Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular targets in acromegaly

Molecular therapeutic targets in growth hormone (GH)-secreting adenomas range from well-characterized surface receptors that recognize approved drugs, to surface and intracellular markers that are potential candidates for new drug development. Currently available medical therapies for patients with acromegaly bind to somatostatin receptors, GH receptor, or dopamine receptors, and lead to attainment of disease control in most patients. The degree of control is variable: however, correlates with both disease aggressiveness and tumor factors that predict treatment response including somatostatin receptor subtype expression, granulation pattern, kinases and their receptors, and other markers of proliferation. A better understanding of the mechanisms underlying these molecular markers and their relationship to outcomes holds promise for expanding treatment options as well as a more personalized approach to treating patients with acromegaly.
Hippocampal ceRNA networks from chronic intermittent ethanol vapor-exposed male mice and functional analysis of top-ranked lncRNA genes for ethanol drinking phenotypes

The molecular mechanisms regulating the development and progression of alcohol use disorder (AUD) are largely unknown. While noncoding RNAs have previously been implicated as playing key roles in AUD, long-noncoding RNA (lncRNA) remains understudied in relation to AUD. In this study, we first identified ethanol-responsive lncRNAs in the mouse hippocampus that are transcriptional network hub genes. Microarray analysis of lncRNA, miRNA, circular RNA, and protein coding gene expression in the hippocampus from chronic intermittent ethanol vapor- or air- (control) exposed mice was used to identify ethanol-responsive competing endogenous RNA (ceRNA) networks. Highly interconnected lncRNAs (genes that had the strongest overall correlation to all other dysregulated genes identified) were ranked. The top four lncRNAs were novel, previously uncharacterized genes named Gm42575, 4930413E15Rik, Gm15767, and Gm33447, hereafter referred to as Pitt1, Pitt2, Pitt3, and Pitt4, respectively. We subsequently tested the hypothesis that CRISPR/Cas9 mutagenesis of the putative promoter and first exon of these lncRNAs in C57BL/6J mice would alter ethanol drinking behavior. The Drinking in the Dark (DID) assay was used to examine binge-like drinking behavior, and the Every-Other-Day Two-Bottle Choice (EOD-2BC) assay was used to examine intermittent ethanol consumption and preference. No significant differences between control and mutant mice were observed in the DID assay. Female-specific reductions in ethanol consumption were observed in the EOD-2BC assay for Pitt1, Pitt3, and Pitt4 mutant mice compared to controls. Male-specific alterations in ethanol preference were observed for Pitt1 and Pitt2. Female-specific increases in ethanol preference were observed for Pitt3 and Pitt4. Total fluid consumption was reduced in Pitt1 and Pitt2 mutants at 15% v/v ethanol and in Pitt3 and Pitt4 at 20% v/v ethanol in females only. We conclude that all lncRNAs targeted altered ethanol drinking behavior, and that lncRNAs Pitt1, Pitt3, and Pitt4 influenced ethanol consumption in a sex-specific manner. Further research is necessary to elucidate the biological mechanisms for these effects. These findings add to the literature implicating noncoding RNAs in AUD and suggest lncRNAs also play an important regulatory role in the disease.
Assessing the interfacial corrosion mechanism of Inconel 617 in chloride molten salt corrosion using multi-modal advanced characterization techniques

