Miracle-dz/UniFAR-FTUs huggingface dataset:
Exenatide regulates pancreatic islet integrity and insulin sensitivity in baboons

The glucagon-like peptide 1 receptor agonist exenatide improves glycemic control by several and not completely understood mechanisms. Herein, we examined the effects of chronic intravenous exenatide infusion on insulin sensitivity, band a-cell function and relative volumes, islet cell apoptosis and replication in nondiabetic non-human primates (baboons). At baseline, baboons received a 2-step hyperglycemic clamp followed by an Larginine bolus (HC/A). After HC/A, baboons underwent a partial pancreatectomy (tail removal) and received a continuous exenatide (n = 12) or saline (n = 12) infusion for 13 weeks. At the end of treatment, HC/A was repeated and the remnant pancreas (head-body) harvested. Insulin sensitivity increased dramatically after exenatide treatment and was accompanied by a decrease in insulin and C-peptide secretion, while the insulin secretion/insulin resistance (disposition) index increased by approximately 2-fold. b-, a-, and d-cell relative volumes in exenatide-treated baboons were significantly increased compared to saline-treated controls, primarily as the result of increased islet cell replication. Features of cellular stress and secretory dysfunction were present in islets of saline-treated baboons and absent in islets of exenatide-treated baboons. In conclusion, chronic administration of exenatide exerts proliferative and cytoprotective effects on b-, a-, and dcells and produces a robust increase in insulin sensitivity in non-human primates. Research Endocrinology
Maternal malaria but not schistosomiasis is associated with a higher risk of febrile infection in infant during the first 3 months of life: A mother-child cohort in Benin

Background Malaria and schistosomiasis represent two of the most prevalent and disabling parasitic infections in developing countries. Few studies have evaluated the effect of maternal schistosomiasis and malaria in the peri-conceptional period on infant’s risk of infection. Methods In Benin, women were followed from the preconception period until delivery. Subsequently, their children were followed from birth to 3 months of age. Pre-pregnancy malaria, malaria in pregnancy (MiP)—determined monthly using a thick blood smear—and urinary schistosomiasis—determined once before pregnancy and once at delivery using urine filtration—were the main maternal exposures. Infant’s febrile infection (fever with respiratory, gastrointestinal and/or cutaneous clinical signs anytime during follow-up) was the main outcome. In a secondary analysis, we checked the relation of malaria and schistosomiasis with infant’s hemoglobin (Hb) concentration. Both effects were separately assessed using logistic/mixed linear regression models. Results The prevalence of MiP was 35.7% with 10.8% occurring during the 1st trimester, and the prevalence of schistosomiasis was 21.8%. From birth to 3 months, 25.3% of infants had at least one episode of febrile infection. In multivariate analysis, MiP, particularly malaria in the 1st trimester, was significantly associated with a higher risk of infant’s febrile infection (aOR = 4.99 [1.1; 22.6], p = 0.03). In secondary results, pre-pregnancy malaria and schistosomiasis were significantly associated with a lower infant’s Hb concentration during the first 3 months. Conclusion We evidenced the deleterious effect of maternal parasitic infections on infant’s health. Our results argue in favor of the implementation of preventive strategies as early as in the peri-conception.
Sequential screening for lung cancer in a high-risk group: randomised controlled trial

Background Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. Methods LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). Results 1568 participants were randomised during 2007–2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75–1.95) or 0.82 (95% CI 0.52–1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. Conclusions Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening. While low-dose CT is now preferred for lung cancer screening, our randomised trial of smokers with COPD showed that a proposed sequential policy using sputum testing to select who receives low-dose CT and autofluorescence bronchoscopy was ineffective http://bit.ly/2JZujnx
Sensitive Detection of Gas-phase Glyoxal by Electron Attachment Reaction Ionization Mass Spectrometry.

Glyoxal (GLY) acts as a key contributor to tropospheric ozone production and secondary organic aerosol (SOA) formation on local to regional scales. The detection of GLY provides useful indicators of fast photochemistry occurring in the lower troposphere. The fast and sensitive detection of GLY is thus important while traditional chemical ionization such as proton-transfer reaction (PTR) is extremely limited by the poor detection limit and the extensive fragmentation. To address these limitations, electron attachment reaction (EAR) ionization was applied to detect GLY. The generation of parent anion (GLY-) without fragmentation was observed and cryogenic photoelectron imaging spectroscopy further characterized the structure of GLY-. The detection limit was estimated to be as low as (52 ± 1) pptv (parts per trillion by volume) with one minute measurements. Other components in ambient air, such as water, carbon dioxide and trace gases (acetone, propanal, etc.) have no effect on the detection of GLY. The EAR ionization is more promising than the PTR ionization in detecting GLY. The detection of GLY in ambient air by the EAR ionization has been demonstrated.
COMPARISON OF MINIATURIZED PERCUTANEOUS NEPHROLITHOTOMY AND STANDARD PERCUTANEOUS NEPHROLITHOTOMY IN SECONDARY PATİENTS: A RANDOMIZED PROSPECTIVE STUDY.

