Miracle-dz/UniFAR-FTUs huggingface dataset:
Deciphering adipose tissue heterogeneity

Obesity is an excess accumulation of adipose tissue mass, and, together with its sequelae, in particular type II diabetes and metabolic syndrome, obesity presents a major health crisis. Although obesity is simply caused by increased adipose mass, the heterogeneity of adipose tissue in humans means that the response to increased energy balance is highly complex. Individual subjects with similar phenotypes may respond very differently to the same treatments; therefore, obesity may benefit from a personalized precision medicine approach. The variability in the development of obesity is indeed driven by differences in sex, genetics, and environment, but also by the various types of adipose tissue as well as the different cell types that compose it. By describing the distinct cell populations that reside in different fat depots, we can interpret the complex effect of these various players in the maintenance of whole‐body energy homeostasis. To further understand adipose tissue, adipogenic differentiation and the transcriptional program of lipid accumulation must be investigated. As the cell‐ and depot‐specific functions are described, they can be placed in the context of energy excess to understand how the heterogeneity of adipose tissue shapes individual metabolic status and condition.
Homologous Recombination Is Very Rare or Absent in Human Influenza A Virus

ABSTRACT To determine the extent of homologous recombination in human influenza A virus, we assembled a data set of 13,852 sequences representing all eight segments and both major circulating subtypes, H3N2 and H1N1. Using an exhaustive search and a nonparametric test for mosaic structure, we identified 315 sequences (∼2%) in five different RNA segments that, after a multiple-comparison correction, had statistically significant mosaic signals compatible with homologous recombination. Of these, only two contained recombinant regions of sufficient length (>100 nucleotides [nt]) that the occurrence of homologous recombination could be verified using phylogenetic methods, with the rest involving very short sequence regions (15 to 30 nt). Although this secondary analysis revealed patterns of phylogenetic incongruence compatible with the action of recombination, neither candidate recombinant was strongly supported. Given our inability to exclude the occurrence of mixed infection and template switching during amplification, laboratory artifacts provide an alternative and likely explanation for the occurrence of phylogenetic incongruence in these two cases. We therefore conclude that, if it occurs at all, homologous recombination plays only a very minor role in the evolution of human influenza A virus.
A SQuaRE-based software quality evaluation framework and its case study

Software stakeholders, including developers, managers, and end users, require high quality software products. Several works have aimed to identify software quality, but the quality of software products is often not comprehensively, specifically, or effectively defined because previous approaches have focused on certain quality aspects. Moreover, the evaluation results of quality metrics often depend on software stakeholders so that it is often hard to compare quality evaluation results across software products. ISO/IEC has tried to define evaluation methods for the quality of software products and provide common standards, called the SQuaRE (Systems and software Quality Requirements and Evaluation) series including ISO/IEC 25022:2016 and ISO/IEC 25023:2016. However, the SQuaRE series include ambiguous metrics so that it is not always easy to apply the series to products and compare results. In this paper, we propose a SQuaRE-based software quality evaluation framework, which successfully concretized many product metrics and quality in use metrics originally defined in the SQuaRE series1. Through a case study targeting a commercial software product, we confirmed that our framework is concretely applicable to the software package/service product.
Effects of angiotensin II in fetal sheep and modification of its actions by indomethacin.

