Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacophore-based virtual screening and molecular docking to identify promising dual inhibitors of human acetylcholinesterase and butyrylcholinesterase

Abstract The dual inhibition of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE) plays an important role in Alzheimer’s disease treatment. Thus, this study aims identify promising dual inhibitors against hAChE and hBuChE by in silico approaches (pharmacophore-based virtual screening and molecular docking). Ten 3 D pharmacophore models for dual inhibitors using default genetic parameters were built by GALAHAD™ available on SYBYL-X 2.0. Validation steps were carried out according to Energy (<100.0 kcal/mol), Pareto = 0, Area under the ROC Curve (>0.70), Boltzmann-Enhanced Discrimination of ROC curve (BEDROC >0.50) and structure–activity relationship (SAR) for known inhibitors. The best dual pharmacophore model based on internal/external statistical parameters and SAR data (one hydrogen bond acceptor, two hydrogen bond donors and four hydrophobic centers) was employed in virtual screening at Sigma-Aldrich® subset (n = 214,446) of ZINC database by UNITY module of SYBYL-X 2.0. According to superposition values (QFIT), the best ranked compounds were prioritized for molecular docking and partition coefficient analysis (clog p < 5.0). 37 top-ranked compounds (QFIT > 64.22) from pharmacophore model showed affinity in hAChE (-10.2 < Affinity energy < −6.3 kcal/mol) and hBuChE (-10.9 < Affinity energy < −2.3 kcal/mol) binding sites. Next, liposolubity prediction and commercially available showed that ZINC43198636, ZINC43198637 and ZINC00390718 can be potential dual inhibitors against hAChE and hBuChE. Communicated by Ramaswamy H. Sarma
EPA guidance on the quality of mental health services: A systematic meta-review and update of recommendations focusing on care coordination

Abstract Background. The quality of mental health services is crucial for the effectiveness and efficiency of mental healthcare systems, symptom reduction, and quality of life improvements in persons with mental illness. In recent years, particularly care coordination (i.e., the integration of care across different providers and treatment settings) has received increased attention and has been put into practice. Thus, we focused on care coordination in this update of a previous European Psychiatric Association (EPA) guidance on the quality of mental health services. Methods. We conducted a systematic meta-review of systematic reviews, meta-analyses, and evidence-based clinical guidelines focusing on care coordination for persons with mental illness in three literature databases. Results. We identified 23 relevant documents covering the following topics: case management, integrated care, home treatment, crisis intervention services, transition from inpatient to outpatient care and vice versa, integrating general and mental healthcare, technology in care coordination and self-management, quality indicators, and economic evaluation. Based on the available evidence, we developed 15 recommendations for care coordination in European mental healthcare. Conclusions. Although evidence is limited, some concepts of care coordination seem to improve the effectiveness and efficiency of mental health services and outcomes on patient level. Further evidence is needed to better understand the advantages and disadvantages of different care coordination models.
University reopening plans under fire.

Come August, hundreds of universities across the United States are poised to reopen their campuses with a mix of online and in-person courses. Only a handful are aiming for an entirely online semester. But as the machinery of higher education cranks back into action, faculty, staff, and students are voicing concerns that, with COVID-19 cases surging in many parts of the country, employees are being forced to put their health—and the health of others—at unnecessary risk. "Everyone is at risk here—by me going into class, I9m increasing the likelihood of my grocery store staff or their families getting ill," one professor said. "The idea of a university playing those kinds of odds is ethically troubling. "
Large-spored Drechslera gigantea is a Bipolaris species causing disease on the invasive grass Microstegium vimineum

