bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composition and short-term stability of gut microbiota in lean and spontaneously overweight healthy Labrador retriever dogs
Authors: Söder Josefin , Wernersson Sara , Höglund Katja , Hagman Ragnvi , Lindåse Sanna , Dicksved Johan 
Published: March 2022

AbstractBackgroundThe gut microbiota and its metabolic end-products act in close collaboration with the nutrient metabolism of the animal. A relationship between excess adiposity and alterations in gut microbiota composition has been identified in humans and rodents, but data are scarce for overweight dogs. This study compared composition and temporal variations of gut microbiota in healthy lean and spontaneously overweight dogs. The analysis was based on three individual fresh faeces samples from each dog during a 10-day period. Twenty-seven healthy and intact male Labrador retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4–5 on a 9-point scale) and 15 as overweight (BCS 6–8). Gut microbiota was analysed by Illumina sequencing of the V3-V4 region of the 16S rRNA gene.ResultsLean and overweight groups of dogs were not separated by principal coordinate analysis (PCoA), analysis of similarity (one-way ANOSIM, P = 0.99) or species indicator analysis (IndVal) using operational taxonomic units (OTU) data. Gut microbial taxa at phylum, family or genus level did not differ between lean and overweight dogs in mixed-model repeated measures analyses. Short-term stability, evaluated by similarity index, did not differ between lean and overweight dogs over the 10-day period. Pooled Firmicutes/Bacteroidetes (F/B) ratio was 3.1 ± 3.7 in overweight dogs and 2.1 ± 1.2 in lean dogs (P = 0.83). Individual dogs, irrespective of body condition (lean or overweight), displayed variation in mean alpha diversity (Chao-1 index range 122–245, Shannon index range 2.6–3.6) and mean similarity index (range 44–85%).ConclusionsHealthy lean and spontaneously overweight Labrador retriever dogs had comparable gut microbiota composition and short-term stability over a 10-day sampling period. There were no alterations in microbial diversity or in relative abundance of specific taxa at phylum, family or genus level in overweight compared to lean dogs. Our findings suggest that there are few detectable differences in gut microbiota composition between healthy spontaneously overweight and lean dogs by the current method. Future application of metagenomic or metabolomic techniques could be used to investigate microbial genes or microbial end-products that may differ even when microbiota compositional analyses fail to detect a significant difference between lean and overweight dogs.
Identifying transferable lessons from cholera epidemic responses by Médecins Sans Frontières in Mozambique, Malawi and the Democratic Republic of Congo, 2015–2018: a scoping review
Authors: D’Mello-Guyett Lauren , Cumming Oliver , Rogers Elliot , D’hondt Rob , Mengitsu Estifanos , Mashako Maria , Van den Bergh Rafael , Welo Placide Okitayemba , Maes Peter , Checchi Francesco 
Published: March 2022

AbstractBackgroundCholera epidemics occur frequently in low-income countries affected by concurrent humanitarian crises. Evaluations of these epidemic response remains largely unpublished and there is a need to generate evidence on response efforts to inform future programmes. This review of MSF cholera epidemic responses aimed to describe the main characteristics of the cholera epidemics and related responses in these three countries, to identify challenges to different intervention strategies based on available data; and to make recommendations for epidemic prevention and control practice and policy.MethodsCase studies from the Democratic Republic of Congo, Malawi and Mozambique were purposively selected by MSF for this review due to the documented burden of cholera in each country, frequency of cholera outbreaks, and risk of humanitarian crises. Data were extracted on the characteristics of the epidemics; time between alert and response; and, the delivery of health and water, sanitation and hygiene interventions. A Theory of Change for cholera response programmes was built to assess factors that affected implementation of the responses.Results and conclusions20 epidemic response reports were identified, 15 in DRC, one in Malawi and four in Mozambique. All contexts experienced concurrent humanitarian crises, either armed conflict or natural disasters. Across the settings, median time between the date of alert and date of the start of the response by MSF was 23 days (IQR 14–41). Almost all responses targeted interventions community-wide, and all responses implemented in-patient treatment of suspected cholera cases in either established health care facilities (HCFs) or temporary cholera treatment units (CTUs). In three responses, interventions were delivered as case-area targeted interventions (CATI) and four responses targeted households of admitted suspected cholera cases. CATI or delivery of interventions to households of admitted suspected cases occurred from 2017 onwards only. Overall, 74 factors affecting implementation were identified including delayed supplies of materials, insufficient quantities of materials and limited or lack of coordination with local government or other agencies. Based on this review, the following recommendations are made to improve cholera prevention and control efforts: explore improved models for epidemic preparedness, including rapid mobilisation of supplies and deployment of trained staff; invest in and strengthen partnerships with national and local government and other agencies; and to standardise reporting templates that allow for rigorous and structured evaluations within and across countries to provide consistent and accessible data.
Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells
Authors: Huang Yue , Si Xiaohui , Shao Mi , Teng Xinyi , Xiao Gang , Huang He 
Published: March 2022

