Miracle-dz/UniFAR-FTUs huggingface dataset:
To Flex or Not to Flex? Is There a Relationship Between Lumbar Spine Flexion During Lifting and Low Back Pain? A Systematic Review With Meta-Analysis.

STUDY DESIGN Prognosis systematic review with meta-analysis. OBJECTIVE To evaluate whether lumbar spine flexion during lifting is a risk factor for low back pain (LBP) onset/persistence, or a differentiator of people with and without LBP. LITERATURE SEARCH Database search of Proquest, CINAHL, Medline and EMBASE until August 2018. STUDY SELECTION CRITERIA We included peer-reviewed articles, investigating lumbar spine position during lifting as a risk factor for LBP onset or persistence, or as a differentiator of people with and without LBP. DATA SYNTHESIS Lifting task comparison data were tabulated and summarised. For meta-analysis, we calculated an n-weighted pooled mean (SD) of the results for each of the LBP and no LBP groups. Where a study contained multiple comparisons (i.e. different lifting tasks that used various weights or directions), only one result for each study was included in the meta-analysis. RESULTS Four studies (one longitudinal study and three cross-sectional studies) measured lumbar flexion with intra-lumbar angles and found no differences in peak lumbar spine flexion when lifting (longitudinal 1.5 degree (95%CI -0.7 to 3.7), p=0.19 and cross-sectional -0.9 (95%CI -2.5 to 0.7), p=0.29). Seven cross-sectional studies measured lumbar flexion with thoraco-pelvic angles and found people with LBP lifted with 6.0 degrees less lumbar flexion than people without LBP (95%CI -11.2 to -.89, p<0.01). Most (9 of 11) studies reported no between-group differences in lumbar flexion during lifting. The included studies were low quality. CONCLUSION There was low quality evidence that greater lumbar spine flexion during lifting was not a risk factor for LBP onset/persistence, nor a differentiator of people with and without LBP. J Orthop Sports Phys Ther, Epub 28 Nov 2019. doi:10.2519/jospt.2020.9218.
Conventional rotator cuff versus all-suture anchors—A biomechanical study focusing on the insertion angle in an unlimited cyclic model

Purpose The purpose of this study was to compare the biomechanical properties of an all-suture anchor to a conventional anchor used commonly in rotator cuff repairs. Furthermore, the biomechanical influence of various implantation angles was evaluated in both anchor types in a human cadaveric model. Methods 30 humeri were allocated into three groups with a similar bone density. The two different anchor types were inserted at a predefined angle of 45°, 90° or 110°. Biomechanical testing included an initial preload of 20N followed by a cyclic protocol with a stepwise increasing force of 0,05N for each cycle at a rate of 1Hz until system failure. Number of cycles, maximum load to failure, stiffness, displacement and failure mode were determined. Results 27 anchors failed by pullout. There was no significant difference between the conventional and the all-suture anchor regarding mean pullout strength. No considerable discrepancy in stiffness or displacement could be perceived. Comparing the three implantation angles no significant difference could be observed for the all-suture or the conventional anchor. Conclusion All-suture anchors show similar biomechanical properties to conventional screw shaped anchors in an unlimited cyclic model. The exact insertion angle is not a significant predictor of failure.
5-hydroxytryptamine 1F Receptor Agonist Induces Mitochondrial Biogenesis and Promotes Recovery from Spinal Cord Injury

