Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Chondroitin Sulfate Proteoglycans in Nervous System Development

The orderly development of the nervous system is characterized by phases of cell proliferation and differentiation, neural migration, axonal outgrowth and synapse formation, and stabilization. Each of these processes is a result of the modulation of genetic programs by extracellular cues. In particular, chondroitin sulfate proteoglycans (CSPGs) have been found to be involved in almost every aspect of this well-orchestrated yet delicate process. The evidence of their involvement is complex, often contradictory, and lacking in mechanistic clarity; however, it remains obvious that CSPGs are key cogs in building a functional brain. This review focuses on current knowledge of the role of CSPGs in each of the major stages of neural development with emphasis on areas requiring further investigation:
Uptake of Trace Elements in the Water Fern Azolla filiculoides after Short-Term Application of Chestnut Wood Distillate (Pyroligneous Acid)

Treatments of crops with additives to increase their productivity may pose environmental risks and induce negative effects also on non-target organisms. In this study, we investigated the potential effect of chestnut wood distillate (pyroligneous acid) used in agriculture, on the accumulation of trace elements in aquatic plants. As a model species, the common water fern Azolla filiculoides Lam. was selected, being often used also in phytoremediation processes. The content of selected elements of toxicological concern (As, Ba, Cd, Cu, Fe, Mn, Ni, Pb, Zn) was assessed in the fern after short-term treatments (1–3 days) over a range of wood distillate concentrations 1:300 (3.33 mL/L), 1:500 (2.00 mL/L), 1:700 (1.43 mL/L). A statistically significant accumulation of Cd, Cu, Mn, Pb, Zn (1:700) and Pb (1:300) was recorded after three days of incubation, despite the concentrations remained overall low. Using treatment vs. control ratios, a trend of increasing temporal uptake was detected for As, Ba, Fe, Mn, Pb (1:700); Mn, Pb (1:500), and only Pb at 1:300. The results suggested that, under the experimental conditions, element uptake is positively influenced by time and negatively by increasing concentrations of wood distillate, likely due to the acidification of the medium. On the whole, the element concentrations measured in A. filiculoides were low and did not pose any toxicological concern.
Process Waters from Hydrothermal Carbonization of Sludge: Characteristics and Possible Valorization Pathways

Hydrothermal carbonization (HTC) is an innovative process capable of converting wet biodegradable residues into value-added materials, such as hydrochar. HTC has been studied for decades, however, a lack of detailed information on the production and composition of the process water has been highlighted by several authors. In this paper the state of the art of the knowledge on this by-product is analyzed, with attention to HTC applied to municipal and agro-industrial anaerobic digestion digestate. The chemical and physical characteristics of the process water obtained at different HTC conditions are compared along with pH, color, organic matter, nutrients, heavy metals and toxic compounds. The possibility of recovering nutrients and other valorization pathways is analyzed and technical feasibility constraints are reported. Finally, the paper describes the main companies which are investing actively in proposing HTC technology towards improving an effective process water valorization.
Identification of high-risk monomorphic post-transplant lymphoproliferative disorder following solid organ transplantation

Abstract Monomorphic post-transplant lymphoproliferative disorder (M-PTLD) occurring after solid organ transplant histologically resembles aggressive non-Hodgkin lymphomas, with diffuse large B-cell lymphoma being the most common. In a cohort of 40 patients with DLBCL-type M-PTLD, inferior progression free survival (PFS) was observed for Revised International Prognostic Index (R-IPI) >2 (p = 0.01) and high-risk pathologic features (p = 0.02), defined by double expressor lymphoma, MYC rearrangement, or increased copy number of either MYC or BCL2. Overall survival (OS) was inferior in R-IPI >2 (p = 0.002) and high-risk pathologic features (p = 0.003). Combining both R-IPI >2 and high-risk pathologic features resulted in well-delineated good, intermediate, and poor risk groups of DLBCL-type M-PTLD with respect to both PFS and OS (p < 0.001). Our results demonstrate a prognostic role for both the R-IPI score and presence of high-risk pathologic features in DLBCL-type M-PTLD.
Downregulation of CDC20 Increases Radiosensitivity through Mcl-1/p-Chk1-Mediated DNA Damage and Apoptosis in Tumor Cells

