Miracle-dz/UniFAR-FTUs huggingface dataset:
Co‐targeting bromodomain and extra‐terminal proteins and MCL1 induces synergistic cell death in melanoma

The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti‐apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra‐terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti‐apoptotic targets regulated by NF‐kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro‐apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I‐BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3‐only protein, BIM, and downregulated anti‐apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT‐199 or ABT‐263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I‐BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance.
Human behavior, not race or geography, is the strongest predictor of microbial succession in the gut bacteriome of infants

ABSTRACT Colonization of the gastrointestinal tract with microorganisms during infancy represents a critical control point for shaping life-long immune-mediated disease susceptibility. Abnormal colonization or an imbalance of microbes, termed dysbiosis, is implicated in several diseases. Consequently, recent research has aimed at understanding ways to manipulate a dysbiotic microbiome during infancy to resemble a normal, healthy microbiome. However, one of the fundamental issues in microbiome research is characterizing what a “normal” infant microbiome is based on geography, ethnicity and cultural variations. This review provides a comprehensive account of what is currently known about the infant microbiome from a global context. In general, this review shows that the influence of cultural variations in feeding practices, delivery modes and hygiene are the biggest contributors to microbial variability. Despite geography or race, all humans have similar microbial succession during infancy.
The Malay version of antenatal and postnatal breastfeeding self-efficacy scale-short form: reliability and validity assessment

Maternal self-efficacy in breastfeeding is one of the potential modifiable factors which is consistently linked with positive breastfeeding outcomes. This study aimed to develop a Malay translation of the original English BSES-SF and to conduct a validity and reliability assessment on both antenatal and postnatal questionnaires among 101 pregnant women in their third trimester and 104 women on their first week postpartum. The Malay translation of the English BSES-SF was conducted by using back-to-back translation processes, followed by validity and reliability evaluation. The validated Malay version of the questionnaire BSES-SF was then administered on the respondents. The questionnaire comprised of socio-demographic, antenatal, and breastfeeding information. Furthermore, data on infant feeding method were collected via telephone call made to the respondents at four weeks postpartum. The Cronbach’s Alpha value for antenatal BSES-SF questionnaire was0.94, while the value for postnatal BSES-SF questionnaire was 0.95. The factor analysis identified a one-dimensional structure which able to explain 59.02% of the variance for antenatal questionnaire and 60.43% of the variance for postnatal questionnaire. In addition, high antenatal and postnatal breastfeeding self-efficacy scores were significantly associated with the practice of exclusive breastfeeding at four weeks postpartum. As a conclusion, Both Malay versions of the antenatal and postnatal BSES-SF questionnaires are valid and reliable tools to assess breastfeeding self-efficacy among Malaysian mothers.
A reappraisal of the value of video-EEG recording in the emergency department

ABSTRACT Introduction: Some neurologic conditions that can quickly and with low costs be recognized, classified and treated thanks to the availability of an EEG recording in an emergency setting. However, although considered a cheap, not invasive, highly accurate diagnostic investigation, still today, an EEG recording in emergency, in real time during the event paroxysmal ictal phase, is not yet been become a routine. Areas covered: This review will cover the role and utility of EEG recording in the emergency setting, both in emergency department and intensive care unit, in adult and pediatric age, in people admitted for status epilepticus (convulsive or non-convulsive), paroxysmal non-epileptic events, or other conditions/diseases presenting with mental status changes. Expert opinion: The prompt recognition of some specific EEG-patterns can permit an immediate and appropriate therapeutic choice with the resolution of dramatic clinical pictures, which, if not recognized, sometimes could result in severe prognostic events with high mortality or neuropsychiatric disability. It is important in the next future, to improve the availability of these EEG digital continuous monitoring, which should be widely used in emergency settings, developing moreover tools and techniques permitting also review, analysis and EEG-reporting by experts who can work away from the hospital.
Using Machine Learning to Predict Dementia from Neuropsychiatric Symptom and Neuroimaging Data

