Miracle-dz/UniFAR-FTUs huggingface dataset:
Web-based physiotherapy for people affected by multiple sclerosis: a single blind, randomized controlled feasibility study

Objective: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis. Design: Multi-centre, randomized controlled, feasibility study. Setting: Three multiple sclerosis out-patient centres. Participants: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4–6.5). Interventions: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy (n = 45; intervention) or a sheet of exercises (n = 45; active comparator). Outcome measures: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists. Results: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%–63% and 53%–71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial. Conclusion: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants.
Obtaining quality data using behavioral measures of impulsivity in gambling research with Amazon’s Mechanical Turk

Background and aims To date, no research has examined the viability of using behavioral tasks typical of cognitive and neuropsychology within addiction populations through online recruitment methods. Therefore, we examined the reliability and validity of three behavioral tasks of impulsivity common in addiction research in a sample of individuals with a current or past history of problem gambling recruited online. Methods Using a two-stage recruitment process, a final sample of 110 participants with a history of problem or disordered gambling were recruited through MTurk and completed self-report questionnaires of gambling involvement symptomology, a Delay Discounting Task (DDT), Balloon Analogue Risk Task (BART), Cued Go/No-Go Task, and the UPPS-P. Results Participants demonstrated logically consistent responding on the DDT. The area under the empirical discounting curve (AUC) ranged from 0.02 to 0.88 (M = 0.23). The BART demonstrated good split-third reliability (ρs = 0.67 to 0.78). The tasks generally showed small correlations with each other (ρs = ±0.06 to 0.19) and with UPPS-P subscales (ρs = ±0.01 to 0.20). Discussion and conclusions The behavioral tasks demonstrated good divergent validity. Correlation magnitudes between behavioral tasks and UPPS-P scales and mean scores on these measures were generally consistent with the existing literature. Behavioral tasks of impulsivity appear to have utility for use with problem and disordered gambling samples collected online, allowing researchers a cost efficient and rapid avenue for conducting behavioral research with gamblers. We conclude with best-practice recommendations for using behavioral tasks using crowdsourcing samples.
Use of IL‐1 &bgr;, IL‐6, TNF‐&agr;, and MMP‐8 biomarkers to distinguish peri‐implant diseases: A systematic review and meta‐analysis

OBJECTIVE To investigate the use of peri-implant crevicular fluid (PICF) interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-8 (MMP-8) biomarkers in distinguishing between healthy implants (H), peri-implant mucositis (MU), and peri-implantitis (PI). MATERIAL AND METHODS Electronic using three databases (Pubmed, EMBASE, and Cochrane) and manual searches were conducted for articles published up to March 2018 by two independent calibrated reviewers. Meta-analyses using a random-effects model were conducted for each of the cytokines; IL-1β, IL-6, and TNF-α, to analyze standardized mean difference (SMD) between H and MU, MU and PI, H and PI with their associated 95% confidence intervals (CI). Qualitative assessment of MMP-8 was provided consequent to the lack of studies that provide valid data for a meta-analysis. RESULTS Nineteen articles were included in this review. IL-1β, IL-6, and TNF-α, levels were significantly higher in MU than H groups (SMD: 1.94; 95% CI: 0.87, 3.35; P < .001, SMD: 1.17; 95% CI: 0.16, 3.19; P = .031 and SMD: 3.91; 95% CI: 1.13, 6.70; P = .006, respectively). Similar results were obtained with PI compared to H sites (SMD: 2.21, 95% CI: 1.32, 3.11; P < .001, SMD: 1.72; 95% CI: 0.56, 2.87; P = .004 and SMD: 3.78; 95% CI: 1.67, 5.89; P < .001, respectively). IL-6 was statistically higher in PI than MU sites (SMD = 1.46; 95% CI: 0.36, 2.55; P = .009); while IL-1ß increase was not significant. Despite absence of meta-analysis, MMP-8 show to be a promising biomarker in detection of PI in literature. CONCLUSION Within the limitations of this study, pro-inflammatory cytokines in PICF, such as IL-1ß and IL-6, can be used as adjunct tools to clinical parameters to differentiate H from MU and PI.
Does the clinical phenotype of mucolipidosis-III&ggr; differ from its &agr;&bgr; counterpart?: supporting facts in a cohort of 18 patients