Spinal cord injury (SCI) is characterized by vascular disruption leading to ischemia, decreased oxygen delivery, and loss of mitochondrial homeostasis. This mitochondrial dysfunction results in loss of cellular functions, calcium overload, and oxidative stress. Pharmacological induction of mitochondrial biogenesis (MB) may be an effective approach to treat SCI. LY344864, a 5-hydroxytryptamine 1F (5-HT1F) receptor agonist, is a potent inducer of MB in multiple organ systems. To assess the efficacy of LY344864-induced MB on recovery post-SCI, female mice were subjected to moderate force-controlled impactor-induced contusion SCI followed by daily LY344864 administration for 21 days. Decreased mitochondrial DNA and protein content was present in the injury site 3 days post-SCI. LY344864 treatment beginning 1 h after injury attenuated these decreases, indicating MB. Additionally, injured mice treated with LY344864 displayed decreased Evan’s Blue dye accumulation in the spinal cord compared with vehicle-treated mice 7 days after injury, suggesting restoration of vascular integrity. LY344864 also increased locomotor capability, with treated mice reaching a Basso-Mouse Scale score of 3.4 by 21 days, whereas vehicle-treated mice exhibited a score of 1.9. Importantly, knockout of the 5-HT1F receptor blocked LY344864-induced recovery. Remarkably, a similar degree of locomotor restoration was observed when treatment initiation was delayed until 8 h after injury. Furthermore, cross-sectional analysis of the spinal cord 21 days after injury revealed decreased lesion volume with delayed LY344864 treatment initiation, emphasizing the potential clinical applicability of this therapeutic approach. These data provide evidence that induction of MB via 5-HT1F receptor agonism may be a promising strategy for the treatment of SCI. SIGNIFICANCE STATEMENT Treatment with LY344864 induces mitochondrial biogenesis in both the naive and injured mouse spinal cord. In addition, treatment with LY344864 beginning after impactor-induced contusion spinal cord injury improves mitochondrial homeostasis, blood–spinal cord barrier integrity, and locomotor function within 7 days. Importantly, similar locomotor results are observed whether treatment is initiated at 1 h after injury or 8 h after injury. These data indicate the potential for pharmacological induction of mitochondrial biogenesis through a 5-hydroxytryptamine 1F agonist as a novel therapeutic approach for spinal cord injury.
Usefulness of Nasal Endoscopy for Diagnosing Patients With Chronic Rhinosinusitis: A Meta-Analysis

Background We evaluated the accuracy of nasal endoscopy in diagnosing chronic rhinosinusitis (CRS) compared with paranasal sinus computed tomography (CT). Methods Two authors independently searched the 5 databases (PubMed, SCOPUS, Embase, the Web of Science, and the Cochrane database) up to March 2019. For all included studies, we calculated correlation coefficients between the endoscopic and CT scores. We extracted data on true-positive and false-positive and true-negative and false-negative results. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool (version 2). Results We included 16 observational or retrospective studies. A high correlation (r = .8543; 95% confidence interval [CI] [0.7685–0.9401], P < .0001, I2 = 76.58%) between endoscopy and CT in terms of the diagnostic accuracy for CRS was apparent. The odds ratio (Lund–Kennedy endoscopic score ≥1) was 7.915 (95% CI [4.435–14.124]; I2 = 28.361%). The area under the summary receiver operating characteristic curve was 0.765. The sensitivity and specificity were 0.726 (95% CI [0.584–0.834]) and 0.767 (95% CI [0.685–0.849]), respectively. However, high interstudy heterogeneity was evident given the different endoscopic score thresholds used (Lund–Kennedy endoscopic score ≥1 vs 2). In a subgroup analysis of studies using a Lund–Kennedy endoscopic score threshold ≥2, the area under the summary curve was 0.881, and the sensitivity and specificity were 0.874 (95% CI [0.783–0.930]) and 0.793 (95% CI [0.366–0.962]), respectively. Conclusion Nasal endoscopy is a useful diagnostic tool; the Lund–Kennedy score was comparable with that of CT.
Titin splicing regulates cardiotoxicity associated with calpain 3 gene therapy for limb-girdle muscular dystrophy type 2A