ABSTRACT Environmentally damaging invasive plants can also serve as reservoir hosts for agricultural pathogens. Microstegium vimineum is an invasive C4 annual grass that is present throughout the midwestern and eastern United States. It can reach high densities in disturbed areas such as crop-forest interfaces, which creates the potential for pathogen spillover from M. vimineum to agricultural crops and native plants. A previous study that surveyed disease on M. vimineum found a large-spored Bipolaris species that was widespread on M. vimineum and also isolated from co-occurring native grasses. Here, we report that the large-spored fungus isolated from M. vimineum and the native grass Elymus virginicus is Drechslera gigantea, based on comparison with published descriptions of morphological traits, and establish that D. gigantea is a pathogen of M. vimineum and E. virginicus. We review the phylogenetic placement and taxonomic history of D. gigantea and propose that it be reassigned to the genus Bipolaris as Bipolaris gigantea.
Growing up with AAC in the digital age: a longitudinal profile of communication across contexts from toddler to teen

Abstract Smart technology (e.g., smartphones, smartwatches, tablets) and the age of information have transformed our society and changed the lives of individuals who rely on assistive technology. This study provides a detailed description of an adolescent growing up in the digital age using augmentative and alternative communication (AAC). It documents the participant’s development across language, cognitive, and social domains from ages 2- to 15-years-old, and explores how changes in AAC technology and contextual factors contributed to broad-based outcomes associated with AAC use. In general, results from standardized assessments show growth or stability across domains from ages 2–15. Data from a parent interview provides a narrative description of AAC device use, AAC interventions, and school and family environments. Despite communicative challenges, the participant leveraged advances in AAC technology to develop communicative competence and creatively used his smart devices and the Internet to interact with friends both online and in person.
Coagulation dysfunction is associated with severity of COVID‐19: A meta‐analysis

To systematically analyze the blood coagulation features of coronavirus disease 2019 (COVID‐19) patients to provide a reference for clinical practice. An electronic search in PubMed, EMbase, Web of Science, Scopus, CNKI, WanFang Data, and VIP databases to identify studies describing the blood coagulation features of COVID‐19 patients from 1 January 2020 to 21 April 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, then, the meta‐analysis was performed by using Stata 12.0 software. Thirty‐four studies involving 6492 COVID‐19 patients were included. Meta‐analysis showed that patients with severe disease showed significantly lower platelet count (weighted mean differences [WMD]: −16.29 × 109/L; 95% confidence interval [CI]: −25.34 to −7.23) and shorter activated partial thromboplastin time (WMD: −0.81 seconds; 95% CI: −1.94 to 0.33) but higher D‐dimer levels (WMD: 0.44 μg/mL; 95% CI: 0.29‐0.58), higher fibrinogen levels (WMD: 0.51 g/L; 95% CI: 0.33‐0.69) and longer prothrombin time (PT; WMD: 0.65 seconds; 95% CI: 0.44‐0.86). Patients who died showed significantly higher D‐dimer levels (WMD: 6.58 μg/mL; 95% CI: 3.59‐9.57), longer PT (WMD: 1.27 seconds; 95% CI: 0.49‐2.06) and lower platelet count (WMD: −39.73 × 109/L; 95% CI: −61.99 to −17.45) than patients who survived. Coagulation dysfunction is common in severe COVID‐19 patients and it is associated with severity of COVID‐19.
The use of carcinoembryonic antigen levels to predict lung nodule malignancy: a meta-analysis

