Miracle-dz/UniFAR-FTUs huggingface dataset:
Pain Management through Neurocognitive Therapeutic Exercises in Hypermobile Ehlers–Danlos Syndrome Patients with Chronic Low Back Pain

Background The hypermobile type of Ehlers–Danlos syndrome (hEDS) is likely the most common hereditary disorder of connective tissue mainly characterized by joint hypermobility. Patients with hEDS suffer joint pain, in particular low back pain, commonly resistant to drug therapy. The aim of this research was to evaluate a neurocognitive rehabilitation approach based not only on the motion and function recovery but also on the pain management. Methods In this nonrandomized clinical trial, eighteen hEDS patients (4 males and 14 females) with mean age 21 years (range 13-55) were recruited and evaluated before and after three months of rehabilitation treatment. Results The outcome scores showed significant statistical results after treatment in reducing pain symptoms (numerical rating scale, P = 0.003; McGill (total score), P = 0.03), fatigue (fatigue severity scale, P = 0.03), fear of movement (Tampa scale, P = 0.003), and pain-associated disability (Oswestry disability index, P = 0.03). Conclusion The clinical results observed in our study seem to confirm the role of a specific neurocognitive rehabilitation program in the chronic pain management in the Ehlers–Danlos syndrome; the rehabilitation treatment should be tailored on patient problems and focused not only in the recovery of movement but also on pain perception.
PD-1 Coexpression Gene Analysis and the Regulatory Network in Endometrial Cancer Based on Bioinformatics Analysis

Gynecological malignancies are tumors of the female reproductive system, mainly cervical cancer, endometrial cancer, and ovarian cancer. Endometrial cancer (EC) is the most common gynecological malignant tumor in developed countries. The aim of this study was to construct a network of programmed cell death protein 1 (PD-1) coexpressed genes through bioinformatics analysis and screen the potential biomarkers of PD-1 in endometrial cancer. In addition, genes and pathways involved in PD-1 and modulating tumor immune status were identified. We select the EC transcriptomic dataset in TCGA to retrieve gene sets on the cBioPortal platform, and the PD-1 coexpressed genes were obtained on the platform. GO and KEGG enrichment analysis of coexpressed genes was performed using the DAVID database. The target protein-protein interaction (PPI) network was constructed using Cytoscape 3.7. 1 software, and the hub genes were then screened. A total of 976 coexpression genes were obtained. The enrichment analysis showed that PD-1 coexpressed genes were significantly enriched in overall components of the cell structure, the interaction of cytokines with cytokine receptors, chemokine signaling pathways, and cell adhesion molecules (CAMs). Ten hub genes were obtained by node degree analysis. CD3E gene is involved in the prognosis and immune process of EC, and the expression level is related to PD-1 (Pearson correlation coefficient is 0.82, P < 0.01). Patients with low CD3E gene expression in EC have a poor prognosis. The coexpression hub genes of PD-1 are related to immunity, in which CD3E is a prognostic marker that is involved in the PD-1/PD-L1-induced tumor immune escape. This study provides a new area to study the mechanism of PD-1/PD-L1 in EC and the precise treatment with targeted drugs.
Cannabis Use and Car Crashes: A Review

In this review, state-of-the-art evidence on the relationship between cannabis use, traffic crash risks, and driving safety were analyzed. Systematic reviews, meta-analyses, and other relevant papers published within the last decade were systematically searched and synthesized. Findings show that meta-analyses and culpability studies consistently indicate a slightly but significantly increased risk of crashes after acute cannabis use. These risks vary across included study type, crash severity, and method of substance application and measurement. Some studies show a significant correlation between high THC blood concentrations and car crash risk. Most studies do not support this relationship at lower THC concentrations. However, no scientifically supported clear cut-off concentration can be derived from these results. Further research is needed to determine dose-response effects on driving skills combined with measures of neuropsychological functioning related to driving skills and crash risk.
Patterns of Lymph Node Metastasis in Patients With T1/T2 Gastroduodenal Neuroendocrine Neoplasms: Implications for Endoscopic Treatment