AbstractShort persistence and early exhaustion of T cells are major limits to the efficacy and broad application of immunotherapy. Exhausted T and chimeric antigen receptor (CAR)-T cells upregulate expression of genes associated with terminated T cell differentiation, aerobic glycolysis and apoptosis. Among cell exhaustion characteristics, impaired mitochondrial function and dynamics are considered hallmarks. Here, we review the mitochondrial characteristics of exhausted T cells and particularly discuss different aspects of mitochondrial metabolism and plasticity. Furthermore, we propose a novel strategy of rewiring mitochondrial metabolism to emancipate T cells from exhaustion and of targeting mitochondrial plasticity to boost CAR-T cell therapy efficacy.
hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
Authors: Martinelli Ilaria , Modica Chiara , Chiriaco Cristina , Basilico Cristina , Hughes James M. , Corso Simona , Giordano Silvia , Comoglio Paolo M. , Vigna Elisa 
Published: March 2022

Abstract
Background
The tyrosine kinase receptor encoded by the MET oncogene is a major player in cancer. When MET is responsible for the onset and progression of the transformed phenotype (MET-addicted cancers), an efficient block of its oncogenic activation results in potent tumor growth inhibition.

Methods
Here we describe a molecular engineered MET antibody (hOA-DN30) and validate its pharmacological activity in MET-addicted cancer models in vitro and in vivo. Pharmacokinetics and safety profile in non-human primates have also been assessed.

Results
hOA-DN30 efficiently impaired MET activation and the intracellular signalling cascade by dose and time dependent removal of the receptor from the cell surface (shedding). In vitro, the antibody suppressed cell growth by blocking cell proliferation and by concomitantly inducing cell death in multiple MET-addicted human tumor cell lines. In mice xenografts, hOA-DN30 induced an impressive reduction of tumor masses, with a wide therapeutic window. Moreover, the antibody showed high therapeutic efficacy against patient-derived xenografts generated from MET-addicted gastric tumors, leading to complete tumor regression and long-lasting effects after treatment discontinuation. Finally, hOA-DN30 showed a highly favorable pharmacokinetic profile and substantial tolerability in Cynomolgus monkeys.

Conclusions
hOA-DN30 unique ability to simultaneously erase cell surface MET and release the ‘decoy’ receptor extracellular region results in a paramount MET blocking action. Its remarkable efficacy in a large number of pre-clinical models, as well as its pharmacological features and safety profile in non-human primates, strongly envisage a successful clinical application of this novel single-arm MET therapeutic antibody for the therapy of MET-addicted cancers.
Retention in RCTs of physical rehabilitation for adults with frailty: a systematic review and meta-analysis
Authors: O’Grady Heather K. , Farley Christopher , Takaoka Alyson , Mayens Elisa , Bosch Jackie , Turkstra Lyn , Kho Michelle E. 
Published: March 2022

Abstract
Background
Physical rehabilitation (PR) interventions can improve physical function for adults with frailty; however, participant retention rates in randomized controlled trials (RCTs) are unknown.
Objective is to summarize participant retention rates in RCTs of PR for adults with frailty.
Design is a systematic review and meta-analysis (DOI:10.17605/OSF.IO/G6XR2).
Participants are adults ≥ 18 years with frailty.
Setting consists of inpatient, outpatient and community-based interventions.
Intervention includes any PR intervention.