The United States Department of Energy (DOE) has committed to expanding the domestic clean energy portfolio in response to the rising challenges of energy security in the wake of climate change. Accordingly, the construction of a series of Generation IV reactor technologies are being demonstrated, including sodium-cooled, small modular, and molten chloride fast reactors (MCFRs). To date, there are no fully qualified structural materials for constructing MCFRs. A number of commercial structural alloys have been considered for the construction of MCFRs, including alloys from the Inconel and Hastelloy series. Informed qualification of structural materials for the construction of MCFRs in the future can only be ensured by expanding the current fundamental knowledgebase of information pertaining to material performance under environmental stressors relevant to operation of the reactor, including corrosion susceptibility. The purpose of this investigation is to illustrate how a correlative multi-modal electron microscopy characterization approach, including the novel application of focused-ion beam 3D reconstruction capabilities, can elucidate the corrosion mechanism of a candidate structural material Inconel 617 for MCFR in NaCl-MgCl2 eutectic salt at 700°C for 1,000 h. Evidence of intergranular corrosion, Ni and Fe dealloying, and Cr-O enrichment along the grain boundary, which most likely corresponds to Cr2O3, is a phenomenon that has been documented in other Ni-based superalloys exposed to chloride molten salt systems. Additional corrosion products, including the formation of insoluble MgAl2O4, within the porous network produced by the salt attack is a novel observation. In addition, Mo3Si5 and τ2 precipitates are detected in the alloy bulk and are dissolved by the salt. Furthermore, the lack of detection of design γ′ precipitates in Inconel 617 after 1,000 h could indicate that the molten salt corrosion mechanism has indirectly induced a phase transformation of Al2TiNi (τ2) and Ni3(Al,Ti) (γ’) phase. This investigation provides a comprehensive understanding of molten salt corrosion mechanisms in a complex material system such as a commercial structural alloy for applications in MCFRs.
Multicolor emission based on a N, N′—Disubstituted dihydrodibenzo [a, c] phenazine crown ether macrocycle

Dynamic fluorophore 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) affords a new platform to produce diverse emission outputs. In this paper, a novel DPAC-containing crown ether macrocycle D-6 is synthesized and characterized. Host-guest interactions of D-6 with different ammonium guests produced a variety of fluorescence with hypsochromic shifts up to 130 nm, which are found to be affected by choice of solvent or guest and host/guest stoichiometry. Formation of supramolecular complexes were confirmed by UV-vis titration, 1H NMR and HRMS spectroscopy.
The morbidity and the spectrum of applied drugs in shelter cats in the Czech Republic

Maintaining appropriate living conditions and good health of the animals should be one of the main priorities of cat shelters. The aim of this study was to assess the morbidity of shelter cats on the basis of analysis of the shelter health records in terms of the nature and quantity of medicaments and other supportive products administered in two no-kill shelters in the Czech Republic. The subject of the study were the health records of 1,884 cats, which were admitted to the selected shelters from 1.1. 2013 to 31.12. 2021 and their stay in the shelter was terminated in the monitored period. More than half of all cats whose records were analyzed had at least one health record made during their stay in the shelter. The overall length of stay of cats in the shelter (regardless of the outcome) in which one or more health records were found was significantly longer compared to the length of stay of cats without any health records. The highest number of health records was found in kittens <6 months old. Antibiotics, antiparasitics, and complementary/protective substances were the most used among all administered drugs. Broad-spectrum antibiotics have been administered to cats most often. In terms of classification of antibiotics according to the active substance, the most used antibiotics were penicillins, tetracyclines, and fluoroquinolones. Antibiotics were mostly used to treat diseases related to the upper and lower respiratory tract and their symptoms and gastrointestinal problems. The findings of the study contribute to understanding health problems and approaches to treating the shelter cats.
Advances in the study of axon–associated vesicles

The central nervous system is the most important and difficult to study system in the human body and is known for its complex functions, components, and mechanisms. Neurons are the basic cellular units realizing neural functions. In neurons, vesicles are one of the critical pathways for intracellular material transport, linking information exchanges inside and outside cells. The axon is a vital part of neuron since electrical and molecular signals must be conducted through axons. Here, we describe and explore the formation, trafficking, and sorting of cellular vesicles within axons, as well as related-diseases and practical implications. Furthermore, with deepening of understanding and the development of new approaches, accumulating evidence proves that besides signal transmission between synapses, the material exchange and vesicular transmission between axons and extracellular environment are involved in physiological processes, and consequently to neural pathology. Recent studies have also paid attention to axonal vesicles and their physiological roles and pathological effects on axons themselves. Therefore, this review mainly focuses on these two key nodes to explain the role of intracellular vesicles and extracellular vesicles migrated from cells on axons and neurons, providing innovative strategy for future researches.
Pharmacokinetics, absorption, distribution, metabolism and excretion of the MEK inhibitor zapnometinib in rats