Mucolipidosis-III&ggr; (ML-III&ggr;) is a recessively inherited slowly progressive skeletal dysplasia caused by mutations in GNPTG. We report the genetic and clinical findings in the largest cohort with ML-III&ggr; so far: 18 affected individuals from 12 families including 12 patients from India, five from Turkey, and one from the USA. With consanguinity confirmed in eight of 12 families, molecular characterization showed that all affected patients had homozygous pathogenic GNPTG genotypes, underscoring the rarity of the disorder. Unlike ML-III&agr;&bgr;, which present with a broader spectrum of severity, the ML-III &ggr; phenotype is milder, with onset in early school age, but nonetheless thus far considered phenotypically not differentiable from ML-III&agr;&bgr;. Evaluation of this cohort has yielded phenotypic findings including hypertrophy of the forearms and restricted supination as clues for ML-III&ggr;, facilitating an earlier correct choice of genotype screening. Early identification of this disorder may help in offering a timely intervention for the relief of carpal tunnel syndrome, monitoring and surgery for cardiac valve involvement, and evaluation of the need for joint replacement. As this condition may be confused with rheumatoid arthritis, confirmation of diagnosis will prevent inappropriate use of immunosuppressants and disease-modifying agents.
Neutrophils Restrict Tumor-Associated Microbiota to Reduce Growth and Invasion of Colon Tumors in Mice.

BACKGROUND & AIMS Neutrophils are among the most prevalent immune cells in the microenvironment of colon tumors; they are believed to promote growth of colon tumors, and their numbers correlate with outcomes of patients with colon cancer. Trials of inhibitors of neutrophil trafficking are underway in patients with cancer, but it is not clear how neutrophils contribute to colon tumorigenesis. METHODS Colitis-associated colon cancer was induced in mice with conditional deletion of neutrophils (LysMCre;Mcl1fl/fl) and wild-type littermates (LysMCre;Mcl1wt/wt, control mice) by administration of azoxythmethane and/or dextran sulfate sodium. Sporadic colon tumorigenesis was assessed in neutrophil-deficient and neutrophil-replete mice with conditional deletion of colon epithelial Apc (Cdx2-CreERT2;Apcfl/fl). Primary colon tumor tissues from these mice were assessed by histology, RNA sequencing, quantitative polymerase chain reaction, and fluorescence in situ hybridization analyses. Fecal and tumor-associated microbiota were assessed by 16s ribosomal RNA sequencing. RESULTS In mice with inflammation-induced and sporadic colon tumors, depletion of neutrophils increased the growth, proliferation, and invasiveness of the tumors. RNA sequencing analysis identified genes that regulate antimicrobial and inflammatory processes that were dysregulated in neutrophil-deficient colon tumors compared with colon tumors from control mice. Neutrophil depletion correlated with increased numbers of bacteria in tumors and proliferation of tumor cells, tumor-cell DNA damage, and an inflammatory response mediated by interleukin 17 (IL17). The 16s ribosomal RNA sequencing identified significant differences in the composition of the microbiota between colon tumors from neutrophil-deficient vs control mice. Administration of antibiotics or a neutralizing antibody against IL17 to neutrophil-deficient mice resulted in development of less-invasive tumors compared with mice given vehicle. We found bacteria in tumors to induce production of IL17, which promotes influx of intratumor B cells that promote tumor growth and progression. CONCLUSIONS In comparisons of mice with vs without neutrophils, we found neutrophils to slow colon tumor growth and progression by restricting numbers of bacteria and tumor-associated inflammatory responses.
Anterior Cranial Vault Reconstruction With Distraction for Primary and Secondary Craniosynostosis Repair

