Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal Muscle and Peripheral Nerve Histopathology in COVID-19

Objective To explore the spectrum of skeletal muscle and nerve pathology of patients who died after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to assess for direct viral invasion of these tissues. Methods Psoas muscle and femoral nerve sampled from 35 consecutive autopsies of patients who died after SARS-CoV-2 infection and 10 SARS-CoV-2–negative controls were examined under light microscopy. Clinical and laboratory data were obtained by chart review. Results In SARS-CoV-2–positive patients, mean age at death was 67.8 years (range 43–96 years), and the duration of symptom onset to death ranged from 1 to 49 days. Four patients had neuromuscular symptoms. Peak creatine kinase was elevated in 74% (mean 959 U/L, range 29–8,413 U/L). Muscle showed type 2 atrophy in 32 patients, necrotizing myopathy in 9, and myositis in 7. Neuritis was seen in 9. Major histocompatibility complex-1 (MHC-1) expression was observed in all cases of necrotizing myopathy and myositis and in 8 additional patients. Abnormal expression of myxovirus resistance protein A (MxA) was present on capillaries in muscle in 9 patients and in nerve in 7 patients. SARS-CoV-2 immunohistochemistry was negative in muscle and nerve in all patients. In the 10 controls, muscle showed type 2 atrophy in all patients, necrotic muscle fibers in 1, MHC-1 expression in nonnecrotic/nonregenerating fibers in 3, MxA expression on capillaries in 2, and inflammatory cells in none, and nerves showed no inflammatory cells or MxA expression. Conclusions Muscle and nerve tissue demonstrated inflammatory/immune-mediated damage likely related to release of cytokines. There was no evidence of direct SARS-CoV-2 invasion of these tissues. Classification of Evidence This study provides Class IV evidence that muscle and nerve biopsies document a variety of pathologic changes in patients dying of coronavirus disease 2019 (COVID-19).
A Muscle Synergy-Inspired Method of Detecting Human Movement Intentions Based on Wearable Sensor Fusion

Detecting human movement intentions is fundamental to neural control of robotic exoskeletons, as it is essential for achieving seamless transitions between different locomotion modes. In this study, we enhanced a muscle synergy-inspired method of locomotion mode identification by fusing the electromyography data with two types of data from wearable sensors (inertial measurement units), namely linear acceleration and angular velocity. From the finite state machine perspective, the enhanced method was used to systematically identify 2 static modes, 7 dynamic modes, and 27 transitions among them. In addition to the five broadly studied modes (level ground walking, ramps ascent/descent, stairs ascent/descent), we identified the transition between different walking speeds and modes of ramp walking at different inclination angles. Seven combinations of sensor fusion were conducted, on experimental data from 8 able-bodied adult subjects, and their classification accuracy and prediction time were compared. Prediction based on a fusion of electromyography and gyroscope (angular velocity) data predicted transitions earlier and with higher accuracy. All transitions and modes were identified with a total average classification accuracy of 94.5% with fused sensor data. For nearly all transitions, we were able to predict the next locomotion mode 300-500ms prior to the step into that mode.
Relation between micro- and nanostructure features and biological properties of the decellularized rat liver

Organ decellularization is one of the promising technologies of regenerative medicine, which allows obtaining cell-free extracellular matrix (ECM), which provide preservation of the composition, architecture, vascular network and biological activity of the ECM. The method of decellularization opens up wide prospects for its practical application not only in the field of creating full-scale bioengineered structures, but also in the manufacture of vessels, microcarriers, hydrogels, and coatings. The main goal of our work was the investigation of structure and biological properties of lyophilized decellularized Wistar rat liver fragments (LDLFs), as well as we assessed the regenerative potential of the obtained ECM. We obtained decellularized liver of a Wistar rat, the vascular network and the main components of the ECM of tissue were preserved. H&E staining of histological sections confirmed the removal of cells. DNA content of ECM is equal to 0.7% of native tissue DNA content. Utilizing scanning probe nanotomogrphy method, we showed sinuous, rough topography and highly nanoporous structure of ECM, which provide high level of mouse 3T3 fibroblast and Hep-G2 cells biocompatibility. Obtained LDLF had a high regenerative potential, which we studied in an experimental model of a full-thickness rat skin wound healing: we observed the acceleration of wound healing by 2.2 times in comparison with the control.
Comparative Analysis of Open Reduction Internal Fixation and Closed Reduction Percutaneous Pinning of Hand Fractures