1. Angiotensin II (AII) was infused I.V. into seven chronically catheterized fetal sheep (gestational age, 120‐136 days). The effects of short‐term infusions of 6 and 12 micrograms kg‐1 h‐1 for 1.5 h were compared with the effects of infusing 6 micrograms kg‐1 h‐1 for 3 or 5 days (long‐term infusion). AII produced an immediate rise in fetal arterial blood pressure (P < 0.025). When infused for 3 or 5 days, 6 micrograms kg‐1 h‐1 AII caused a greater increase in arterial blood pressure (P < 0.05). 2. Infusions of 6 micrograms kg‐1 h‐1 AII for 1.5 h had no effect on fetal placental blood flow or on flow to the fetal membranes, but after AII infusion for 3 or 5 days both flows were reduced (P < 0.01 and P < 0.005, respectively). Fetal blood gas status and pH were maintained. The only change in fetal renal function observed with short‐term infusions of AII was a rise in sodium excretion when 12 micrograms kg‐1 h‐1 AII was given (P < 0.05). Infusion of 6 micrograms kg‐1 h‐1 for 3 or 5 days also caused a rise in sodium excretion (P < 0.025) because total and proximal fractional sodium reabsorptions were depressed (P < 0.01). Infusions of AII had no effects on the volume of lung liquid produced or on its composition. 3. Administration of indomethacin to the ewe (10 mg kg‐1) and to the fetus (12 mg kg‐1), during the infusion of AII, caused a rise in maternal arterial pressure (P < 0.01) but no change in fetal arterial pressure. 4. After indomethacin, umbilicoplacental blood flow rose (P < 0.05), as did fetal arterial PO2 (P < 0.05). Fetal arterial PCO2, pH and bicarbonate levels fell (P < 0.01). Glomerular filtration rate (GFR) rose (P < 0.01); there was a natriuresis (P < 0.01), chloriuresis (P < 0.01) and a kaliuresis (P < 0.05) but urine flow rate did not change. Lung liquid flow fell (P < 0.01). 5. It is concluded that in the fetus, long‐term infusions of AII at a constant dose rate cause a progressive rise in arterial pressure. In addition, effects of AII on placental blood flow and on renal function develop. Thus, short‐term infusions of AII cannot be used to predict the renal and cardiovascular effects of sustained high levels of this peptide in the fetus. (ABSTRACT TRUNCATED AT 400 WORDS)
Initiation of rapid, P53-dependent growth arrest in cultured human skin fibroblasts by reactive chlorine species.

Oxidants produced by neutrophils have been implicated in causing cancers associated with chronic inflammation. Hypochlorous acid is the most potent oxidant produced by these cells in appreciable amounts. It reacts with amines to form chloramines, which are weaker oxidants but are mutagenic. Recently, we showed that sublethal doses of hypochlorous acid increased levels of the transcription factor protein 53 (p53) and the wild-type activating fragment-1/cyclin-dependent kinase inhibitory protein-1 (WAF1/CIP1) in cultured human skin fibroblasts. WAF1/CIP1 is an important intermediate in the pathway leading to growth arrest. We now show that low doses of hypochlorous acid and physiological chloramines lead to an inhibition of both DNA synthesis and division of cultured human skin fibroblasts. Inhibition of DNA synthesis occurred within 1 h of hypochlorous acid treatment, was maintained for 24 h, and returned to a normal rate after 48 h. Cell division was inhibited by hypochlorous acid and chloramines for 48 h and returned to normal 72 h after treatment. Growth arrest was dependent on p53 because it was blocked when cells were transfected with a p53-binding oligonucleotide. We propose that reactive chlorine species will initiate WAF1/CIP1-dependent growth arrest that will counteract their mutagenic effects and minimize the possibility of the malignant transformation of cells surrounding sites of inflammation.
Effectiveness and Toxicity of Gentamicin in an Experimental Model of Pyelonephritis: Effect of the Time of Administration

ABSTRACT Temporal variations in the renal toxicity of aminoglycosides have been reported for experimental animals as well as for humans. In fact, maximal renal toxicity of aminoglycosides was observed when the drug was given during the rest period, while a lower toxicity was observed when the drug was injected during the activity period. The aim of the present study was to evaluate temporal variations in the effectiveness and renal toxicity of gentamicin in an experimental model of pyelonephritis in rats. The experiments were carried out with female Sprague-Dawley rats (185 to 250 g). They had free access to food and water throughout the study and were maintained on a 14-h light–10-h dark cycle. Animals were divided into four groups corresponding to the respective time of induction of pyelonephritis and treatment: 0700, 1300, 1900, and 0100 h. Pyelonephritis was induced by a direct inoculation of Escherichia coli(107 to 108 CFU) in the left kidney. Animals were treated for 3 and 7 days with a single daily dose of gentamicin (20 and 40 mg/kg of body weight, respectively) or saline (NaCl, 0.9%) at either 0700, 1300, 1900, or 0100 h. Animals treated at 0100 h for 3 days with gentamicin (20 mg/kg) showed a significantly lower number of bacteria in their kidneys than did all other groups (P < 0.01). After 7 days of treatment, the efficacy, evaluated by the log CFU per gram of tissue and by the percentage of sterilized kidneys, was also higher when gentamicin was administered at 0100 h. The β-galactosidase and theN-acetyl-β-d-glucosaminidase activities were significantly higher in urine of rats given gentamicin at 1300 h than in urine of rats treated at another time of day (P < 0.05). Gentamicin injected at 1300 h induced a significantly greater increase of [3H]thymidine incorporation into DNA of renal cortex (P < 0.01), a significantly greater inhibition of sphingomyelinase activity (P < 0.05), and significantly more histopathological lesions than the same dose injected at another time of the day. Creatinine and blood urea nitrogen levels in serum were significantly higher (P < 0.05) and the creatinine clearance was significantly lower (P < 0.05) when gentamicin was injected at 1300 h than when it was injected at another time of day. Our data suggest temporal variations in both the toxicity and the effectiveness of gentamicin, the drug being more effective and less toxic when injected during the activity period of the animals.
Pilates-based therapeutic exercise: effect on subjects with nonspecific chronic low back pain and functional disability: a randomized controlled trial.

