Miracle-dz/UniFAR-FTUs huggingface dataset:
FADU: a Quantification Tool for Prokaryotic Transcriptomic Analyses

Most currently available quantification tools for transcriptomics analyses have been designed for human data sets, in which full-length transcript sequences, including the untranslated regions, are well annotated. In most prokaryotic systems, full-length transcript sequences have yet to be characterized, leading to prokaryotic transcriptomics analyses being performed based on only the coding sequences. ABSTRACT Quantification tools for RNA sequencing (RNA-Seq) analyses are often designed and tested using human transcriptomics data sets, in which full-length transcript sequences are well annotated. For prokaryotic transcriptomics experiments, full-length transcript sequences are seldom known, and coding sequences must instead be used for quantification steps in RNA-Seq analyses. However, operons confound accurate quantification of coding sequences since a single transcript does not necessarily equate to a single gene. Here, we introduce FADU (Feature Aggregate Depth Utility), a quantification tool designed specifically for prokaryotic RNA-Seq analyses. FADU assigns partial count values proportional to the length of the fragment overlapping the target feature. To assess the ability of FADU to quantify genes in prokaryotic transcriptomics analyses, we compared its performance to those of eXpress, featureCounts, HTSeq, kallisto, and Salmon across three paired-end read data sets of (i) Ehrlichia chaffeensis, (ii) Escherichia coli, and (iii) the Wolbachia endosymbiont wBm. Across each of the three data sets, we find that FADU can more accurately quantify operonic genes by deriving proportional counts for multigene fragments within operons. FADU is available at https://github.com/IGS/FADU. IMPORTANCE Most currently available quantification tools for transcriptomics analyses have been designed for human data sets, in which full-length transcript sequences, including the untranslated regions, are well annotated. In most prokaryotic systems, full-length transcript sequences have yet to be characterized, leading to prokaryotic transcriptomics analyses being performed based on only the coding sequences. In contrast to eukaryotes, prokaryotes contain polycistronic transcripts, and when genes are quantified based on coding sequences instead of transcript sequences, this leads to an increased abundance of improperly assigned ambiguous multigene fragments, specifically those mapping to multiple genes in operons. Here, we describe FADU, a quantification tool for prokaryotic RNA-Seq analyses designed to assign proportional counts with the purpose of better quantifying operonic genes while minimizing the pitfalls associated with improperly assigning fragment counts from ambiguous transcripts.
Quercetin ameliorates the hepatic apoptosis of foetal rats induced by in utero exposure to fenitrothion via the transcriptional regulation of paraoxonase-1 and apoptosis-related genes

Abstract Background & purpose Exposure to organophosphorus during different phases of pregnancy induces many adverse impacts on the developing foetuses due to their immature detoxification system. We have estimated the potential amelioration role of quercetin against hepatic injury-induced apoptosis in rat foetuses following gestational exposure to fenitrothion and probable involvement of paraoxonase-1. Methods Forty pregnant rats were allocated into four groups; the first one kept as control, the second intubated with quercetin (100 mg/kg), the third orally administrated fenitrothion (4.62 mg/kg) and the last group received quercetin two hours before fenitrothion intoxication. Results Fenitrothion significantly elevated the foetal hepatic levels of thiobarbituric acid reactive substances, protein carbonyl, and nitric oxide, but it reduced the enzymatic activities of glutathione-S-transferase, superoxide dismutase, catalase, and acetylcholinesterase. Furthermore, fenitrothion provoked many histopathological changes in the foetal liver and markedly up-regulated the mRNA gene expression of p53, caspase-9 along with elevation in the immunoreactivity of Bax and caspase-3, but it down-regulated the expression level of paraoxonase-1. Remarkably, quercetin co-treatment successfully ameliorated the hepatic oxidative injury and apoptosis prompted by fenitrothion. Conclusions Dietary supplements with quercetin can be used to reduce the risk from organophosphorus exposure probably through paraoxonase-1 up-regulation and enhancement of the cellular antioxidant system.
Minilaparoscopy in gynecology: applications, benefits and limitations.

