of incubation, and the biofilm formation was performed by means of a spectrophotometric assay and by confocal laser scan microscopy after 72 hours of incubation.

Results
Overall, Staphylococcus aureus and Staphylococcus epidermidis, among the most common bacteria responsible for PJIs, displayed a significantly decreased attachment in the first hours of contact and, when cultured in presence of TiNbN coating, in comparison with CoCrMo. Biofilm formation of the four tested strains was comparable on all alloys.

Conclusions
Although the onset of a PJI is more complex than in an in vitro scenario, these findings suggest that TiNbN-coated orthopedic implants do not increase PJIs risk while ameliorating tribological and surface properties could represent a valid choice to limit possible complications such as metal hypersensitivity.
Laryngeal chondritis as a differential for upper airway diseases in German sheep
Authors: Reineking Wencke , Punsmann Teresa Maria , Wagener Matthias Gerhard , Verspohl Jutta , Ganter Martin , Baumgärtner Wolfgang , Puff Christina 
Published: March 2020

Abstract
Background
Ovine laryngeal chondritis is a rare entity of sheep in the USA, Great Britain, New Zealand and Iceland, but has not been reported in Germany so far. Here, two German cases are reported.

Case presentation
Two rams showed severe and progressive signs of dyspnea. Endoscopically, a severe bilateral swelling of the larynx was identified in both rams. Due to poor prognosis and progression of clinical signs one ram was euthanized, while the other ram died overnight. In both cases, a necrosuppurative laryngitis and chondritis of arytenoid cartilages was found at necropsy. Fusobacterium necrophorum and Streptococcus ovis were isolated from the laryngeal lesion in one animal.

Conclusions
This is the first report of ovine laryngeal chondritis in continental Europe. This entity should be considered a differential diagnosis for upper airway disease in sheep.
Genome‐wide meta‐analysis identified novel variant associated with hallux valgus in Caucasians
Authors: Arbeeva Liubov , Yau Michelle , Mitchell Braxton D. , Jackson Rebecca D. , Ryan Kathleen , Golightly Yvonne M. , Hannan Marian T. , Nelson Amanda , Jordan Joanne M. , Hochberg Marc C. 
Published: March 2020

AbstractBackgroundHallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome‐wide association study (GWAS) conducted in 4409 Caucasians did not identify genome‐wide significant associations with hallux valgus in both gender‐specific and sex‐combined GWAS meta‐analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus.MethodsA total of 5925 individuals of European Ancestry were categorized into two groups: ‘hallux valgus present’ (n = 2314) or ‘no deformity’ (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex‐specific and sex‐combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed‐effects inverse‐variance meta‐analyses. Functional Mapping and Annotation web‐based platform (FUMA) was used for positional mapping, gene and gene‐set analyses.ResultsWe identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E‐09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family.ConclusionIn this report of the largest GWAS of hallux valgus to date, we identified a novel genome‐wide significant locus for hallux valgus. Additional replication and functional follow‐up will be needed to determine the functional role of this locus in hallux valgus biology.
Association between furosemide administration and outcomes in critically ill patients with acute kidney injury
Authors: Zhao Guang-ju , Xu Chang , Ying Jian-chao , Lü Wen-biao , Hong Guang-liang , Li Meng-fang , Wu Bing , Yao Yong-ming , Lu Zhong-qiu 
Published: March 2020

Abstract
Background
Although current guidelines for AKI suggested against the use of furosemide in AKI management, the effect of furosemide on outcomes in real-world clinical settings remains uncertain. The aim of the present study was to investigate the association between furosemide administration and outcomes in critically ill patients with AKI using real-world data.

Methods
Critically ill patients with AKI were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) matched analysis was used to match patients receiving furosemide to those without diuretics treatment. Linear regression, logistic regression model, and Cox proportional hazards model were used to assess the associations between furosemide and length of stay, recovery of renal function, and in-hospital and 90-day mortality, respectively.

