Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and toxinological divergence among populations of Tityus trivittatus Kraepelin, 1898 (Scorpiones: Buthidae) inhabiting Paraguay and Argentina

Envenoming by scorpions in genus Tityus is a public health problem in Tropical America. One of the most medically significant species is Tityus trivittatus, which is known to occur from southwest Brazil to central-northern and eastern Argentina. In this work, we studied the lethality, composition, antigenicity, and enzymatic activity of venom from a T. trivittatus population found further north in urban areas of eastern Paraguay, where it has caused serious envenomation of children. Our results indicate that the population is of medical importance as it produces a potently toxic venom with an LD50 around 1.19 mg/kg. Venom neutralization in preliminary mouse bioassays was complete when using Brazilian anti-T. serrulatus antivenom but only partial when using Argentinean anti-T. trivittatus antivenom. Venom competitive solid-phase enzyme immunoassays and immunoblotting from Argentinean and Paraguayan T. trivittatus populations indicated that antigenic differences exist across the species range. SDS-PAGE showed variations in type and relative amounts of venom proteins between T. trivitattus samples from Argentina and Paraguay. MALDI-TOF mass spectrometry indicated that while some sodium channel toxins are shared, including β-toxin Tt1g, others are population-specific. Proteolytic activity by zymography and peptide identification through nESI-MS/MS also point out that population-specific proteases may exist in T. trivitattus, which are postulated to be involved in the envenoming process. A time-calibrated molecular phylogeny of mitochondrial COI sequences revealed a significant (8.14%) genetic differentiation between the Argentinean and Paraguayan populations, which appeared to have diverged between the mid Miocene and early Pliocene. Altogether, toxinological and genetic evidence indicate that T. trivitattus populations from Paraguay and Argentina correspond to distinct, unique cryptic species, and suggest that further venom and taxonomic diversity exists in synanthropic southern South American Tityus than previously thought.
First ring-opening metathesis polymerization in an ionic liquid. Efficient recycling of a catalyst generated from a cationic ruthenium allenylidene complex

Ring-opening metathesis polymerization (ROMP) of norbornene was carried out in a biphasic medium consisting of the ionic liquid [bdmim][PF6] and toluene with a cationic ruthenium allenylidene precatalyst. The ionic liquid contained the ruthenium allenylidene complex and toluene dissolved the formed polymer. Both the catalyst and the ionic liquid were reused several times and led to very good polymer yields.
‘Hot phase’ clinical presentation in arrhythmogenic cardiomyopathy

Abstract Aims The aim of this study is to evaluate the clinical features of patients affected by arrhythmogenic cardiomyopathy (AC), presenting with chest pain and myocardial enzyme release in the setting of normal coronary arteries (‘hot phase’). Methods and results We collected detailed anamnestic, clinical, instrumental, genetic, and histopathological findings as well as follow-up data in a series of AC patients who experienced a hot phase. A total of 23 subjects (12 males, mean age at the first episode 27 ± 16 years) were identified among 560 AC probands and family members (5%). At first episode, 10 patients (43%) already fulfilled AC diagnostic criteria. Twelve-lead electrocardiogram recorded during symptoms showed ST-segment elevation in 11 patients (48%). Endomyocardial biopsy was performed in 11 patients, 8 of them during the acute phase showing histologic evidence of virus-negative myocarditis in 88%. Cardiac magnetic resonance was performed in 21 patients, 12 of them during the acute phase; oedema and/or hyperaemia were detected in 7 (58%) and late gadolinium enhancement in 11 (92%). At the end of follow-up (mean 17 years, range 1–32), 12 additional patients achieved an AC diagnosis. Genetic testing was positive in 77% of cases and pathogenic mutations in desmoplakin gene were the most frequent. No patient complained of sustained ventricular arrhythmias or died suddenly during the ‘hot phase’. Conclusion ‘Hot phase’ represents an uncommon clinical presentation of AC, which often occurs in paediatric patients and carriers of desmoplakin gene mutations. Tissue characterization, family history, and genetic test represent fundamental diagnostic tools for differential diagnosis.
Treating Sexual Dysfunctions Among Survivors of Child Sexual Abuse: An Overview of Empirical Research

