Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolism, Excretion, and Mass Balance of Solithromycin in Humans

ABSTRACT Solithromycin, a novel macrolide and the first fluoroketolide, is being developed as a therapy for community-acquired bacterial pneumonia, with a distinct mechanism that provides activity against macrolide-resistant bacteria. The pharmacokinetics, metabolism, and excretion of solithromycin were studied in healthy male subjects after oral administration of a single 800-mg (∼100-μCi) dose of [14C]solithromycin. Solithromycin was well tolerated, and absorption from the solution occurred with a median time to peak concentration of 4.0 h. Solithromycin and the total radioactivity had similar profiles with no long-lived metabolites. The whole-blood total radioactivity was approximately 75% of the plasma total radioactivity. Recovery was essentially complete (mean, 90.6%), with 76.5% and 14.1% of the dose recovered in feces and urine, respectively. Unchanged solithromycin (CEM-101) was the predominant circulating radioactive component in plasma (77% of the total radioactivity area under the concentration-time curve [AUC]), with two minor plasma metabolites, CEM-214 and CEM-122 (N-acetyl-CEM-101), each accounting for approximately 5% of the total radioactivity. Urinary excretion was predominantly like that of the parent. Solithromycin was primarily eliminated in the feces after extensive metabolism via a complex metabolic pathway with CEM-262 as the major constituent (27.36% of the administered dose). Overall oxidative pathways, presumably carried out mostly by CYP3A4, represented the majority of the metabolism, with N-acetylation present to a lesser extent. No disproportionate human metabolites were observed.
Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer

Background We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial. Methods TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided. Results With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4. Conclusions Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.
Mobile Phone Apps for Behavioral Interventions for At-Risk Drinkers in Australia: Literature Review

Background The mobile technology era has ushered in the use of mobile phone apps for behavioral intervention for at-risk drinkers. Objective Our objective was to review recent research relevant to mobile phone apps that can be used for behavioral intervention for at-risk drinkers in Australia. Methods The inclusion criteria for this review were articles published in peer-reviewed journals from 2001 to 2017 with use of the search terms “smartphone application,” “alcohol,” “substance,” “behavioural intervention,” “electronic health,” and “mobile health. ” Results In total, we identified 103 abstracts, screened 90 articles, and assessed 50 full-text articles that fit the inclusion criteria for eligibility. We included 19 articles in this review. Conclusions This review highlighted the paucity of evidence-based and empirically validated research into effective mobile phone apps that can be used for behavioral interventions with at-risk drinkers in Australia.
Cytosolic Glutamine Synthetase Isozymes Play Redundant Roles in Ammonium Assimilation Under Low-Ammonium Conditions in Roots of Arabidopsis thaliana

Ammonium is a major nitrogen source for plants; it is assimilated into glutamine via a reaction catalyzed by glutamine synthetase (GLN). Arabidopsis expresses four cytosolic GLN genes, GLN1; 1, GLN1; 2, GLN1; 3 and GLN1; 4, in roots. However, the function and organization of these GLN1 isozymes in ammonium assimilation in roots remain unclear. In this study, we aimed to characterize the four GLN1 isozymes. The levels of growth of the wild type and gln1 single and multiple knockout lines were compared in a hydroponic culture at ammonium concentrations of 0.1 and 3 mM. Under the low-ammonium concentration, in single mutants for each GLN1 gene, there was little effect on growth, whereas the triple mutant for GLN1; 1, GLN1; 2 and GLN1; 3 grew slowly and accumulated ammonium. Under the high-ammonium concentration, the single mutant for GLN1; 2 showed 50% decreases in fresh weight and glutamine, whereas the other gln1 single mutants did not show notable changes in the phenotype. The double mutant for GLN1; 1 and GLN1; 2 showed less growth and a lower glutamine concentration than the single mutant for GLN1; 2. Promoter analysis indicated an overlapping expression of GLN1; 1 with GLN1; 2 in the surface layers of the roots. We thus concluded that: (i) at a low concentration, ammonium was assimilated by GLN1; 1, GLN1; 2 and GLN1; 3, and they were redundant; (ii) low-affinity GLN1; 2 could contribute to ammonium assimilation at concentrations ranging from 0.1 to 3 mM; and (iii) GLN1; 1 supported GLN1; 2 within the outer cell layers of the root.
COMMENTS ON THE GONOTYL OF PROCTOCAECUM MACROCLEMIDIS (TKACH AND SNYDER, 2003) N. COMB. (DIGENEA: ACANTHOSTOMIDAE: ACANTHOSTOMINAE), WITH A KEY TO THE GENERA OF ACANTHOSTOMINAE AND NEW PHYLOGENETIC TREE FOR PROCTOCAECUM BAUGH, 1957