Preclinical studies demonstrate the potential of calpain 3 gene therapy for limb-girdle muscular dystrophy type 2A while avoiding cardiotoxicity. Safety through splicing Limb-girdle muscular dystrophy type 2A is characterized by progressive muscle weakness resulting from deficiency in calpain 3. Lostal et al. investigated the therapeutic effect of recombinant adeno-associated viral (AAV) vector expressing CAPN3 and a miR-208a target sequence in mice and nonhuman primates. Mice lacking calpain 3 and dysferlin (a severe model of myopathy) showed reduced dystrophy and restoration of calpain 3 expression after AAV treatment. In contrast to previous murine studies, treatment did not cause cardiotoxicity in nonhuman primates, although transgene was expressed in the heart. The authors identified species-specific differences in calpain 3 binding sites on titin between mice, nonhuman primates, and humans, which could account for differences in cardiotoxicity. Results support further investigation into calpain 3 gene therapy as a treatment for limb-girdle muscular dystrophy. Limb-girdle muscular dystrophy type 2A (LGMD2A or LGMDR1) is a neuromuscular disorder caused by mutations in the calpain 3 gene (CAPN3). Previous experiments using adeno-associated viral (AAV) vector–mediated calpain 3 gene transfer in mice indicated cardiac toxicity associated with the ectopic expression of the calpain 3 transgene. Here, we performed a preliminary dose study in a severe double-knockout mouse model deficient in calpain 3 and dysferlin. We evaluated safety and biodistribution of AAV9-desmin-hCAPN3 vector administration to nonhuman primates (NHPs) with a dose of 3 × 1013 viral genomes/kg. Vector administration did not lead to observable adverse effects or to detectable toxicity in NHP. Of note, the transgene expression did not produce any abnormal changes in cardiac morphology or function of injected animals while reaching therapeutic expression in skeletal muscle. Additional investigation on the underlying causes of cardiac toxicity observed after gene transfer in mice and the role of titin in this phenomenon suggest species-specific titin splicing. Mice have a reduced capacity for buffering calpain 3 activity compared to NHPs and humans. Our studies highlight a complex interplay between calpain 3 and titin binding sites and demonstrate an effective and safe profile for systemic calpain 3 vector delivery in NHP, providing critical support for the clinical potential of calpain 3 gene therapy in humans.
Impact of pressure, self-efficacy, and self-competency on students’ plagiarism in higher education

ABSTRACT To explore students’ plagiarism in higher level education, we designed a quantitative study and collected data from enrolled university students from Islamabad, the capital city of Pakistan. This was done by distributing a web-link for an online survey (Google form) through WhatsApp social media mobile software. We applied structural equation modeling (SEM) techniques by using IBM SPSS AMOS 24.0. 0 software to analyze collected data. The research findings suggest that some human factors do in fact exist and that these factors drive students to engage in certain unethical practices of plagiarism. Apart from poor training and lack of skills on the students’ part, the pressures and the self-efficacy they face as they engage in research practices can make students susceptible to plagiarize.
Cognitive Fusion Mediates the Relationship between Dispositional Mindfulness and Negative Affects: A Study in a Sample of Spanish Children and Adolescent School Students

Nowadays, mindfulness-based interventions (MBI) have experienced a remarkable development of studies among childhood and adolescent interventions. For this reason, dispositional mindfulness (DM) measures for children and adolescents have been developed to determine the effectiveness of MBI at this age stage. However, little is known about how key elements of DM (for example, cognitive de/fusion or experiential avoidance that both confirm psychological inflexibility) are involved in the mechanisms of the children and adolescents’ mental health outcomes. This research examined the mediating effect of cognitive fusion between DM and anxiety and other negative emotional states in a sample of 318 Spanish primary-school students (aged between 8 and 16 years, M = 11.24, SD = 2.19, 50.8% males). Participants completed the AFQ-Y (Avoidance and Fusion Questionnaire for youth), which is a measure of psychological inflexibility that encompasses cognitive defusion and experiential avoidance; CAMM (DM for children and adolescents), PANAS-N (positive and negative affect measure for children, Spanish version of PANASC), and STAIC (an anxiety measure for children). The study accomplished ethical standards. As MBI relevant literature has suggested, cognitive defusion was a significant mediator between DM and symptoms of both negative emotions and anxiety in children and adolescents. However, experiential avoidance did not show any significant mediating relationship. Probably, an improvement of the assessment of experiential avoidance is needed. MBI programs for children and adolescents may include more activities for reducing effects of the cognitive defusion on their emotional distress.
Decreased Bioimpedance Phase Angle in Patients with Diabetic Chronic Kidney Disease Stage 5

