Miracle-dz/UniFAR-FTUs huggingface dataset:
Candidate Strategies for Development of a Rapid-Acting Antidepressant Class That Does Not Result in Neuropsychiatric Adverse Effects: Prevention of Ketamine-Induced Neuropsychiatric Adverse Reactions

Non-competitive N-methyl-D-aspartate/glutamate receptor (NMDAR) antagonism has been considered to play important roles in the pathophysiology of schizophrenia. In spite of severe neuropsychiatric adverse effects, esketamine (racemic enantiomer of ketamine) has been approved for the treatment of conventional monoaminergic antidepressant-resistant depression. Furthermore, ketamine improves anhedonia, suicidal ideation and bipolar depression, for which conventional monoaminergic antidepressants are not fully effective. Therefore, ketamine has been accepted, with rigorous restrictions, in psychiatry as a new class of antidepressant. Notably, the dosage of ketamine for antidepressive action is comparable to the dose that can generate schizophrenia-like psychotic symptoms. Furthermore, the psychotropic effects of ketamine precede the antidepressant effects. The maintenance of the antidepressive efficacy of ketamine often requires repeated administration; however, repeated ketamine intake leads to abuse and is consistently associated with long-lasting memory-associated deficits. According to the dissociative anaesthetic feature of ketamine, it exerts broad acute influences on cognition/perception. To evaluate the therapeutic validation of ketamine across clinical contexts, including its advantages and disadvantages, psychiatry should systematically assess the safety and efficacy of either short- and long-term ketamine treatments, in terms of both acute and chronic outcomes. Here, we describe the clinical evidence of NMDAR antagonists, and then the temporal mechanisms of schizophrenia-like and antidepressant-like effects of the NMDAR antagonist, ketamine. The underlying pharmacological rodent studies will also be discussed.
Covid-19: Fat, Obesity, Inflammation, Ethnicity, and Sex Differences

Although obesity is known to be a risk factor for COVID-19 severity, there is an urgent need to distinguish between different kinds of fat—visceral and subcutaneous fat—and their inflammation status in COVID-19. These different fat types have partially diverging biochemical roles in the human body, and they are differentially associated with SARS-CoV-2, which targets the angiotensin-converting enzyme 2 (ACE2) for cell entry. ACE2 is highly expressed in adipose tissue, especially in visceral fat, suggesting an important role for this tissue in determining COVID-19 disease severity. In this perspective article, we discuss group differences in the amount of visceral fat levels and the extent of inflammation in adipocytes of visceral fat tissue, which may, in part, drive population, cross-national, ethnic, and sex differences in COVID-19 disease. It is vital to steer the scientific community’s attention to the effects of visceral fat in creating individual and population differences in COVID-19 severity. This can help researchers unravel the reasons for the reported population, ethnic, and sex differences in COVID-19 severity and mortality.
On the Reliability of Examining Dual-Tasking Abilities Using a Novel E-Health Device—A Proof of Concept Study in Multiple Sclerosis

The assessment of neuropsychological functions and especially dual-tasking abilities is considered to be increasingly relevant in the assessment of neurological disease, and Multiple Sclerosis (MS) in particular. However, the assessment of dual-tasking abilities is hindered by specific software requirements and extensive testing times. We designed a novel e-health (progressive web application-based) device for the assessment of dual-tasking abilities usable in “bedside” and outpatient clinic settings and examined its reliability in a sample of N = 184 MS patients in an outpatient setting. Moreover, we examined the relevance of dual-tasking assessment using this device with respect to clinically relevant parameters in MS. We show that a meaningful assessment of dual-tasking is possible within 6 min and that the behavioral readouts overall show good reliability depending on dual-tasking difficulty. We show that dual-tasking readouts were correlated with clinically relevant parameters (e.g., EDSS, disease duration, processing speed) and were not affected by fatigue levels. We consider the tested dual-tasking assessment device suitable for routine clinical neuropsychological assessments of dual-tasking abilities. Future studies may further evaluate this test regarding its suitability in the long-term follow up assessments and to assess dual-tasking abilities in other neurological and psychiatric disorders.
CaSpER: Identification, visualization and integrative analysis of CNV events in multiscale resolution using single-cell or bulk RNA sequencing data