The species recently described as Acanthostomum macroclemidis possesses the gonotyl in the form of a solid muscular pad uniquely diagnostic for species of Proctocaecum and is accordingly transferred to that genus. An artificial key to the 5 acanthostomine genera, as well as an updated phylogenetic hypothesis for the 10 known species of Proctocaecum, based on 11 characters and including 2 species described since the last phylogenetic analysis, are presented. The single most parsimonious phylogenetic tree with a consistency index of 87.5% suggests that Proctocaecum originated in Africa and spread to North America and South America before the breakup of Pangaea. As a result, the 2 North American and 1 South American species are most closely related to different African members of the genus. African and Indo-Pacific species inhabit crocodylids; hence, the occurrence of North American species in alligatorids and chelonians and a South American species in alligatorids are the result of host switches.
Season Exerts Differential Effects of Ocean Acidification and Warming on Growth and Carbon Metabolism of the Seaweed Fucus vesiculosus in the Western Baltic Sea

Warming and acidification of the oceans as a consequence of increasing CO2-concentrations occur at large scales. Numerous studies have shown the impact of single stressors on individual species. However, studies on the combined effect of multiple stressors on a multi-species assemblage, which is ecologically much more realistic and relevant, are still scarce. Therefore, we orthogonally crossed the two factors warming and acidification in mesocosm experiments and studied their single and combined impact on the brown alga Fucus vesiculosus associated with its natural community (epiphytes and mesograzers) in the Baltic Sea in all seasons (from April 2013 to April 2014). We superimposed our treatment factors onto the natural fluctuations of all environmental variables present in the Benthocosms in so-called delta-treatments. Thereby we compared the physiological responses of F. vesiculosus (growth and metabolites) to the single and combined effects of natural Kiel Fjord temperatures and pCO2 conditions with a 5 °C temperature increase and/or pCO2 increase treatment (1100 ppm in the headspace above the mesocosms). Responses were also related to the factor photoperiod which changes over the course of the year. Our results demonstrate complex seasonal pattern. Elevated pCO2 positively affected growth of F. vesiculosus alone and/or interactively with warming. The response direction (additive, synergistic or antagonistic), however, depended on season and daylength. The effects were most obvious when plants were actively growing during spring and early summer. Our study revealed for the first time that it is crucial to always consider the impact of variable environmental conditions throughout all seasons. In summary, our study indicates that in future F. vesiculosus will be more affected by detrimental summer heat-waves than by ocean acidification although the latter consequently enhances growth throughout the year. The mainly negative influence of rising temperatures on the physiology of this keystone macroalga may alter and/or hamper its ecological functions in the shallow coastal ecosystem of the Baltic Sea.
Biology and Rearing of Cleruchoides noackae (Hymenoptera: Mymaridae), an Egg Parasitoid for the Biological Control of Thaumastocoris peregrinus (Hemiptera: Thaumastocoridae)

