Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-30 Family miRNAs Mediate the Effect of Chronic Social Defeat Stress on Hippocampal Neurogenesis in Mouse Depression Model

Depression is a debilitating psychiatric disorder with a high rate of relapse and a low rate of response to antidepressant treatment. There is a dearth of new antidepressants due to an incomplete understanding of the molecular mechanisms involved in its etiopathology. Chronic stress appears to be one of the foremost underlying causes of depression. Studies in animal models in the past decade have implicated epigenetic mechanisms in mediating the negative effects of chronic stressful events on the progression/manifestation of depression and other co-morbid neuropsychiatric disorders. However, non-coding RNAs, another layer of epigenetic regulation is relatively less studied in depression. Here, using the chronic social defeat stress (CSDS)-induced depression model, we hypothesized dysregulation in miRNA-mRNA networks in the neurogenic dentate gyrus (DG) region of male C57BL/6 mice. Among several dysregulated miRNAs identified via miRNA arrays, the most striking finding was the downregulation of miRNAs of the miR-30 family in stressed/defeated mice. To investigate miRNAs in the DG-resident neural stem/progenitor cells (NSCs/NPCs), we used the in vitro neurosphere culture, where proliferating NSCs/NPCs were subjected to differentiation. Among several differentially expressed miRNAs, we observed an upregulation of miR-30 family miRNAs upon differentiation. To search for the gene targets of these miRNAs, we performed gene arrays followed by bioinformatics analysis, miRNA manipulations and luciferase assays. Our results suggest that miR-30 family miRNAs mediate chronic stress-induced depression-like phenotype by altering hippocampal neurogenesis and neuroplasticity via controlling the epigenetic and transcription regulators such as Mll3 and Runx1; and cell signaling regulators like Socs3, Ppp3r1, Gpr125, and Nrp1.
Ontogenetic Dietary Shifts and Microscopic Tooth Wear in Western Chimpanzees

Microscopic tooth wear studies on primates have largely focused on interspecific dietary comparisons, while few have addressed intraspecific variations such as those among age groups. Here, we examined to what extent dietary shifts during ontogeny can be revealed from microscopic tooth wear in a western chimpanzee population using 3D surface texture (3DST) analysis. To this end, we analyzed feeding observation data of 14 chimpanzees of the Taї National Park (Ivory Coast) and matched them to 3DST data analyzed on two wear facets (f9, f3) of deciduous fourth premolars and permanent molars of 41 specimens (infants, juveniles, adolescents, adults) of the same population. We expected to find an age-dependent increase in texture complexity resulting from the more frequent consumption of seeds and insects in older compared to younger individuals. Furthermore, we expected the introduction of phytolith-producing plants to the diet of post-weaned individuals to result in many small and parallel-orientated 3DST features in juveniles, adolescents and adults compared to infants. We found that the 3DST pattern did not mirror the observed increase in dietary breadth from infants to adults. However, we found that age-dependent differences in the consumption of phytolith-producing plants were reflected to some extent in the 3DST pattern: infants and adolescents who spent more time feeding on phytolith-producing plants than older individuals had more parallel orientated 3DSTs with higher peaks, while adults had flatter and more randomly orientated 3DST features. Our results suggest that phytoliths as small abrasive particles may be of greater importance for the 3DST formation than food categories such as fruits, leaves or seeds. However, compared to the variation in the feeding data, 3DST results show only little variation among age groups. We conclude that 3DST does not explicitly reflect ontogenetic dietary changes in chimpanzees. Rather, other factors, such as individual- or sex-based feeding habits as well as seasonal variation in dust accumulation, may be of greater importance for 3DST formation.
Gonadal Failure Is Common in Long-Term Survivors of Childhood High-Risk Neuroblastoma Treated With High-Dose Chemotherapy and Autologous Stem Cell Rescue

