Miracle-dz/UniFAR-FTUs huggingface dataset:
Biopharmaceutical Activities Related to Ellagic Acid, Chitosan, and Zein and Their Improvement by Association.

Ellagic acid (EA) has demonstrated several biological properties, such as antioxidant, antimicrobial, and enzymatic inhibition. Zein and chitosan (CHI) are natural polymers whose biological potential has also gained attention. Therefore, this paper aimed to evaluate the antimicrobial, antioxidant, anticollagenase, and antielastase properties of EA, zein, and chitosan isolated or in combination. The microdilution method was used to assess the minimum inhibitory and bactericide concentrations. The antioxidant activity was determined using the 2,2-diphenyl-1-picryl-hydrazila free radical scavenging method. The anticollagenase and antielastase activities were evaluated by specific colorimetric tests. EA has shown inhibitory activity against Staphylococcus aureus and Pseudomonas aeruginosa together with an antioxidant IC50 of 0.079 mg/mL. EA also showed significant collagenase and elastase inhibition. Zein has shown antimicrobial and antioxidant activities itself and enhanced sinergically the antioxidant activity and the antimicrobial activity against P. aeruginosa when combined with EA. CHI increased sinergically the inhibitory activity of EA against both bacterial strains, while showed itself an acceptable antimicrobial activity. 1 H saturation transfer-difference nuclear magnetic resonance experiment confirmed the formation of a complex between EA and zein that could be related with the improvement on its biological performance over the individual compounds, while no chemical interaction was detected between CHI and EA. PRACTICAL APPLICATION: The results reinforce the potential of ellagic acid in combination with zein and/or chitosan as an antimicrobial, antienzimatic, and antioxidant agent. Those findings reinforce the use of these substances, protecting this bioactive from degradation and/or improving the functional characteristics and biopharmaceutical properties.
Relationship between occlusion schemes and temporomandibular disorders in Malaysian population

Aims: To evaluate the type of occlusal schemes and its relation to temporomandibular disorders and to compare their relation in different ethnic groups of Malaysia. Methods: The population for this study consisted of 240 human subjects with the age ranges from 20-30 years. Through random sampling, subjects were divided into 3 groups. Group A: 80 human subjects of Chinese origin, Group B: 80 human subjects of Indian origin and, Group C: 80 human subjects of Malay origin. The static and dynamic occlusion of each subject was assessed by intraoral examination. Occlusion on laterotrusive movements was categorized into four groups: Group I: Canine guided occlusion on both the sides (CGB), Group II: Canine guided occlusion on Left side and Group function occlusion on Right side (CGL+GFR), Group III: Canine guided occlusion on Right side and Group function occlusion on Left side (CGR+GFL) and, Group IV: Group function occlusion on both the sides (GFB). The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis-I was used as a guideline in clinical examination procedures. Results: Most prevalent occlusal scheme amongst all three races was found to be GFB occlusion with Malays predominance followed by Chinese and Indians with p value 0.001. TMD’s was found to be most prevalent in Chinese population followed by Malays and Indians with p value 0.028 and in GFB, followed by CGB, CGL+GFR and CGR+GFL occlusal schemes with p value 0.04. Conclusion: GFB has an influence in developing TMD’s, but we could not find any significant difference in occlusion schemes and its relation with TMD’s amongst three racial groups studied. Further long term randomized clinical trials studies with larger sample size are required.
Robust forecast aggregation

Significance The problem of conflicting advice from multiple experts is common to policy makers, corporate governors, patients facing medical prognosis, individuals requiring financial advice, and more. We ask, How should an ignorant advisee (one that observes experts’ forecasts only) aggregate information when this is provided in probabilistic terms (such as forecasts over events)? We propose a robustness criterion based on the classical notions of scoring rule and regret. Under reasonable assumptions on the underlying information structure of the experts, we provide formulas that allow an ignorant aggregator to perform almost as well as an omniscient expert (one that aggregates perfectly all of the information) whenever there are two experts. We also show that this is hopeless when facing many experts. Bayesian experts who are exposed to different evidence often make contradictory probabilistic forecasts. An aggregator, ignorant of the underlying model, uses this to calculate his or her own forecast. We use the notions of scoring rules and regret to propose a natural way to evaluate an aggregation scheme. We focus on a binary state space and construct low regret aggregation schemes whenever there are only two experts that either are Blackwell-ordered or receive conditionally independent and identically distributed (i.i.d.) signals. In contrast, if there are many experts with conditionally i.i. d. signals, then no scheme performs (asymptotically) better than a (0.5,0.5) forecast.
Continuous Versus Intermittent Vital Signs Monitoring Using a Wearable, Wireless Patch in Patients Admitted to Surgical Wards: Pilot Cluster Randomized Controlled Trial

