Miracle-dz/UniFAR-FTUs huggingface dataset:
Endothelial Senescence and Chronic Fatigue Syndrome, a COVID-19 Based Hypothesis

Myalgic encephalomyelitis/chronic fatigue syndrome is a serious illness of unknown etiology, characterized by debilitating exhaustion, memory impairment, pain and sleep abnormalities. Viral infections are believed to initiate the pathogenesis of this syndrome although the definite proof remains elusive. With the unfolding of COVID-19 pandemic, the interest in this condition has resurfaced as excessive tiredness, a major complaint of patients infected with the SARS-CoV-2 virus, often lingers for a long time, resulting in disability, and poor life quality. In a previous article, we hypothesized that COVID-19-upregulated angiotensin II triggered premature endothelial cell senescence, disrupting the intestinal and blood brain barriers. Here, we hypothesize further that post-viral sequelae, including myalgic encephalomyelitis/chronic fatigue syndrome, are promoted by the gut microbes or toxin translocation from the gastrointestinal tract into other tissues, including the brain. This model is supported by the SARS-CoV-2 interaction with host proteins and bacterial lipopolysaccharide. Conversely, targeting microbial translocation and cellular senescence may ameliorate the symptoms of this disabling illness.
Outbreaks of Root Rot Disease in Different Aged American Ginseng Plants Are Associated With Field Microbial Dynamics

American ginseng (Panax quinquefolium L.) is a perennial plant that is cultivated for medicinal purposes. Unfortunately, outbreaks of root rot disease in American ginseng (AG) reduce yields and result in serious economic losses. Information on the dynamics of soil microbial communities associated with healthy and diseased AG of different ages is limited. The present study explored the differences in field soil microbial community structure, composition, interaction, and their predictive functions associated with healthy and diseased AG at different growth ages. Changes in soil physicochemical properties were also examined to determine the possible reasons for disease outbreaks. Results revealed that in different growth years, the genera of soil-borne pathogens, such as Alternaria, Botrytis, Cladosporium, Sarocladium, and Fusarium, were increased in diseased AG soil samples in comparison with those in the healthy AG soil samples. In contrast, the abundance of some key and potentially beneficial microbes, such as Bacillus, Chaetomium, Dyella, Kaistobacter, Paenibacillus, Penicillium, and Trichoderma, was decreased. Additionally, as AG plants age, the relative abundance of symbiotic fungi tended to decrease, while the relative abundance of potential plant pathogenic fungi gradually increased. Various soil properties, such as available phosphorus, the ratio of total nitrogen to total phosphorus (N/P), and pH, were significantly (P < 0.05) associated with microbial community composition. Our findings provide a scientific basis for understanding the relationship among the root rot disease outbreaks in American ginseng as well as their corresponding soil microbial communities and soil physicochemical properties.
Atrial Fibrillation Burden Detected by Dual-Chamber Pacemakers as a Predictor for Cardiac Outcomes: A Retrospective Single-Center Cohort Study

Background: Atrial fibrillation (AF) might lead to adverse cardiac consequences. The association between AF burden and cardiac prognosis is unknown. Methods and Results: This retrospective cohort study enrolled 204 patients (117 males; age 74.5 ± 11.5 years) who underwent dual-chamber pacemaker implantation in our center from October 2003 to May 2017. During a median follow-up of 66.5 months, AF could be detected in 153 (75%) of the 204 pacemaker patients. Primary endpoint events (composite cardiac readmission, stroke or systemic embolism, and all-cause death) occurred in 83 cases (40.7%). In logistic regression analysis, AF detection was associated with increased risks of composite endpoints [odds ratio (OR) = 2.9, 95% confidence interval (CI): 1.3–6.2, p = 0.007], and the hazard was mainly driven by increased cardiac readmission (OR = 2.2, 95% CI: 1.1–4.7, p = 0.034). No significantly elevated risk for new-onset stroke, systemic embolism, or deaths were found in patients with AF detected than those without AF recorded. AF duration grade of more than 6 min suggested progressively increased composite endpoints (OR = 1.8, 95% CI: 1.2–2.7, p for trend = 0.005), cardiac readmission (OR = 1.8, 95% CI: 1.2–2.7, p for trend = 0.005), especially heart failure or acute coronary syndrome-associated readmission (OR = 1.8, 95% CI: 1.2–2.9, p for trend = 0.010), than those with shorter (<6 min) or no AF episodes. Kaplan–Meier analyses and Cox regression also suggested that episodes of AF more than 6 min predicted future cardiac events. Conclusions: AF detected by pacemakers were common. Higher AF burden predicted more adverse cardiac outcomes and might suggest the intervention of rhythm control in these population.
Are Steroids Still Useful in Immunosuppressed Patients With Inflammatory Bowel Disease? A Retrospective, Population-Based Study