RNA sequencing experiments generate large amounts of information about expression levels of genes. Although they are mainly used for quantifying expression levels, they contain much more biologically important information such as copy number variants (CNV). Here, we propose CaSpER, a signal processing approach for identification, visualization, and integrative analysis of focal and large-scale CNV events in multiscale resolution using either bulk or single-cell RNA sequencing data. CaSpER performs smoothing of the genome-wide RNA sequencing signal profiles in different multiscale resolutions, identifying CNV events at different length scales. CaSpER also employs a novel methodology for generation of genome-wide B-allele frequency (BAF) signal profile from the reads and utilizes it in multiscale fashion for correction of CNV calls. The shift in allelic signal is used to quantify the loss-of-heterozygosity (LOH) which is valuable for CNV identification. CaSpER uses Hidden Markov Models (HMM) to assign copy number states to regions. The multiscale nature of CaSpER enables comprehensive analysis of focal and large-scale CNVs and LOH segments. CaSpER performs well in accuracy compared to gold standard SNP genotyping arrays. In particular, analysis of single cell Glioblastoma (GBM) RNA sequencing data with CaSpER reveals novel mutually exclusive and co-occurring CNV sub-clones at different length scales. Moreover, CaSpER discovers gene expression signatures of CNV sub-clones, performs gene ontology (GO) enrichment analysis and identifies potential therapeutic targets for the sub-clones. CaSpER increases the utility of RNA-sequencing datasets and complements other tools for complete characterization and visualization of the genomic and transcriptomic landscape of single cell and bulk RNA sequencing data, especially in cancer research.
Energy Availability in Male and Female Elite Wheelchair Athletes over Seven Consecutive Training Days

Background: Low energy availability (LEA) is a major problem as athletes often restrict their energy intake. It has been shown that LEA occurs often in female and endurance athletes and in athletes from weight-sensitive or aesthetic sports. The purpose of this study was to investigate energy availability (EA) in elite wheelchair athletes. Methods: Fourteen elite wheelchair athletes (8 males; 6 females) participated. Data were collected using a weighed seven-day food and training diary to estimate energy intake and exercise energy expenditure. Resting energy expenditure and body composition were measured, whereas energy balance (EB) was calculated. Results: Measured over 7 days, EA was significantly different (36.1 ± 6.7 kcal kg−1 FFM day−1) in male compared to female (25.1 ± 7.1 kcal kg−1 FFM day−1) athletes (p < 0.001). From all analyzed days, LEA occurred in 73% of the days in female athletes and in 30% of the days in male athletes. EB was positive in male athletes (+169.1 ± 304.5 kcal) and negative (−288.9 ± 304.8 kcal) in female athletes. Conclusions: A higher prevalence of LEA was found in female compared to male athletes. A higher energy intake would be recommended to meet energy needs and to maximize training adaptation.
Exploring the Importance of Players’ Characteristics and Performance on Serve and Return of Serve in Winning the Women’s Singles Grand Slam Tennis Tournaments

Sports analytics has become very popular in recent years. Many researchers have been using the tools and technique to study tennis player performance in various aspects during matches. However, much of the studies were performed on male players while much less attention were made on female players. This study explores the female players’ characteristics and serve performance that leads to winning matches in women’s singles 2018 Grand Slam tennis tournaments. Using data provided by the official website of the Women Tennis Association (WTA), 1016 single matches in all four 2018 Grand Slam Tournaments were analysed to evaluate winning traits in tennis specifically looking at the two most important strokes in tennis which are the serve and return of serve. Additionally, other personal player characteristics that would influence the match outcomes were also evaluated. To achieve the objectives of the study, odds ratio and chi-square test were used to compare between the match winner and match loser. The study revealed that percentage of first serve return won (PFSRW) has the highest odds ratio value (OR=1.263) followed by the percentage of first serve won (PFSW) with odds ratio equal to 1.244. These showed that having a good first serve, plays an important factor in increasing the winning odds as compared to second serve either in serve or in return of serve. This study also reveals that a taller player had the advantage over a shorter player for faster serve speed (p-value<0.05).
Correlation between the Antimicrobial Activity and Metabolic Profiles of Cell Free Supernatants and Membrane Vesicles Produced by Lactobacillus reuteri DSM 17938