STUDY DESIGN A randomized controlled trial, prestest-posttest design, with a 3-, 6-, and 12-month follow-up. OBJECTIVES To investigate the efficacy of a therapeutic exercise approach in a population with chronic low back pain (LBP). BACKGROUND Therapeutic approaches developed from the Pilates method are becoming increasingly popular; however, there have been no reports on their efficacy. METHODS AND MEASURES Thirty-nine physically active subjects between 20 and 55 years old with chronic LBP were randomly assigned to 1 of 2 groups. The specific-exercise-training group participated in a 4-week program consisting of training on specialized (Pilates) exercise equipment, while the control group received the usual care, defined as consultation with a physician and other specialists and healthcare professionals, as necessary. Treatment sessions were designed to train the activation of specific muscles thought to stabilize the lumbar-pelvic region. Functional disability outcomes were measured with The Roland Morris Disability Questionnaire (RMQ/RMDQ-HK) and average pain intensity using a 101-point numerical rating scale. RESULTS There was a significantly lower level of functional disability (P = .023) and average pain intensity (P = .002) in the specific-exercise-training group than in the control group following the treatment intervention period. The posttest adjusted mean in functional disability level in the specific-exercise-training group was 2.0 (95% CI, 1.3 to 2.7) RMQ/RMDQ-HK points compared to a posttest adjusted mean in the control group of 3.2 (95% CI, 2.5 to 4.0) RMQ/RMDQ-HK points. The posttest adjusted mean in pain intensity in the specific-exercise-training group was 18.3 (95% CI, 11.8 to 24.8), as compared to 33.9 (95% CI, 26.9 to 41.0) in the control group. Improved disability scores in the specific-exercise-training group were maintained for up to 12 months following treatment intervention. CONCLUSIONS The individuals in the specific-exercise-training group reported a significant decrease in LBP and disability, which was maintained over a 12-month follow-up period. Treatment with a modified Pilates-based approach was more efficacious than usual care in a population with chronic, unresolved LBP.
Gemfibrozil greatly increases plasma concentrations of cerivastatin

Concomitant use of gemfibrozil with statins, particularly with cerivastatin, increases the risk of rhabdomyolysis, but the mechanism of this potentially fatal drug interaction remains unclear. Our aim was to study the effect of gemfibrozil on cerivastatin pharmacokinetics.
Analysis of peripheral leucocyte populations in N'Dama and Boran cattle following a rechallenge infection with Trypanosoma congolense

Summary Monoclonal antibodies, flow cytometry and routine hacmatological techniques were used to analyse circulating leucocyte populations in trypanotoler‐ant (N'Dama) and trypanosusceptible (Boran) cattle following a homologous rechallenge with Trypanosoma congolense clone 1L13‐E3. The N'Damas developed a low, transient parasitaemia and did not develop anaemia. The Borans became parasitaemic and developed chronic anaemia but three of the five animals eventually self‐cured, whilst, a group of primary‐challenged Borans experienced a severe infection characterized by high levels of parasilacmia and acute anaemia.
Liquid gentamicin in bone cement spacers: in vivo antibiotic release and systemic safety in two-stage revision of infected hip arthroplasty.