Background: Effectiveness of corticosteroids in immunosuppressed patients with inflammatory bowel disease (IBD) has not been completely elucidated. Aims: To assess the effectiveness and examine the long-term follow-up of systemic or low-bioavailability oral steroid treatment for moderate flare-ups in patients treated with immunosuppressive drugs. Methods: Immunosuppressed patients with inflammatory bowel disease (IBD) from our population-data registry were analyzed. For statistical analysis, the chi-square test, Mann-Whitney U test, and Kaplan-Meier survival analysis were used as appropriate. Results: A total of 392 patients with IBD and a median of 82 (range, 6–271) months of immunosuppressive (IMM) treatment were identified. The mean follow-up was 87 months (range, 6–239 months). A total of 89 patients (23%) needed at least one steroid course during their follow-up. Average time from IMM to steroid treatment was 26 (range, 6–207) months. In patients with CD, fibrostenotic (B2) and fistulizing (B3) behaviors [p = 0.005; odds ratio (OR): 2.284] were risk factors for using steroids after IMM treatment. In patients with UC, no statistically significant variables were identified. Of the 89 patients who received one first steroid course, 49 (55%) stepped up to biological treatment or surgery after a median of 13 months (range, 0–178), 19 (21%) were treated with repeated steroid courses, and 31 (35%) required no further treatment. Patients with CD had a higher risk (p = 0.007; OR: 3.529) of receiving biological treatment or surgery than patients with UC. The longer the patients with UC (more months) spent using steroids, the greater the risk of requiring treatment with biological drugs or surgery (p = 0.009). Conclusion: A total of 23% of the immunosuppressed patients with IBD received at least one course of steroid treatment. In patients under immunosuppression treated with at least a course of steroids, CD patients were more likely stepped up to biologics and/or surgery than UC patients. In patients with CD, B2/B3 behavior pattern were significant risk factors. After one course of steroids only 35% of immunosuppressed IBD patients remained in remission without needing treatment scalation.
Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

Pancreatic beta (β)-cell dysfunction and reduced mass play a central role in the development and progression of diabetes mellitus. Conventional histological β-cell mass (BCM) analysis is invasive and limited to cross-sectional observations in a restricted sampling area. However, the non-invasive evaluation of BCM remains elusive, and practical in vivo and clinical techniques for β-cell-specific imaging are yet to be established. The lack of such techniques hampers a deeper understanding of the pathophysiological role of BCM in diabetes, the implementation of personalized BCM-based diabetes management, and the development of antidiabetic therapies targeting BCM preservation and restoration. Nuclear medical techniques have recently triggered a major leap in this field. In particular, radioisotope-labeled probes using exendin peptides that include glucagon-like peptide-1 receptor (GLP-1R) agonist and antagonist have been employed in positron emission tomography and single-photon emission computed tomography. These probes have demonstrated high specificity to β cells and provide clear images accurately showing uptake in the pancreas and transplanted islets in preclinical in vivo and clinical studies. One of these probes, 111indium-labeled exendin-4 derivative ([Lys12(111In-BnDTPA-Ahx)]exendin-4), has captured the longitudinal changes in BCM during the development and progression of diabetes and under antidiabetic therapies in various mouse models of type 1 and type 2 diabetes mellitus. GLP-1R-targeted imaging is therefore a promising tool for non-invasive BCM evaluation. This review focuses on recent advances in non-invasive in vivo β-cell imaging for BCM evaluation in the field of diabetes; in particular, the exendin-based GLP-1R-targeted nuclear medicine techniques.
Development of a Low-Cost EEG-Controlled Hand Exoskeleton 3D Printed on Textiles