INTRODUCTION The word "minilaparoscopy" refers to laparoscopic surgical procedures performed using < 5-mm trocars, with the exception of the umbilical access. The aim of this review is to explore the feasibility of minilaparoscopy in gynecologic surgery, focusing on instruments, surgical techniques, application and limits of this approach. EVIDENCE ACQUISITION In this review the Authors discuss positive features and limitation of 3-mm laparoscopy for gynecologic surgery. EVIDENCE SYNTHESIS Using smaller trocars decreases incisional and postoperative pain, and shortens hospitalization, and provides a better cosmetic outcome. Transvaginal specimen extraction can be used to maximize the aesthetic outcomes. A minilaparoscopic surgical procedure is accomplished with lower carbon dioxide pressures, reducing pneumoperitoneum related complications. Accurate patient selection is critical in order to offer the best laparoscopic approach, considering that obesity and endometriosis may represent a challenge for 3-mm surgical tools, which are more flexible and have lower grasping ability. Minilaparoscopy has been shown as a valid alternative to conventional laparoscopy both for diagnostic purpose, major surgical procedures and oncological surgery. CONCLUSIONS Minilaparoscopy in gynecologic surgery represents an option for selected patients, for both benign and malignant indications. The aesthetic outcome represents the main benefit of this approach. Surgeons have to be aware of few limitations of this technique such as severe obesity and endometriosis.
Synthesis of Novel Triazolyl/Oxadiazolyl/Thiadiazolyl-Piperazine as Potential Anticonvulsant Agents

Abstract Reaction of piperazine with chloroacetylchloride in dry acetone yield compound 1 , which on reaction with hydrazine hydrate yielded compound 2, which was further reacted with various substituted phenylisothiocyanates in absolute alcohol to afford compounds 3–8 i. e. 2-(carbazolylacetyl)-N-(substitutedphenyl)-hydrazinepiperazinothioamides. Compounds 3–8 on reaction with aqueous NaOH, ethanolic NaOH and conc. H2SO4 afford triazoles 9–14, oxadiazoles 15–20 and thiadiazoles 21–26 respectively. Twenty four newly synthesized compounds were evaluated for their anticonvulsant activity and acute toxicity. The structures of these compounds were established on the basis of analytical and spectral data.
Refrigeration and child growth: What is the connection?

Abstract Child stunting in Latin America and the Caribbean (LAC) decreased from 22.9% in 1990 to 9.6% in 2017. While stunting rates in the region were falling, access to electricity and refrigeration were on the rise. Despite a large body of evidence surrounding the effects of refrigeration on food consumption, and separately of the importance of food consumption for child health and nutrition, surprisingly few studies explore the potential effects of refrigeration on child nutrition. We studied the relationship between refrigeration and child nutrition outcomes using rich panel data for 1298 low‐income households with children younger than 12 months at baseline in El Alto, Bolivia. We estimated the effects of refrigerator ownership on diet and nutrition outcomes using a difference‐in‐difference approach. Owning a refrigerator was associated with increased food expenditures and improved child nutrition. We found evidence that households that acquired a refrigerator were more likely to buy food that requires refrigeration, and children in households that acquired refrigerators were 0.17 standard deviations taller for their age after 2 years. We also found that refrigeration was associated with a 0.26 standard deviation decline in BMI‐for‐age, an effect driven by increased height rather than lower weight. These results suggest that refrigeration may play a role in explaining reductions in undernutrition observed in low‐ and middle‐income countries in recent decades.
Functionality of Food Components and Emerging Technologies

This review article introduces nutrition and functional food ingredients, explaining the widely cited terms of bioactivity, bioaccessibility, and bioavailability. The factors affecting these critical properties of food components are analyzed together with their interaction and preservation during processing. Ultimately, the effect of emerging (non-thermal) technologies on different food components (proteins, carbohydrates, lipids, minerals, vitamins, polyphenols, glucosinolates, polyphenols, aroma compounds, and enzymes) is discussed in spite of preserving their functional properties. Non-thermal technologies can maintain the bioavailability of food components, improve their functional and technological properties, and increase the recovery yields from agricultural products. However, the optimization of operational parameters is vital to avoid degradation of macromolecules and the oxidation of labile compounds.
Using Multi-Arm Designs to Test Operating Welfare-to-Work Programs