Background Vital signs monitoring is a universal tool for the detection of postoperative complications; however, unwell patients can be missed between traditional observation rounds. New remote monitoring technologies promise to convey the benefits of continuous monitoring to patients in general wards. Objective The aim of this pilot study was to evaluate whether continuous remote vital signs monitoring is a practical and acceptable way of monitoring surgical patients and to optimize the delivery of a definitive trial. Methods We performed a prospective, cluster-randomized, parallel-group, unblinded, controlled pilot study. Patients admitted to 2 surgical wards at a large tertiary hospital received either continuous and intermittent vital signs monitoring or intermittent monitoring alone using an early warning score system. Continuous monitoring was provided by a wireless patch, worn on the patient’s chest, with data transmitted wirelessly every 2 minutes to a central monitoring station or a mobile device carried by the patient’s nurse. The primary outcome measure was time to administration of antibiotics in sepsis. The secondary outcome measures included the length of hospital stay, 30-day readmission rate, mortality, and patient acceptability. Results Overall, 226 patients were randomized between January and June 2017. Of 226 patients, 140 were randomized to continuous remote monitoring and 86 to intermittent monitoring alone. On average, patients receiving continuous monitoring were administered antibiotics faster after evidence of sepsis (626 minutes, n=22, 95% CI 431.7-820.3 minutes vs 1012.8 minutes, n=12, 95% CI 425.0-1600.6 minutes), had a shorter average length of hospital stay (13.3 days, 95% CI 11.3-15.3 days vs 14.6 days, 95% CI 11.5-17.7 days), and were less likely to require readmission within 30 days of discharge (11.4%, 95% CI 6.16-16.7 vs 20.9%, 95% CI 12.3-29.5). Wide CIs suggest these differences are not statistically significant. Patients found the monitoring device to be acceptable in terms of comfort and perceived an enhanced sense of safety, despite 24% discontinuing the intervention early. Conclusions Remote continuous vital signs monitoring on surgical wards is practical and acceptable to patients. Large, well-controlled studies in high-risk populations are required to determine whether the observed trends translate into a significant benefit for continuous over intermittent monitoring. Trial Registration International Standard Randomised Controlled Trial Number ISRCTN60999823; http://www.isrctn. com /ISRCTN60999823 (Archived by WebCite at http://www.webcitation.org/73ikP6OQz)
Gaussian Process Surrogate Models for the CMA Evolution Strategy

This article deals with Gaussian process surrogate models for the Covariance Matrix Adaptation Evolutionary Strategy (CMA-ES)—several already existing and two by the authors recently proposed models are presented. The work discusses different variants of surrogate model exploitation and focuses on the benefits of employing the Gaussian process uncertainty prediction, especially during the selection of points for the evaluation with a surrogate model. The experimental part of the article thoroughly compares and evaluates the five presented Gaussian process surrogate and six other state-of-the-art optimizers on the COCO benchmarks. The algorithm presented in most detail, DTS-CMA-ES, which combines cheap surrogate-model predictions with the objective function evaluations in every iteration, is shown to approach the function optimum at least comparably fast and often faster than the state-of-the-art black-box optimizers for budgets of roughly 25–100 function evaluations per dimension, in 10- and less-dimensional spaces even for 25–250 evaluations per dimension.
Kadınlarda Obezite ve Dürtüsellik İlişkisinin Değerlendirilmesi