Abstract Traditional fronto-orbital advancement continues to be a useful operation for correction of craniosynostosis involving the coronal or metopic sutures. Recently, distraction osteogenesis has been used to correct a variety of cranial deformities. Studies have mostly focused on posterior vault distraction due to its simplicity and greater volume gain when compared with anterior vault distraction. However, certain patients are not candidates for posterior distraction due to anterior deformity and need for expansion of the frontal skull. The authors have developed a technique that allows for both reshaping as well as distraction of the anterior cranial vault. This was a retrospective chart review performed between March 2012 and October 2016 at a single institution by a single plastic surgeon. Thirty-nine (39) patients were included in this study. The indications for surgical intervention were signs of increased intracranial pressure or severe anterior skull deformity in the setting of craniosynostosis. The authors reviewed patient characteristics, length of follow-up, number of previous and subsequent surgeries, complications, and rate of relapse. The average age of patients undergoing the procedure was 5.2 years (range 6 months–15 years). Twenty-four (24) patients had 1 previous surgery, 3 had 2 previous surgeries, 1 had 3 previous surgeries, and 11 had no previous surgeries. The average follow-up was 2.5 years (range 6 months–4 years). One patient had a broken activation wire requiring return to the operating room. Three (3) patients (2 Apert and 1 Crouzon) underwent subsequent posterior vault distraction surgery. All patients demonstrated significant improvement in forehead cosmesis. Anterior cranial vault reconstruction with distraction is a safe alternative to traditional cranial vault reconstruction. It can improve forehead shape and position in older children who have had previous surgery as well as patients with severe anterior skull deformity associated with craniosynostosis.
A Novel Class of Human Cardiac Stem Cells

Following the recognition that hematopoietic stem cells improve the outcome of myocardial infarction in animal models, bone marrow mononuclear cells, CD34-positive cells, and mesenchymal stromal cells have been introduced clinically. The intracoronary or intramyocardial injection of these cell classes has been shown to be safe and to produce a modest but significant enhancement in systolic function. However, the identification of resident cardiac stem cells in the human heart (hCSCs) has created great expectation concerning the potential implementation of this category of autologous cells for the management of the human disease. Although phase 1 clinical trials have been conducted with encouraging results, the search for the most powerful hCSC for myocardial regeneration is in its infancy. This manuscript discusses the efforts performed in our laboratory to characterize the critical biological variables that define the growth reserve of hCSCs. Based on the theory of the immortal DNA template, we propose that stem cells retaining the old DNA represent 1 of the most powerful cells for myocardial regeneration. Similarly, the expression of insulin-like growth factor-1 receptors in hCSCs recognizes a cell phenotype with superior replicating reserve. However, the impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the “mother” DNA underscores the clinical relevance of this hCSC class for the treatment of human heart failure.
Improving screening for malnourished children at high risk of death: a study of children aged 6–59 months in rural Senegal

Abstract Objective To investigate whether children with concurrent wasting and stunting require therapeutic feeding and to better understand whether multiple diagnostic criteria are needed to identify children with a high risk of death and in need of treatment. Design Community-based cohort study, following 5751 children through time. Each child was visited up to four times at 6-month intervals. Anthropometric measurements were taken at each visit. Survival was monitored using a demographic surveillance system operating in the study villages. Setting Niakhar, a rural area of the Fatick region of central Senegal. Participants Children aged 6–59 months living in thirty villages in the study area. Results Weight-for-age Z-score (WAZ) and mid-upper arm circumference (MUAC) were independently associated with near-term mortality. The lowest WAZ threshold that, in combination with MUAC, detected all deaths associated with severe wasting or concurrent wasting and stunting was WAZ <−2·8. Performance for detecting deaths was best when only WAZ and MUAC were used. Additional criteria did not improve performance. Risk ratios for near-term death in children identified using WAZ and MUAC suggest that children identified by WAZ <−2·8 but with MUAC≥115 mm may require lower-intensity treatment than children identified using MUAC <115 mm. Conclusions A combination of MUAC and WAZ detected all near-term deaths associated with severe anthropometric deficits including concurrent wasting and stunting. Therapeutic feeding programmes may achieve higher impact if WAZ and MUAC admission criteria are used.
Lymph node upstaging for non-small cell lung cancer after uniportal video-assisted thoracoscopy.