Background: In the early 1970s, most researchers thought that randomized controlled trials (RCTs) could not be used to measure the effectiveness of large-scale operating welfare reform and employment programs. By the mid-1970s, the Supported Work Demonstration showed that, under certain conditions, this was both feasible and valuable. However, the experimental design was simple; a multi-arm test had been rejected as unrealistic. Within 10 years, a three-arm design was implemented in San Diego to assess both a welfare-to-work program’s overall impact and the contribution of a specific component. Less than 10 years later, the Job Opportunities and Basic Skills Training (JOBS)/National Evaluation of Welfare-to-Work Strategies (NEWWS) study used a more complex design to determine the relative effectiveness of two strategies operated in the same locations: one emphasizing getting a job quickly and the other requiring basic education. In San Diego and JOBS/NEWWS, the tested reforms emerged from political processes and were funded through regular program budgets. In both cases, researchers inserted multi-arm RCTs into operating welfare offices, trading control over the treatment for scale (thousands of people) and real-world conditions. Both RCTs were successfully implemented. Objectives and Results: This article examines why multi-arm designs were attempted, how they were structured, why public administrators cooperated, what various actors sought to learn, and how the researchers determined what strategies the different experimental arms ended up to truly represent. The article concludes that these designs provide convincing evidence and can be inserted into operating programs if the studies address questions that are of keen and immediate interest to state or local program administrators and researchers.
Non-Redundant tRNA Reference Sequences for Deep Sequencing Analysis of tRNA Abundance and Epitranscriptomic RNA Modifications

Analysis of RNA by deep-sequencing approaches has found widespread application in modern biology. In addition to measurements of RNA abundance under various physiological conditions, such techniques are now widely used for mapping and quantification of RNA modifications. Transfer RNA (tRNA) molecules are among the frequent targets of such investigation, since they contain multiple modified residues. However, the major challenge in tRNA examination is related to a large number of duplicated and point-mutated genes encoding those RNA molecules. Moreover, the existence of multiple isoacceptors/isodecoders complicates both the analysis and read mapping. Existing databases for tRNA sequencing provide near exhaustive listings of tRNA genes, but the use of such highly redundant reference sequences in RNA-seq analyses leads to a large number of ambiguously mapped sequencing reads. Here we describe a relatively simple computational strategy for semi-automatic collapsing of highly redundant tRNA datasets into a non-redundant collection of reference tRNA sequences. The relevance of the approach was validated by analysis of experimentally obtained tRNA-sequencing datasets for different prokaryotic and eukaryotic model organisms. The data demonstrate that non-redundant tRNA reference sequences allow improving unambiguous mapping of deep sequencing data.
Building a Fit for Purpose Clinical Trials Infrastructure to Accelerate the Assessment of Novel Hematopoietic Cell Transplantation Strategies and Cellular Immunotherapies.

Rapid progress in cancer therapy cannot be achieved without active patient participation in clinical trials. The past 5 years witnessed remarkable improvements in cancer response rates and survival, realized predominantly through prospective clinical research, and firmly established immunotherapy as a pillar of cancer treatment. Allogeneic hematopoietic cell transplantation (HCT) is the epitome of cancer immunotherapy, with the landmark discovery of the graft-versus-leukemia effect made . 40 years ago. HCT also created the reality of cures for lifethreatening nonmalignant diseases. Yet before the 21st century, progress in HCT was stifled by lack of a collaborative, adequately funded, and effective infrastructure for trials that could definitively test potentially breakthrough therapies. In 2000, the National Institutes of Health (NIH) recognized the gaps in translating scientific discoveries, funded predominantly through independent investigator R01 awards, into novel therapies that could change HCT practice. To address this deficiency, the NIH issued a request for applications (Request for Application No. HL-01-004) in 2001 for establishment of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Now in its 19th year, the BMT CTN has provided a successful infrastructure for clinical trials in HCT and cellular immunotherapy (CIT), enrolling . 11,000 patients on prospective studies and publishing 116 manuscripts, including 29 detailing primary study end points. In this review, we describe development of the BMT CTN infrastructure, its current research capabilities, the means for developing its scientific priorities, lessons learned, and a roadmap for its future role in assessing novel HCT strategies and CITs targeting hematologic malignancies, solid tumors, and serious nonmalignant disorders. We foresee leveraging this experience to evolve the BMT CTN into a framework for accelerating evaluation of a burgeoning variety of cell and gene therapies, including those used to treat patients with solid tumors (Appendix, online only). ESTABLISHING A FIT FOR PURPOSE HCT/CIT CLINICAL TRIALS INFRASTRUCTURE: KEYS TO SUCCESS
Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes

Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific cis and trans factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA[Ser]Sec, encoded in mice by the gene Trsp. Whole-body deletion of Trsp in mouse is embryonically lethal, while targeted deletion of Trsp in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues. We developed a mouse model with the targeted deletion of Trsp in brown adipocytes (Trspf/f-Ucp1-Cre+/−), a cell type predominant in brown adipose tissue (BAT) controlling energy expenditure via activation of adaptive thermogenesis, mostly using uncoupling protein 1 (Ucp1). At room temperature, Trspf/f-Ucp1-Cre+/− mice maintain oxygen consumption and Ucp1 expression, with male Trspf/f-Ucp1-Cre+/− mice accumulating more triglycerides in BAT than both female Trspf/f-Ucp1-Cre+/− mice or Trspf/f controls. Acute cold exposure neither reduced core body temperature nor changed the expression of selenoprotein iodothyronine deiodinase type II (Dio2), a marker of adaptive thermogenesis, in Trspf/f-Ucp1-Cre+/− mice. Microarray analysis of BAT from Trspf/f-Ucp1-Cre+/− mice revealed glutathione S-transferase alpha 3 (Gsta3) and ELMO domain containing 2 (Elmod2) as the transcripts most affected by the loss of Trsp. Male Trspf/f-Ucp1-Cre+/− mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes Thrsp and Tshr in their BATs. In summary, modest changes in the BAT of Trspf/f-Ucp1-Cre +/− mice implicate a mild thyroid hormone dysfunction in brown adipocytes.
NONEQUILIBRIUM DISTRIBUTION FUNCTION FORMALISM FOR DIFFUSION-INFLUENCED BIMOLECULAR REACTIONS : BEYOND THE SUPERPOSITION APPROXIMATION

We introduce an improved and systematic procedure for solving the diffusion-influenced reaction kinetics problem based on a hierarchical set of kinetic equations for many-particle distribution functions. As a representative example, we apply the formalism to the reversible association kinetics problem. The new method gives an approximate analytic solution which is in almost perfect agreement with the Brownian dynamics simulation results for the whole time range. It is shown that results of previous nonequilibrium distribution function theories are reproduced as lower order solutions in the present formalism.
Thyrotoxic dilated cardiomyopathy: personal experience and case collection from the literature

Summary The authors examine several reports of the literature concerning thyrotoxic dilated cardiomyopathy. In particular, it is pointed out that this clinical manifestation of hyperthyroidism is rare in readily diagnosed and properly treated hyperthyroidism. Case reports are analyzed comparatively. A case deriving from the direct experience of the authors is also presented. Learning points: Dilated cardiomyopathy has been reported as the initial presentation of hyperthyroidism in only 6% of patients although <1% developed severe LV dysfunction. Clinical picture of thyrotoxic dilated cardiomyopathy can degenerate into an overt cardiogenic shock sometimes requiring the use of devices for mechanical assistance to the circulation, or extracorporeal membrane oxygenation. For thyrotoxic dilated cardiomyopathy, evidence-based pharmacologic measures valid for heart failure should always be supplemented by the administration of specific thyroid therapies such as thionamides (methimazole, carbimazole or propylthiouracil), whose relatively long latency of action should be supported by the i.v. administration of small doses of beta-blocker. In cases of cardiogenic shock, the administration of beta-blocker should be carried out only after the restoration of satisfactory blood pressure levels- with the prudent use of synthetic catecholamines, if necessary.
Fast 3D Indoor Scene Synthesis by Learning Spatial Relation Priors of Objects