Results
A total of 14,154 AKI patients were included in the data analysis. After PS matching, 4427 pairs of patients were matched between the patients who received furosemide and those without diuretics treatment. Furosemide was associated with reduced in-hospital mortality [hazard ratio (HR) 0.67; 95% CI 0.61–0.74; P < 0.001] and 90-day mortality [HR 0.69; 95% CI 0.64–0.75; P < 0.001], and it was also associated with the recovery of renal function [HR 1.44; 95% CI 1.31–1.57; P < 0.001] in over-all AKI patients. Nevertheless, results illustrated that furosemide was not associated with reduced in-hospital mortality in patients with AKI stage 0–1 defined by UO criteria, AKI stage 2–3 according to SCr criteria, and in those with acute-on-chronic (A-on-C) renal injury.

Conclusions
Furosemide administration was associated with improved short-term survival and recovery of renal function in critically ill patients with AKI. Furosemide was especially effective in patients with AKI UO stage 2–3 degree. However, it was not effective in those with AKI SCr stage 2–3 and chronic kidney disease. The results need to be verified in randomized controlled trials.
A nurse-led health coaching intervention for stroke survivors and their family caregivers in hospital to home transition care in Chongqing, China: a study protocol for a randomized controlled trial
Authors: Lin Shuanglan , Xiao Lily Dongxia , Chamberlain Diane 
Published: March 2020

Abstract
Background
Hospital to home transition care is a most stressful period for stroke survivors and their caregivers to learn self-management of stroke-related health conditions and to engage in rehabilitation. Health coaching has been identified as a strategy to enhance self-management of poststroke care at home. However, interventions in this field that are informed by a health coaching framework are scarce. This study will address a gap in research by testing the hypothesis that a nurse-led health coaching intervention can improve health outcomes for stroke survivors and their family caregivers in hospital to home transition care.

Methods
This is a single-blind, two-arm parallel randomized controlled trial of a nurse-led health coaching program versus routine care situated in two tertiary hospitals in Chongqing, China. Stroke survivors and their primary family caregivers will be recruited together as “participant dyads”, and the estimated sample size is 140 (70 in each group). The intervention includes a 12-week nurse-led health coaching program in hospital to home transition care commencing at discharge from the hospital. The primary outcome is changes in self-efficacy of stroke survivors at 12 weeks from the baseline. The secondary outcomes are changes in stroke survivors’ and quality of life, functional ability, stroke-related knowledge, the number of adverse events, and unplanned hospital admissions, and caregivers’ self-efficacy and caregiver-related burden at 12 weeks from the baseline. The outcomes will be measured at 12 weeks and 24 weeks from the baseline.

Discussion
This study will examine the effect of nurse-led health coaching on hospital to home transition care for stroke survivors and their caregivers. It is anticipated that findings from this trial will provide research evidence to inform policy, and resource and practice development to improve hospital to home transition care for stroke survivors and their caregivers.

Trial registration
The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000321145. Registered on 1 March 2019.
Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes
Authors: Mahadevan Iyer Aditya , Kumar Sanjeev , Rao Manchanahalli R. Satyanarayana 
Published: March 2020

Abstract
Background
H1t is the major linker histone variant in pachytene spermatocytes, where it constitutes 50–60% of total H1. This linker histone variant was previously reported to localize in the nucleolar rDNA element in mouse spermatocytes. Our main aim was to determine the extra-nucleolar localization of this linker histone variant in pachytene spermatocytes.