Stroke survivors can be affected by motor deficits in the hand. Robotic equipment associated with brain–machine interfaces (BMI) may aid the motor rehabilitation of these patients. BMIs involving orthotic control by motor imagery practices have been successful in restoring stroke patients' movements. However, there is still little acceptance of the robotic devices available, either by patients and clinicians, mainly because of the high costs involved. Motivated by this context, this work aims to design and construct the Hand Exoskeleton for Rehabilitation Objectives (HERO) to recover extension and flexion movements of the fingers. A three-dimensional (3D) printing technique in association with textiles was used to produce a lightweight and wearable device. 3D-printed actuators have also been designed to reduce equipment costs. The actuator transforms the torque of DC motors into linear force transmitted by Bowden cables to move the fingers passively. The exoskeleton was controlled by neuroelectric signal—electroencephalography (EEG). Concept tests were performed to evaluate control performance. A healthy volunteer was submitted to a training session with the exoskeleton, according to the Graz-BCI protocol. Ergonomy was evaluated with a two-dimensional (2D) tracking software and correlation analysis. HERO can be compared to ordinary clothing. The weight over the hand was around 102 g. The participant was able to control the exoskeleton with a classification accuracy of 91.5%. HERO project resulted in a lightweight, simple, portable, ergonomic, and low-cost device. Its use is not restricted to a clinical setting. Thus, users will be able to execute motor training with the HERO at hospitals, rehabilitation clinics, and at home, increasing the rehabilitation intervention time. This may support motor rehabilitation and improve stroke survivors life quality.
Psychopathological Symptom Load and Distinguishable Cerebral Blood Flow Velocity Patterns in Patients With Schizophrenia and Healthy Controls: A Functional Transcranial Doppler Study

Introduction: Schizophrenia is a severe psychiatric disorder, with executive dysfunction and impaired processing speed playing a pivotal role in the course of the disease. In patients with schizophrenia, neurocognitive deficits appear to be related to alterations in cerebral hemodynamics. It is not fully understood if psychopathological symptom load (i.e., presence and severity of symptoms) is also related to alterations in cerebral hemodynamics. We aim to study the relationship between psychopathological symptom load and cerebral hemodynamics in the Middle Cerebral Artery (MCA) during a cognitive task in patients with schizophrenia and healthy controls. Methodology: Cerebral hemodynamics in the MCA were examined in 30 patients with schizophrenia and 15 healthy controls using functional Transcranial Doppler (fTCD) during the Trail Making Test (TMT). Psychopathological symptoms were measured using the Brief Psychiatric Rating Scale (BPRS). Patients were dichotomized according to BPRS scores: mild-moderate (BPRS < 41, n = 15) or marked-severe (BPRS ≧ 41, n = 15). Mean blood flow velocity (MFV) in the MCA and processing speed of the TMT were analyzed. Cerebral hemodynamics were analyzed using the general additional model (GAM) with a covariate analysis of variance (ANCOVA) for group comparisons. Results: Patients and healthy controls were comparable regarding demographics. Patients had a slower processing speed for the TMT-A (patients-severe: 52s, patients-moderate: 40s, healthy-controls: 32s, p = 0.019) and TMT-B [patients-severe: 111s, patients-moderate: 76s, healthy-controls: 66s, p < 0.001)]. Patients demonstrated differing hemodynamic profiles in both TMTs: TMT- A [F(6, 1,792) = 17, p < 0.000); TMT-B [F(6, 2,692) = 61.93, p < 0.000], with a delay in increase in MFV and a failure to return to baseline values. Conclusions: Patients with schizophrenia demonstrated slower speeds of processing during both the TMT-A and TMT-B. The speed of processing deteriorated with increasing psychopathological symptom load, additionally a distinct cerebral hemodynamic pattern in the MCA was observed. Our results further support the view that severity of schizophrenia, particularly psychopathological symptom load, influences performance in neurocognitive tasks and is related to distinct patterns of brain hemodynamics.
TRAL 2.0: Tandem Repeat Detection With Circular Profile Hidden Markov Models and Evolutionary Aligner