We present a framework for fast synthesizing indoor scenes, given a room geometry and a list of objects with learnt priors. Unlike existing data-driven solutions, which often learn priors by co-occurrence analysis and statistical model fitting, our method measures the strengths of spatial relations by tests for complete spatial randomness (CSR), and learns discrete priors based on samples with the ability to accurately represent exact layout patterns. With the learnt priors, our method achieves both acceleration and plausibility by partitioning the input objects into disjoint groups, followed by layout optimization using position-based dynamics (PBD) based on the Hausdorff metric. Experiments show that our framework is capable of measuring more reasonable relations among objects and simultaneously generating varied arrangements in seconds compared with the state-of-the-art works.
Orbifloxacin: A Review of Properties, Its Antibacterial Activities, Pharmacokinetic/Pharmacodynamic Characteristics, Therapeutic Use, and Analytical Methods

Orbifloxacin is a third generation of fluoroquinolone that exhibits increased antibacterial activity against the Enterobacteriaceae, gram-negative and gram-positive bacteria, anaerobes, and mycobacteria. This drug was synthesized in 1987 and developed as a veterinary chemotherapeutic to use for livestock and domestic pets. Orbifloxacin is labeled for the treatment of skin, soft tissue, and urinary tract infections in dogs, and skin and soft tissue infections in cats, but in some countries, orbifloxacin has been given for the treatment of gastrointestinal and respiratory infections in cattle and swine and other animals. The in vitro activity and clinical efficacy of orbifloxacin against naturally occurring bacterial infections of the skin, ear, soft tissue, udder, and gastrointestinal and respiratory systems in different animals have been evaluated and good responses have been found. The minimum inhibitory concentration of orbifloxacin has been determined in various different pathogens and the results found in the literature are shown in this work. The pharmacokinetics of orbifloxacin has been evaluated by different routes of administration in goats, horses, pigs, rabbits, dogs, cats, camels, cattle, sheep, and fish. Orbifloxacin exhibits excellent pharmacokinetic parameters that suggest that this drug may have good clinical effects on various bacterial infections in these species. All methods described in the scientific literature for determination of orbifloxacin in different matrices were collected and discussed.
Detecting rare haplotype association with two correlated phenotypes of binary and continuous types

Multiple correlated traits/phenotypes are often collected in genetic association studies and they may share a common genetic mechanism. Joint analysis of correlated phenotypes has well‐known advantages over one‐at‐a‐time analysis including gain in power and better understanding of genetic etiology. However, when the phenotypes are of discordant types such as binary and continuous, the joint modeling is more challenging. Another research area of current interest is discovery of rare genetic variants. Currently there is no method available for detecting association of rare (or common) haplotypes with multiple discordant phenotypes jointly. Our goal is to fill this gap specifically for two discordant phenotypes. We consider a rare haplotype association method for a binary phenotype, logistic Bayesian LASSO (univariate LBL) and its extension for two correlated binary phenotypes (bivariate LBL‐2B). Under this framework, we propose a haplotype association test with binary and continuous phenotypes jointly (bivariate LBL‐BC). Specifically, we use a latent variable to induce correlation between the two phenotypes. We carry out extensive simulations to investigate bivariate LBL‐BC and compare it with univariate LBL and bivariate LBL‐2B. In most settings, bivariate LBL‐BC performs the best. In only two situations, bivariate LBL‐BC has similar performance—when the two phenotypes are (1) weakly or not correlated and the target haplotype affects the binary phenotype only and (2) strongly positively correlated and the target haplotype affects both phenotypes in positive direction. Finally, we apply the method to a data set on lung cancer and nicotine dependence and detect several haplotypes including a rare one.