Background: Machine learning (ML) is a promising technique for patient-specific prediction of mild cognitive impairment (MCI) and dementia development. Neuropsychiatric symptoms (NPS) might improve the accuracy of ML models but have barely been used for this purpose. Objectives: To investigate if baseline mild behavioral impairment (MBI) status used for NPS quantification along with brain morphology features are predictive of follow-up diagnosis, median 40 months later in patients with normal cognition (NC) or MCI. Method: Baseline neuroimaging, neuropsychiatric, and clinical data from 102 individuals with NC and 239 with MCI were extracted from the Alzheimer’s Disease Neuroimaging Initiative database. Neuropsychiatric inventory questionnaire items were transformed to MBI domains using a published algorithm. Diagnosis at latest follow-up was used as the outcome variable and ground truth classification. A logistic model tree classifier combined with information gain feature selection was trained to predict follow-up diagnosis. Results: In the binary classification (NC versus MCI/AD), the optimal ML model required only two features from over 200, MBI total score and left hippocampal volume. These features correctly classified participants as remaining normal or developing cognitive impairment with 84.4% accuracy (area under the receiver operating characteristics curve [ROC-AUC] = 0.86). Seven features were selected for the three-class model (NC versus MCI versus dementia) achieving an accuracy of 58.8% (ROC-AUC=0.73). Conclusion: Baseline NPS, categorized for MBI domain and duration, have prognostic utility in addition to brain morphology measures for predicting diagnosis change using ML. MBI total score, followed by impulse dyscontrol and affective dysregulation were most predictive of future diagnosis.
Charting the structural and thermodynamic determinants in phenolic acid natural product – cyclodextrin encapsulations

Abstract Cyclodextrins are pliable platforms that have served to optimize the pharmaceutic profile of numerous compounds and to enhance the stability of natural food additives. Caffeic and rosmarinic acid are natural products with proven health benefits, though their full therapeutic potential has not been exploited. To enhance their pharmaceutic profile, we developed cyclodextrin-based formulates and unveiled their thermodynamic and structural principles. The complexes’ stoichiometry was determined by ESI-MS. Solid-state and liquid NMR spectroscopy revealed the interactions and the topographical location of the caffeic and rosmarinic acid inside the cyclodextrin cavity. The theoretically analyzed HP-β-CD’s degree of substitution (DS) of caffeic and rosmarinic acids can explain the intensities obtained by 2D NOESY experiments. The thermodynamics and the affinity of the complexes were evaluated through isothermal titration calorimetry. In addition, the rosmarinic and caffeic acids as, also, their complexes showed considerable antimicrobial activity against common food spoilage and pathogenic bacteria. The generated data could provide the basis to understand the structural and thermodynamic determinants implicated in natural products – CD recognition and to develop platforms for the optimization of their pharmaceutical and stability profiles in order to be utilized as safe and stable natural antimicrobial food additives. Communicated by Ramaswamy H. Sarma
Influence of vertical soft tissue thickness on occurrence of peri-implantitis in patients with periodontitis: a prospective cohort study.

BACKGROUND The influence of vertical soft tissue thickness on health of peri-implant tissue has been addressed in few studies; thus, further research is needed. PURPOSE To evaluate the influence of vertical soft tissue thickness on the risk of peri-implantitis and peri-implant condition in patients with a history of periodontitis. DESIGN/METHODS A total of 92 patients with a history of periodontitis were included in this study. During the implant placement, the distance from palatal soft tissue edge to the alveolar crest, which was defined as vertical soft tissue thickness, was measured. The characteristics of patients and implants were recorded at baseline (T1). After more than 2 years follow-up period, 65 patients with 159 implants finally came back for T2 evaluation, and parameters of peri-implant tissue were recorded. The associations of vertical soft tissue thickness with peri-implant parameter and occurrence of peri-implantitis were analyzed using the generalized estimating equation accompanying linear regression and logistic regression. In addition to conventional multivariate analysis, a propensity score for adjustment was used to reduce confounding bias. RESULTS At follow-up examination (T2), survival rate at implant-level was 98.8%. The peri-implant parameters, including peri-implant probing depth and marginal bone loss, increased significantly with the increasing of soft tissue thickness (P < 0.05) after adjusting for a propensity score. In multivariate analysis adjusted for different confounding factors and propensity score, the odd ratios were all approximately 2.5, which meant that the risk of peri-implantitis increased 1.5 times for 1 mm increase of soft tissue thickness. CONCLUSIONS The excessive vertical soft tissue thickness around implants in patients with history of periodontitis has an adverse influence on health of the peri-implant tissue. This observation raises an important question on the association between vertical soft tissue thickness during implant surgery and history of periodontitis. Effective approaches to prevent the adverse effect of excessive soft tissue thickness on peri-implant tissue are necessary to be further investigated.
Structural variations in human ACE2 may influence its binding with SARS‐CoV‐2 spike protein