The Tandem Repeat Annotation Library (TRAL) focuses on analyzing tandem repeat units in genomic sequences. TRAL can integrate and harmonize tandem repeat annotations from a large number of external tools, and provides a statistical model for evaluating and filtering the detected repeats. TRAL version 2.0 includes new features such as a module for identifying repeats from circular profile hidden Markov models, a new repeat alignment method based on the progressive Poisson Indel Process, an improved installation procedure and a docker container. TRAL is an open-source Python 3 library and is available, together with documentation and tutorials via vital-it.ch/software/tral.
Creating a Supportive Classroom Environment Through Effective Feedback: Effects on Students’ School Identification and Behavioral Engagement

Previous research revealed the connection between students’ behavioral and emotional engagement and a supportive classroom environment. One of the primary tools teachers have to create a supportive classroom environment is effective feedback. In this study, we assessed the supportive classroom environment using the perception shared by all students from the same classroom of teachers’ use of effective feedback. We aimed to explore the effect of such an environment on students’ behavioral engagement and school identification. Using a probabilistic sample of 1,188 students from 75 classrooms across 6th, 7th, 9th, and 10th grades, we employed multilevel regression modeling with random intercept and fixed slopes. We explored the effects of both individual perceptions of teachers’ use of effective feedback and the supportive classroom environment on student engagement. The analyses identified that students who perceived that their teachers use more effective feedback had a higher level of behavioral engagement and school identification. Once we controlled the effects of these individual perceptions of teachers’ effective feedback, we still observed the effect of a supportive classroom environment on student engagement. So, in classrooms where teachers used more effective feedback creating a supportive classroom environment, students had higher school identification and behavioral engagement levels, regardless of their individual perceptions of teachers’ feedback. The association between variables remained significant even after controlling students’ characteristics (gender, nationality, mother’s level of education, history of grade retention) and classroom characteristics (grade level, type of school, number of students at grade level). Our findings support the potential of teachers’ feedback practices to foster students’ school identification and behavioral engagement to build a more inclusive school environment and value students’ diversity.
Nasal Septum Deviation as the Consequence of BMP-Controlled Changes to Cartilage Properties

The nasal septum cartilage is a specialized hyaline cartilage important for normal midfacial growth. Abnormal midfacial growth is associated with midfacial hypoplasia and nasal septum deviation (NSD). However, the underlying genetics and associated functional consequences of these two anomalies are poorly understood. We have previously shown that loss of Bone Morphogenetic Protein 7 (BMP7) from neural crest (BMP7ncko) leads to midfacial hypoplasia and subsequent septum deviation. In this study we elucidate the cellular and molecular abnormalities underlying NSD using comparative gene expression, quantitative proteomics, and immunofluorescence analysis. We show that reduced cartilage growth and septum deviation are associated with acquisition of elastic cartilage markers and share similarities with osteoarthritis (OA) of the knee. The genetic reduction of BMP2 in BMP7ncko mice was sufficient to rescue NSD and suppress elastic cartilage markers. To our knowledge this investigation provides the first genetic example of an in vivo cartilage fate switch showing that this is controlled by the relative balance of BMP2 and BMP7. Cellular and molecular changes similar between NSD and knee OA suggest a related etiology underlying these cartilage abnormalities.
Stimuli-Responsive Polymeric Nanoplatforms for Cancer Therapy

Polymeric nanoparticles have been widely used as carriers of drugs and bioimaging agents due to their excellent biocompatibility, biodegradability, and structural versatility. The principal application of polymeric nanoparticles in medicine is for cancer therapy, with increased tumor accumulation, precision delivery of anticancer drugs to target sites, higher solubility of pharmaceutical properties and lower systemic toxicity. Recently, the stimuli-responsive polymeric nanoplatforms attracted more and more attention because they can change their physicochemical properties responding to the stimuli conditions, such as low pH, enzyme, redox agents, hypoxia, light, temperature, magnetic field, ultrasound, and so on. Moreover, the unique properties of stimuli-responsive polymeric nanocarriers in target tissues may significantly improve the bioactivity of delivered agents for cancer treatment. This review introduces stimuli-responsive polymeric nanoparticles and their applications in tumor theranostics with the loading of chemical drugs, nucleic drugs and imaging molecules. In addition, we discuss the strategy for designing multifunctional polymeric nanocarriers and provide the perspective for the clinical applications of these stimuli-responsive polymeric nanoplatforms.
Sense of Purpose Promotes Resilience to Cognitive Deficits Attributable to Depressive Symptoms