Background Radical lymph node dissection (LND) plays a major role in the treatment of non-small cell lung cancer (NSCLC). This study presents the analysis of the results after uniportal video-assisted thoracoscopy (VATS) lymphadenectomy during anatomical lung resections for NSCLC, focusing on pathological nodal upstaging. Any possible risk factor affecting nodal upstaging was also investigated. Methods The prospectively collected clinical data of 136 patients undergone uniportal VATS anatomical lung resections, from June 2012 to September 2017, were reviewed. In particular, all details inherent the clinical and pathological node stage and any possible risk factor affecting nodal upstaging were analyzed. Results The patient population consisted of 90 males and 46 females; their mean age was 67.42±10.64 years. The mean number of lymph nodes retrieved during uniportal VATS lymphadenectomy was 20.14±10.73 (7.27±5.90 and 12.60±7.96 in N1 and N2 stations, respectively). The incidence of nodal upstaging was 13.3% (18 cases). In particular there was a N0-1 upstaging in 10 cases (7.4%), a N1-2 upstaging in 3 (2.2%) and a N0-2 in 4 (3%). The ROC analysis showed that the resection of 18 lymph nodes was the best predictor of a general upstaging with an AUC-ROC of 0.595, while the resection of 7 hilar lymph nodes was the best predictor of N1 upstaging (AUC-ROC: 0.554) and 11 mediastinal nodes was the best predictor of N2 upstaging (AUC-ROC: 0.671). The number of positive lymph nodes of stations 5-6 (OR: 2.035, 95% CI: 1.082-3.826, P=0.027) and stations 2-3-4 (OR: 6.198, 95% CI: 1.580-24.321, P=0.009) were confirmed to be the only independent risk factors for N2 upstaging by multivariate analysis. Conclusions According to our experience, uniportal VATS allows a safe and effective radical lymphadenectomy, with a satisfactory pathological nodal upstaging, comparable to other minimally invasive techniques.
Roles for HB‐EGF in Mesenchymal Stromal Cell Proliferation and Differentiation During Skeletal Growth

HB‐EGF, a member of the EGF superfamily, plays important roles in development and tissue regeneration. However, its functions in skeletal stem cells and skeleton development and growth remain poorly understood. Here, we used the Cre/LoxP system to ablate or express HB‐EGF in Dermo1+ mesenchymal stromal cells and their progenies, including chondrocytes and osteoblast lineage cells, and bone marrow stromal cells (BMSCs). Dermo1‐Cre; HB‐EGFf/f mice only showed a modest increase in bone mass, whereas Dermo1‐HB‐EGF mice developed progressive chondrodysplasia, chondroma, osteoarthritis‐like joint defects, and loss of bone mass and density, which were alleviated by treatment with EGFR inhibitor AG1478. The cartilage defects were recapitulated in chondrocyte‐specific HB‐EGF overexpression (Col2‐HB‐EGF) mice with a lesser severity. Dermo1‐HB‐EGF mice showed an increase in proliferation but defects in differentiation of chondrocytes and osteoblasts. HB‐EGF promoted BMSC proliferation via the Akt1 and Erk pathways but inhibited BMSC differentiation via restraining Smad1/5/8 activation. However, Dermo1‐HB‐EGF mice showed normal osteoclastogenesis and bone resorption. These results reveal an important function of autocrine or paracrine HB‐EGF in mesenchymal stromal cell proliferation and differentiation and suggest that EGF signaling needs to be tightly controlled to maintain bone and articular cartilage integrity. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Nurses' descriptions of person-centred care for older people in an acute medical ward-On the individual, team and organisational levels'.