BACKGROUND Powdered antibiotics are widely used in acrylic bone cement. Liquid antibiotics, however, have rarely been employed. This study investigated the application of liquid gentamicin, a much less costly antibiotic with a broad antimicrobial spectrum, in bone cement to treat musculoskeletal infections. METHODS Forty-two patients undergoing two-stage revision hip arthroplasty for periprosthetic infection were managed with an interim cement spacer loaded with liquid gentamicin (480 mg per 20 mL pack of cement monomer) with or without vancomycin (3.0 g per 40 g pack cement polymer). Serum and aliquots of drainage collected after the first-stage surgery; joint fluid obtained at the time of the second-stage surgery were analyzed for antibiotic concentrations and bioactivity. Antibiotic levels in the peripheral blood and renal function were also monitored. RESULTS Antibiotic levels in joint fluid peaked on the first day after implantation of the spacer and then gradually declined during the first week, with levels of gentamicin and vancomycin reached 43.6 mg/L +/- 12.3 mg/L and 485.5 mg/L +/- 103.5 mg/L, respectively. Bioassay confirmed the antimicrobial activity of the released antibiotics. The systemic antibiotic concentrations were below detectable levels in the majority of patients, and no nephrotoxicity was noted. At a mean 87 days after implantation, antibiotic concentrations in joint fluid remained clinically effective (gentamicin, 5.1 mg/L +/- 2.2 mg/L and vancomycin, 21.6 mg/L +/- 8.5 mg/L). CONCLUSIONS Incorporation of liquid gentamicin in bone cement spacers led to effective drug delivery with systemic safety. Substantial health care dollars could be saved by the use of liquid gentamicin in bone cement to treat musculoskeletal infections.
Predicting child PTSD: the relationship between acute stress disorder and PTSD in injured children.

OBJECTIVE To examine the prevalence of acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in injured children and to evaluate the utility of ASD as a predictor of PTSD. METHOD Children hospitalized for injuries sustained in a traffic crash were enrolled in a prospective study. ASD was assessed in 243 children within 1 month after injury, and PTSD was assessed in 177 of these children 3 or more months after injury. The relationship between ASD and PTSD was examined via correlations between symptom severity scores and calculation of sensitivity, specificity, and positive and negative predictive values for categorical prediction of PTSD from ASD or subsets of ASD symptoms. RESULTS Eight percent of children met the symptom criteria for ASD and another 14% had subsyndromal ASD; 6% met the symptom criteria for PTSD and another 11% had subsyndromal PTSD. ASD and PTSD symptom severity were associated. Sensitivity was low for prediction of child PTSD from child ASD. Subsyndromal ASD was a more effective predictor of PTSD. CONCLUSIONS A substantial minority of injured children are affected by traumatic stress disorders. ASD in children may not be an optimal categorical predictor of PTSD. With increasing attention to early posttrauma services for children, empirically valid assessment/triage models deserve further study.
cuRRBS: simple and robust evaluation of enzyme combinations for reduced representation approaches

Abstract DNA methylation is an important epigenetic modification in many species that is critical for development, and implicated in ageing and many complex diseases, such as cancer. Many cost-effective genome-wide analyses of DNA modifications rely on restriction enzymes capable of digesting genomic DNA at defined sequence motifs. There are hundreds of restriction enzyme families but few are used to date, because no tool is available for the systematic evaluation of restriction enzyme combinations that can enrich for certain sites of interest in a genome. Herein, we present customised Reduced Representation Bisulfite Sequencing (cuRRBS), a novel and easy-to-use computational method that solves this problem. By computing the optimal enzymatic digestions and size selection steps required, cuRRBS generalises the traditional MspI-based Reduced Representation Bisulfite Sequencing (RRBS) protocol to all restriction enzyme combinations. In addition, cuRRBS estimates the fold-reduction in sequencing costs and provides a robustness value for the personalised RRBS protocol, allowing users to tailor the protocol to their experimental needs. Moreover, we show in silico that cuRRBS-defined restriction enzymes consistently out-perform MspI digestion in many biological systems, considering both CpG and CHG contexts. Finally, we have validated the accuracy of cuRRBS predictions for single and double enzyme digestions using two independent experimental datasets.
Strategies for cutting hospital beds: the impact on patient service.