Methods
We searched 7 electronic databases from inception to April 15, 2020 for published RCTs. Our primary outcome was participant retention rate to primary outcome measurement. Secondary outcomes included retention by study group, participant retention to intervention completion, reported reasons for attrition and reported strategies for maximizing retention. We completed screening, data extraction and risk of bias (ROB) assessments independently and in duplicate. We conducted a meta-analysis, calculating retention rates and 95% confidence intervals (CIs) using fixed or random-effects models, as appropriate.

Results
We included 21 RCTs, enrolling 1685 adults with frailty (median age 82.5 years (79.0, 82.2), 59.8% female (57.5, 69.8)). Twenty RCTs reported retention data, of which 90.0% (n = 18) had high ROB. The pooled participant retention rate to primary outcome measurement was 85.0% [95%CI (80.0, 90.0), I2 = 83.9%, p < 0.05]. There were no differences by group for retention to the primary outcome [intervention 87.0% (83.0, 91.0), p < 0.05, comparator 85.0% (79.0, 90.0), p < 0.05] or in retention to intervention completion [83.0% (95.0% CI (78.0–87.0), p < 0.05]. Of the 18 studies reporting 24 reasons for attrition, 51.3% were categorized as potentially modifiable by the research team (e.g. low motivation). Only 20.0% (n = 4) of studies reported strategies for maximizing retention.

Conclusions
In this review of 21 RCTs of PR, we identified acceptable rates of retention for adults with frailty. High retention in PR interventions appears to be feasible in this population; however, our results are limited by a high ROB and heterogeneity.
Electrical dry needling versus conventional physiotherapy in the treatment of active and latent myofascial trigger points in patients with nonspecific chronic low back pain
Authors: Lara-Palomo Inmaculada Carmen , Gil-Martínez Esther , Antequera-Soler Eduardo , Castro-Sánchez Adelaida María , Fernández-Sánchez Manuel , García-López Héctor 
Published: March 2022

Abstract
Background
Chronic low back pain is considered to be one of the main causes of absenteeism from work and primary and specialized consultations. The symptoms of nonspecific chronic low back pain may be accompanied by the activation of myofascial trigger points in the muscles, together with local and/or referred pain. Electrical dry needling is increasingly used in the treatment of lumbar myofascial pain. Conventional physiotherapy, however, is a popular approach to chronic pathologies, and there is evidence of different modalities of physiotherapy being used in the treatment of chronic low back pain. The aim of this study has been to determine the effectiveness of electrical dry needling versus conventional physiotherapy when applied to active and latent myofascial trigger points in patients with nonspecific chronic low back pain.

Methods
This is a controlled, randomized, two-arm, double-blind study. A total of 92 patients with chronic low back pain (time to onset ≥ 3 months, Roland Morris Disability Questionnaire score ≥ 4) will be recruited from the University of Almería. Participants will be divided into two study groups (n = 40) to receive treatment of low back pain with electrical dry needling and conventional physiotherapy (ischaemic compression, analytic stretching and postural education training dossier). A total of 6 sessions will be administered once a week for 6 weeks. Pain intensity, disability, fear of movement, quality of life, quality of sleep, anxiety and depression, pressure pain threshold, abdominal strength and lumbar mobility will be recorded at 6 weeks (post-immediate) and 2 months after the end of treatment.

Discussion
We believe that an approach including electrical dry needling to chronic low back pain dysfunction will be more effective in these patients. The results of this study will inform clinicians on which type of treatment is more beneficial for patients with chronic low back pain.

Trial registration
ClinicalTrials.gov NCT04804228. Registered on 14 January 2021
Clinical- and cost-effectiveness of a technology-supported and solution-focused intervention (DIALOG+) in treatment of patients with chronic depression—study protocol for a multi-site, cluster randomised controlled trial [TACK]
Authors: McNamee Philip , Matanov Aleksandra , Jerome Lauren , Kerry Sally , Walker Neil , Feng Yan , Molodynski Andrew , Scott Shonagh , Guruvaiah Latha , Collinson Sue , McCabe Rose , Geddes John , Priebe Stefan , Bird Victoria 
Published: March 2022

Abstract
Background
Many with an acute depressive disorder go on to develop chronic depression, despite ongoing care. There are few specifically designed interventions to treat chronic depression. DIALOG+, a technology-assisted intervention based on the principles of solution-focused therapy, may be beneficial. It has been shown to be effective as a treatment for patients with psychotic disorders, especially in regards to increasing quality of life. DIALOG+ was designed to be flexibly applied and not diagnosis-specific, aiming to structure communication and generate a personally-tailored care plan. This cluster randomised controlled trial (RCT) is part of a programme of research to adapt and test DIALOG+ for patients with chronic depression.