Objective Individuals higher in depressive symptoms commonly present with neuropsychological deficits including poorer memory performance. Sense of purpose in life has been shown to promote resilience to cognitive impairment in older adulthood, but it is unclear whether it may also protect against cognitive deficits associated with higher depressive symptoms. Method Cognitive functioning among 4599 older American adults (Mage = 74.33 years, range = 65–104 years, 56.84% female) was examined across a 12-year follow-up period. Depressive symptomatology was assessed at each wave using the 8-item Center for Epidemiologic Studies Depression Scale. Multilevel models assessed the influence of depressive symptoms and the interaction with sense of purpose in life on changes in memory performance and mental status. Results Higher depressive symptoms were associated with poorer memory performance at baseline, but did not predict rate of change over time. A negative interaction was observed between sense of purpose in life and depressive symptoms such that individuals higher in purpose experienced a less negative association between depressive symptoms and baseline memory performance. No significant interaction of sense of purpose and depressive symptoms was observed on mental status. Conclusion Having a sense of purpose in life may help protect older adults from memory deficits associated with higher depressive symptoms. The present findings underscore the potential for sense of purpose to promote cognitive reserve in older adulthood, allowing individuals to maintain cognitive performance in the face of accruing neurological insults.
Propofol Ameliorates ox-LDL-Induced Endothelial Damage Through Enhancing Autophagy via PI3K/Akt/m-TOR Pathway: A Novel Therapeutic Strategy in Atherosclerosis

Objective: Atherosclerosis (AS) represents a common age-associated disease, which may be accelerated by oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell injury. This study aimed to investigate the effects of Propofol on ox-LDL-induced endothelial damage and the underlying molecular mechanisms. Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to ox-LDL to induce endothelial damage. HUVECs were pretreated with 0, 5, 25 and 100°μM Propofol, followed by exposure to 100°μg/ml ox-LDL for 24°h. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. The expression of autophagy- and apoptosis-related proteins was detected via western blot. Autophagosome was investigated under a transmission electron microscope. After co-treatment with autophagy inhibitor Bafilomycin A1 or si-Beclin-1, cell apoptosis was detected by flow cytometry. Furthermore, under cotreatment with PI3K activator 740Y-P, PI3K/Akt/m-TOR pathway- and autophagy-related proteins were examined by western blot. Results: With a concentration-dependent manner, Propofol promoted the viability of HUVECs exposed to ox-LDL, and increased LC3-II/I ratio and Beclin-1 expression, and decreased P62 expression. The formation of autophagosome was enhanced by Propofol. Furthermore, Propofol treatment elevated Bcl-2/Bax ratio and lowered Caspase-3 expression. Bafilomycin A1 or si-Beclin-1 distinctly ameliorated the inhibitory effects of Propofol on apoptosis in ox-LDL-exposed HUVECs. Moreover, Propofol lowered the activation of PI3K/Akt/m-TOR pathway in HUVECs under exposure to ox-LDL. However, its inhibitory effects were weakened by 740Y-P. Conclusion: Collectively, this study revealed that Propofol could ameliorate ox-LDL-induced endothelial damage through enhancing autophagy via PI3K/Akt/m-TOR pathway, which might offer a novel therapeutic strategy in AS.
Targeting Long Non-Coding RNAs in Hepatocellular Carcinoma: Progress and Prospects

Hepatocellular carcinoma is the fifth-ranked cancer worldwide with a relatively low five-year survival rate. Long non-coding RNAs are a group of RNAs with remarkable aberrant expression which could act on multiple bioprocesses and ultimately impact upon tumor proliferation, invasion, migration, metastasis, apoptosis, and therapy resistance in cancer cells including hepatocellular carcinoma cells. In recent years, long non-coding RNAs have been reported to be indispensable targets in clinical target therapy to stop the growth of cancer and prolong the lifespan of patients with hepatocellular carcinoma. In this review, we enumerate the signaling pathways and life activities affected by long non-coding RNAs in hepatocellular carcinoma cells to illustrate the role of long non-coding RNAs in the development and therapy resistance of hepatocellular carcinoma.