Amac: Gunumuzde ulkemizde her bes kisiden birisi obezdir. Kadinlarda obezite ve fazla kiloluluk erkeklere kiyasla daha fazla gorulur. Neden bazi kisilerin saglikli yasam tarzini benimseyemedigi, kolayca ulasilabilen, kiskirtici reklamlarla tanitilan gidalara hayir diyemediginin veya tedavi sonrasi kaybettigi agirligi hizla tekrar aldiginin sebeplerinin arastirilmasi ve bunun durtusellikle iliskisinin tespiti arastirilmasi gereken onemli bir kavramdir. Calismamizda normal, kilolu ve obez kadinlarda durtusellik duzeyini saptamayi amacladik. Gerec ve Yontemler: Arastirma kesitsel tiptedir ve veriler gonullu katilim esasina gore toplanmistir. Calisma 200 kadin katilimci ile gerceklestirildi. Ornekleme alinan kadinlara Barrat durtusellik olcegi (BDO-11) ve demografik bilgi formu uygulanmistir. Normal, kilolu ve obez gruplarda durtusellik duzeyi saptanarak karsilastirilmistir. Bulgular: Katilimcilarin demografik verileri arasinda istatistiksel anlamli fark yoktu(p>0,05). Normal, kiloluve obez grup karsilastirmasinda BDO-11 toplam skorunda istatistiksel anlamli fark saptandi(62,20±4,29, 61,44±4,64, 64,65±6,37)(p<0,05). Plan yapmama alt olceginde de gruplar arasi istatistiksel anlamli fark mevcuttur(23,88±2,39, 23,70±2,15, 25,07±3,12)(p<0,05). Sonuc: Calismamizda obez grupta durtusellik puanlari literaturdeki calismalarla uyumlu olarak yuksek saptandi.Bulasici olmayan hastalik yukunun azaltilmasinda en onemli sorunlardan biri olan ve gunumuz tuketim dunyasinda hizla artan obezitede bireylerin durtusellik duzeylerinin olculmesi faydali olabilir.
Structures and activities of widely conserved small prokaryotic aminopeptidases‐P clarify classification of M24B peptidases

M24B peptidases cleaving Xaa‐Pro bond in dipeptides are prolidases whereas those cleaving this bond in longer peptides are aminopeptidases‐P. Bacteria have small aminopeptidases‐P (36‐39 kDa), which are diverged from canonical aminopeptidase‐P of Escherichia coli (50 kDa). Structure‐function studies of small aminopeptidases‐P are lacking. We report crystal structures of small aminopeptidases‐P from E. coli and Deinococcus radiodurans, and report substrate‐specificities of these proteins and their ortholog from Mycobacterium tuberculosis. These are aminopeptidases‐P, structurally close to small prolidases except for absence of dipeptide‐selectivity loop. We noticed absence of this loop and conserved arginine in canonical archaeal prolidase (Maher et al., Biochemistry. 43, 2004, 2771‐2783) and questioned its classification. Our enzymatic assays show that this enzyme is an aminopeptidase‐P. Further, our mutagenesis studies illuminate importance of DXRY sequence motif in bacterial small aminopeptidases‐P and suggest common evolutionary origin with human XPNPEP1/XPNPEP2. Our analyses reveal sequence/structural features distinguishing small aminopeptidases‐P from other M24B peptidases.
Synthesis-guided structure revision of the monoterpene alcohol isolated from Mentha haplocalyx

ABSTRACT The monoterpene isolated from Mentha haplocalyx, 3,3,5-trimethyl-2-oxabicyclo[2.2. 2]oct-5-en-4-ol, was synthesized according to its proposed structure. However, the NMR data of the synthetic sample were not in agreement with those reported for the natural product. After considerable efforts, the genuine structure was confirmed as (1R*,2R*)-4-(1′-hydroxy-1′-methylethyl)-1-methylycyclohex-3-ene-1,2-diol. Graphical Abstract Pantothenate-auxotrophic strains of Methylobacterium show symbiotic colonization on plants through acquisition of pantothenate and its precursors.
Bioengineering nisin to overcome the nisin resistance protein