AIM AND OBJECTIVES To describe nurses' experiences of providing person-centred care for older people on an acute medical ward. BACKGROUND There is evidence that person-centred care for older people contributes to a higher quality care and increased satisfaction with care. However, there is a shortness of studies providing concrete examples of what facilitates nurses providing person-centred care for older people in acute care. DESIGN An interview study with qualitative content analysis. COREQ guidelines have been applied. METHOD Fourteen registered nurses and enrolled nurses from an acute care ward participated in semi structured research interviews. The interviews were conducted during 2016 and interpreted using qualitative content analyses. RESULTS Person-centred care was described at different levels in care; at the individual nurse level, person-centred care was described as involving person-centred assessing, relating and spacing which involved personalising assessments, relationships as well as the physical environment. At the team level, person-centred care was described in terms of person-centred goal setting, team responsibilities and team support, and involved having shared and personalised goals, different team responsibilities and a climate of support and collaboration. At the organisational level, person-centred care was described in terms of having person-centred routines, workloads and staff roles that all contributed to put the person at the core of the organisation and build routines to support this. CONCLUSIONS The current study emphasises that, rather than confining person-centred care to specific moments or relationships, a systematic, multilevel organisational approach seems needed to enable nurses as individuals and teams to provide person-centred care consistently and continuously to older people in acute care settings. RELEVANCE TO CLINICAL PRACTICE The results of this study should inspire nurses and managers to expedite implementation of person-centred care for older care recipients hospitalised in acute care wards. Examples of person-centred care are presented herein at clearly identified sites, namely, the "individual," "team" and "organisational levels. "
Hif-1α–Induced Expression of Il-1β Protects against Mycobacterial Infection in Zebrafish

Drug-resistant mycobacteria are a rising problem worldwide. There is an urgent need to understand the immune response to tuberculosis to identify host targets that, if targeted therapeutically, could be used to tackle these currently untreatable infections. In this study we use an Il-1β fluorescent transgenic line to show that there is an early innate immune proinflammatory response to well-established zebrafish models of inflammation and Mycobacterium marinum infection. We demonstrate that host-derived hypoxia signaling, mediated by the Hif-1α transcription factor, can prime macrophages with increased levels of Il-1β in the absence of infection, upregulating neutrophil antimicrobial NO production, leading to greater protection against infection. Our data link Hif-1α to proinflammatory macrophage Il-1β transcription in vivo during early mycobacterial infection and importantly highlight a host protective mechanism, via antimicrobial NO, that decreases disease outcomes and that could be targeted therapeutically to stimulate the innate immune response to better deal with infections.
APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and ROS

Loss‐of‐function mutations in APOPT1, a gene exclusively found in higher eukaryotes, cause a characteristic type of cavitating leukoencephalopathy associated with mitochondrial cytochrome c oxidase (COX) deficiency. Although the genetic association of APOPT1 pathogenic variants with isolated COX defects is now clear, the biochemical link between APOPT1 function and COX has remained elusive. We investigated the molecular role of APOPT1 using different approaches. First, we generated an Apopt1 knockout mouse model which shows impaired motor skills, e.g., decreased motor coordination and endurance, associated with reduced COX activity and levels in multiple tissues. In addition, by achieving stable expression of wild‐type APOPT1 in control and patient‐derived cultured cells we ruled out a role of this protein in apoptosis and established instead that this protein is necessary for proper COX assembly and function. On the other hand, APOPT1 steady‐state levels were shown to be controlled by the ubiquitination–proteasome system (UPS). Conversely, in conditions of increased oxidative stress, APOPT1 is stabilized, increasing its mature intramitochondrial form and thereby protecting COX from oxidatively induced degradation.
Non‐adherence to psychotropic medication assessed by plasma level in newly admitted psychiatric patients: Prevalence before acute admission

Non‐adherence or partial adherence to psychotropic medication is found in 18–70% of patients. Many previously used methods for the assessment of adherence (e.g. questionnaires, pill counts, and electronic systems), however, might underreport actual rates of non‐adherence to medication. The aim of this study was to quantify adherence using plasma level.