ABSTRACT Objectives To assess the diagnostic value of serum carcinoembryonic antigen (CEA) as a diagnostic biomarker that can be used to differentiate between benign and malignant lung nodules (LNs). Methods PubMed, Cochrane Library, and Embase were reviewed from January 2000 to April 2020 for eligible studies. Stata v12.0 was used to conduct this meta-analysis. Results Our initial literature search identified 511 potentially relevant studies, of which 11 were ultimately included in the present meta-analysis. Ten studies were retrospective and only 1 study was prospective. Overall these studies incorporated 2760 patients and 2760 total LNs (1733 malignant, 1027 benign). Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) values for these studies were 0.33 (95% CI: 0.20–0.49), 0.92 (95% CI: 0.85–0.96), 3.96 (95% CI: 2.84–5.54), 0.73 (95% CI: 0.62–0.87), and 5.42 (95% CI: 3.77–7.78), respectively. The area under curve (AUC) value was 0.77, consistent with moderate diagnostic accuracy. We detected significant heterogeneity when calculating pooled sensitivity (I2 = 95.9%, P = 0.00), specificity (I2 = 92.0%, P = 0.00), PLR (I2 = 61.7%, P = 0.00), NLR (I2 = 92.8%, P = 0.00), and DOR (I2 = 93.8%, P = 0.00). No significant evidence of publication bias was detected via Deeks’ funnel plot asymmetry test (P = 0.371). Meta-regression analysis revealed different reference standards to be closely associated with both sensitivity and specificity. Conclusions Serum CEA can achieve moderate diagnostic performance as a means of differentiating between malignant and benign LNs.
Professional Identity of Male Nursing Students in 3-Year Colleges and Junior Male Nurses in China

Purpose: To investigate the changing tendency and influencing factors of the professional identity of male nursing students in 3-year colleges and junior male nurses in China. Background: In China, the majority of nurses are 3-year nursing college graduates, among which male nurses are underrepresented. Many male nurses leave the profession 3 or 4 years after graduation. Little is known about the professional identity of Chinese male nursing students in 3-year colleges and junior male nurses. Methods: This study included 237 male nursing students from a 3-year college and 33 junior male nurses with less than 3 years of experience in China. By using the data collected with the Professional Identity Questionnaire of Nursing Students and through in-depth semistructured interviews from November 2019 to April 2020, t-test, and ANOVA analysis in SPSS22.0 were conducted and thematic analysis was applied to interviews. Results: Compared with undergraduate nursing students, Chinese male nursing students in 3-year colleges had a better professional identity, displaying a declining tendency with grades. Junior male nurses reported the lowest professional identity. Demographic factors such as family residence and presence of relatives in medical service were positively related to professional identity. Low professional identity was related to heavy workload as well as gender stereotypes. Two unique contextual factors influenced the professional identity: (a) curriculum setting and (b) nurse exams. Conclusion: College education and initial working experience were critical to professional identity formation for male nurses. Appropriate measures need to be taken to improve professional identity and promote gender diversity.
Care complexity individual factors associated with adverse events and in-hospital mortality

Introduction Measuring the impact of care complexity on health outcomes, based on psychosocial, biological and environmental circumstances, is important in order to detect predictors of early deterioration of inpatients. We aimed to identify care complexity individual factors associated with selected adverse events and in-hospital mortality. Methods A multicenter, case-control study was carried out at eight public hospitals in Catalonia, Spain, from January 1, 2016 to December 31, 2017. All adult patients admitted to a ward or a step-down unit were evaluated. Patients were divided into the following groups based on the presence or absence of three adverse events (pressure ulcers, falls or aspiration pneumonia) and in-hospital mortality. The 28 care complexity individual factors were classified in five domains (developmental, mental-cognitive, psycho-emotional, sociocultural and comorbidity/complications). Adverse events and complexity factors were retrospectively reviewed by consulting patients’ electronic health records. Multivariate logistic analysis was performed to identify factors associated with an adverse event and in-hospital mortality. Results A total of 183,677 adult admissions were studied. Of these, 3,973 (2.2%) patients experienced an adverse event during hospitalization (1,673 [0.9%] pressure ulcers; 1,217 [0.7%] falls and 1,236 [0.7%] aspiration pneumonia). In-hospital mortality was recorded in 3,996 patients (2.2%). After adjustment for potential confounders, the risk factors independently associated with both adverse events and in-hospital mortality were: mental status impairments, impaired adaptation, lack of caregiver support, old age, major chronic disease, hemodynamic instability, communication disorders, urinary or fecal incontinence, vascular fragility, extreme weight, uncontrolled pain, male sex, length of stay and admission to a medical ward. High-tech hospital admission was associated with an increased risk of adverse events and a reduced risk of in-hospital mortality. The area under the ROC curve for both outcomes was > 0.75 (95% IC: 0.78–0.83). Conclusions Several care complexity individual factors were associated with adverse events and in-hospital mortality. Prior identification of complexity factors may have an important effect on the early detection of acute deterioration and on the prevention of poor outcomes.
Relationship between cam morphology, hip symptoms, and hip osteoarthritis: the Musculoskeletal pain in Ullersaker STudy (MUST) cohort