The emergence and dissemination of antibiotic resistant bacteria is a major medical challenge. Lantibiotics are highly modified bacterially produced antimicrobial peptides that have attracted considerable interest as alternatives or adjuncts to existing antibiotics. Nisin, the most widely studied and commercially exploited lantibiotic, exhibits high efficacy against many pathogens. However, some clinically relevant bacteria express highly specific membrane‐associated nisin resistance proteins. One notable example is the nisin resistance protein that acts by cleaving the peptide bond between ring E and the adjacent serine 29, resulting in a truncated peptide with significantly less activity. We utilised a complete bank of bioengineered nisin (nisin A) producers in which the serine 29 residue has been replaced with every alternative amino acid. The nisin A S29P derivative was found to be as active as nisin A against a variety of bacterial targets but, crucially, exhibited a 20‐fold increase in specific activity against a strain expressing the nisin resistance protein. Another derivative, nisin PV, exhibited similar properties but was much less prone to oxidation. This version of nisin with enhanced resistance to specific resistance mechanisms could prove useful in the fight against antibiotic resistant pathogens.
Contribution of non-circadian neurons to the temporal organization of locomotor activity

ABSTRACT In the fruit fly, Drosophila melanogaster, the daily cycle of rest and activity is a rhythmic behavior that relies on the activity of a small number of neurons. The small ventral lateral neurons (sLNvs) are considered key in the control of locomotor rhythmicity. Previous work from our laboratory has showed that these neurons undergo structural remodeling on their axonal projections on a daily basis. Such remodeling endows sLNvs with the possibility to make synaptic contacts with different partners at different times throughout the day, as has been previously described. By using different genetic tools to alter membrane excitability of the sLNv putative postsynaptic partners, we tested their functional role in the control of locomotor activity. We also used optical imaging to test the functionality of these contacts. We found that these different neuronal groups affect the consolidation of rhythmic activity, suggesting that non-circadian cells are part of the circuit that controls locomotor activity. Our results suggest that new neuronal groups, in addition to the well-characterized clock neurons, contribute to the operations of the circadian network that controls locomotor activity in D. melanogaster. Summary: Here we characterized the impact of different putative postsynaptic partners of the sLNvs on the control of rhythmic locomotor behavior. We found that some of these novel neuronal clusters are relevant for the control of locomotor activity.
Measuring the Impact of Academic Cancer Network Development on Clinical Integration, Quality of Care, and Patient Satisfaction.

PURPOSE Many US academic centers have acquired community practices to expand their clinical care and research footprint. The objective of this assessment was to determine whether the acquisition and integration of community oncology practices by Yale/Smilow Cancer Hospital improved outcomes in quality of care, disease team integration, clinical trial accrual, and patient satisfaction at network practice sites. METHODS We evaluated quality of care by testing the hypothesis that core Quality Oncology Practice Initiative measures at network sites that were acquired in 2012 were significantly different after their 2016 integration into the network. Clinical and research integration were measured using the number of tumor board case presentations and total accruals in clinical trials. We used Press-Ganey scores to measure patient satisfaction pre- and postintegration. RESULTS Mean Quality Oncology Practice Initiative scores at Smilow Care Centers were significantly higher in 2016 than in 2012 for core measures related to improvement in tumor staging ( z = 1.33; P < .05), signed consent and documentation plans for antineoplastic treatment ( z = 2.69; P < .01; and z = 2.36; P < .05, respectively), and appropriately quantifying and addressing pain during office visits ( z = 2.95; P < .05; and z = 3.1; P < .01, respectively). A total of 493 cases were presented by care center physicians at the tumor board in 2017 compared with 45 presented in 2013. Compared with 2012, Smilow Care Center clinical trial accrual increased from 25 to 170 patients in 2017. Last, patient satisfaction has remained at greater than the 90th percentile pre- and postintegration. CONCLUSION The process of integration facilitates the ability to standardize cancer practice and provides a platform for quality improvement.
Observing Erotic Videos With Heterosexual Content Induces Different Cerebral Responses in Homosexual and Heterosexual Men