Abstract The recent pandemic of COVID‐19, caused by SARS‐CoV‐2, is unarguably the most fearsome compared with the earlier outbreaks caused by other coronaviruses, SARS‐CoV and MERS‐CoV. Human ACE2 is now established as a receptor for the SARS‐CoV‐2 spike protein. Where variations in the viral spike protein, in turn, lead to the cross‐species transmission of the virus, genetic variations in the host receptor ACE2 may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS‐CoV‐2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2‐spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS‐CoV‐2 spike protein, respectively. Despite strong overall structural similarities, the spatial orientation of the key interacting residues varies in the ACE2 variants compared with the wild‐type molecule. Most ACE2 variants showed a similar binding affinity for SARS‐CoV‐2 spike protein as observed in the complex structure of wild‐type ACE2 and SARS‐CoV‐2 spike protein. However, ACE2 alleles, rs73635825 (S19P) and rs143936283 (E329G) showed noticeable variations in their intermolecular interactions with the viral spike protein. In summary, our data provide a structural basis of potential resistance against SARS‐CoV‐2 infection driven by ACE2 allelic variants.
“Music First”: An Alternative or Adjunct to Psychotropic Medications for the Behavioral and Psychological Symptoms of Dementia

Existing research has primarily evaluated music therapy (MT) as a means of reducing the negative affect, behavioral, and/or cognitive symptoms of dementia. Music listening (ML), on the other hand, offers a less-explored, potentially equivalent alternative to MT and may further reduce exposure to potentially harmful psychotropic medications traditionally used to manage negative behavioral and psychological symptoms of dementia (BPSD). This 5-month prospective, naturalistic, interprofessional, single-center extended care facility study compared usual care (45 residents) and usual care combined with at least thrice weekly personalized ML sessions (47 residents) to determine the influence of ML. Agitation decreased for all participants (p < .001), and the ML residents receiving antipsychotic medications at baseline experienced agitation levels similar to both the usual care group and the ML patients who were not prescribed antipsychotics (p < .05 for medication × ML interaction). No significant changes in psychotropic medication exposure occurred. This experimental study supports ML as an adjunct to pharmacological approaches to treating agitation in older adults with dementia living in long-term care facilities. It also highlights the need for additional research focused on how individualized music programs affect doses and frequencies of antipsychotic medications and their associated risk of death and cerebrovascular events in this population.
Rural–Urban Disparities in Otolaryngology: The State of Illinois

To highlight rural–urban disparities in otolaryngology, and to quantify the disparities in access to otolaryngology specialist care across Illinois. Several studies across disciplines have shown increased prevalence and severity of disease in rural communities, relative to their urban counterparts. There is very little published quantifying a disparity in rural access to otolaryngologists.
Beneficial effects of Aronia melanocarpa berry extract on hepatic insulin resistance in type 2 diabetes mellitus rats.

We aimed to investigate) the effects of Aronia melanocarpa berry extract (AMBE) on hepatic insulin resistance and its mechanism at the molecular level in high-fat diet (HFD)- and streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The rats were supplemented with AMBE at doses of 100 and 400 mg/kg body weight (bw) daily for 8 weeks. AMBE significantly reduced blood glucose and serum insulin levels and the homeostatic model assessment for insulin resistance score; improved glucose tolerance; increased hepatic glycogen content; and regulated glucose metabolism enzyme activity, including glucokinase, pyruvate kinase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase in the liver. AMBE also reduced lipid accumulation and oxidative stress along with inflammation in the hepatic tissue of T2DM rats and improved hepatic function. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by AMBE through the elevation of insulin receptor substrate-2, PI3K, Akt, and glycogen synthase kinase-3β phosphorylation and glucose transporter 2, which might contribute to the promotion of glycogen synthesis and improvement of hepatic insulin resistance. AMBE shows promise as an ingredient of functional foods for alleviating hepatic insulin resistance in T2DM. PRACTICAL APPLICATION: The extract from the berries of Aronia melanocarpa (Michx.) Elliott (AMBE), with its relatively high content of polyphenolic compounds, has been shown to exert hypoglycemic effects in animal models of diabetes. Our findings support the use of A. melanocarpa as a functional food additive for the alleviation of hepatic insulin resistance and the management of glucose homeostasis in T2DM.
Practitioner Review: Effectiveness of indicated school-based interventions for adolescent depression and anxiety - a meta-analytic review.