Zapnometinib is a MEK inhibitor currently under clinical development for the treatment of COVID-19 and influenza. Zapnometinib has both antiviral and immunomodulatory effects. Information concerning the absorption, distribution, metabolism, and excretion of the compound following single oral doses of 30 mg/kg [14C]-zapnometinib to rats was required to support pharmacology and toxicology studies in animals and clinical studies in man. As part of the development and safety assessment of this substance, zapnometinib was radioactively labeled and used for the investigation of time-dependent plasma concentrations, the rates and routes of excretion, the extent and time-course of compound distribution in body tissues, the metabolite profiles in plasma, urine and feces and the chemical nature of its metabolites. The present study reveals a rapid but low absorption of zapnometinib from the gastrointestinal tract, with more than 90% of the compound being excreted within 48 h, mainly via feces. Whole body autoradiography confirms that zapnometinib was rapidly and widely distributed, with greatest concentrations in the circulatory and visceral tissues. Maximum plasma and tissue concentrations occurred between two and 8 h post dose. Penetration into the brain was low, and elimination from most tissues almost complete after 168 h. Metabolic profiles showed that the main clearance routes were metabolism via oxidative reactions and glucuronidation. These results further strengthen the knowledge of zapnometinib with respect to the clinical development of the drug.
Edible marijuana and cycle ergometer exercise

Purpose: There is extensive public and scientific interest in the influence of cannabis and the psychoactive cannabinoid, delta-9-tetrahydrocannabinol (THC), on exercise performance. Unfortunately, recent, up-to-date studies are lacking. The aim of the current study was to address the hypothesis that ingestion of edible marijuana, prior to exercise, would have unfavorable effects on the physiological response to exercise and on exercise performance. Methods: 17 Healthy adult male and female habitual exercisers, who were regular users of cannabis products, were screened for study participation. 10 were enrolled, and data from 9 [8 males, 1 female, aged 25±3 years, with peak oxygen uptake of 56.5±11.7 ml/kg/min (mean ± SD)] were retained. Participation included two exercise sessions, each preceded by self-administration and ingestion of either edible marijuana (containing 10 mg THC) or placebo. Cardio-respiratory responses (via indirect calorimetry) to stationary cycle ergometer exercise (8 min at 50, 100 and 150 W) were recorded before completion of a 20-min Functional Threshold Power test (FTP20) and a sprint test involving maximal effort until volitional fatigue. Results: Edible marijuana increased the concentration of circulating THC and THC metabolites, and evoked sensations of intoxication and altered psychoactive state. Cardio-respiratory responses to staged cycle ergometer exercise were normal and were unaffected by edible marijuana. Compared with placebo, edible marijuana did not influence FTP20 (Placebo 253±75 vs THC: 251±72 W (mean±SD); p > 0.45) or peak power output during the sprint test (Placebo: 710±201 vs. THC: 732±136 W; p = 0.864). Conclusion: 10 mg of THC, when ingested prior to exercise by regular exercisers and habitual users of cannabis, had little effect on the physiological response to standardized cycle ergometer exercise, and was neither ergogenic nor ergolytic.
Validation of the Ukrainian version of the Parental Burnout Assessment