AIM We aimed to compare the efficacy and safety of mini percutaneous nephrolithotomy (mPNL) and standard PNL in a group of patients who had history of PNL and/or open renal surgery (secondary patients). MATERIALS AND METHODS The study included 148 patients who underwent secondary PNL between November 2016 and September 2018. The patients with kidney stone≥ 2 cm were included in the study. Patients were randomly divided into two groups as mPNL and sPNL. For both groups, demographic data, stone characteristics, operative and postoperative data were recorded prospectively. Data were analyzed at 95% confidence interval and considered significant when p value was less than 0.05. RESULTS A total of 148 (76 mPNL, 72 sPNL) patients with a history of PNL and/or open surgery were included in the study. The mean duration of operation was longer in mPNL (106.9 vs 91.2 min, p:0.016). The mean duration of fluoroscopy in mPNL was shorter (4.4 vs 5.3 min, p:0.021). The tubeless procedure was higher in the mPNL (21.1 vs 2.8%, p:0.001). The hemoglobin drop was less in mPNL (0.7 vs 1.4 gr/dl, p:0.011). Duration of nephrostomy and hospitalization was longer in sPNL (p:0.001 and p:0.005, respectively). The success rate in the mPNL group was higher compared to the standard PNL group; however this difference was statistically insignificant (75.0 vs 72.2%, p:0.558). CONCLUSION mPNL is superior to standard PNL in terms of hemoglobin drop, duration of fluoroscopy, applicability of a tubeless procedure and duration of nephrostomy and hospitalization among secondary patients. Duration of operation was found to be longer for mPNL. Success rate was higher in the mPNL group, though not statistically significant.
Loss of interleukin‐10 exacerbates early Type‐1 diabetes‐induced bone loss

Type‐1 diabetes (T1D) increases systemic inflammation, bone loss, and risk for bone fractures. Levels of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) are decreased in T1D, however their role in T1D‐induced osteoporosis is unknown. To address this, diabetes was induced in male IL‐10 knockout (KO) and wild‐type (WT) mice. Analyses of femur and vertebral trabecular bone volume fraction identified bone loss in T1D‐WT mice at 4 and 12 weeks, which in T1D‐IL‐10‐KO mice was further reduced at 4 weeks but not 12 weeks. IL‐10 deficiency also increased the negative effects of T1D on cortical bone. Osteoblast marker osterix was decreased, while osteoclast markers were unchanged, suggesting that IL‐10 promotes anabolic processes. MC3T3‐E1 osteoblasts cultured under high glucose conditions displayed a decrease in osterix which was prevented by addition of IL‐10. Taken together, our results suggest that IL‐10 is important for promoting osteoblast maturation and reducing bone loss during early stages of T1D.
Nipped‐A regulates the Drosophila circadian clock via histone deubiquitination

Psychiatric diseases are often accompanied by circadian disruptions, but the molecular underpinnings remain largely unclear. To address this, we screened genes that have been previously reported to be associated with psychiatric diseases and found that TRRAP, a gene associated with schizophrenia, is involved in circadian rhythm regulation. Knocking down Nipped‐A, the Drosophila homolog of human TRRAP, leads to lengthened period of locomotor rhythms in flies. Molecular analysis demonstrates that NIPPED‐A sets the pace of the clock by increasing the mRNA and protein levels of core clock genes timeless (tim) and Par domain protein 1ε (Pdp1ε). Furthermore, we found that NIPPED‐A promotes the transcription of tim and Pdp1ε possibly by facilitating deubiquitination of histone H2B via the deubiquitination module of the transcription co‐activator Spt‐Ada‐Gcn5 acetyltransferase complex. Taken together, these findings reveal a novel role for NIPPED‐A in epigenetic regulation of the clock.
Complete Genome Sequence of Lysinibacillus sp. Strain SGAir0095, Isolated from Tropical Air Samples Collected in Singapore