Results
We generated H1t-specific antibodies in rabbits and validated its specificity by multiple assays like ELISA, western blot, etc. Genome-wide occupancy studies, as determined by ChIP-sequencing in P20 mouse testicular cells revealed that H1t did not closely associate with active gene promoters and open chromatin regions. Annotation of H1t-bound genomic regions revealed that H1t is depleted from DSB hotspots and TSS, but are predominantly associated with retrotransposable repeat elements like LINE and LTR in pachytene spermatocytes. These chromatin domains are repressed based on co-association of H1t observed with methylated CpGs and repressive histone marks like H3K9me3 and H4K20me3 in vivo. Mass spectrometric analysis of proteins associated with H1t-containing oligonucleosomes identified piRNA–PIWI pathway proteins, repeat repression-associated proteins and heterochromatin proteins confirming the association with repressed repeat-element genomic regions. We validated the interaction of key proteins with H1t-containing oligonucleosomes by use of ChIP-western blot assays. On the other hand, we observe majority of H1t peaks to be associated with the intergenic spacer of the rDNA element, also in association with SINE elements of the rDNA element. Thus, we have identified the genomic and chromatin features of both nucleolar and extranucleolar localization patterns of linker histone H1t in the context of pachytene spermatocytes.

Conclusions
H1t-containing repeat-element LINE and LTR chromatin domains are associated with repressive marks like methylated CpGs, histone modifications H3K9me3 and H4K20me3, and heterochromatin proteins like HP1β, Trim28, PIWIL1, etc. Apart from localization of H1t at the rDNA element, we demonstrate the extranucleolar association of this linker histone variant at repeat-associated chromatin domains in pachytene spermatocytes. We hypothesize that H1t might induce local chromatin relaxation to recruit heterochromatin and repeat repression-associated protein factors necessary for TE (transposable element) repression, the final biological effect being formation of closed chromatin repressed structures.
Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study
Authors: Ochi Sae , Saito Kazuyoshi , Mizoguchi Fumitaka , Kato Shigeaki , Tanaka Yoshiya 
Published: March 2020

Abstract
Background
With advancement in the treatment options of rheumatoid arthritis (RA), optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice. In particular, insensitivity to first-line biologic disease-modifying anti-rheumatic drugs (bDMARD) is becoming a significant problem because it may decrease the treatment adherence of patients. This study aimed to compare RA patients with an insensitivity and those with a poor response to initial treatment with tumour necrosis factor inhibitors (TNFis), which are the most frequently used bDMARDs.

Methods
This is a retrospective cohort study using clinical data from the FIRST registry. bDMARD-naïve RA patients treated with tumour necrosis factor inhibitors (TNFis) from August 2003 to May 2019 were included and categorised into three groups: TNFi insensitivity, poor response to TNFis and controls. TNFi insensitivity was defined as follows: (1) discontinuation of TNFi treatment within 22 weeks due to lack of any response, or (2) an increase in the disease activity score in 28 joints–C-reactive protein (DAS28-CRP) of > 0.6 at week 22 compared with week 0. Among the remaining patients, those with a DAS28-CRP > 2.6 at week 22 were categorised in the poor response group.

Results
Of the included patients, 94 were classified in the insensitivity, 604 in the poor response and 915 in the control. A higher DAS28-CRP before treatment was a risk factor for a poor response but not for insensitivity. In contrast, dose escalation of infliximab decreased the risk of a poor response but not that of insensitivity.

Conclusions
In future research, poor and insensitivity to bDMARDs should be assessed separately to fully elucidate the aetiology of, and risk factors for, bDMARD refractoriness.
Factors related to poor adherence in Latvian asthma patients
Authors: Smits Dins , Brigis Girts , Pavare Jana , Urtane Inga , Kovalovs Sandis , Barengo Noël Christopher 
Published: March 2020

Abstract
Background
The problem of nonadherence to therapy is a key reason of insufficient asthma control. Evaluating the beliefs about asthma medication, cognitive and emotional perceptions may help to identify patients with poor adherence to treatment in clinical practice which need additional attention in order to increase the likelihood of them taking their asthma medication according to the prescribed treatment protocol. The purpose of this study is to assess whether beliefs about asthma medication, cognitive and emotional factors are related to poor treatment adherence of asthma medication in a sample of asthma patients in Latvia.