Guidelines have differed in their opinion regarding the indications for endoscopic resection of gastric-neuroendocrine neoplasms (g-NENs) and duodenal-NENs (d-NENs). We examined the association between size and lymph node metastasis (LNM) to identify candidates most suitable for endoscopic resection. We identified 706 patients with T1/T2 g-NENs and 621 patients with T1/T2 d-NENs from the SEER database. The prevalence of LNM and risk factors associated with LNM were analyzed. LNM was present in 8.1% of patients with gastroduodenal neuroendocrine tumors (NETs) and 31.6% of patients with neuroendocrine carcinomas (NECs). Multivariate logistic regression indicated that tumor size >10mm, greater invasion depth, and poor differentiation were independently associated with LNM. In addition, the percentage of g-NETs invading submucosa with LNM increased with tumor size (≤10 mm,3.9%;11–20 mm,8.6%;>20 mm,16.1%). However, in contrast to the low LNM risk in patients with small g-NETs (≤10 mm), we found that LNM rate exceeded 5% even for patients with small submucosal-infiltrating d-NETs. Among patients with nodal-negative g-NETs, the cause specific survival (CSS) was similar for those who received surgical resection and endoscopic resection. Among patients with d-NETs, the CSS was better for those who received endoscopic resection. In conclusion, patients with d-NETs had a higher probability of LNM than those with g-NETs. Endoscopic resection can be utilized for curative treatment of submucosa-infiltrating g-NETs and intramucosal d-NETs when the size is 10 mm or less. These results reinforce the need to search for LNM in lesions that are larger than 10 mm.
The Influence of Donor and Recipient Complement C3 Polymorphisms on Liver Transplant Outcome

Despite early reports of an impact of complement C3 polymorphism on liver transplant patient and graft survival, subsequent evidence has been conflicting. Our aim was to clarify the contributions of donor and recipient C3 genotype, separately and together, on patient and graft outcomes and acute rejection incidence in liver transplant recipients. Eight donor/recipient groups were analyzed according to their genotype and presence or absence of C3 F allele (FFFS, FFSS, FSFF, FSFS, FSSS, SSFF, SSFS, and SSSS) and correlated with clinical outcomes of patient survival, graft survival, and rejection. The further impact of brain death vs. circulatory death during liver donation was also considered. Over a median 5.3 y follow-up of 506 patients with clinical information and matching donor and recipient tissue, five-year patient and graft survival (95% confidence interval) were 90(81-91)% and 77(73-85)%, respectively, and 72(69-94)% were rejection-free. Early disadvantages to patient survival were associated with donor C3 F variant, especially in brain-death donors. Recipient C3 genotype was an independent determinant of graft survival by Cox proportional hazards analysis (hazard ratio 0.26, P = 0.04), and the C3 F donor variant was again associated with worse liver graft survival, particularly in brain-death donors. C3 genotype did not independently determine rejection incidence, but a greater proportion of recipient C3 F carriers were rejection-free in the circulatory death, but not the brain-death cohort. Cox proportional hazards analysis revealed significant effects of acute rejection on patient survival (hazard ratio 0.24, P = 0.018), of retransplantation on rejection risk (hazard ratio 6.3, P = 0.009), and of donor type (circulatory-death vs. brain-death) on rejection incidence (hazard ratio 4.9, P = 0.005). We conclude that both donor and recipient complement C3 genotype may influence patient and graft outcomes after liver transplantation but that the type of liver donor is additionally influential, possibly via the inflammatory environment of the transplant.
A Study of the Identification, Fragmentation Mode and Metabolic Pathways of Imatinib in Rats Using UHPLC-Q-TOF-MS/MS