Lysinibacillus sp. strain SGAir0095 was isolated from tropical air samples collected in Singapore, and its complete genome was sequenced with a hybrid strategy using single-molecule real-time sequencing and short reads. The genome consists of one chromosome of 4.14 Mbp and encompasses 3,885 protein-coding genes, 39 rRNAs, and 101 tRNAs. ABSTRACT Lysinibacillus sp. strain SGAir0095 was isolated from tropical air samples collected in Singapore, and its complete genome was sequenced with a hybrid strategy using single-molecule real-time sequencing and short reads. The genome consists of one chromosome of 4.14 Mbp and encompasses 3,885 protein-coding genes, 39 rRNAs, and 101 tRNAs.
First Draft Genome Sequence of Wheat Spot Blotch Pathogen Bipolaris sorokiniana BS_112 from India, Obtained Using Hybrid Assembly

Bipolaris sorokiniana is a devastating fungal pathogen causing spot blotch of wheat. We report here the first draft genome of Bipolaris sorokiniana strain BS_112 from India using sequence reads from the Ion Torrent, Illumina HiSeq, and Nanopore platforms. The genome size was estimated at 35.64 Mb with an average G+C content of 50.20%. ABSTRACT Bipolaris sorokiniana is a devastating fungal pathogen causing spot blotch of wheat. We report here the first draft genome of Bipolaris sorokiniana strain BS_112 from India using sequence reads from the Ion Torrent, Illumina HiSeq, and Nanopore platforms. The genome size was estimated at 35.64 Mb with an average G+C content of 50.20%.
Agreement between the Cochrane risk of bias tool and Physiotherapy Evidence Database (PEDro) scale: A meta-epidemiological study of randomized controlled trials of physical therapy interventions

Background The Cochrane risk of bias (CROB) tool and Physiotherapy Evidence Database (PEDro) scale are used to evaluate risk of bias of randomized controlled trials. We assessed the level of agreement between the instruments. Methods We searched the Cochrane Library to identify trials included in systematic reviews evaluating physical therapy interventions. For trials that met our inclusion criteria (primary reference in Cochrane review, review used CROB (2008 version), indexed in PEDro), CROB items were extracted from the reviews and PEDro items and total score were downloaded from PEDro. Kappa statistics were used to determine the agreement between CROB and PEDro scale items that evaluate similar constructs (e.g., randomization). The total PEDro score was compared to the CROB summary score (% of items met) using an Intraclass Correlation Coefficient. Sensitivity analyses explored the impact of the CROB “unclear” category and variants of CROB blinding items. Kappa statistics were used to determine agreement between different thresholds for “acceptable” risk of bias between CROB and PEDro scale summary scores. Results We included 1442 trials from 108 Cochrane reviews. Agreement was “moderate” for three of the six CROB and PEDro scale items that evaluate similar constructs (allocation concealment, participant blinding, assessor blinding; Kappa = 0.479–0.582). Agreement between the summary scores was “poor” (Intraclass Correlation Coefficient = 0.285). Agreement was highest when the CROB “unclear” category was collapsed with “high” and when participant, personnel and assessor blinding were evaluated separately in CROB. Agreement for different thresholds for “acceptable” risk of bias between CROB and PEDro summary scores was, at best, “fair”. Conclusion There was moderate agreement for half of the PEDro and CROB items that evaluate similar constructs. Interpretation of the CROB “unclear” category and variants of the CROB blinding items substantially influenced agreement. Either instrument can be used to quantify risk of bias, but they can’t be used interchangeably.
Evaluating the impact of policies recommending PrEP to subpopulations of men and transgender women who have sex with men based on demographic and behavioral risk factors

Introduction Developing guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings. Methods We use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies. Results A policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%). Conclusions These findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings.
Synteny and phylogenetic analysis of paralogous thyrostimulin beta subunits (GpB5) in vertebrates

At some point early in the vertebrate lineage, two whole genome duplication events (1R, 2R) took place that allowed for the diversification and sub-/neo-functionalization of the glycoprotein hormones (GpHs). All jawed vertebrates possess the GpHs luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH), each of which are heterodimers with a common alpha subunit and unique beta subunits. In 2002, a novel glycoprotein hormone named thyrostimulin was described to have unique GpA2 and GpB5 subunits that were homologous to the vertebrate alpha and beta subunits. The presence of GpA2 and GpB5 in representative protostomes and deuterostomes indicates their ancestry in the GpH family. There are several reports of GpH subunit evolution, but none have included GpA2 and GpB5 for species in each major vertebrate class. Thus, we addressed the ancestry of two paralogous GpB5 subunits (GpB5a and GpB5b) that were previously only recognized in two teleost species. Our search for orthologous GpB5a and GpB5b sequences in representative vertebrates and phylogenetic analysis, in addition to the currently published evolutionary scenarios of the GpH family, supports that GpB5a and GpB5b are paralogs that arose from the first vertebrate whole genome duplication event (1R). Syntenic analysis supports lineage specific losses of GpB5a in chondrichthyes, basal actinopterygians, and tetrapods, and retention in coelacanth and teleosts. Additionally, we were unable to identify GpA2 transcripts from tilapia mRNA, suggesting that this species does not produce heterodimeric thyrostimulin. While the conserved or even species-specific functional role of thyrostimulin or its individual subunits are still unknown in vertebrates, the analyses presented here provide context for future studies on the functional divergence of the GpH family.
Distribution patterns of fungal taxa and inferred functional traits reflect the non-uniform vertical stratification of soil microhabitats in a coastal pine forest