Background: The primary aim of this study was to determine the prevalence of cam morphology in a cohort of people aged 40–55 years. Secondary aims were to: (1) determine differences in participant characteristics, physical impairments, radiographic and ultrasound appearances of people with and without cam morphology; and (2) explore associations between cam morphology and radiographic measures of hip osteoarthritis (OA). Methods: 107 people (68% women; 49 ± 4 years) from the Musculoskeletal pain in Ullensaker (MUST) Study underwent the clinical and imaging examinations. Examinations included questionnaires, hip range, functional task performance, pelvic radiographs and ultrasound. Alpha angle and radiographic hip OA (Kellgren Lawrence (KL) and minimal joint space (MJS)) were determined. Results: The prevalence of cam morphology was 42% and was bilateral in 47%. People with cam morphology were 6 times more likely to have a KL score ⩾2 (adjusted odds ratio [95% confidence intervals, p-value]) 6.386 [1.582–37.646, p = 0.012]) and 4 times more likely to have MJS <2.0 mm (adjusted odds ratio 4.032 [1.031–12.639, p = 0.045]). The prevalence of radiographic OA features ranged from 4–13% in people with cam morphology, and 0–3% in those without. Those with cam morphology also demonstrated reduced hip flexion and rotation range (p = 0.018–0.036) compared with those without. There was no association between ultrasonic features and patient reported outcomes, and cam morphology. Conclusions: In a cohort aged 40–55 years, the prevalence of cam morphology was high (42%), with a significant relationship between cam morphology and radiographic measures of hip OA. Further longitudinal studies should explore the relationship between cam morphology and hip OA in younger people.
The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis.

Psoriasis is a frequent inflammatory skin disease characterized by keratinocyte hyperproliferation and a disease-related infiltration of immune cells. Here, we identified a novel pro-inflammatory signaling pathway driven by the cyclin-dependent kinases (CDK) 4 and 6 and the methyltransferase EZH2 as a valid target for psoriasis therapy. Delineation of the pathway revealed that CDK4/6 phosphorylated EZH2 in keratinocytes, thereby triggering a methylation-induced activation of STAT3. Subsequently, active STAT3 resulted in the induction of IκBζ (IkappaBzeta), which is a key pro-inflammatory transcription factor required for cytokine synthesis in psoriasis. Pharmacological or genetic inhibition of CDK4/6 or EZH2 abrogated psoriasis-related pro-inflammatory gene expression by suppressing IκBζ induction in keratinocytes. Importantly, topical application of CDK4/6 or EZH2 inhibitors on the skin was sufficient to fully prevent the development of psoriasis in various mouse models by suppressing STAT3-mediated IκBζ expression. Moreover, we found a hyperactivation of the CDK4/6-EZH2 pathway in human and mouse psoriatic skin lesions. Thus, this study not only identifies a novel psoriasis-relevant pro-inflammatory pathway, but also proposes the repurposing of CDK4/6 or EZH2 inhibitors as a new therapeutic option for psoriasis patients.
Frailty in patients with interstitial lung disease.