Purpose The purpose of our study was to compare postoperative outcomes between patients receiving closed reduction percutaneous pinning (CRPP) to open reduction internal fixation (ORIF) following metacarpal and phalanx fractures. Methods A retrospective chart review was performed at a single academic center for all patients suffering a metacarpal or phalanx fracture and receiving either CRPP or ORIF between 2012 and 2018. Patients were divided into fracture mechanism, high-energy mechanism of injury, low-energy mechanism of injury, or unknown, and treatment of fracture with either ORIF or CRPP. High-energy mechanism of injury included gunshot wounds, motor vehicle crash, and blast injuries, whereas low-energy mechanism of injury included all other causes. Patient demographics, postoperative complications, 30-day readmission, and return to the operating room were recorded. Results A total of 408 patients, with 524 fractures, were included in the study. There were 127 fractures that resulted from high-energy mechanisms and 394 fractures that resulted from low-energy mechanisms. Open reduction internal fixation was used to treat 299 fractures, whereas CRPP was used for 225 fractures. Among fracture fixation, there was a total of 8.4% complication rate with ORIF, accounting for 10.4% of complications, and CRPP accounting for 5.8%. Among the fracture mechanism, the high-energy mechanism of injury had a 21.3% complication rate, whereas the low-energy mechanism of energy was 4.3%. When comparing the above variables, only high-energy mechanism of injury was a statistically significant predictor of complications (odds ratio, 3.2; confidence interval, 1.5–7.0; P = 0.002). The average operating room time for the ORIF group was 124.82 minutes compared with 97.6 minutes for the CRPP group. Conclusion Patients with hand fractures corrected by ORIF appeared to have a higher postoperative complication rate. When the 2 procedures, ORIF and CRPP, were controlled for mechanism of injury, there was not a statistically significant difference in postoperative complication rate (P = 0.14). However, a fracture sustained by a high-energy mechanism was a statistically significant predictor of postoperative complications (P = 0.002).
Selective Phosphodiesterase 1 Inhibition Ameliorates Vascular Function, Reduces Inflammatory Response, and Lowers Blood Pressure in Aging Animals

Diminished nitric oxide-cGMP–mediated relaxation plays a crucial role in cardiovascular aging, leading to decreased vasodilation, vascular hypertrophy and stiffening, and ultimately, cardiovascular dysfunction. Aging is the time-related worsening of physiologic function due to complex cellular and molecular interactions, and it is at least partly driven by DNA damage. Genetic deletion of the DNA repair enzyme ERCC1 endonuclease in Ercc1Δ/− mice provides us an efficient tool to accelerate vascular aging, explore mechanisms, and test potential treatments. Previously, we identified the cGMP-degrading enzyme phosphodiesterase 1 as a potential treatment target in vascular aging. In the present study, we studied the effect of acute and chronic treatment with ITI-214, a selective phosphodiesterase 1 inhibitor on vascular aging features in Ercc1Δ/− mice. Compared with wild-type mice, Ercc1Δ/− mice at the age of 14 weeks showed decreased reactive hyperemia, diminished endothelium-dependent and -independent responses of arteries in organ baths, carotid wall hypertrophy, and elevated circulating levels of inflammatory cytokines. Acute ITI-214 treatment in organ baths restored the arterial endothelium-independent vasodilation in Ercc1Δ/− mice. An 8-week treatment with 100 mg/kg per day ITI-214 improved endothelium-independent relaxation in both aorta and coronary arteries, at least partly restored the diminished reactive hyperemia, lowered the systolic and diastolic blood pressure, normalized the carotid hypertrophy, and ameliorated inflammatory responses exclusively in Ercc1Δ/− mice. These findings suggest phosphodiesterase 1 inhibition would provide a powerful tool for nitric oxide-cGMP augmentation and have significant therapeutic potential to battle arteriopathy related to aging. Significance Statement The findings implicate the key role of phosphodiesterase 1 in vascular function and might be of clinical importance for the prevention of mortalities and morbidities related to vascular complications during aging, as well as for patients with progeria that show a high risk of cardiovascular disease.
Heart rate variability moderates the effects of COVID-19-related stress and family adversity on emotional problems in adolescents: Testing models of differential susceptibility and diathesis stress