Methods
Patients will be eligible for the trial, if they have exhibited symptoms of depression or non-psychotic low mood for at least 2 years, have regular contact with a clinician and have a low subjective quality of life and moderate depressive symptoms. Clinicians, who routinely see eligible patients, will be recruited from a number of sites across NHS England. Clusters will have between 1 and 6 patients per clinician and will be randomised in a 1:1 ratio to either the intervention (DIALOG+) or active control group (treatment as usual + DIALOG scale). Clinicians in the intervention group are trained and asked to deliver the intervention regularly for 12 months. Active control participants receive treatment as usual and are asked to rate their satisfaction with areas of life and treatment on the DIALOG scale at the end of the clinical session. Approximately 112 clinician clusters will be recruited to reach a total patient sample size of 376. Clinical and social outcomes including costs are assessed at baseline and 3, 6 and 12 months post randomisation. The primary outcome will be subjective quality of life at 12 months.

Discussion
This definitive multi-site, cluster RCT aims to evaluate the clinical- and cost-effectiveness of DIALOG+ for people with chronic depression. If shown to be effective for this patient population it could be used to improve outcomes of mental health care on a larger scale, ensuring that patients with complex and co-morbid diagnoses can benefit.

Trial registration
ISRCTN11301686. Registered on 13 Jun 2019.
Nyssorhynchus darlingi genome-wide studies related to microgeographic dispersion and blood-seeking behavior
Authors: Alvarez Marcus Vinicius Niz , Alonso Diego Peres , Kadri Samir Moura , Rufalco-Moutinho Paulo , Bernardes Isabella Ariadne Ferrari , de Mello Ana Carolina Florindo , Souto Ana Carolina , Carrasco-Escobar Gabriel , Moreno Marta , Gamboa Dionicia , Vinetz Joseph M. , Conn Jan E. , Ribolla Paulo E. M. 
Published: March 2022

Abstract
Background
In Brazil, malaria is concentrated in the Amazon Basin, where more than 99% of the annual cases are reported. The main goal of this study was to investigate the population structure and genetic association of the biting behavior of Nyssorhynchus (also known as Anopheles) darlingi, the major malaria vector in the Amazon region of Brazil, using low-coverage genomic sequencing data.

Methods
Samples were collected in the municipality of Mâncio Lima, Acre state, Brazil between 2016 and 2017. Different approaches using genotype imputation and no gene imputation for data treatment and low-coverage sequencing genotyping were performed. After the samples were genotyped, population stratification analysis was performed.

Results
Weak but statistically significant stratification signatures were identified between subpopulations separated by distances of approximately 2–3 km. Genome-wide association studies (GWAS) were performed to compare indoor/outdoor biting behavior and blood-seeking at dusk/dawn. A statistically significant association was observed between biting behavior and single nucleotide polymorphism (SNP) markers adjacent to the gene associated with cytochrome P450 (CYP) 4H14, which is associated with insecticide resistance. A statistically significant association between blood-seeking periodicity and SNP markers adjacent to genes associated with the circadian cycle was also observed.

Conclusion
The data presented here suggest that low-coverage whole-genome sequencing with adequate processing is a powerful tool to genetically characterize vector populations at a microgeographic scale in malaria transmission areas, as well as for use in GWAS. Female mosquitoes entering houses to take a blood meal may be related to a specific CYP4H14 allele, and female timing of blood-seeking is related to circadian rhythm genes.