The aim of the work is to assess the antimicrobial activities of Cell Free Supernatants (CFS) and Membrane Vesicles (MVs), produced by Lactobacillus reuteri DSM 17938, versus Gram-positive and Gram-negative bacteria and investigate their metabolic profiles. The Minimum Inhibitory Concentration was determined through the broth microdilution method and cell proliferation assay while the Minimum Bactericidal Concentration was determined by Colony Forming Units counts. The characteristics of the antimicrobial compounds were evaluated by pH adjustments, proteinase treatment, and size fractionation of the CFS. The cytotoxicity of CFS was tested on two human cell lines. A detailed snapshot of the L. reuteri metabolism was attained through an untargeted metabolic profiling by means of high resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS) coupled with Electrospray Ionization Source (ESI). The results showed (i) a greater efficacy of CFS and its fractions towards Gram-negative compared to Gram-positive bacteria; (ii) an antimicrobial effect related to pH-dependent compounds but not to MVs; (iii) a molecular weight < 3 KDa as well as an a non-proteinaceous nature of the antimicrobial compounds; and (iv) more than 200 and 500 putative metabolites annotated in MVs and supernatants, covering several classes of metabolites, including amino acids, lipids, fatty and organic acids, polyalcohols, nucleotides, and vitamins. Some putative compounds were proposed not only as characteristic of specific fractions, but also possibly involved in antimicrobial activity.
Profile of fatty acid lipid fractions of omega-3 fatty acid-enriched table eggs.

The omega-3 fatty acid (FA) enrichment of yolk is a key means one of the main objectives to improve the nutraceutical properties of eggs. We evaluated the effect of the dietary inclusion of extruded linseed fed to laying hens on the fatty acid composition of the polar and non-polar lipid classes of the eggs. Two groups of 36 Lohmann White Leghorn layers (65 weeks old) were each fed one of two different diets for a period of 12 weeks. The two diets consisted of a conventional cereal-based diet concentrate (C) and a diet concentrate containing 5% linseed (L). The inclusion of linseed in the diet increased the content of α-linolenic (C18:3n-3), eicosapentaenoic (C20:5n-3) and docosahexaenoic (C22:6n-3) acids in neutral lipids, while a concomitant decrease in arachidonic acid (C20:4n-6) was observed. As regards the polar fraction, the fatty acid composition was slightly affected by the dietary treatments except for C18:0 (+1.14 fold), C18:2n-6 (+1.23 fold), C18:3n-3 (+2.8 fold) and C22:6n-3 (+1.41 fold). Principal component analysis demonstrated that very long-chain FAs were more representative of polar lipids, except for C20:5n-3, while neutral lipids were characterized by dietary n-3 FA (C18:3n-3).
Placental effects on the maternal brain revealed by disrupted placental gene expression in mouse hybrids

The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signalling on the maternal brain are insufficiently studied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behaviour. Using a cross between the house mouse and the Algerian mouse, in which hybrid placental development is abnormal, we sequenced late-gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression of Fmn1 and Drd3 was significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families and Drd3 in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally derived placental genome can influence the expression of maternal–fetal communication genes, including placental hormones, suggesting an effect of the offspring's father on the mother's brain.
Indonesian smart schools: Their influence on the ability of information literacy on the biology field

Information literacy in the information society era is very important for every individual, especially for students to prevent misunderstandings and misconceptions. Digital-based learning can influence on students' information literacy abilities. The purpose of the study is to look at the effect of digital-based learning (Indonesian Smart Schools) on students' information literacy abilities. This research was conducted from February to June 2019, at SMA Negeri 2 Tasikmalaya. The research method was a true-experimental design with randomized pretest-posttest control group design. This study population was class X, amounting to 299 people, with cluster random sampling technique, the results were class X MIPA 1 (experimental) and X MIPA 5 (control). The information literacy research instrument uses a validated instrument from SAILS® (30 items). Based on the ANCOVA analysis at the significance level (α) = 0.05 and based on the comparison of the values gain, it can be concluded that there was an effect of digital-based learning on students' information literacy abilities on Animalia material. Indonesian Smart Schools can be alternative digital learning to hone the ability of information literacy on Animalia material. Indonesian Smart Schools can be an alternative to digital learning to hone the ability of information literacy.
BDNF controls bidirectional endocannabinoid-plasticity at corticostriatal synapses