Abstract The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents’ mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13–19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who previously exhibited higher resting HRV or higher HRV reactivity. For adolescents who exhibited lower resting HRV or HRV augmentation, COVID-19 stress was not associated with emotional problems. Conversely, lower resting HRV indicated vulnerability to the effect of COVID-19 family adversity on emotional problems. Different patterns of parasympathetic functioning may reflect differential susceptibility to the effects of COVID-19 stress versus vulnerability to the effects of COVID-19 family adversity on mental health during the pandemic.
Association between well-being and compliance with COVID-19 preventive measures by healthcare professionals: A cross-sectional study

Importance Knowledge and attitude influence compliance and individuals’ practices. The risk and protective factors associated with high compliance to these preventive measures are critical to enhancing pandemic preparedness. Objective This survey aims to assess differences in mental health, knowledge, attitudes, and practices (KAP) of preventive measures for COVID-19 amongst healthcare professionals (HCP) and non-healthcare professionals. Design Multi-national cross-sectional study was carried out using electronic surveys between May-June 2020. Setting Multi-national survey was distributed across 36 countries through social media, word-of-mouth, and electronic mail. Participants Participants ≥21 years working in healthcare and non-healthcare related professions. Main outcome Risk factors determining the difference in KAP towards personal hygiene and social distancing measures during COVID-19 amongst HCP and non-HCP. Results HCP were significantly more knowledgeable on personal hygiene (AdjOR 1.45, 95% CI -1.14 to 1.83) and social distancing (AdjOR 1.31, 95% CI -1.06 to 1.61) compared to non-HCP. They were more likely to have a positive attitude towards personal hygiene and 1.5 times more willing to participate in the contact tracing app. There was high compliance towards personal hygiene and social distancing measures amongst HCP. HCP with high compliance were 1.8 times more likely to flourish and more likely to have a high sense of emotional (AdjOR 1.94, 95% CI (1.44 to 2.61), social (AdjOR 2.07, 95% CI -1.55 to 2.78), and psychological (AdjOR 2.13, 95% CI (1.59–2.85) well-being. Conclusion and relevance While healthcare professionals were more knowledgeable, had more positive attitudes, their higher sense of total well-being was seen to be more critical to enhance compliance. Therefore, focusing on the well-being of the general population would help to enhance their compliance towards the preventive measures for COVID-19.
Injury Incidence and Severity in Musical Theatre Dance Students: 5-year Prospective Study