Sexual problems are very prevalent among survivors of child sexual abuse (CSA). Yet, various approaches to therapy do not seem to address this issue when treating these individuals. Traditional sex therapy may also not suit the experiences of CSA survivors, as CSA was not considered when the most well-known and frequently used techniques were developed. The present review sought to identify (1) theory-based therapeutic approaches that address sexual problems among CSA survivors and offer treatment protocols (including an outline of specific therapy stages, sessions, or techniques) to treat these sexual problems and (2) identify therapeutic approaches that include a protocol for treating sexual problems among CSA survivors that was empirically tested and validated. In total, six approaches for treating sexual dysfunctions among CSA survivors that provide detailed guidelines for implementing the approach within sex therapy for CSA survivors were identified in the literature. Only two of the studies conducted a randomized controlled trial to test the intervention. This overview concludes with important issues to address when treating sexual problems among CSA survivors and a call for additional evidence-based practices for treating sexual problems among survivors of CSA.
SWI/SNF complex mutations promote thyroid tumor progression and insensitivity to redifferentiation therapies.

Mutations of subunits of the SWI/SNF chromatin remodeling complexes occur commonly in cancers of different lineages, including advanced thyroid cancers. Here we show that thyroid-specific loss of Arid1a, Arid2 or Smarcb1 in mouse BrafV600E-mutant tumors promotes disease progression and decreased survival, associated with lesion-specific effects on chromatin accessibility and differentiation. As compared to normal thyrocytes, BrafV600E-mutant mouse PTCs have decreased lineage transcription factor expression and accessibility to their target DNA binding sites, leading to impairment of thyroid differentiated gene expression and radioiodine incorporation, which is rescued by MAPK inhibition. Loss of individual Swi/Snf subunits in Braf tumors leads to a repressive chromatin state that cannot be reversed by MAPK pathway blockade, rendering them insensitive to its redifferentiation effects. Our results show that SWI/SNF complexes are central to the maintenance of differentiated function in thyroid cancers, and their loss confers radioiodine refractoriness and resistance to MAPK inhibitor-based redifferentiation therapies.
Empirical Expression for Ionic Character and the Determination of s Hybridization from Nuclear Quadrupole Coupling Constants

An empirical expression between the amount of ionic character in a bond and the electronegativities of the atoms has been suggested. By using the ionic characters determined from this expression, the halogen nuclear quadrupole coupling constants have been interpreted to determine the percentage s hybridization of the halogen bonding orbital. The results indicate that the amount of s hybridization increases with the s hybridization of the bonding atom and with the increasing electronegativity difference of the two atoms in the bond. A qualitative explanation of these results is discussed.
Density functional and vibrational spectroscopic analysis of β‐carotene

We report a computational study on the structural, energetic and vibrational spectroscopic characteristics of β-carotene employing density functional theory (DFT). The optimized geometry and the complete vibrational spectrum calculated at the BPW91/6–31G* level, including infrared (IR) intensities and Raman activities, are presented. The centrosymmetric structure of β-carotene is verified both theoretically and experimentally, by identifying a stable calculated structure with Ci symmetry and the mutually exclusive occurrence of bands in the experimental Fourier transform IR and Raman spectrum, respectively. The calculated vibrational spectra reflect the major characteristic features observed experimentally. Differences in the calculated IR intensities and Raman activities for a few dominant modes of two β-carotene configuration isomers, the all-trans and the natural abundant (C6–C7) s-cis form, are explained qualitatively by the corresponding eigenvectors. At the level of theory employed, s-cis-β-carotene was found to be 8.8 kJ mol−1 more stable than the all-trans form. Calculations on β-carotene model systems were performed to separate electronic from steric contributions. The higher stability of s-cis-β-carotene is explained by an energetically favored β-ionone ring conformation, compensating for its shorter conjugation length in comparison with the all-trans form. Copyright © 2003 John Wiley & Sons, Ltd.
Have socio-economic inequalities in sugar purchasing widened? A longitudinal analysis of food and beverage consumer data from British households, 2014–2017