ABSTRACT Cleruchoides noackae Lin and Huber (Hymenoptera: Mymaridae) is a solitary egg parasitoid of Thaumastocoris peregrinus Carpintero and Dellapé (Hemiptera: Thaumastocoridae). The parasitoid was first described in 2009 and its biology and rearing are poorly understood. A key obstacle to the use of C. noackae as a biological control agent has been the ability to consistently rear it under quarantine conditions. This study reports on a series of experiments conducted in quarantine to rear C. noackae and to examine the effects of diet on longevity, per capita reproduction, and progeny sex ratio, as well as to determine development time, and preference and suitability of host eggs of different ages. When supplemented with honey solution, the longevity of C. noackae females increased significantly by 2.4 d and that of males by 1.7 d, relative to the unfed adults. Mean per capita reproduction for the honey-fed wasps was 7.7 offspring per female, with progeny sex ratio slightly skewed toward males. Mean percentage parasitism was 32.2%. C. noackae was capable of parasitizing and completing development from oviposition to adult eclosion within 15.7 d in host eggs between 0 and 5 d old. The ability of C. noackae to parasitize a wide range of host egg ages increases the period of vulnerability of T. peregrinus to attack, increasing its potential efficacy as a biological control agent. The methods and results reported here represent a crucial step in the ongoing efforts to develop this potential biological control system.
The current prevalence of bovine babesiosis and theileriosis infection in Egypt

Egypt, cattle are very important economically because they are the main sources of animal protein and income. Their by-products such as hoof, bones, blood, hides and skin are also variously used (Sansoucy, 1995). Beef is the third most widely consumed meat in the world, accounting for about 25% of meat production worldwide, after pork and poultry at 38% and 30% respectively [1]. Furthermore, beef is an excellent source of complete protein, minerals such as zinc, selenium, phosphorus and iron and the B vitamins. Nowadays Haemoparasitic infections are major public health, veterinary and socio-economic problems in Africa, where they impose a burden on the healthcare infrastructure of both animals and animal handlers in endemic areas.
Association between Picky Eating Behaviors and Nutritional Status in Early Childhood: Performance of a Picky Eating Behavior Questionnaire

Picky eating behaviors are frequently observed in childhood, leading to concern that an unbalanced and inadequate diet will result in unfavorable growth outcomes. However, the association between picky eating behaviors and nutritional status has not been investigated in detail. This study was conducted to assess eating behaviors and growth of children aged 1–5 years from the Seoul Metropolitan area. Primary caregivers completed self-administered questionnaires and 3-day diet records. Differences in the nutrient intake and growth indices between picky and non-picky eaters were tested by analysis of covariance. Children “eating small amounts” consumed less energy and micronutrients (with the exception of calcium intake), but picky behaviors related to a “limited variety” resulted in a significant difference regarding nutrient density for some micronutrients. Children with the behavior of “eating small amounts” had a lower weight-for-age than that of non-picky eaters; especially, the older children with the behaviors of “eating small amounts” or “refusal of specific food groups” had lower height-for-age compared with non-picky eaters. These results suggest that specific picky eating behaviors are related to different nutrient intake and unfavorable growth patterns in early childhood. Thus, exploration of potential interventions according to specific aspects of picky eating and their efficacy is required.
Metabolic Profiling of Dendrobium officinale in Response to Precursors and Methyl Jasmonate

Alkaloids are the main active ingredients in the medicinal plant Dendrobium officinale. Based on the published genomic and transcriptomic data, a proposed terpenoid indole alkaloid (TIA) biosynthesis pathway may be present in D. officinale. In this study, protocorm-like bodies (PLBs) with a high-yielding production of alkaloids were obtained by the optimization of tryptophan, secologanin and methyl jasmonate (MeJA) treatment. The results showed that the total alkaloid content was 2.05 times greater than that of the control group when the PLBs were fed with 9 µM tryptophan, 6 µM secologanin and 100 µM MeJA after 36 days. HPLC analysis showed that strictosidine synthase (STR) activity also increased in the treated plants. A total of 78 metabolites were identified using gas chromatography-mass spectrometry (GC-MS) in combination with liquid chromatography-mass spectrometry (LC-MS) methods; 29 differential metabolites were identified according to the multivariate statistical analysis. Among them, carapanaubine, a kind of TIA, exhibited dramatically increased levels. In addition, a possible underlying process of the metabolic flux from related metabolism to the TIA biosynthetic pathway was enhanced. These results provide a comprehensive view of the metabolic changes related to alkaloid biosynthesis, especially TIA biosynthesis, in response to tryptophan, secologanin and MeJA treatment.
Statin Therapy Reduces Future Risk of Lower-Limb Amputation in Patients With Diabetes and Peripheral Artery Disease