Abstract Dance injury research has mainly focused on ballet and modern dance with little data on musical theatre dancers. The purpose was to assess the incidence and severity of injuries in a musical theatre dance college over a 5-year period; 198 pre-professional musical theatre dancers (3 cohorts on a 3-year training course) volunteered for the study; 21 students left the course over the study period. Injury aetiology data were collected by an in-house physiotherapy team. Differences between academic year and sex were analysed using a Poisson distribution model; significant difference was set at p≤0.05. In total, 913 injuries were recorded, and more injuries occurred in academic year 1 than year 2 and 3. Overall injury incidence was 1.46 injuries per 1000 hours (95% CI 1.34, 1.56); incidence significantly decreased between year 1, 2 and 3 (p<0.05). There was no significant sex difference for incidence or severity. Most injuries were classified as overuse (71% female, 67% male). Pre-professional musical theatre dancers report a high proportion of lower limb and overuse injuries comparable to other dance genres. Unlike other studies on pre-professional dancers, injury incidence and severity decreased with academic year, even though workload increased across the course.
The efficacy, acceptability and continuation of postpartum, post-abortive progestin-only pill: a pioneering prospective multicentric study from Turkey

Objective: The aim of this study was to evaluate the efficacy, side-effects and continuation rate of the desogestrel-progestin-only-pill (POP) in postpartum and post-abortive Turkish women and its relation with breast-feeding. Material and Methods: In this prospective multicentric study women who delivered (or had surgical abortion) and wanted to receive POP for contraception were recruited to the study. The follow-up visits were scheduled at the third, sixth and ninth months. Results: Overall A total of 7,468 women (66.5% postpartum, 33.5% post-abortive) participated in the study. The number of women who attended follow-up visits in relation to the previous visit at the third, sixth and ninth months was 944/7,468 (12.6%), 406/944 (43%) and 121/406 (29.8%) respectively. The incidence of breastfeeding at all visits was between 54.8% and 68.4%. Out of the 7,468 women recruited only 6% continued with the method at the end of the ninth month. There was a statistically significant increase in hemoglobin level at the third month compared to initial values. Oligomenorrhea, spotting and headache were the three leading side-effects. There was no pregnancy among the patients who were followed up. Conclusion: This study demonstrated that POP was an effective postpartum and post-abortive contraceptive method that had no negative impact on breast-feeding. A change in bleeding patterns was the most common side-effect. However, the possible causes of low contraceptive maintenance rates need to be investigated.
Presenilin mutations and their impact on neuronal differentiation in Alzheimer’s disease

The presenilin genes (PSEN1 and PSEN2) are mainly responsible for causing early-onset familial Alzheimer’s disease, harboring ~300 causative mutations, and representing ~90% of all mutations associated with a very aggressive disease form. Presenilin 1 is the catalytic core of the γ-secretase complex that conducts the intramembranous proteolytic excision of multiple transmembrane proteins like the amyloid precursor protein, Notch-1, N- and E-cadherin, LRP, Syndecan, Delta, Jagged, CD44, ErbB4, and Nectin1a. Presenilin 1 plays an essential role in neural progenitor maintenance, neurogenesis, neurite outgrowth, synaptic function, neuronal function, myelination, and plasticity. Therefore, an imbalance caused by mutations in presenilin 1/γ-secretase might cause aberrant signaling, synaptic dysfunction, memory impairment, and increased Aβ42/Aβ40 ratio, contributing to neurodegeneration during the initial stages of Alzheimer’s disease pathogenesis. This review focuses on the neuronal differentiation dysregulation mediated by PSEN1 mutations in Alzheimer’s disease. Furthermore, we emphasize the importance of Alzheimer’s disease-induced pluripotent stem cells models in analyzing PSEN1 mutations implication over the early stages of the Alzheimer’s disease pathogenesis throughout neuronal differentiation impairment.
YeiE Regulates Motility and Gut Colonization in Salmonella enterica Serotype Typhimurium