In this study, The metabolites, metabolic pathways, and metabolic fragmentation mode of a tyrosine kinase inhibitor- (TKI-) imatinib in rats were investigated. The samples for analysis were pretreated via solid-phase extraction, and the metabolism of imatinib in rats was studied using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). Eighteen imatinib metabolites were identified in rat plasma, 21 in bile, 18 in urine, and 12 in feces. Twenty-seven of the above compounds were confirmed as metabolites of imatinib and 9 of them were newly discovered for the first time. Oxidation, hydroxylation, dealkylation, and catalytic dehydrogenation are the main metabolic pathways in phase I. For phase II, the main metabolic pathways were N-acetylation, methylation, cysteine, and glucuronidation binding. The fragment ions of imatinib and its metabolites were confirmed to be produced by the cleavage of the C-N bond at the amide bond. The newly discovered metabolite of imatinib was identified by UHPLC-Q-TOF-MS/MS. The metabolic pathway of imatinib and its fragmentation pattern were summarized. These results could be helpful to study the safety of imatinib for clinical use.
Altered Genes and Biological Functions in Response to Severe Burns

Severe burns are acute wounds caused by local heat exposure, resulting in life-threatening systemic effects and poor survival. However, the specific molecular mechanisms remain unclear. First, we downloaded gene expression data related to severe burns from the GEO database (GSE19743, GSE37069, and GSE77791). Then, a gene expression analysis was performed to identify differentially expressed genes (DEGs) and construct protein-protein interaction (PPI) network. The molecular mechanism was identified by enrichment analysis and Gene Set Enrichment Analysis. In addition, STEM software was used to screen for genes persistently expressed during response to severe burns, and receiver operating characteristic (ROC) curve was used to identify key DEGs. A total of 2631 upregulated and 3451 downregulated DEGs were identified. PPI network analysis clustered these DEGs into 13 modules. Importantly, module genes mostly related with immune responses and metabolism. In addition, we identified genes persistently altered during the response to severe burns corresponding to survival and death status. Among the genes with high area under the ROC curve in the PPI network gene, CCL5 and LCK were identified as key DEGs, which may affect the prognosis of burn patients. Gene set variation analysis showed that the immune response was inhibited and several types of immune cells were decreased, while the metabolic response was enhanced. The results showed that persistent gene expression changes occur in response to severe burns, which may underlie chronic alterations in physiological pathways. Identifying the key altered genes may reveal potential therapeutic targets for mitigating the effects of severe burns.
Metabolite Characteristics in Tongue Coating from Damp Phlegm Pattern in Patients with Gastric Precancerous Lesion

Objective In this study, we analyzed the metabolite profile of the tongue coating of patients having gastric precancerous lesion (GPL) with damp phlegm pattern and proposed a mechanism of pathological transition. Methods The changes in tongue-coating metabolites in patients with GPL damp phlegm pattern were analyzed using GC-TOF-MS and UHPLC-QE-MS metabolomics methods. Results When compared with 20 patients who did not exhibit a nondamp phlegm pattern, 12 metabolites were highly expressed and 10 metabolites were under expressed in 40 cases of damp phlegm pattern, of which involved 9 metabolic pathways. Compared with 15 healthy people, 134 metabolites were upregulated and 3 metabolites were downregulated in 40 cases exhibiting a damp phlegm pattern, of which involved 17 metabolic pathways. The patients with damp phlegm pattern were compared with nondamp phlegm pattern patients and healthy people, the main differential metabolites were primarily lipids and lipid-like molecules, and the main differential metabolic pathways were related to glycerophospholipid metabolism. In the glycerophospholipid metabolism, the metabolites with changes were phosphatidylethanolamine and lysoPC(18 : 1 (9z)). Among them, phosphatidylethanolamine exists in the synthesis stage of glycerophospholipid metabolism. Conclusions Abnormal expression of lipids and lipid-like molecules, as the major metabolic change, was involved in the formation of GPL patients with damp phlegm pattern.
Influence of CYP19A1 gene expression levels in women with breast cancer: a systematic review of the literature