Radiotherapy is an important modality for the local control of human cancers, but the radioresistance induced by aberrant apoptotic signaling is a hallmark of cancers. Restoring the aberrant apoptotic pathways is an emerging strategy for cancer radiotherapy. In this study, we determined that targeting cell division cycle 20 (CDC20) radiosensitized colorectal cancer (CRC) cells through mitochondrial-dependent apoptotic signaling. CDC20 was overexpressed in CRC cells and upregulated after radiation. Inhibiting CDC20 activities genetically or pharmacologically suppressed the proliferation and increased radiation-induced DNA damage and intrinsic apoptosis in CRC cells. Mechanistically, knockdown of CDC20 suppressed the expression of antiapoptotic protein Mcl-1 but not other Bcl-2 family proteins. The expressions of CDC20 and Mcl-1 respond to radiation simultaneously through direct interaction, as evidenced by immunoprecipitation and glutathione S-transferase (GST) pull-down assays. Subsequently, decreased Mcl-1 expression inhibited the expression level of phosphorylated checkpoint kinase 1 (p-Chk1), thereby resulting in impaired DNA damage repair through downregulating the homologous recombination repair protein Rad51 and finally causing apoptotic signaling. In addition, both CDC20 and Chk1 inhibitors together, through in vivo studies, confirmed the radiosensitizing effect of CDC20 via inhibiting Mcl-1 and p-Chk1 expression. In summary, our results indicate that targeting CDC20 is a promising strategy to improve cancer radiotherapy.
Erectile Dysfunction in a Sample of Sexually Active Young Adult Men from a US Cohort: Demographic, Metabolic, and Mental Health Correlates.

PURPOSE Little is understood about physiologic and psychologic correlates of erectile dysfunction (ED) among younger men. This study examined prevalence and correlates of ED in a large US sample of 18-31 year old men. MATERIALS AND METHODS ED prevalence and severity (defined using the International Index of Erectile Function-5 scale) were examined in cross-sectional survey data from 2,660 sexually active men, aged 18-31 years, from the 2013 Growing Up Today Study. ED medication and supplement usage was self-reported. Multivariable models estimated associations of moderate-to-severe ED with demographic (age; marital status), metabolic (body mass index; waist circumference; history of diabetes, hypertension, hypercholesterolemia), and mental health (depression; anxiety; antidepressant, tranquilizer use) variables. RESULTS Among sexually active men, 11.3% reported mild ED; 2.9% reported moderate-to-severe ED. Married/partnered men had 65% lower odds of ED compared to single men. Adjusting for history of depression, antidepressant use was associated>3 times the odds of moderate-to-severe ED. Anxiety was associated with greater odds of moderate-to-severe ED, as was tranquilizer use. Few men (2%) reported using ED medication or supplements; however, among them, 29.7% misused prescription ED medication. Limitations include reliance upon cross-sectional data and the sample's limited racial/ethnic and socioeconomic diversity. CONCLUSION Erectile dysfunction was common in a large sample of sexually active young adult men from a US cohort and was associated with relationship status and mental health. Health providers should screen for ED in young men, and monitor use of prescription ED medications and supplements for sexual functioning.
Covid-19: contribution of clinical characteristics and laboratory features for early detection of patients with high risk of severe evolution

ABSTRACT Background The aim of this study was to identify early clinical and laboratory predictive factors of a severe coronavirus disease 2019 (COVID-19). Methods A retrospective study was conducted on adult patients hospitalized for COVID-19 in our hospital. Diagnosis was based on a positive real-time reverse transcription‐polymerase chain reaction (RT-PCR) on nasopharyngeal samples. The cohort was divided into two groups, i.e. a favorable evolution (FE) group and an unfavorable evolution (UFE) group, including intensive care unit (ICU) and deceased patients. Results: A total of 198 patients were enrolled in the study, with 138 FE (70%) and 60 UFE (30%). Older age, male gender, comorbidities and dyspnea at admission constituted significantly worse prognosis factors. Among laboratory features, lymphocyte and platelet counts as well as corrected glomerular filtration rate were significantly lower in UFE patients, while neutrophil to lymphocyte ratio, inflammation biomarkers, creatinine, aspartate aminotransferase, lactate dehydrogenase (LDH), glycemia and D-dimer were significantly higher. Procalcitonin and LDH appeared as the most accurate variables according to receiver operating characteristic curves. Conclusions This Belgian study revealed clinical and laboratory features able to predict high risk of ICU requirement, or even death, at admission time. These results provide a potential tool for patient’s triage in a context of pandemic. Abbreviations: COVID-19: coronavirus disease 2019; ARDS: acute respiratory distress syndrome; DIC: disseminated intravascular coagulopathy; MOF: multi-organ failure; RT-PCR: real-time reverse transcription‐polymerase chain reaction; UFE: unfavorable evolution; ICU: intensive care unit; EDTA: ethylenediamine tetraacetic acid; WBC: white blood cell count; Hb: hemoglobin level; PCT: procalcitonin; Na: sodium; K: potassium; PT: total protein, CRP: c-reactive protein; Cr: creatinine; ALAT: alanine aminotransferase; ALAT: aspartate aminotransferase; TB: total bilirubin, LDH: lactate dehydrogenase, FERR: ferritin; hs-Tnt: high sensitive-troponin T; cGFR: corrected glomerular filtration rate; QR: quick ratio; DDIM: D-dimer; FIB: fibrinogen; SD: standard deviation; IQR: interquartile ranges; ROC: receiver operating characteristics; ECMO: extracorporeal membrane oxygenation; NLR: neutrophil to lymphocyte ratio; AUC: area under the curve; BMI: body mass index
Identification of Potential Drug Targets in Helicobacter pylori Using In Silico Subtractive Proteomics Approaches and Their Possible Inhibition through Drug Repurposing