The dorsal striatum exhibits bidirectional corticostriatal synaptic plasticity, NMDAR- and endocannabinoids-(eCB)-mediated, necessary for the encoding of procedural learning. Therefore, characterizing factors controlling corticostriatal plasticity is of crucial importance. Brain-derived neurotrophic factor (BDNF) and its receptor, the tropomyosine receptor kinase-B (TrkB), shape striatal functions and their dysfunction deeply affects basal ganglia. BDNF/TrkB signaling controls NMDAR-plasticity in various brain structures including the striatum. However, despite cross-talk between BDNF and eCBs, the role of BDNF in eCB-plasticity remains unknown. Here, we show that BDNF/TrkB signaling promotes eCB-plasticity (LTD and LTP) induced by rate-based (low-frequency stimulation) or spike-timing-based (spike-timing-dependent plasticity, STDP) paradigm in striatum. We show that TrkB activation is required for the expression and the scaling of both eCB-LTD and eCB-LTP. Using two-photon imaging of dendritic spines combined with patch-clamp recordings, we show that TrkB activation prolongs intracellular calcium transients, thus increasing eCB synthesis and release. We provide a mathematical model for the dynamics of the signaling pathways involved in corticostriatal plasticity. Finally, we show that TrkB activation enlarges the domain of expression of eCB-STDP. Our results reveal a novel role for BDNF/TrkB signaling in governing eCB-plasticity expression in striatum, and thus the engram of procedural learning.
Utilization of cytology smears improves success rates of RNA‐based next‐generation sequencing gene fusion assays for clinically relevant predictive biomarkers

The use of RNA‐based next‐generation sequencing (NGS) assays to detect gene fusions for targeted therapy has rapidly become an essential component of comprehensive molecular profiling. For cytology specimens, the cell block (CB) is most commonly used for fusion testing; however, insufficient cellularity and/or suboptimal RNA quality are often limiting factors. In the current study, the authors evaluated the factors affecting RNA fusion testing in cytology and the added value of smears in cases with a suboptimal or inadequate CB.
Knowledge and barriers of PrEP delivery among diverse groups of potential PrEP users in Central Uganda

Background Scale-up of oral pre-exposure prophylaxis (PrEP) for HIV prevention in Uganda began with serodiscordant couples (SDC) and has expanded to other most at-risk populations (MARPs). We explored knowledge, acceptability, barriers and facilitators of PrEP use among potential PrEP users in four MARPs (SDC; men who have sex with men [MSM]; female sex workers [FSW], and fisher folk). Methods We administered quantitative surveys to potential PrEP users in multiple settings in Central Uganda at baseline and approximately 9 months after healthcare worker (HCW) training on PrEP. Results The survey was completed by 250 potential PrEP users at baseline and 125 after HCW training; 55 completed both surveys. For these 250 participants, mean age was 28.5 years (SD 6.9), 47% were male and 6% were transgender women, with approximately even distribution across MARPs and recruitment locations (urban, peri-urban, and rural). Most (65%) had not heard about PrEP. After HCW training, 24% of those sampled were aware of PrEP, and the proportion of those who accurately described PrEP as “antiretrovirals to be used before HIV exposure” increased from 54% in the baseline survey to 74% in the second survey (p<0.001). The proportion of participants who reported HCW as a source of PrEP information increased after training (59% vs 91%, p<0.001). In both surveys, nearly all participants indicated they were willing to take PrEP if offered. The most common anticipated barriers to PrEP were stigma, transportation, accessibility, busy schedules, and forgetfulness. Closeness to home was a common facilitator for all participant categories. Conclusions Initial awareness of PrEP was low, but PrEP knowledge and interest increased among diverse MARPs after HCW training. Demand creation and HCW training will be critical for increasing PrEP awareness among key populations, with support to overcome barriers to PrEP use. These findings should encourage the acceleration of PrEP rollout in Uganda.
Comparison of Dosimetry Characteristics from Some Bolus Materials for 6 and 10 MV Photons Beam Radiation Therapy