ABSTRACT To determine the cerebral functionality associated with the perception and processing of erotic stimuli in men with different sexual orientation, this work evaluated the electroencephalographic activity (EEG) from several cortical areas, as well as subjective arousal in homosexual and heterosexual men during observation of an erotic film with heterosexual content. The heterosexual men rated the erotic video with higher general and sexual arousal than the homosexual participants. During observation of the neutral and erotic videos, both groups showed a decreased amplitude of the alpha band in prefrontal and parietal cortices, indicating increased attention. When watching the erotic video, the homosexual men showed an increased amplitude of the theta and fast bands only in the prefrontal cortex, which could be related to the cognitive processing of the erotic stimulus. These EEG results should broaden our knowledge of the cortical mechanisms related to the different perception and processing of erotic stimuli in men with different sexual orientations.
Tacrolimus in non-Asian patients with SLE: a real-life experience from three European centres

Objectives To analyse the real-life practice on the use of Tacrolimus (TAC) in patients with systemic lupus erythematosus (SLE) from three European SLE referral centres. Methods Adult patients with SLE regularly followed at three European referral centres were included. Demographics, cumulative organ involvement, treatment history, Systemic Lupus Disease Activity Index (SLEDAI), laboratory features and physician’s judgement were collected at baseline and at 3–6–12 months after starting TAC. Results 29 patients were included (89% female, mean age 38±9 years). Ethnicity was predominantly Caucasian (82%), Black African (11%), Hispanic (3.5%) and Caribbean (3.5%). The main indications for TAC prescription were renal involvement (82.7%), arthritis (10.3%), cutaneous manifestations (6.8%), haematological manifestations (6.8%), serositis (3.4%). At 3 months, there was a clinical improvement in 21 patients (72.4%) and 9 of these experienced a complete resolution of symptoms (31%). This corresponds to: (1) a significant decrease in the mean SLEDAI; (2) a significant decrease in the mean 24 hours proteinuria; a significant increase in C3 and stable creatinine values. At 6 months (n=25), the physician declared an improvement in 19 patients (76%) and a complete resolution of symptoms in 9 (36%). The same trend was observed at 12 months of follow-up. TAC was discontinued in nine pts (31%); reasons for discontinuation were inefficacy (13.8%), drug intolerance (10%) and disease remission (6.9%). Conclusions Despite the limitation due to the small number of patients and the uncontrolled nature of the study, these data show that TAC can be considered a valid therapeutic option in patients with SLE, especially for renal involvement.
A prediction model of working memory across health and psychiatric disease using whole-brain functional connectivity

Individual differences in cognitive function have been shown to correlate with brain-wide functional connectivity, suggesting a common foundation relating connectivity to cognitive function across healthy populations. However, it remains unknown whether this relationship is preserved in cognitive deficits seen in a range of psychiatric disorders. Using machine learning methods, we built a prediction model of working memory function from whole-brain functional connectivity among a healthy population (N = 17, age 19-24 years). We applied this normative model to a series of independently collected resting state functional connectivity datasets (N = 968), involving multiple psychiatric diagnoses, sites, ages (18-65 years), and ethnicities. We found that predicted working memory ability was correlated with actually measured working memory performance in both schizophrenia patients (partial correlation, ρ = 0.25, P = 0.033, N = 58) and a healthy population (partial correlation, ρ = 0.11, P = 0.0072, N = 474). Moreover, the model predicted diagnosis-specific severity of working memory impairments in schizophrenia (N = 58, with 60 controls), major depressive disorder (N = 77, with 63 controls), obsessive-compulsive disorder (N = 46, with 50 controls), and autism spectrum disorder (N = 69, with 71 controls) with effect sizes g = −0.68, −0.29, −0.19, and 0.09, respectively. According to the model, each diagnosis’s working memory impairment resulted from the accumulation of distinct functional connectivity differences that characterizes each diagnosis, including both diagnosis-specific and diagnosis-invariant functional connectivity differences. Severe working memory impairment in schizophrenia was related not only with fronto-parietal, but also widespread network changes. Autism spectrum disorder showed greater negative connectivity that related to improved working memory function, suggesting that some non-normative functional connections can be behaviorally advantageous. Our results suggest that the relationship between brain connectivity and working memory function in healthy populations can be generalized across multiple psychiatric diagnoses. This approach may shed new light on behavioral variances in psychiatric disease and suggests that whole-brain functional connectivity can provide an individual quantitative behavioral profile in a range of psychiatric disorders.