Background: Neuroblastoma is the most common extra-cranial solid tumor in children. Intensive therapy including autologous stem-cell transplantation (HSCT) has improved the poor prognosis of high-risk neuroblastoma (HR-NBL) but may impair gonadal function. Objectives: To investigate the gonadal function and fertility in long-term survivors of childhood HR-NBL. Design: A cohort including all Finnish (n = 20; 11 females) long-term (>10 years) survivors of HR-NBL and an age- and sex-matched control group (n = 20) was examined at a median age of 22 (16–30) years. Oncologic treatments, pubertal timing, hormonal therapies and the number of off-spring were recorded, and pituitary and gonadal hormones were measured. Results: Altogether 16/20 of the long-term survivors of HR-NBL entered puberty spontaneously; puberty was hormonally induced in four survivors (three females). Among the 8/11 female survivors with spontaneous puberty, seven had spontaneous menarche, but 5/8 developed ovarian failure soon after puberty. Nine females currently needed estrogen substitution. AMH, a marker of ovarian reserve, was lower in the female survivors than controls (median 0.02 vs. 1.7 μg/l, p < 0.001). As a group, male survivors had smaller testicular size (8.5 vs. 39 ml, p < 0.001) and lower inhibin B (<10 vs. 170 ng/l, p < 0.001) compared with control males, with altogether 6/9 survivor males fulfilling the criteria of gonadal failure (absent puberty, small testicle size or increased FSH with need of testosterone substitution). Gonadal failure was more common in female and male survivors treated with total-body irradiation. Three survivors (one male) had offspring, all treated without total-body irradiation and moderate dose of alkylating chemotherapy. Growth velocity was compromised in all survivors after HR-NBL diagnosis, with absent pubertal growth spurt in 7/17 survivors with complete growth data. Conclusion: Gonadal failure is common in long-term survivors of HR-NBL treated with HSCT. Fertility may be preserved in some survivors treated without total-body irradiation.
Post-transcriptional Regulation of Colorectal Cancer: A Focus on RNA-Binding Proteins

Colorectal cancer (CRC) is a major health problem with an estimated 1. 8 million new cases worldwide. To date, most CRC studies have focused on DNA-related aberrations, leaving post-transcriptional processes under-studied. However, post-transcriptional alterations have been shown to play a significant part in the maintenance of cancer features. RNA binding proteins (RBPs) are uprising as critical regulators of every cancer hallmark, yet little is known regarding the underlying mechanisms and key downstream oncogenic targets. Currently, more than a thousand RBPs have been discovered in humans and only a few have been implicated in the carcinogenic process and even much less in CRC. Identification of cancer-related RBPs is of great interest to better understand CRC biology and potentially unveil new targets for cancer therapy and prognostic biomarkers. In this work, we reviewed all RBPs which have a role in CRC, including their control by microRNAs, xenograft studies and their clinical implications.
Treating ischemia via recruitment of antigen-specific T cells

Recruitment of antigen-specific T cells promotes vascularization in ischemic injuries in mice. Ischemic diseases are a leading cause of mortality and can result in autoamputation of lower limbs. We explored the hypothesis that implantation of an antigen-releasing scaffold, in animals previously vaccinated with the same antigen, can concentrate TH2 T cells and enhance vascularization of ischemic tissue. This approach may be clinically relevant, as all persons receiving childhood vaccines recommended by the Centers for Disease Control and Prevention have vaccines that contain aluminum, a TH2 adjuvant. To test the hypothesis, mice with hindlimb ischemia, previously vaccinated with ovalbumin (OVA) and aluminum, received OVA-releasing scaffolds. Vaccinated mice receiving OVA-releasing scaffolds locally concentrated antigen-specific TH2 T cells in the surrounding ischemic tissue. This resulted in local angiogenesis, increased perfusion in ischemic limbs, and reduced necrosis and enhanced regenerating myofibers in the muscle. These findings support the premise that antigen depots may provide a treatment for ischemic diseases in patients previously vaccinated with aluminum-containing adjuvants.
Manifestations of muscle fatigue in baseball pitchers: a systematic review