ABSTRACT In boreal systems, soil profiles typically consist of distinct stratified horizons, with organic layers at the surface overlying deeper mineral horizons providing microhabitat variation along a depth gradient, and vertical stratification of fungal communities along such soil profiles is commonly observed. We studied fungal community structure in a coastal pine forest along a gradient of decreasing influence from the coast. In this system, the vertical stratification pattern of soil microhabitats (defined here as organic, mineral with roots and mineral without roots: O, MR and MN, respectively) is non-uniform; organic horizons are sometimes buried under drifting sand dunes. Our results show that soil microhabitats are distinct with respect to physiochemical characteristics, community composition and OTU richness. While community composition was partly related to depth and distance from the coastal forest edge, microhabitat appeared to have the strongest influence. A closer inspection of the OTUs with the highest relative sequence abundance within each microhabitat revealed that microhabitats support functionally distinct fungal communities with respect to trophic mode and growth morphology. These results suggest that in coastal pine forests, variation in soil microhabitats contributes to the high fungal diversity found belowground and may play an important role in optimizing nutrient cycling.
Neighbouring plants modify maize-root foraging for phosphorus: coupling nutrients and neighbours for improved nutrient-use efficiency.

Nutrient-distribution and neighbours can impact plant growth, but how neighbours shape root foraging strategy for nutrients is unclear. Here, we explore new patterns of plant foraging for nutrients as affected by neighbours to improve nutrient-acquisition. Maize (Zea mays) was grown alone (maize), or with maize (maize/maize) or faba bean (Vicia faba) (maize/faba bean) as a neighbour on one side and with or without phosphorus (P)-rich zone on the other in a rhizo-box experiment. Maize demonstrated root avoidance in maize/maize, with reduced root-growth in 'shared' soil, and increased growth away from its neighbours. Inversely, maize proliferated roots in the proximity of neighbouring faba bean roots that had greater P availability in the rhizosphere (due to citrate and acid phosphatase exudation) than maize roots. Maize proliferated more roots, but spent less time to reach, and grow out of, the P-patches away from neighbours in maize/maize than maize/faba bean. Maize shoot-biomass and P uptake were greater in the heterogeneous P treatment with maize/faba bean than maize/maize. The foraging strategy of maize roots is an integrated function of heterogeneous distribution of nutrients and neighbouring plants, consequently improving nutrient acquisition and maize growth. Understanding the foraging patterns is critical for optimizing nutrient management in crops.
A cross-sectional survey of the pharmacy workforce in general practice in Scotland.

BACKGROUND In Scotland, there has been significant investment in pharmacy teams in general medical practices over recent years, aligned to current government policy. OBJECTIVES To characterize the national pharmacy workforce including activities undertaken, perceived competence and confidence, as well as perception of integration of the intervention. METHODS A cross-sectional survey of all pharmacists and pharmacy technicians in general practices. Survey items were demographics, activities undertaken and experiences. The NoMAD tool (Improving the Normalization of Complex Interventions) was included as a measure of perspectives of implementation. Post-piloting, a questionnaire link was sent to all pharmacists (n = 471) and pharmacy technicians (n = 112). A total NoMAD score was obtained by assigning 1 (strongly disagree) to 5 (strongly agree) to each item. RESULTS Responses were received from 393 (83.4%) pharmacists and 101 (91.8%) pharmacy technicians. Three quarters of pharmacists (74.6%) and pharmacy technicians (73.3%) had been qualified for over 10 years. Two-thirds of pharmacists (68.4%) were independent prescribers, with three quarters (72.3%) currently prescribing. Respondents worked in a median of two practices and were providing a range of activities including medication/polypharmacy reviews, medicines reconciliation, prescribing efficiencies and training. Respondents reported high levels of competence and confidence (median 8, scale 0-10 highest). Median NoMAD total score (scale 20-100 highest, Cronbach's alpha 0.89) was 80 for pharmacists and 75 for pharmacy technicians, P ≤ 0.001. CONCLUSIONS The general practice pharmacy workforce in Scotland is experienced, well-qualified and integrated within general practices, delivering a range of activities. These findings have implications for workforce planning and future education and training.