The class 1 carcinogen, Helicobacter pylori, is one of the World Health Organization’s high priority pathogens for antimicrobial development. We used three subtractive proteomics approaches using protein pools retrieved from: chokepoint reactions in the BIOCYC database, the Kyoto Encyclopedia of Genes and Genomes, and the database of essential genes (DEG), to find putative drug targets and their inhibition by drug repurposing. The subtractive channels included non-homology to human proteome, essentiality analysis, sub-cellular localization prediction, conservation, lack of similarity to gut flora, druggability, and broad-spectrum activity. The minimum inhibitory concentration (MIC) of three selected ligands was determined to confirm anti-helicobacter activity. Seventeen protein targets were retrieved. They are involved in motility, cell wall biosynthesis, processing of environmental and genetic information, and synthesis and metabolism of secondary metabolites, amino acids, vitamins, and cofactors. The DEG protein pool approach was superior, as it retrieved all drug targets identified by the other two approaches. Binding ligands (n = 42) were mostly small non-antibiotic compounds. Citric, dipicolinic, and pyrophosphoric acid inhibited H. pylori at an MIC of 1.5–2.5 mg/mL. In conclusion, we identified potential drug targets in H. pylori, and repurposed their binding ligands as possible anti-helicobacter agents, saving time and effort required for the development of new antimicrobial compounds.
Electronic Consultation Systems: Impact on Pediatric Orthopaedic Care.

BACKGROUND The demand for pediatric orthopaedic surgery consultation has grown rapidly, leading to longer wait times for elective consultation in some regions. Some specialties are addressing this increased demand through electronic consultation services. We wanted to examine the impact of pediatric orthopaedic e-consultations in Canada's Eastern Ontario region. METHODS We developed a cross-sectional study of all the cases directed to a pediatric orthopaedic surgery specialist using the Champlain Building Access to Specialists through eConsultation (BASE) eConsult service over a 2-year period and examined their impact on in-person referrals, time of e-consultation and primary care satisfaction as well as types of clinical questions that were asked. RESULTS Electronic consultations avoided in-person appointments in 68% of the submitted cases. The median response by specialists received by the primary care providers (PCPs) was <20 hours. A total of 69% of consultations involve >1 type of clinical questions, most commonly about basic trauma/fracture care and management recommendations. Ninety-seven percent of the PCPs found the overall value for the care of the patients to be good or excellent. CONCLUSIONS This cross-sectional study demonstrates the effective and timely use of eConsult in pediatric orthopaedic surgery. It also shows a significant reduction in the number of in-person consultations required and demonstrates a high satisfaction rate by PCPs using the service. CLINICAL RELEVANCE In addition to the efficacy and time-sensitive care provided to the patients, the study shows that, professionally, 89% of PCPs found this service to be excellent or good. The broader implications of electronic consultation on overall quality of care, population health, and patient satisfaction requires further investigation.
Understanding Cannabis-Based Therapeutics in Sports Medicine

Context: With increased use of cannabis-based products by the public for both recreational and medical use, sports medicine clinicians should be informed of historical context, current legal considerations, and existing evidence with regard to efficacy, safety, and risks in the athletic community. Evidence Acquisition: A review of ClinicalTrials.gov, MEDLINE, and CINAHL from 2015 to present was conducted with emphasis on the most recent literature using search terms, cannabis, nabiximols, cannabinoids, pain management, THC, CBD, and marijuana. Bibliographies based on original search were utilized to pursue further literature search. Study Design: Clinical review. Level of Evidence: Level 3. Results: At present, limited high-quality studies exist for use of cannabinoids for acute pain, chronic pain, or concussion. None of the trials involving cannabinoids included the athletic population. Thus, results from this clinical review are extrapolated to conditions of the sports medicine population. For acute pain, 2 small-randomized double-blinded crossover trials concluded no immediate effect of cannabinoid therapy. More robust evidence exists for treatment of chronic pain conditions through meta-analysis and systemic reviews. Cannabinoid therapy exhibits moderate efficacy as a treatment for some chronic pain conditions. Investigations included a broad spectrum of chronic pain conditions, including neuropathic, musculoskeletal, inflammatory, and central pain conditions, and reveal reduction in pain and improvement of quality of life with limited adverse effects. For concussion, evidence is based on preclinical in vitro and animal models revealing possible neuroprotective effects as well as 2 clinical studies involving the presence of cannabinoids for concussion (some sports-related), but there are no high-quality trials evaluating efficacy for treatment with cannabinoids at this time. Conclusion: Although various biochemical explanations exist on the use of cannabinoid therapy through modulation of the endocannabinoid system for several medical issues affecting athletes, recommendations from clinicians must be extrapolated from a majority of research done in the nonathletic population. Lack of strong-quality clinical evidence, coupled with inconsistent federal and state law as well as purity issues with cannabis-based products, make it difficult for the sports medicine clinician to widely recommend cannabinoid therapeutics at present. Future larger, higher quality clinical research studies with standardized pure extracts will better guide appropriate medical use going forward. At present, evidence for a multitude of therapeutic applications is emerging for cannabinoid treatment approaches. With emphasis placed on patient-centered clinical decisions, cannabinoids hold promise of treatment for athletes with chronic pain conditions. Clinicians who treat the athletic community must consider legal and ethical issues when discussing and recommending the use of cannabinoids, with acknowledgment of inconsistencies in purity of various formulations and concerns of drug testing.
TSPO-targeted PET and Optical Probes for the Detection and Localization of Premalignant and Malignant Pancreatic Lesions