Graphical Abstract
Use of novel lab assays to examine the effect of pyrethroid-treated bed nets on blood-feeding success and longevity of highly insecticide-resistant Anopheles gambiae s.l. mosquitoes
Authors: Barreaux Priscille , Koella Jacob C. , N’Guessan Raphael , Thomas Matthew B. 
Published: March 2022

Abstract
Background
There is a pressing need to improve understanding of how insecticide resistance affects the functional performance of insecticide-treated nets (ITNs). Standard WHO insecticide resistance monitoring assays are designed for resistance surveillance and do not necessarily provide insight into how different frequencies, mechanisms or intensities of resistance affect the ability of ITNs to reduce malaria transmission.

Methods
The current study presents some novel laboratory-based assays that attempt to better simulate realistic exposure of mosquitoes to ITNs and to quantify impact of exposure not only on instantaneous mortality, but also on blood-feeding and longevity, two traits that are central to transmission. The assays evaluated the performance of a standard ITN (Permanet® 2.0; Vestergaard Frandsen), a ‘next generation’ combination ITN with a resistance-breaking synergist (Permanet® 3.0) and an untreated net (UTN), against field-derived Anopheles gambiae sensu lato mosquitoes from Côte d’Ivoire exhibiting a 1500-fold increase in pyrethroid resistance relative to a standard susceptible strain.

Results
The study revealed that the standard ITN induced negligible instantaneous mortality against the resistant mosquitoes, whereas the resistance-breaking net caused high mortality and a reduction in blood-feeding. However, both ITNs still impacted long-term survival relative to the UTN. The impact on longevity depended on feeding status, with blood-fed mosquitoes living longer than unfed mosquitoes following ITN exposure. Exposure to both ITNs also reduced the blood-feeding success, the time spent on the net and blood-feeding duration, relative to the untreated net.

Conclusion
Although a standard ITN did not have as substantial instantaneous impact as the resistance-breaking net, it still had significant impacts on traits important for transmission. These results highlight the benefit of improved bioefficacy assays that allow for realistic exposure and consider sub- or pre-lethal effects to help assess the functional significance of insecticide resistance.

Graphical Abstract
Geographical distribution of ixodid ticks and tick-borne pathogens of domestic animals in Ethiopia: a systematic review
Authors: Kaba Tamirat 
Published: March 2022

Abstract
Background
In Ethiopia, ixodid ticks and associated tick-borne pathogens (TBPs) are of great importance from both a veterinary and public health point of view. This review aimed at compiling available published data on the distribution of ixodid tick species and TBPs in the country.

Methods
A standard review approach was employed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Published peer-reviewed articles and theses/dissertations reporting on ixodid ticks and TBPs in Ethiopia were searched using different keywords in many electronic databases including PubMed, Scopus, Web of Science, Google Scholar, African Journals OnLine, and institutional repositories. Articles were screened based on inclusion and exclusion criteria using the PRISMA flowchart. Data were retrieved from eligible articles and recorded in a preformed data record sheet. Descriptive statistics were employed to present data using graphs. QGIS (Quantum GIS) software version 3.4.5 was used to show the distribution of ixodid tick species and TBPs.

Results
Overall, 35 articles that met the inclusion criteria were included in this review. Of these, 24 articles report only on ixodid ticks of domestic animals, six articles report only on TBPs in livestock or ticks, and five articles report on both ticks and TBPs in either animals or ticks. Of these studies, 54% were in the Oromia region, while only 3% of studies were in the Benishangul-Gumuz region. The Gambela region lacked studies on ticks and TBPs. At least 19 ixodid tick species have been recorded from different domestic animals including cattle, small ruminants, donkeys, horses, camels, dogs, and cats. Morphological characterization appears to be the sole method of tick species identification in the country. The distribution and abundance of specific tick species depend on geographical locations and agroecological factors. Sixteen molecularly confirmed TBPs have been identified in animal and tick tissue using molecular methods from only four administrative regions, despite the wide distribution of ticks. Among TBPs, five Anaplasma, two Ehrlichia, two Rickettsia, five Theileria, two Babesia, and one Coxiella species are the major pathogens in both livestock and humans.

Conclusions
Many ixodid ticks circulate in a wide geographical zone of Ethiopia. However, the limited reports on TBPs at the country level in general, and the absence of either tick or TBP reports around the border region with neighboring countries in particular, highlights the need for further study.

Graphical Abstract