PURPOSE OF REVIEW The incidence of age-related diseases such as interstitial lung disease (ILD) is rising, and the importance of multimorbidity and accumulation of health deficits in patients with chronic lung diseases is increasingly recognized. There are multiple relationships between aging and ILD on a demographic and a biological level. Frailty conceptualizes the decline of a patient's physiological reserves and complements the chronological and biological aspects of aging. RECENT FINDINGS Frailty affects more than 50% of patients with ILD, with respiratory impairment, accelerated biological aging, comorbidities, medication adverse effects, and social factors collectively playing important roles. Frailty is an independent risk factor for adverse health outcomes such as hospitalizations and early mortality, including before and after lung transplant. Given the multicomponent determinants of frailty, programs such as pulmonary rehabilitation are promising strategies for managing this complex issue. SUMMARY Frailty is a common risk factor for adverse outcomes in patients with ILD. The multiple pathways leading to frailty are not completely understood, and further studies are needed to determine the optimal tools for assessment and to develop strategies to prevent and counteract frailty in the aging ILD population.
Structural insight into TNF-α inhibitors through combining pharmacophore-based virtual screening and molecular dynamic simulation

Abstract Tumor Necrosis Factor-alpha (TNF-α), a multifunctional cytokine responsible for providing resistance against infections, inflammation, and cancers. TNF-α has emerged as a promising drug target against several autoimmune and inflammatory disorders. Several synthetic antibodies (Infliximab, Etanercept, and Adalimumab) are available, but their potential to cause severe side effects has prompted them to develop alternative small molecules-based therapies for inhibition of TNF-α. In the present study, combined in silico approaches based on pharmacophore modeling, virtual screening, molecular docking, and molecular dynamics studies were employed to understand significant direct interactions between TNF-α protein and small molecule inhibitors. Initially, four different small molecule libraries (∼17.5 million molecules) were virtually screened against the selected pharmacophore model. The identified hits were further subjected to molecular docking studies. The three potent lead compounds (ZINC05848961, ZINC09402309, ZINC04502991) were further subjected to 100 ns molecular dynamic studies to examine their stability. Our docking and molecular dynamic analysis revealed that the selected lead compounds target the TNF receptor (TNFR) and efficiently block the production of TNF. Moreover, in silico ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) analysis revealed that all the predicted compounds have good pharmacokinetic properties with high gastrointestinal absorption and a decent bioavailability score. Furthermore, toxicity profiles further evidenced that these compounds have no risk of being mutagenic, tumorigenic, reproductive and irritant except ZINC11915498. In conclusion, the present study could serve as the starting point to develop new therapeutic regimens to treat various TNF- related diseases. Communicated by Ramaswamy H. Sarma
Presence of red flags in patients with cerebral venous sinus thrombosis admitted to the emergency department because of headache

Abstract Cerebral venous sinus thrombosis (CVST) is a cause of secondary headache with substantial morbimortality. Headache dominates the clinical presentation, but no typical phenotype has been described. We aim to evaluate the presence of red flags in headache in patients with confirmed CVST at the moment of emergency department (ED) presentation. Retrospective STROBE compliant cohort study including patients with confirmed CVST that consulted because of headache at the ED. We analyzed presence and type of red flags at the moment of consult. We evaluated whether CVST was suspected at the moment of imaging request and analyzed delay in the diagnosis. Nineteen patients fulfilled inclusion and exclusion criteria. Mean age was 48.5 years, 47.4% were female. All the studied patients exhibited at least 1 red flag, being abnormal neurological examination the most frequent (79%), followed by the presence of other neurological symptoms (68%), alarm data related with headache phenotype (63%), or risk factors concerning prior medical history (47%). Temporal pattern of the headache was acute in 42.1%, thunderclap in 31.6%, and subacute in 26.3%. In none patient CVST was the specific suspicion when imaging was requested. Median time since headache onset and ED presentation was 84 hours, being different in patients with associated symptoms (48 hours) when compared with isolated headache patients (168 hours). Time since ED presentation and the diagnosis also differed between the 2 groups, being more prolonged in patients with an isolated headache at presentation. Headache attributed with CVST did not exhibit any distinctive phenotype, but all the patients presented some red flag, being abnormal neurological examination the most frequent.