Early detection and regular monitoring of the nutritional status of patients with diabetic chronic kidney disease (DMCKD) with reliable tools are necessary. We aimed to determine the clinical significance of the phase angle (PhA) in patients with DMCKD stage 5 not undergoing dialysis. A total of 219 patients (non-diabetic CKD stage 5 [nDMCKD5], n = 84; diabetic CKD stage 5 [DMCKD5], n = 135) were analyzed. The nDMCKD5 group had a significantly higher PhA (p = 0.001), intracellular water/body weight (p = 0.001), and albumin level (p = 0.010) than the DMCKD5 group. The DMCKD5 group experienced significantly more overhydration (p < 0.001). The PhA was positively associated with the lean tissue index (LTI) (r = 0.332; p < 0.001), hemoglobin level (r = 0.223; p = 0.010), albumin level (r = 0.524; p < 0.001), and estimated glomerular filtration rate (eGFR; r = 0.204; p = 0.018) in the DMCKD5 group. Multivariate logistic regression analysis showed the eGFR (odds ratio [OR]: 0.824, 95% confidence interval [CI]: 0.698–0.974); p = 0.023), LTI (OR: 0.771, 95% CI: 0.642–0.926; p = 0.005), and albumin level (OR: 0.131, 95% CI: 0.051–0.338; p < 0.001) were significantly associated with undernutrition (PhA < 4.17°) in the DMCKD5 group. Our observations suggest that the PhA could be used as a marker to reflect the nutritional status in patients with DMCKD5.
Loss of HIPK2 Protects Neurons from Mitochondrial Toxins by Regulating Parkin Protein Turnover

Mitochondria are important sources of energy, but they are also the target of cellular stress, toxin exposure, and aging-related injury. Persistent accumulation of damaged mitochondria has been implicated in many neurodegenerative diseases. One highly conserved mechanism to clear damaged mitochondria involves the E3 ubiquitin ligase Parkin and PTEN-induced kinase 1 (PINK1), which cooperatively initiate the process called mitophagy that identifies and eliminates damaged mitochondria through the autophagosome and lysosome pathways. Parkin is a mostly cytosolic protein, but is rapidly recruited to damaged mitochondria and target them for mitophagy. Moreover, Parkin interactomes also involve signaling pathways and transcriptional machinery critical for survival and cell death. However, the mechanism that regulates Parkin protein level remains poorly understood. Here, we show that the loss of homeodomain interacting protein kinase 2 (HIPK2) in neurons and mouse embryonic fibroblasts (MEFs) has a broad protective effect from cell death induced by mitochondrial toxins. The mechanism by which Hipk2−/− neurons and MEFs are more resistant to mitochondrial toxins is in part due to the role of HIPK2 and its kinase activity in promoting Parkin degradation via the proteasome-mediated mechanism. The loss of HIPK2 leads to higher cytosolic Parkin protein levels at basal conditions and upon exposure to mitochondrial toxins, which protects mitochondria from toxin-induced damage. In addition, Hipk2−/− neurons and MEFs show increased expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator 1), a Parkin downstream target that can provide additional benefits via transcriptional activation of mitochondrial genes. Together, these results reveal a previously unrecognized avenue to target HIPK2 in neuroprotection via the Parkin-mediated pathway. SIGNIFICANCE STATEMENT In this study, we provide evidence that homeodomain interacting protein kinase 2 (HIPK2) and its kinase activity promote Parkin degradation via the proteasome-mediated pathway. The loss of HIPK2 increases cytosolic and mitochondrial Parkin protein levels under basal conditions and upon exposure to mitochondrial toxins, which protect mitochondria from toxin-induced damage. In addition, Hipk2−/− neurons and mouse embryonic fibroblasts also show increased expression of PGC-1α (peroxisome proliferator-activated receptor-γ coactivator 1), a Parkin downstream target that can provide additional benefits via transcriptional activation of mitochondrial genes. These results indicate that targeting HIPK2 and its kinase activity can have neuroprotective effects by elevating Parkin protein levels.
Polarized PtdIns(4,5)P2 distribution mediated by a voltage-sensing phosphatase (VSP) regulates sperm motility