Abstract Objective: To examine socio-economic inequalities in decreases in household sugar purchasing in Great Britain (GB). Design: Longitudinal, population-based study. Setting: Data were obtained from the GB Kantar Fast-Moving Consumer Goods (FMCG) panel (2014–2017), a nationally representative panel study of food and beverages bought and brought into the home. We estimated changes in daily sugar purchases by occupational social grade from twenty-three food groups, using generalised estimating equations (household-level clustering). Participants: British households who regularly reported food and beverages to the GB Kantar FMCG (n 28 033). Results: We found that lower social grades obtained a lower proportion of sugar from healthier foods and a greater proportion of sugar from less healthy foods and beverages. In 2014, differences in daily sugar purchased between the lowest and the highest social grades were 3·9 g/capita/d (95 % CI 2·9, 4·8) for table sugar, 2·4 g (95 % CI 1·8, 3·1) for sugar-sweetened beverages, 2·2 g (95 % CI 1·5, 2·8) for chocolate and confectionery and 1·0 g (95 % CI 0·7, 1·3) for biscuits. Conversely, the lowest social grade purchased less sugar from fruits (2·1 g (95 % CI 1·5, 2·8)) and vegetables (0·7 g (95 % CI 0·5, 0·8)) than the highest social grade. We found little evidence of change in social grade differences between 2014 and 2017. These results suggest that recent overall declines in sugar purchases are largely equally distributed across socio-economic groups. Conclusions: This suggests that recent population-level policy activity to reduce sugar consumption in GB does not appear to exacerbate or reduce existing socio-economic inequalities in sugar purchasing. Low agency, population-level policies may be the best solution to improving population diet without increasing inequalities.
Eigenspectral Analysis of Pendant Vertex-and Pendant Edge-Weighted Graphs of Linear Chains, Cycles, and Stars

Three classes of pendent vertex- and pendant edge-weighted graphs of linear chains (class I), stars (class II), and cycles (class III) have been presented. These graphs (particularly class I and III) represent heteroconjugated π-systems. Sometimes such graphs appear as factored subgraphs of some complicated graphs. The eigenspectra of these graphs have been found out in analytical forms. These eigenspectra have been utilized i) to calculate the band (i.e., HOMO-LUMO) gaps of such graphs, ii) to find out three classes of inversely proportional graphs (with inversely proportional pairs of eigenvalues), and iii) to express eigenspectra of some complicated graphs in analytical forms along with some subspectral relationships. In the limit of n (number of vertices) to infinity, the band gap of the graph of class I has been shown to be the same with that calculated by considering its hypothetical "cyclic dimer. " Reciprocal graphs have also been considered in this context. These graphs are not all hypothetical. A few of them have also been synthesized.
Potentiality of Self-Cloned Lactobacillus plantarum Taj-Apis362 for Enhancing GABA Production in Yogurt under Glucose Induction: Optimization and Its Cardiovascular Effect on Spontaneous Hypertensive Rats

The current study evaluated the γ-aminobutyric acid (GABA) producing ability from three novel strains of lactic acid bacteria (L. plantarum Taj-Apis362, assigned as UPMC90, UPMC91, and UPMC1065) co-cultured with starter culture in a yogurt. A combination of UPMC90 + UPMC91 with starter culture symbiotically revealed the most prominent GABA-producing effect. Response surface methodology revealed the optimized fermentation conditions at 39.0 °C, 7.25 h, and 11.5 mM glutamate substrate concentration to produce GABA-rich yogurt (29.96 mg/100 g) with desirable pH (3.93) and water-holding capacity (63.06%). At 2% glucose to replace pyridoxal-5-phosphate (PLP), a cofactor typically needed during GABA production, GABA content was further enhanced to 59.00 mg/100 g. In vivo study using this sample revealed a blood pressure-lowering efficacy at 0.1 mg/kg GABA dosage (equivalent to 30 mg/kg GABA-rich yogurt) in spontaneously hypertensive rats. An improved method to produce GABA-rich yogurt has been established, involving shorter fermentation time and lower glutamate concentration than previous work, along with glucose induction that omits the use of costly PLP, fostering the potential of developing a GABA-rich functional dairy product through natural fermentation with desirable product quality and antihypertensive property.
Effects of electrostatic interactions on orientational order of solutes in liquid crystals