Breast cancer is the most frequently diagnosed malignant neoplasm in women and is considered a multifactorial disease of unknown etiology. One of the major risk factors is genetic alteration. Changes in CYP19A1 gene expression levels have been associated with increased risk and increased aggressiveness of breast cancer. Increased CYP19A1 gene expression and/or aromatase activity are among the major regulatory events for intratumoral production of estrogens in breast malignant tissues. This systematic review aimed to investigate the influence of CYP19A1 gene expression levels in women with breast cancer. The research was carried out using the PubMed, Scopus, and Web of Science databases. Searches were conducted between February 2 and May 15, 2019. Inclusion criteria were studies published between 2009 and 2019, English language publications, and human studies addressing the gene expression of CYP19A1 in breast cancer. A total of 6.068 studies were identified through PubMed (n=773), Scopus (n=2,927), and the Web of Science (n=2,368). After selecting and applying the inclusion and exclusion criteria, six articles were included in this systematic review. This systematic review provides evidence that increased or decreased levels of CYP19A1 gene expression may be related to pathological clinical factors of disease, MFS, OS, DFS, WATi, markers of metabolic function, concentrations of E1, FSH, and in the use of multiple exons 1 of the CYP19A1 gene in breast cancer.
Screening for potential familial hypercholesterolaemia in general practice: an observational study on prevalence and management

Background Familial hypercholesterolaemia (FH) is a common genetic disorder causing premature cardiovascular disease (CVD). The estimated prevalence of probable or definite FH is 1:200–250 individuals, according to the Dutch Lipid Clinic Network (DLCN) criteria for FH. In Denmark approximately 12% of cases are identified. Aim To provide knowledge of the prevalence and management of FH in general practice. Design & setting A collaboration between six general practice clinics and the department of cardiology at Bispebjerg hospital in Denmark. Method A total of 9652 patient records were screened for hypercholesterolaemia. All patients with a low-density lipoprotein cholesterol (LDL-C) ≥5.0 mmol/l were included in the study population and their records were investigated in order to perform a diagnostic score according to the DLCN criteria. Results It was found that 2382 individuals had a lipid measurement available, and 236 of those had an LDL-C ≥5.0 mmol/l. In total, 34 individuals were found to have probable or definite FH (DLCN score ≥5). Only three individuals had been diagnosed and treated with lipid-lowering therapy. Of 236 individuals with high LDL-C, only 25 individuals met their treatment target. By excluding patients with signs of secondary hypercholesterolaemia, a subgroup of 115 individuals with potential primary hypercholesterolaemia was established. Among those, 21 individuals were found to have probable or definite FH (1:114 individuals). Conclusion The study shows that there is a massive lack of recognition of FH in general practice. Despite a measured high LDL-C, the diagnosis is rarely made and only a few patients are treated accordingly. Of the patients undergoing treatment, only a few reached their treatment target.
Clinicians' Views on the Need for Cultural Adaptation of Intervention for Children with ADHD from the Ultraorthodox Community

Culture is a core context within occupational therapy, with a recent literature emphasizing the importance of cultural competence, as well as culturally sensitive assessment and intervention. The recent literature has indicated the efficacy of the Cognitive-Functional intervention (Cog-Fun) for children with ADHD among the general Israeli population, yet no studies to date have examined the necessity of cultural adaptations for minority groups. The current study examines the necessity of adapting the intervention protocol and process to the Ultraorthodox (UO) population, as perceived by occupational therapists. The study included 28 occupational therapists certified to use the Cog-Fun intervention, who reported using this approach with UO children. Participants responded to an online questionnaire developed for this study, regarding characteristics of the UO population and necessary adaptions to the Cog-Fun intervention process and protocol. Findings were analyzed using descriptive statistics and qualitative content analysis. Results of the study point to the necessity of addressing various features of the UO community, including daily routines and habits, cultural values, knowledge regarding ADHD, and accessibility of information. Participants also reported a need to adapt the graphic content of the intervention materials. The qualitative data expanded on the perceptions of the participants through four main themes: (a) knowledge regarding ADHD diagnosis and intervention; (b) perceptions and attitudes regarding ADHD diagnosis and medication; (c) factors affecting communication between the OT, parents, and teachers; and (d) adapting the intervention protocol to habits, routines, and lifestyle of UO families. This study has direct implications for therapists utilizing the Cog-Fun with UO children and may also provide insights relevant to occupational therapists using other treatment approaches with children from this culture, as well as other minority or traditional groups. Furthermore, this study may serve as an important addition to the limited literature describing cultural adaptations of evidence-based interventions.
A lymphodepleted non‐human primate model for the assessment of acute on‐target and off‐tumor toxicity of human chimeric antigen receptor‐T cells