Significance Voltage-sensing phosphatase (VSP) is a unique protein that consists of both the voltage-sensor domain and phosphoinositide phosphatase domain. In contrast with intensive studies on its molecular mechanisms, its physiological role has not been clear. Here, we report that VSP plays critical roles in mouse sperm motility. We found that VSP generates a polarized distribution of PtdIns(4,5)P2 in the sperm flagellum, which is critical for regulation of ion channel activity and calcium influx in sperm function. This provides a mode of regulation of ion channel activity by biased distribution of PtdIns(4,5)P2. The voltage-sensing phosphatase (VSP) is a unique protein that shows voltage-dependent phosphoinositide phosphatase activity. Here we report that VSP is activated in mice sperm flagellum and generates a unique subcellular distribution pattern of PtdIns(4,5)P2. Sperm from VSP−/− mice show more Ca2+ influx upon capacitation than VSP+/− mice and abnormal circular motion. VSP-deficient sperm showed enhanced activity of Slo3, a PtdIns(4,5)P2-sensitive K+ channel, which selectively localizes to the principal piece of the flagellum and indirectly enhances Ca2+ influx. Most interestingly, freeze-fracture electron microscopy analysis indicates that normal sperm have much less PtdIns(4,5)P2 in the principal piece than in the midpiece of the flagellum, and this polarized PtdIns(4,5)P2 distribution disappeared in VSP-deficient sperm. Thus, VSP appears to optimize PtdIns(4,5)P2 distribution of the principal piece. These results imply that flagellar PtdIns(4,5)P2 distribution plays important roles in ion channel regulation as well as sperm motility.
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder.

BACKGROUND Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system and is associated with autoantibodies to anti-aquaporin-4 (AQP4-IgG) in approximately two thirds of patients. Interleukin-6 is involved in the pathogenesis of the disorder. Satralizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor. The efficacy of satralizumab added to immunosuppressant treatment in patients with NMOSD is unclear. METHODS In a phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, patients with NMOSD who were seropositive or seronegative for AQP4-IgG to receive either satralizumab, at a dose of 120 mg, or placebo, administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter, added to stable immunosuppressant treatment. The primary end point was the first protocol-defined relapse in a time-to-event analysis. Key secondary end points were the change from baseline to week 24 in the visual-analogue scale (VAS) pain score (range, 0 to 100, with higher scores indicating more pain) and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (range, 0 to 52, with lower scores indicating more fatigue). Safety was also assessed. RESULTS A total of 83 patients were enrolled, with 41 assigned to the satralizumab group and 42 to the placebo group. The median treatment duration with satralizumab in the double-blind period was 107.4 weeks. Relapse occurred in 8 patients (20%) receiving satralizumab and in 18 (43%) receiving placebo (hazard ratio, 0.38; 95% confidence interval [CI], 0.16 to 0.88). Multiple imputation for censored data resulted in hazard ratios ranging from 0.34 to 0.44 (with corresponding P values of 0.01 to 0.04). Among 55 AQP4-IgG-seropositive patients, relapse occurred in 11% of those in the satralizumab group and in 43% of those in the placebo group (hazard ratio, 0.21; 95% CI, 0.06 to 0.75); among 28 AQP4-IgG-seronegative patients, relapse occurred in 36% and 43%, respectively (hazard ratio, 0.66; 95% CI, 0.20 to 2.24). The between-group difference in the change in the mean VAS pain score was 4.08 (95% CI, -8.44 to 16.61); the between-group difference in the change in the mean FACIT-F score was -3.10 (95% CI, -8.38 to 2.18). The rates of serious adverse events and infections did not differ between groups. CONCLUSIONS Among patients with NMOSD, satralizumab added to immunosuppressant treatment led to a lower risk of relapse than placebo but did not differ from placebo in its effect on pain or fatigue. (Funded by Chugai Pharmaceutical; ClinicalTrials.gov number, NCT02028884.).