Background Fatigue in baseball pitchers is a process linked to lowered physical and mental performance, injury, and changes in kinematics. Numerous studies have associated fatigue with overuse, high ball velocities, lack of rest time, poor mechanics, and degree of self-satisfaction. The aim of this study was to systematically review the literature to identify a theoretical framework for the relationship between outcomes and the manifestation of fatigue on baseball pitching. The synthesized data may identify areas requiring further research. Methodology This protocol was registered with PROSPERO (ID: CRD42018114194). SPORTDiscus, Medline, PubMed, Cochrane Database of Systematic Reviews, and Google Scholar were searched, using keywords such as fatigue in pitchers and changes in kinematics (e.g., pitching mechanics, valgus elbow torque), performance (e.g., pitch count, pitch type), and injury (e.g., pain, elbow, and shoulder soreness). Three reviewers independently screened the articles, selected relevant literature based on abstract eligibility, and assessed the methods described therein for final inclusion. Results A total of 31,860 articles were screened for eligibility and 25 articles were included for the review. The selected articles included epidemiological, longitudinal, experimental, conference papers, and crossover laboratory studies. Evidence extracted from the 25 studies demonstrates a relationship between fatigue in baseball pitching, and three overarching outcomes: changes in kinematics, a decrease in performance, and an increase in injury risk. Conclusions Findings show that a co-dependence between changes in kinematics and a decrease in performance, which stems from central and peripheral fatigue, is a contributing factor of injury in baseball pitchers. A large percentage of baseball pitchers exhibit pain or soreness in either their elbow or shoulder, or both at some point in a season. Initially, kinematic changes occur that could maintain performance, but may increase joint and tissue loading. Performance decreased with elevated pitch counts and innings thrown, and pitching further into games or the season. Evidence was found to be consistent across all studies; however, more work is needed in the area of fatigue as an injury mechanism during pitching. With a proof of concept established, the prevention of negative outcomes associated with fatigue must be the focus of future research and performance should not be the only criteria.
Expression changes of CX3CL1 and CX3CR1 proteins in the hippocampal CA1 field of the gerbil following transient global cerebral ischemia

Chemokine C-X3-C motif ligand 1 (CX3CL1) and its sole receptor, CX3CR1, are known to be involved in neuronal damage/death following brain ischemia. In the present study, time-dependent expression changes of CX3CL1 and CX3CR1 proteins were investigated in the hippocampal CA1 field following 5 min of transient global cerebral ischemia (tgCI) in gerbils. To induce tgCI in gerbils, bilateral common carotid arteries were occluded for 5 min using aneurysm clips. Expression changes of CX3CL1 and CX3CR1 proteins were assessed at 1, 2 and 5 days after tgCI using western blotting and immunohistochemistry. CX3CL1 immunoreactivity was strong in the CA1 pyramidal cells of animals in the sham operation group. Weak CX3CL1 immunoreactivity was detected at 6 h after tgCI, recovered at 1 day after tgCI and disappeared from 5 days after tgCI. CX3CR1 immunoreactivity was very weak in CA1 pyramidal cells of the sham animals. CX3CR1 immunoreactivity in CA1 pyramidal cells was significantly increased at 1 days after tgCI and gradually decreased thereafter. On the other hand, CX3CR1 immunoreactivity was significantly increased in microglia from 5 days after tgCI. These results showed that CX3CL1 and CX3CR1 protein expression levels in pyramidal cells and microglia in the hippocampal CA1 field following tgCI were changed, indicating that tgCI-induced expression changes of CX3CL1 and CX3CR1 proteins might be closely associated with tgCI-induced delayed neuronal death and microglial activation.
Patients’ perceptions of recovery following a 6-week exercise intervention for the treatment of patellofemoral pain: A mixed methods study