In radiation therapy, bolus material is often used for increased surface dose, compensate for surface irregularities and internal heterogeneities. Bolus has properties equivalent to water and soft tissue. In this study, the mixture of Silicone Rubber (SR) and Bismuth was used for bolus fabrication and then compared to commercial boluses such as Paraffin, Play-Doh, and Paraffin Wax. The study aims to evaluate the comparison of relative electron density (RED), effective mass attenuation coefficient, transmission factor, percentage of surface dose (PSD), and Percentage Depth Dose (PDD) for all boluses. The bolus was made with the size 11 × 11 × 0.5 cm3. Physical density of the synthesized bolus was assessed by computerized tomography (CT) Scanning. The results of the RED analysis for the mixture of Silicone Rubber (SR) and Bismuth, Paraffin, Play-Doh, and Paraffin Wax were 0.954; 0.743; 0.933; and 0.878, respectively. The values of RED for all boluses has a similar to water and soft tissue. These results prove that the bolus is equivalent to soft tissue density such as fat, breast, lungs, and liver. Furthermore, for other dosimetry tests such as transmission factors and attenuation coefficients using Linear Accelerator (LINAC) with photon energy sources 6 and 10 MV. In general, Percentage of surface dose at 6 MV is higher than 10 MV. The highest percentage of the surface dose was achieved by paraffin wax at 6 MV energy by 85%. For effective mass attenuation coefficient result, the highest is the mixture of silicone rubber and bismuth at -0.0030 cm2/g for 6 MV and Play-Doh at -0.0114 cm2/g for 10 MV.
New perspective in a cross-sectional study on muscles and tendons impairments due to neuromuscular maladapted funtion found in chronic spinal cord injury

Introduction: Spinal cord injury (SCI) impairments result in movement disorders manifested by paralyzed muscles, with preserved innervations susceptible to activation by electrical stimulation. Objective: To evaluate changes and associations in neuromuscular function and musculoskeletal structure in paralyzed muscles with preserved innervations in people with SCI in comparison with able-bodied people. Methods: A cross-sectional case-control study was designed to compare healthy and impaired muscles (biceps brachii [BB], rectus femoris [RF], vastus lateralis [VL], vastus medialis [VM], and anterior tibialis [TA]) and tendons (quadriceps and patellar) obtained from the stimulus electrodiagnostic testing (chronaxie, rheobase, accommodation, and accommodation index) and ultrasound assessment (thickness, pennation angle, fascicle length, and eco intensity). At the same time, repeated measures from two independent raters to check the inter-rater reliability of the measures were performed. Results: Thirty participants (fifteen in each group) were evaluated. Regarding US parameters, a significant muscles versus impairment interaction was found in the muscle thickness (F = 2.96, p <0.022, ICC 0.91), echo intensity (F = 6.74, p <0.0001, ICC 0.90), pennation angle (F = 5.52, p <0.0001, ICC 0.89), and fascicle length (F = 2.71, p <0.0497). In tendon architecture, we found quadriceps tendon thickness reduction comparing SCI and ablebodied individuals (p <0.046, ICC 0.94). Regarding chronaxie values, muscles versus impairment (F = 15.58, p <0.0003, ICC 0.87) revealed relevant differences. In addition, the SCI had a higher prevalence of Neuromuscular Electrophysiological Disorders (NED) of 33.3% in the RF and VL, and 26.6% in the VM and TA muscles. Conclusion: Disuse atrophy occurs globally in individuals with chronic SCI for the muscles under the lesion level, reducing muscle thickness, pennation angle, and fascicular length, as well as increasing muscle and tendon echogenicity. The increased chronaxie values and higher NED prevalence for SCI seem to play a key-role in the maladaptation of musculotendinous architecture, revealing a possible acquired peripheral neuropathy.