The aim of the present study was to develop a Ukrainian version of the Parental Burnout Assessment (PBA) and examine its psychometric properties among Ukrainian parents. We examined the factorial structure of the Ukrainian version of the PBA (PBA-UA) and its relation with other variables, both antecedents and consequences of PB, in a sample of 1896 parents including 1735 (91,5%) mothers and 161 (8,5%) fathers. The original four-factor model (exhaustion from parental role, emotional distancing from one’s child, feelings of being fed up with parenting and contrast with previous parental self) and second-order model with a global parental burnout as a second-order factor fit the data well. The results of both subscale and global scores were reliable. The PBA-UA showed a positive association with perfectionism and general stress and a negative association with resilience. The low association with socio-demographic factors (i.e., marital status, number of children, number of children living in the household, work status) was replicated in accordance with previous studies of parental burnout, nevertheless mothers had higher level of parental burnout than fathers. PBA-UA also predicted both parental neglect and parental violence, even beyond general stress. The good psychometric properties of the PBA-UA suggests that this questionnaire can be used to assess parental burnout among Ukrainian parents.
Anti-hyperglycemic contours of Madhugrit are robustly translated in the Caenorhabditis elegans model of lipid accumulation by regulating oxidative stress and inflammatory response

Background The prevalence of diabetes has considerably increased in recent years. In the long run, use of dual therapy of anti-diabetic agents becomes mandatory to attain euglycemia. Also, the incidences of diabetes-related co-morbidities have warranted the search for new therapeutic approaches for the management of the disease. Traditional herbo-mineral, anti-diabetic agents like Madhugrit are often prescribed to mitigate diabetes and related complications. The present study aimed to thoroughly characterize the pharmacological applications of Madhugrit. Methods Phytometabolite characterization of Madhugrit was performed by ultra-high performance liquid chromatography. Evaluation of cell viability, α-amylase inhibition, glucose uptake, inflammation, and wound healing was performed by in vitro model systems using AR42J, L6, THP1, HaCaT cells, and reporter cell lines namely NF-κB, TNF-α, and IL-1β. The formation of advanced glycation end products was determined by cell-free assay. In addition, the therapeutic potential of Madhugrit was also analyzed in the in vivo Caenorhabditis elegans model system. Parameters like brood size, % curling, glucose and triglyceride accumulation, lipid deposition, ROS generation, and lipid peroxidation were determined under hyperglycemic conditions induced by the addition of supraphysiological glucose levels. Results Madhugrit treatment significantly reduced the α-amylase release, enhanced glucose uptake, decreased AGEs formation, reduced differentiation of monocyte to macrophage, lowered the pro-inflammatory cytokine release, and enhanced wound healing in the in vitro hyperglycemic (glucose; 25 mM) conditions. In C. elegans stimulated with 100 mM glucose, Madhugrit (30 µg/ml) treatment normalized brood size, reduced curling behavior, decreased accumulation of glucose, triglycerides, and lowered oxidative stress. Conclusions Madhugrit showed multimodal approaches in combating hyperglycemia and related complications due to the presence of anti-diabetic, anti-inflammatory, anti-oxidant, wound healing, and lipid-lowering phytoconstituents in its arsenal. The study warrants the translational use of Madhugrit as an effective medicine for diabetes and associated co-morbidities.
Further thoughts on Newton’s zero‐order rainbow

A zero‐order rainbow angle may be defined as the relative minimum angle of deviation of geometrical light rays transmitted without internal reflections through a transparent particle. If the incident rays are parallel and the particle is a sphere, such a minimum does not exist. But if the incident rays are not parallel or if the particle has an elliptical rather than circular cross section, an angle of minimum deviation, hence a zero‐order rainbow, can occur. For a spherical water droplet, the zero‐order rainbow will occur when a point source is placed less than a droplet radius away from its surface. If a column of water with an elliptical cross section is illuminated by a plane wave, a zero‐order rainbow will occur if the length of the major axis of the cross section is more than twice the length of the minor axis.
Executive function in early childhood: Harnessing the potential of nature-based practices to elevate and equalize outcomes

This study examined the effect of nature-based practices on preschoolers’ executive function (EF). The Minnesota Executive Function Scale was administered to 147 children within one school district at the beginning and end of the preschool year. Results suggest incorporating nature-based practices into preschool was effective, as children in preschool classrooms where nature-based practices were used had significantly higher levels of EF at the end of the school year than children in programs where nature-based practices were more minimally used. Preschools that used a blended approach (some incorporation of nature-based practices) were significantly more effective than preschools that had lesser incorporation of nature-based practices. Results also point to the effectiveness of a blended approach for supporting EF in lower SES children. This study contributes to the literature regarding effective practices for supporting EF development and adds to the growing body of research surrounding the impact of nature play on child development and school readiness.
Internet search data with spatiotemporal analysis in infectious disease surveillance: Challenges and perspectives