Background Patellofemoral pain (PFP) is a common and complex condition. The diagnosis and causal mechanisms are not well understood and therefore the long-term prognosis tends to be poor. Exercise is currently the only evidence-based treatment strategy suggested to improve pain and function in the long term. However, no qualitative studies have been conducted to establish patients’ perceptions of recovery in the long term following an exercise intervention. Objectives To measure self-reported recovery on a 7-point Likert scale in 31 participants with PFP 6 months after a 6-week physiotherapy intervention. To explore the subjective accounts of patients who received a physiotherapy intervention for PFP, regarding their expectations and perceptions of recovery. Method Semi-structured exit interviews were conducted electronically 6 months after intervention to ascertain the patients’ perspectives on whether expectations of treatment were met, and factors that influenced their recovery experience. Results Quantitative analysis of self-reported recovery on a 7-point Likert scale showed that 48.4% of participants felt that they were ‘recovered’. Qualitative analysis showed three main categories: expectations of treatment, perceptions of recovery and changes in functional abilities. Conclusion Clinicians should address patients’ expectations of treatment and include the patients in decision-making regarding their treatment. Long-term follow-up is essential to ensure that treatment effects have been maintained, and this should include information about patients’ self-reported recovery. Clinical implications This study suggests that patients’ expectations of treatment and perceptions of recovery from PFP may influence prognosis. Clinicians need to collaborate with patients and involve them in decision-making to achieve their goals. An individualised treatment approach is essential to adequately address patients’ experiences, priorities and beliefs.
A 15-Minute Incremental Increase in Operative Duration Is Associated With an Additional Risk of Complications Within 30 Days After Arthroscopic Rotator Cuff Repair

Background: Operative time is a risk factor for short-term complications after orthopaedic procedures; however, it has yet to be investigated as an independent risk factor for postoperative complications after arthroscopic rotator cuff repair. Purpose: To determine whether operative time is an independent risk factor for complications, readmissions, and extended hospital stays within 30 days after arthroscopic rotator cuff repair. Study Design: Descriptive epidemiology study. Methods: The American College of Surgeons National Surgical Quality Improvement Program was queried for all hospital-based inpatient and outpatient arthroscopic rotator cuff repairs (Current Procedural Terminology code 29827) from 2005 to 2016. Concomitant procedures such as subacromial decompression, biceps tenodesis, superior labrum anterior and posterior (SLAP) repair, labral repair, and distal clavicle excision were also included, whereas patients undergoing arthroplasty were excluded from the study. Operative time was correlated with patient demographics, comorbidities, and concomitant procedures. All adverse events were correlated with operative time, while controlling for the above preoperative variables, using multivariate Poisson regression with a robust error variance. Results: A total of 27,524 procedures met inclusion and exclusion criteria. The mean age of patients was 58.4 ± 10.9 years, the mean operative time was 86.9 ± 37.4 minutes, and the mean body mass index was 30.4 ± 7.0 kg/m2. Concomitant biceps tenodesis, glenohumeral debridement, SLAP repair, labral repair, and distal clavicle excision significantly increased operative time (P < .001) but not the risk of adverse events (P > .05). The overall rate of adverse events was 0.88%. After adjusting for demographic and procedural characteristics, a 15-minute increase in operative duration was associated with an increased risk of anemia requiring transfusion (relative risk [RR], 1.27 [95% CI, 1.14-1.42]; P < .001), venous thromboembolism (RR, 1.17 [95% CI, 1.02-1.35]; P = .029), surgical site infection (RR, 1.13 [95% CI, 1.03-1.24]; P = .011), and extended length of hospital stay (RR, 1.07 [95% CI, 1.00-1.14]; P = .036). Conclusion: Although the rate of short-term complications after arthroscopic rotator cuff repair is low, incremental increases in operative time are associated with an increased risk of adverse events such as surgical site infection, pulmonary embolism, transfusion, and extended length of hospital stay. Efforts should be made to maximize surgical efficiency in the operating room through optimal coordination of the staff or increased preoperative planning.
Meniscus Repair Outcomes with and without Bone Marrow Aspiration Concentrate