A mean-field model for the analysis of electrostatic interactions in liquid crystal phases is proposed. The model is based on a realistic description of the probe molecule and a continuum approximation for its environment. Electrostatic interactions, treated with the reaction field model, are superimposed to short-range interactions, which are accounted for by a shape method. The model is used to predict orientational order parameters of some representative solutes, characterized by different shapes and charge distributions, dissolved in nematics with different dielectric permittivities.
Mental awareness improved mild cognitive impairment and modulated gut microbiome

There is ample scientific and clinical evidence of the effects of gut microbiota on the brain but no definitive evidence that the brain can affect changes in gut microbiota under the bi-directional gut-brain axis concept. As there is no pharmacotherapeutic intervention for the early stages of cognitive decline, research has focused on cognitive stimulation in reversing or slowing the impairment. Elderly patients diagnosed with mild cognitive impairment underwent a randomized-control trial of mindful awareness practice. Neuropsychological assessments, inflammatory markers, and gut microbiota profiles were tested. Here, we report that their cognitive impairment was improved and associated with changes in gut bacterial profile. A cognition-score-dependent-abundance was observed in Ruminococcus vs Recognition Trials (RT), Digit Span Backward (DSB), Semantic Fluency Span (SFS) and Memory Domain (MD); Coprococcus vs DSB, Color Trails Test 2 (CTT2) and Block Design (BD); Parabacteroides vs DSB and SFS; Fusobacterium vs DSB and CTT2; Enterobacteriaceae vs BD and SFS; Ruminococcaceae vs DSB; Phascolarctobacterium vs MD. The study showed for the first-time, alteration in the cognitive capacity leading to the corresponding changes in microbiota profiles. This strongly suggests that signals from the different segments of brain could dictate directly or indirectly the abundances of specific gut microbes.
The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis

Significance Among all cancer types, lung cancer patients exhibit the highest prevalence of brain metastasis, often associated with cognitive impairment, seizures, decline in quality of life, and decreased survival. Limited therapeutic options are currently available to treat brain metastasis. A comprehensive understanding of the signaling pathways and transcriptional networks required for survival and growth of brain-metastatic cancer cells is needed to develop effective strategies to treat this disease. Here, we report that the Heat Shock Transcription Factor 1 (HSF1) is upregulated in brain-metastatic lung cancer cells and is required for brain metastasis in mice. Importantly, we show that the HSF1-dependent expression of E2F target genes implicated in cell cycle progression and survival is decreased by blood–brain barrier-penetrant ABL allosteric inhibitors. Brain metastases are the most common intracranial tumors in adults and are associated with increased patient morbidity and mortality. Limited therapeutic options are currently available for the treatment of brain metastasis. Here, we report on the discovery of an actionable signaling pathway utilized by metastatic tumor cells whereby the transcriptional regulator Heat Shock Factor 1 (HSF1) drives a transcriptional program, divergent from its canonical role as the master regulator of the heat shock response, leading to enhanced expression of a subset of E2F transcription factor family gene targets. We find that HSF1 is required for survival and outgrowth by metastatic lung cancer cells in the brain parenchyma. Further, we identify the ABL2 tyrosine kinase as an upstream regulator of HSF1 protein expression and show that the Src-homology 3 (SH3) domain of ABL2 directly interacts with HSF1 protein at a noncanonical, proline-independent SH3 interaction motif. Pharmacologic inhibition of the ABL2 kinase using small molecule allosteric inhibitors, but not ATP-competitive inhibitors, disrupts this interaction. Importantly, knockdown as well as pharmacologic inhibition of ABL2 using allosteric inhibitors impairs expression of HSF1 protein and HSF1-E2F transcriptional gene targets. Collectively, these findings reveal a targetable ABL2-HSF1-E2F signaling pathway required for survival by brain-metastatic tumor cells.
HIV/AIDS knowledge and attitudes assessment among women of child-bearing age in South Sudan: Findings from a Household Survey