Purpose: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic “incidentalomas,” particularly cysts, are frequently identified in asymptomatic patients through anatomic imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions. Experimental Design: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in premalignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted PET agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-IR optical imaging based upon the V-1008 pharmacophore, was developed and evaluated. Results: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, premalignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to premalignant pancreatic lesions and advanced tumors enabling real-time IGS. Conclusions: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.
Evaluation of anti-inflammatory activity of seeds extract of Luffa cylindrica.

The present work emphasizes on screening of the seed oils and other secondary metabolites from Cucurbitaceae seeds. The oil, CU-01, its unsaponifiable matter, CU-02 and the cucurbitacin, CU-03 extracted by Soxhlet method from the seeds of Luffa cylindrica was examined for its acute anti-inflammatory at doses of 1ml, 50mg and 50mg/kg body weight respectively. It was evident that CU-02 significantly inhibited the paw edema formation induced by carrageenan when compared to CU-01 and CU-03. However the percentage of inhibition was lesser when compared to the standards diclofenac sodium gel and flurbiprofen gel. So, by observing the all comparison studies, we concluded that CU-2 is having the maximum potency for the anti-inflammatory activity.
Phenotypic expansion in KIF1A‐related dominant disorders: A description of novel variants and review of published cases

KIF1A is a molecular motor for membrane‐bound cargo important to the development and survival of sensory neurons. KIF1A dysfunction has been associated with several Mendelian disorders with a spectrum of overlapping phenotypes, ranging from spastic paraplegia to intellectual disability. We present a novel pathogenic in‐frame deletion in the KIF1A molecular motor domain inherited by two affected siblings from an unaffected mother with apparent germline mosaicism. We identified eight additional cases with heterozygous, pathogenic KIF1A variants ascertained from a local data lake. Our data provide evidence for the expansion of KIF1A‐associated phenotypes to include hip subluxation and dystonia as well as phenotypes observed in only a single case: gelastic cataplexy, coxa valga, and double collecting system. We review the literature and suggest that KIF1A dysfunction is better understood as a single neuromuscular disorder with variable involvement of other organ systems than a set of discrete disorders converging at a single locus.
Aldehyde Dehydrogenase 2 Ameliorates Chronic Alcohol Consumption-Induced Atrial Fibrillation through Detoxification of 4-HNE

Aldehyde dehydrogenase 2 (ALDH2) is an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts such as 4-hydroxy-trans-2-nonenal (4-HNE). Previous meta-analyses have shown an increase in the risk of atrial fibrillation (AF) in patients with chronic alcohol consumption. ALDH2*2, a common dysfunctional polymorphism in the ALDH2 gene, has been linked to an increased risk of cancer and heart disease. We tested the effect of ALDH2 deficiency on alcohol-induced AF in a murine model of chronic-binge ethanol feeding, with ALDH2*2 knock-in (KI) mice generated by a CRISPR/CAS9 system. In addition, right atrial appendages were obtained from eight patients with AF undergoing open heart surgery. The results showed that burst atrial pacing induced a greater susceptibility to AF in ALDH2*2 KI mice exposed to chronic ethanol intoxication than in wild-type mice, resulting from a higher degree of 4-HNE accumulation and collagen deposition in their atria. Alda-1 attenuated transforming growth factor beta 1 (TGF-β1) expression and collagen deposition in the atria and reduced AF inducibility. Patients with AF and the ALDH2*2 allele exhibited greater oxidative stress and substrate remodeling in their atria than non-carriers. In conclusion, ALDH2 deficiency may increase the risk of chronic alcohol and tachypacing-induced AF through the accumulation of 4-HNE and increased ROS production.