Methods
Study subjects were asthma patients attending outpatient pulmonologist consultations in Latvia during September 2013 to December 2015. Beliefs about asthma medicine, cognitive and emotional factors related to asthma were determined in a cross-sectional, self-administered survey. The validated Beliefs about Medicines Questionnaire (BMQ) and the Brief Illness Perception Questionnaire (brief IPQ) were used. Treatment adherence was assessed using 5-item version of the Medication Adherence Reporting Scale (MARS). The total sample size was 352 patients. Logistic regression models were used to predict poor adherence to asthma treatment. The validity of each logistic regression model was assessed by the Hosmer/Lemeshow test. The main outcome measure was self-reported adherence to treatment.

Results
The more the patients agreed with the statement “My future health depends on my asthma medication” the lower the possibility of poor adherence to asthma treatment (OR 0.42; 95% CI 0.24–0.74). The more concerned the patients were in regard to long-term effects of their medication (OR 2; 95% CI 1.22–3.27), the higher the probability of poor treatment adherence.

Conclusions
Screening asthma patients using the BMQ may help to identify those to benefit from interventions targeting their concerns and medication beliefs in order to improve adherence to asthma medication.
Mesenchymal stem cell-derived exosomes protect beta cells against hypoxia-induced apoptosis via miR-21 by alleviating ER stress and inhibiting p38 MAPK phosphorylation
Authors: Chen Jin , Chen Junqiu , Cheng Yuanhang , Fu Yunfeng , Zhao Hongzhou , Tang Minying , Zhao Hu , Lin Na , Shi Xiaohua , Lei Yan , Wang Shuiliang , Huang Lianghu , Wu Weizhen , Tan Jianming 
Published: March 2020

Abstract
Background
Hypoxia is a major cause of beta cell death and dysfunction after transplantation. The aim of this study was to investigate the effect of exosomes derived from mesenchymal stem cells (MSCs) on beta cells under hypoxic conditions and the potential underlying mechanisms.

Methods
Exosomes were isolated from the conditioned medium of human umbilical cord MSCs and identified by WB, NTA, and transmission electron microscopy. Beta cells (βTC-6) were cultured in serum-free medium in the presence or absence of exosomes under 2% oxygen conditions. Cell viability and apoptosis were analysed with a CCK-8 assay and a flow cytometry-based annexin V-FITC/PI apoptosis detection kit, respectively. Endoplasmic reticulum stress (ER stress) proteins and apoptosis-related proteins were detected by the WB method. MiRNAs contained in MSC exosomes were determined by Illumina HiSeq, and treatment with specific miRNA mimics or inhibitors of the most abundant miRNAs was used to reveal the underlying mechanism of exosomes.

Results
Exosomes derived from MSC-conditioned culture medium were 40–100 nm in diameter and expressed the exosome markers CD9, CD63, CD81, HSP70, and Flotillin 1, as well as the MSC markers CD73, CD90, and CD105. Hypoxia significantly induced beta cell apoptosis, while MSC exosomes remarkably improved beta cell survival. The WB results showed that ER stress-related proteins, including GRP78, GRP94, p-eIF2α and CHOP, and the apoptosis-related proteins cleaved caspase 3 and PARP, were upregulated under hypoxic conditions but were inhibited by MSC exosomes. Moreover, the p38 MAPK signalling pathway was activated by hypoxia and was inhibited by MSC exosomes. The Illumina HiSeq results show that MSC exosomes were rich in miR-21, let-7 g, miR-1246, miR-381, and miR-100. After transfection with miRNA mimics, the viability of beta cells under hypoxia was increased significantly by miR-21 mimic, and the p38 MAPK and ER stress-related proteins in beta cells were downregulated. These changes were reversed after exosomes were pretreated with miR-21 inhibitor.

Conclusions
Exosomes derived from MSCs could protect beta cells against apoptosis induced by hypoxia, largely by carrying miR-21, alleviating ER stress and inhibiting p38 MAPK signalling. This result indicated that MSC exosomes might improve encapsulated islet survival and benefit diabetes patients.