The ability to finely tune virulence factor gene expression is required for bacterial pathogens to successfully colonize a host. Flagellum-mediated motility is critical for many gut pathogens to establish productive infections. ABSTRACT Regulation of flagellum biosynthesis is a hierarchical process that is tightly controlled to allow for efficient tuning of flagellar expression. Flagellum-mediated motility directs Salmonella enterica serovar Typhimurium toward the epithelial surface to enhance gut colonization, but flagella are potent activators of innate immune signaling, so fine-tuning flagellar expression is necessary for immune avoidance. In this work, we evaluate the role of the LysR transcriptional regulator YeiE in regulating flagellum-mediated motility. We show that yeiE is necessary and sufficient for swimming motility. A ΔyeiE mutant is defective for gut colonization in both the calf ligated ileal loop model and the murine colitis model due to its lack of motility. Expression of flagellar class 2 and 3 but not class 1 genes is reduced in the ΔyeiE mutant. We linked the motility dysregulation of the ΔyeiE mutant to repression of the anti-FlhD4C2 factor STM1697. Together, our results indicate that YeiE promotes virulence by enhancing cell motility, thereby providing a new regulatory control point for flagellar expression in Salmonella Typhimurium. IMPORTANCE The ability to finely tune virulence factor gene expression is required for bacterial pathogens to successfully colonize a host. Flagellum-mediated motility is critical for many gut pathogens to establish productive infections. However, flagella activate the immune system, leading to bacterial clearance; therefore, tight control of flagellar gene expression enhances bacterial fitness in the host. Here, we demonstrate that the transcriptional regulator YeiE acts as a control point for flagellar gene expression and is required for Salmonella Typhimurium to establish a productive infection in mammals. The expression of an inhibitor of flagellar biogenesis is repressed in the absence of yeiE. Our work adds a new layer to the tightly controlled cascade regulating control of flagellar gene expression to facilitate the fitness of an enteric pathogen.
Enterovirus-A71 Rhombencephalitis Outbreak in Catalonia: Characteristics, Management and Outcome

Background: Between April and June 2016, an outbreak of rhombencephalitis (RE) caused by enterovirus (EV) A71 was detected in Catalonia, Spain—the first documented in Western Europe. The clinical characteristics and outcome of patients with this condition differed from those reported in outbreaks occurring in Southeast Asia. Methods: Observational, multicenter study analyzing characteristics, treatment and outcome of patients with EV-A71 rhombencephalitis diagnosed in 6 publicly funded hospitals within the Catalonian Health Institute. A review of clinical characteristics, diagnosis, treatment and outcome of these patients was conducted. Results: Sixty-four patients met the clinical and virologic criteria for rhombencephalitis caused by EV-A71. All patients had symptoms suggesting viral disease, mainly fever, lethargy, ataxia and tremor, with 30% of hand-foot-mouth disease. Intravenous immunoglobulin therapy was given to 44/64 (69%) patients and methylprednisolone to 27/64 (42%). Six patients (9%) required pediatric intensive care unit admission. Three patients had acute flaccid paralysis of 1 limb, and another had autonomic nervous system (ANS) dysfunction with cardiorespiratory arrest. Outcome in all patients (except the patient with hypoxic-ischemic encephalopathy) was good, with complete resolution of the symptoms. Conclusions: During the 2016 outbreak, rhombencephalitis without ANS symptoms was the predominant form of presentation and most patients showed no hand-foot-mouth disease. These findings contrast with those of other patient series reporting associated ANS dysfunction (10%–15%) and hand-foot-mouth disease (60%–80%). Complete recovery occurred in almost all cases. In light of the favorable outcome in untreated mild cases, therapies for this condition should be reserved for patients with moderate-severe infection. The main relevance of this study is to provide useful information for setting priorities, management approaches and adequate use of resources in future EV-A71 associated rhombencephalitis outbreaks.
TDO2 overexpression correlates with poor prognosis, cancer stemness, and resistance to cetuximab in bladder cancer

Bladder cancer (BC) is the 10th most common cancer in the world. BC with muscle invasion results in a poor prognosis and is usually fatal. Cancer cell metabolism has an essential role in the development and progression of tumors. Expression of tryptophan 2,3‐dioxygenase (TDO2) is associated with tumor progression and worse survival in some other cancers. However, no studies have been performed to uncover the biofunctional roles of TDO2 in BC.