OBJECTIVE To develop insights on the impact of size, average length of stay, variability, and organization of clinical services on the relationship between occupancy rates and delays for beds. DATA SOURCES The primary data source was Beth Israel Deaconess Medical Center in Boston. Secondary data were obtained from the United Hospital Fund of New York reflecting data from about 150 hospitals. STUDY DESIGN Data from Beth Israel Deaconess on discharges and length of stay were analyzed and fit into appropriate queueing models to generate tables and graphs illustrating the relationship between the variables mentioned above and the relationship between occupancy levels and delays. In addition, specific issues of current concern to hospital administrators were analyzed, including the impact of consolidation of clinical services and utilizing hospital beds uniformly across seven days a week rather than five. PRINCIPAL FINDINGS Using target occupancy levels as the primary determinant of bed capacity is inadequate and may lead to excessive delays for beds. Also, attempts to reduce hospital beds by consolidation of different clinical services into single nursing units may be counterproductive. CONCLUSIONS More sophisticated methodologies are needed to support decisions that involve bed capacity and organization in order to understand the impact on patient service.
Heteronormativity hurts everyone: Experiences of young men and clinicians with sexually transmitted infection/HIV testing in British Columbia, Canada

Heteronormative assumptions can negatively influence the lives of young gay and bisexual men, and recent sociological analyses have identified the negative impacts of heteronormativity on heterosexual men (e.g. ‘fag discourse’ targeted at heterosexual adolescents). However, insights into how heteronormative discourses may be (re)produced in clinical settings and how they contribute to health outcomes for gay, bisexual and heterosexual men are poorly understood. This analysis draws on in-depth interviews with 45 men (15–25 years old) and 25 clinicians in British Columbia, Canada, to examine how heteronormative discourses affect sexually transmitted infection testing. The sexually transmitted infection/HIV testing experience emerged as a unique situation, whereby men’s (hetero)sexuality was explicitly ‘interrogated’. Risk assessments discursively linked sexual identity to risk in ways that reinforced gay men as the risky ‘other’ and heterosexual men as the (hetero)normal and, therefore, relatively low-risk patient. This, in turn, alleviated concern for sexually transmitted infection/HIV exposure in heterosexual men by virtue of their sexual identity (rather than their sexual practices), which muted discussions around their sexual health. The clinicians also positioned sexual identities and practices as important ‘clues’ for determining their patients’ social contexts and supports while concurrently informing particular tailored clinical communication strategies. These findings highlight how men’s experiences with sexually transmitted infection/HIV testing can (re)produce heteronormative assumptions and expectations or create opportunities for more equitable gendered relations and discourses.
Fetal weight estimation by ultrasound: comparison of 11 different formulae and examiners with differing skill levels.

PURPOSE Fetal weight is an important predictive parameter of neonatal morbidity and mortality. Precise estimation of fetal weight is therefore a valuable item of information for further prenatal and obstetric management. Many regression formulae for sonographic fetal weight estimation have been published during the last 30 years, which, unfortunately, generally show poor rates of accuracy. The aim of this study was to compare commonly used formulae in different birth weight groups in order to assess whether any of the formulae are more or less favourable. The second purpose was to estimate the role of examiners on the accuracy of fetal weight estimation. MATERIALS AND METHODS 11 different formulae were evaluated in a group of 1941 pregnancies. Each fetus underwent ultrasound examination with complete biometric parameters within seven days before delivery. The assessment was carried out by either experienced or inexperienced sonographers. RESULTS Over the whole weight range and in the subgroup of newborns with a birth weight less than 2500 g (n = 160), two Hadlock regression formulae (including abdominal circumference, femur length, head circumference, biparietal diameter, and abdominal circumference, femur length, biparietal diameter, respectively) showed the best levels of accuracy. Infants with a birth weight between 2500 and 3999 g (n = 1570) were best estimated using the gender-specific Schild formula. Macrosomic newborns (n = 211) were best evaluated using Merz's regression formula. The more skilled sonographers were able to achieve much higher intraclass correlation coefficients for all formulae. CONCLUSION Some regression formulae appear to be favourable within defined weight ranges. Accuracy of the formulae, however, is still unsatisfactory, and new formulae focusing on specific weight ranges (e. g., macrosomic fetuses) are needed. In addition, experience in obstetric ultrasound improves accuracy of fetal weight estimation.