This study assessed the determinants that shape HIV knowledge and attitudes among South Sudanese women by analysing a Multiple Indicator Cluster Survey collected from 9,061 women in 9,369 households. Generalised linear mixed model regression was performed. Fifty percent of respondents were aware of HIV/AIDS, with 21% and 22% exhibiting good knowledge and positive attitudes towards people with HIV/AIDS, respectively. When controlled for individual and community-level variables, younger women (AOR = 1.28, 95% CI: 1.01–162), women with primary (AOR = 2.19; 95% CI: 1.86–2.58) and secondary (AOR = 4.48; 95% CI: 3.38–5.93) education, and those living in urban areas (AOR = 1.40; 95% CI: 1.12–1.76) had significantly good knowledge. Women in the richer (AOR = 1.60; 95% CI: 1.08–2.36) and the richest (AOR = 2.02; 95% CI: 1.35–3.02) wealth quintiles had significant positive attitudes towards people with HIV/AIDS. Well-designed social and behavioural campaigns targeting uneducated women and those living in rural and remote settings will enhance knowledge of perceived risk, awareness, and ability to carry out preventive behaviours.
Clustering Analysis Supports the Detection of Biological Processes Related to Autism Spectrum Disorder

Genome sequencing has identified a large number of putative autism spectrum disorder (ASD) risk genes, revealing possible disrupted biological pathways; however, the genetic and environmental underpinnings of ASD remain mostly unanswered. The presented methodology aimed to identify genetically related clusters of ASD individuals. By using the VariCarta dataset, which contains data retrieved from 13,069 people with ASD, we compared patients pairwise to build “patient similarity matrices”. Hierarchical-agglomerative-clustering and heatmapping were performed, followed by enrichment analysis (EA). We analyzed whole-genome sequencing retrieved from 2062 individuals, and isolated 11,609 genetic variants shared by at least two people. The analysis yielded three clusters, composed, respectively, by 574 (27.8%), 507 (24.6%), and 650 (31.5%) individuals. Overall, 4187 variants (36.1%) were common to the three clusters. The EA revealed that the biological processes related to the shared genetic variants were mainly involved in neuron projection guidance and morphogenesis, cell junctions, synapse assembly, and in observational, imitative, and vocal learning. The study highlighted genetic networks, which were more frequent in a sample of people with ASD, compared to the overall population. We suggest that itemizing not only single variants, but also gene networks, might support ASD etiopathology research. Future work on larger databases will have to ascertain the reproducibility of this methodology.
20‐HETE synthesis inhibition attenuates traumatic brain injury–induced mitochondrial dysfunction and neuronal apoptosis via the SIRT1/PGC‐1α pathway: A translational study

20‐hydroxyeicosatetraenoic acid (20‐HETE) is a metabolite of arachidonic acid catalysed by cytochrome P450 enzymes and plays an important role in cell death and proliferation. We hypothesized that 20‐HETE synthesis inhibition may have protective effects in traumatic brain injury (TBI) and investigated possible underlying molecular mechanisms.
Low 25-Hydroxyvitamin D Levels on Admission to the Intensive Care Unit May Predispose COVID-19 Pneumonia Patients to a Higher 28-Day Mortality Risk: A Pilot Study on a Greek ICU Cohort

We aimed to examine whether low intensive care unit (ICU) admission 25-hydroxyvitamin D (25(OH)D) levels are associated with worse outcomes of COVID-19 pneumonia. This was a prospective observational study of SARS-CoV2 positive critically ill patients treated in a multidisciplinary ICU. Thirty (30) Greek patients were included, in whom 25(OH)D was measured on ICU admission. Eighty (80%) percent of patients had vitamin D deficiency, and the remaining insufficiency. Based on 25(OH)D levels, patients were stratified in two groups: higher and lower than the median value of the cohort (15.2 ng/mL). The two groups did not differ in their demographic or clinical characteristics. All patients who died within 28 days belonged to the low vitamin D group. Survival analysis showed that the low vitamin D group had a higher 28-day survival absence probability (log-rank test, p = 0.01). Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors. When the cohort was divided at the median 25(OH)D value, the low vitamin D group had an increased risk of 28-day mortality. It seems plausible, therefore, that low 25(OH)D levels may predispose COVID-19 patients to an increased 28-day mortality risk.