BACKGROUND Interest in delivering psychological interventions within schools to facilitate early intervention is increasing. However, most reviews have focused on universal or preventative programmes rather than interventions designed to decrease existing symptoms of depression or anxiety. This paper aims to provide a meta-analytic review of randomised controlled trials of indicated psychological interventions for young people aged 10-19 with elevated symptoms of depression and/or anxiety. METHODS Eight electronic databases were systematically searched from inception to April 2019 for eligible trials. Study quality was assessed using two scales designed to evaluate psychotherapy intervention trials. Random effects meta-analyses were conducted separately for trials that recruited participants based on symptoms of depression and based on symptoms of anxiety. RESULTS Data from 45 trials were analysed. Most interventions studied used cognitive and behavioural strategies. Few studies met methodological quality criteria, but effect size was not associated with study quality. Indicated school-based interventions had a small effect on reducing depression symptoms (SMD = .34, 95% CI -0.48, -0.21) and a medium effect on reducing anxiety symptoms (SMD = -.49, 95% CI -0.79, -0.19) immediately postintervention. Subgroup analyses indicated that interventions delivered by internal school staff did not have significant effects on symptoms. Reductions in depression were maintained at short-term (≤6 months) but not medium (>6 months ≤ 12) or long-term (>12-month) follow-up. Reductions in anxiety symptoms were not maintained at any follow-up. CONCLUSIONS Indicated school-based interventions are effective at reducing symptoms of depression and anxiety in adolescents immediately postintervention but there is little evidence that these reductions are maintained. Interventions delivered by school staff are not supported by the current evidence base. Further high-quality randomised controlled trials incorporating assessment of longer-term outcomes are needed to justify increased investment in school-based interventions for adolescent depression and anxiety.
Measuring impulsivity in Parkinson’s disease: a correlational and structural neuroimaging study using different tests

Impulsivity is an aspect of personality and a major component of multiple neuropsychiatric conditions. In Parkinson’s disease, it has been associated with the expression of impulse control disorders, a highly prevalent non‐motor complication. Even though multiple tests of impulsivity have been used in this context, the impact of test choice has not been addressed. The aim was to evaluate whether different impulsivity measures in Parkinson’s disease share substantial inter‐scale and anatomical correlations or rather mirror different underlying phenomena.
STUDIES ON EPIDEMIOLOGY OF MAJOR DISEASES OF HORTICULTURAL CROPS

The field experiment was carried out to understand the development of Purple leaf blotch of onion, Early blight of Tomato and Turmeric leaf spot with respect to weather conditions during kharif 2011, 2012, 2013 and 2014 at Horticultural Research Station, Mahanandi, Kurnool dt. , Andhra Pradesh, India. The data on these three diseases was recorded at each standard week. Corresponding daily weather data was recorded on four consecutive years (2011-2014) during rainy season (July to December). Four years disease data was correlated with corresponding weather data. The weather variables, which showed significant correlation with disease incidence were used for the development of regression equation. The purple leaf blotch, early blight of tomato and turmeric leaf spot were high during 41-46 weeks. Prediction equations were developed for Purple leaf blotch of onion, Early blight of Tomato and Turmeric leaf spot by using three years (2011, 2012 and 2013) disease incidence (Arc sine transformed) and corresponding historical weather data (weekly average). Validation was done with current year disease data (2014) and corresponding weather data. Validation was done for testing the goodness of fit using 2014-15 data. The three equations predicting the next week’s disease incidence and showing the disease trend very efficiently in the three pathosystems.
Rbfox-1 contributes to CaMKIIα expression and intracerebral hemorrhage-induced secondary brain injury via blocking micro-RNA-124

RNA-binding protein fox-1 homolog 1 (Rbfox-1), an RNA-binding protein in neurons, is thought to be associated with many neurological diseases. To date, the mechanism on which Rbfox-1 worsens secondary cell death in ICH remains poorly understood. In this study, we aimed to explore the role of Rbfox-1 in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) and to identify its underlying mechanisms. We found that the expression of Rbfox-1 in neurons was significantly increased after ICH, which was accompanied by increases in the binding of Rbfox-1 to Ca2+/calmodulin-dependent protein kinase II (CaMKIIα) mRNA and the protein level of CaMKIIα. In addition, when exposed to exogenous upregulation or downregulation of Rbfox-1, the protein level of CaMKIIα showed a concomitant trend in brain tissue, which further suggested that CaMKIIα is a downstream-target protein of Rbfox-1. The upregulation of both proteins caused intracellular-Ca2+ overload and neuronal degeneration, which exacerbated brain damage. Furthermore, we found that Rbfox-1 promoted the expression of CaMKIIα via blocking the binding of micro-RNA-124 to CaMKIIα mRNA. Thus, Rbfox-1 is expected to be a promising therapeutic target for SBI after ICH.