Chimeric antigen receptor (CAR)‐T cell therapy possesses the potential to cause unexpected on‐target toxicities that may be life‐threatening. Non‐human primates (NHPs) share considerable structural homology and expression profiles of most proteins with humans and are therefore utilised as an animal model for non‐clinical safety studies. We have developed a lymphodepleted NHP model by conditioning the animals with immunosuppressive chemotherapy designed to simulate clinical practice conditions, to induce transient mixed chimerism before the administration of human CAR‐T cells redirected to target Ephrin type‐B receptor 4 (EPHB4‐CAR‐T cells) to evaluate the toxicity of these cells.
Qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance

Background: Data sharing enables researchers to conduct novel research with previously collected datasets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing, even de-identified, quantitative data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to sharing quantitative data remain, there are additional challenges for sharing qualitative data in trials. Incorporating the necessary information about how qualitative data will be shared into already complex trial recruitment and consent processes proves challenging. The aim of this study was to explore whether and how trial teams share qualitative data collected as part of the design, conduct, analysis, or delivery of clinical trials. Methods: Phase 1 involved semi-structured, in-depth qualitative interviews and focus groups with key trial stakeholder groups including trial managers and clinical trialists (n=3), qualitative researchers in trials (n=9), members of research funding bodies (n=2) and trial participants (n=1). Data were analysed using thematic analysis. In Phase 2, we conducted a content analysis of 16 participant information leaflets (PIL) and consent forms (CF) for trials that collected qualitative data. Results: Three key themes were identified from our Phase 1 findings: ‘ Understanding and experiences of the potential benefits of sharing qualitative data from trials’, ‘Concerns about qualitative data sharing’, and ‘ Future guidance and funding’. In phase 2, the PILs and CFs received revealed that the benefits of data sharing for participants were only explained in two of the study documents. Conclusions: The value of sharing qualitative data was acknowledged, but there are many uncertainties as to how, when, and where to share this data. In addition, there were ethical concerns in relation to the consent process required for qualitative data sharing in trials. This study provides insight into the existing practice of qualitative data sharing in trials.
The Immediate Effects of Foam Rolling and Stretching on Iliotibial Band Stiffness: A Randomized Controlled Trial

Background Iliotibial Band Syndrome (ITBS) is a common clinical condition likely caused by abnormal compressive forces to the iliotibial band (ITB). Stretching interventions are common in ITBS treatment and may predominantly affect tensor fascia latae (TFL). Another ITBS treatment is foam rolling, which may more directly affect the ITB. Shear wave ultrasound elastography (SWUE) measures real-time soft tissue stiffness, allowing tissue changes to be measured and compared. Purpose To examine effects of foam rolling and iliotibial complex stretching on ITB stiffness at 0˚ and 10˚ of hip adduction and hip adduction passive range of motion (PROM). Study Design Randomized controlled trial. Methods Data from 11 males (age = 30.5 ± 9.0 years, Body Mass Index (BMI) = 27.8 ± 4.0) and 19 females (age = 23.5 ± 4.9, BMI = 23.2 ± 2.1) were analyzed for this study. Subjects were randomly assigned to one of three groups: control, stretching, and foam rolling. Shear wave ultrasound elastography measurements included ITB Young’s modulus at the mid-thigh, the distal femur and the TFL muscle belly. ITB-to-femur depth was measured at mid-thigh level. Hip adduction PROM was measured from digital images taken during the movement. Results No significant interactions or main effects were found for group or time differences in ITB Young’s modulus at the three measured locations. The ITB stiffness at the mid-thigh and distal femur increased with 10° adduction, but TFL stiffness did not increase. A main effect for adduction PROM was observed, where PROM increased 0.8˚ post-treatment (p = 0.02). Conclusion A single episode of stretching and foam rolling does not affect short-term ITB stiffness. The lack of ITB stiffness changes may be from an inadequate intervention stimulus or indicate that the interventions have no impact on ITB stiffness. Levels of Evidence 1b