Objectives: The purpose of the current study is to review the results of meniscus repairs with and without bone marrow aspiration concentrate (BMAC). It is hypothesized that with BMAC, meniscus repair outcomes will be improved when compared to without BMAC at 1 year after surgery. Methods: This is a prospective case control study performed from August 2014 until August 2017. Patients were included if they had a meniscus repair performed with no history of prior meniscus surgery to the operative knee. Patients were excluded if there was a full thickness cartilage tear or International Cartilage Repair Society (ICRS) Grade IV cartilage tear not treated in a single staged surgery. Patients were also excluded if they did not reach the one year follow-up, had a multi-ligamentous knee injury requiring multiple staged procedures. From August 2014 until November 2015, patients had meniscus repair without BMA. Menisci were all repaired arthroscopically using inside-out, outside-in and all-inside techniques. After November 2015, all meniscus repairs were augmented with BMAC. In the BMAC group, all bone marrow was obtained from the ipsilateral femur during the time of surgery. The Biocue BMAC system (Zimmer Biomet, Warsaw Indiana) was used for bone marrow aspiration and BMAC was injected directly into the tear site after repair. Numerical data such as VAS, lysholm and IKDC was analyzed using a 2 sample T-test. Categorical data such as sex, tear location, type of tear and zone of tear were analyzed using a chi-square. Results: A total of 150 patients were initially included in the study. The average age in the control group was 26.3 versus 29.4 in the BMAC group (P=0.27). Thirty seven percent of the control group had an ACL reconstruction versus 40% in the BMAC group (P= .77). The control group improved from an average pain level of 6.1 to 1.2 and the BMAC group improved from an average pain level of 5.9 to 0.7 at the 1 year end point. Both the control group and BMAC group improved with respect to pain with no difference at the 1 year end point (P=.19). There was, however a significantly larger reduction in pain at the 6 week and 3 month time point with BMAC compared to the control group (P=.02 and P=.02 respectively). At the 1-year follow-up, the mean lysholm score improved from 43 to 92 in the control group and 43 to 90 in the BMAC group. The mean IKDC score improved from 37 to 87 in the control group and 36 to 83 in the BMAC group at the one year follow-up. Conclusion: Meniscus repair outcomes were improved at 6 weeks and 3 months post-operatively, when BMAC is used to augment meniscus repair compared to repair without BMAC. Both groups, control group and BMAC meniscus repair group had improved outcomes at 1 year post-operatively with respect to VAS, lysholm and IKDC, with no difference in complication rate.
The conduction pathway of potassium channels is water free under physiological conditions

Detection of bound water in a potassium channel by solid-state NMR supports the “direct” knock-on ion permeation mechanism. Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a “water-mediated” knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a “direct” knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism.
Validity and feasibility of the self-report EQ-5D-Y as a generic Health-Related Quality of Life outcome measure in children and adolescents with Juvenile Idiopathic Arthritis in Western Cape, South Africa

Background Health-Related Quality of Life (HRQoL) data together with clinical findings allow for monitoring of intervention efficacy and the effect on HRQoL. Children with Juvenile Idiopathic Arthritis (JIA) experience symptoms often persisting into adulthood, emphasising the need to track HRQoL. Objectives The aim of this study was to investigate psychometric properties of the EuroQol five-dimensional youth questionnaire (EQ-5D-Y) in children with JIA. Methods A cross-sectional, analytical study design was used. Children 8 to 15 years were recruited, completing the self-report EQ-5D-Y and two other HRQoL questionnaires. Known group validity was established by comparing the effect size between children with different disease severities. Concurrent validity was tested using Kruskal–Wallis to compare the ranking of scores on different questionnaires. Feasibility was assessed by number of missing responses and time to complete each questionnaire. Results All questionnaires were able to distinguish between children with different JIA severity. There was a significant difference in ranking of most Juvenile Arthritis Multidimensional Assessment Report dimension scores across EQ-5D-Y levels, (p < 0.05), indicating concurrent validity. There was poor concurrent validity with the PedsQL dimensions tested with EQ-5D-Y, except for ‘pain’ (p = 0.001). The EQ-5D-Y was the quickest to complete with no missing values. Conclusion This study showed that the EQ-5D-Y is valid and feasible in measuring HRQoL in JIA children and adequately responsive to detect change over time. Clinical implications It is quick and easy to use in a busy clinical setting, allowing for effective JIA management monitoring.