With the rapid development of the internet, the application of internet search data has been seen as a novel data source to offer timely infectious disease surveillance intelligence. Moreover, the advancements in internet search data, which include rich information at both space and time scales, enable investigators to sufficiently consider the spatiotemporal uncertainty, which can benefit researchers to better monitor infectious diseases and epidemics. In the present study, we present the necessary groundwork and critical appraisal of the use of internet search data and spatiotemporal analysis approaches in infectious disease surveillance by updating the current stage of knowledge on them. The study also provides future directions for researchers to investigate the combination of internet search data with the spatiotemporal analysis in infectious disease surveillance. Internet search data demonstrate a promising potential to offer timely epidemic intelligence, which can be seen as the prerequisite for improving infectious disease surveillance.
Growth and genome-based insights of Fe(III) reduction of the high-temperature and NaCl-tolerant Shewanella xiamenensis from Changqing oilfield of China

Introduction A facultative anaerobe bacterium Shewanella xiamenensis CQ-Y1 was isolated from the wastewater of Changqing oilfield in Shaanxi Province of China. Shewanella is the important dissimilatory metal-reducing bacteria. It exhibited a well potential application in biodegradation and bioremediation. Methods Genome sequencing, assembling and functional annotation were conducted to explore the genome information of CQ-Y1. The effect of temperatures and NaCl concentrations on the CQ-Y1 growth and Fe(III) reduction were investigated by UV visible spectrophotometry, SEM and XRD. Results Genomic analysis revealed its complete genome was a circular chromosome of 4,710,887 bp with a GC content of 46.50% and 4,110 CDSs genes, 86 tRNAs and 26 rRNAs. It contains genes encoding for Na+/H+ antiporter, K+/Cl− transporter, heat shock protein associated with NaCl and high-temperature resistance. The presence of genes related to flavin, Cytochrome c, siderophore, and other related proteins supported Fe(III) reduction. In addition, CQ-Y1 could survive at 10% NaCl (w/v) and 45°C, and temperature showed more pronounced effects than NaCl concentration on the bacterial growth. The maximum Fe(III) reduction ratio of CQ-Y1 reached 70.1% at 30°C without NaCl, and the reduction reaction remained active at 40°C with 3% NaCl (w/v). NaCl concentration was more effective than temperature on microbial Fe(III) reduction. And the reduction products under high temperature and high NaCl conditions were characterized as Fe3(PO4)2, FeCl2 and Fe(OH)2. Discussion Accordingly, a Fe(III) reduction mechanism of CQ-Y1 mediated by Cytochrome c and flavin was hypothesised. These findings could provide information for a better understanding of the origin and evolution of genomic and metabolic diversity of S. xiamenensis.
Gleason 6 prostate cancer: That which cannot be named

COPYRIGHT © 2022 Burke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Opinion PUBLISHED 05 December 2022 DOI 10.3389/fonc.2022. 1073580
Communicative Intentions Annotation Scheme for Natural Language Processing Applications

Communicative intentions are one of the linguistic elements that usually determine the content of any message we want to express in our social interactions. With the purpose of contributing to the improvement of natural language processing systems, this thesis aims to create a communicative intention annotation scheme based on the taxonomy presented in the Speech Act Theory. In this way, language processing tools could consider communicative intentions as a starting point to help classify any message and its content depending first on the intention it reflects. To do so, the scheme will be created with the help of an already annotated corpus of Spanish tweets and subsequently evaluated by external annotators so that we can confirm the appropriateness and reliability of the tagged intentions before applying the scheme to an NLP system. Thus, it will be possible to check up to which point communicative intentions can improve the identification of the purpose of a message in an already created NLP system so that we can gain more linguistic information from any text automatically.