Context Although there is evidence to support the beneficial effects of statins on major cardiovascular events, few studies address the protective effect of statins on limb outcome. Objective To investigate whether the use of statin is associated with a risk reduction in lower-extremity amputation in type 2 diabetes mellitus (DM) patients with peripheral arterial disease (PAD). Design Observational cohort study. Setting A nationwide DM database in Taiwan from 2000 to 2011. Patients A total of 69,332 patients aged ≥20 years with DM and PAD were identified. Intervention Patients were divided into three groups: 11,409 patients were statin users, 4430 patients used nonstatin lipid-lowering agents, and 53,493 patients were nonusers. Main Outcome Measures The primary outcome was lower-extremity amputation. Secondary outcomes were in-hospital cardiovascular death and all-cause mortality. Results Compared with nonusers, statin users were associated with lower risks of lower-extremity amputation [adjusted hazard ration (aHR), 0.75; 95% confidence interval (CI), 0.62 to 0.90], in-hospital cardiovascular death (aHR, 0.78; 95% CI, 0.69 to 0.87), and all-cause mortality (aHR, 0.73; 95% CI, 0.69 to 0.77). In the propensity score matching analysis, the effect of statin on the risk of lower-extremity amputation was consistent. Only statin users were associated with the risk reduction of lower-extremities amputation (HR, 0.77; 95% CI, 0.61 to 0.97) and cardiovascular death (HR, 0.78; 95% CI, 0.68 to 0.89) when taking competing risk of death into consideration. Conclusions Compared with statin nonusers who were never treated with lipid-lowering drugs, this study found that statin users had a lower risk of lower-extremity amputation and cardiovascular death in patients with DM and PAD.
A Fully Decentralized Control of Grid-Connected Cascaded Inverters

This letter proposes a decentralized power balance control for grid-connected cascaded modular inverters without any communication, and each module makes decisions based on its own local information. In contrast, the conventional methods are usually centralized control and depend on real-time communication. Thus, the proposed scheme has advantages of improved reliability and decreased costs. The overall system stability is analyzed, and the stability condition is derived as well. The feasibility of the proposed method is verified by simulation.
A Study on the Waiting Time for the First Employment of Arts Graduates in Sri Lanka

 Abstract — Transition from tertiary level education to employment is one of the challenges that many fresh university graduates face after graduation. The transition period or the waiting time to obtain the first employment varies with the socio-economic factors and the general characteristics of a graduate. Compared to other fields of study, Arts graduates in Sri Lanka, have to wait a long time to find their first employment. The objective of this study is to identify the determinants of the transition from higher education to employment of these graduates using survival models. The study is based on a survey that was conducted in the year 2016 on a stratified random sample of Arts graduates from Sri Lankan universities who had graduated in 2012. Among the 469 responses, 36 (8%) waiting times were interval censored and 13 (3%) were right censored. Waiting time for the first employment varied between zero to 51 months. Initially, the log-rank and the Gehan-Wilcoxon tests were performed to identify the significant factors. Gender, ethnicity, GCE Advanced level English grade, civil status, university, class received, degree type, sector of first employment, type of first employment and the educational qualifications required for the first employment were significant at 10%. The Cox proportional hazards model was fitted to model the waiting time for first employment with these significant factors. All factors, except ethnicity and type of employment were significant at 5%. However, since the proportional hazard assumption was violated, the lognormal Accelerated failure time (AFT) model was fitted to model the waiting time for the first employment. The same factors were significant in the AFT model as in Cox proportional model.
Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria

Getting to the guts of mosquito control Malaria persistently evades our best efforts to eliminate it. Pike et al. genetically modified malaria vector mosquitoes to be more immune-resistant to infection by the parasite, which altered the composition of the mosquitoes' gut bacteria. Genetically modified male (female) mosquitoes preferentially mated with wild-type females (males). Ten generations later, the genetically modified mosquitoes constituted 90% of a caged population without losing resistance to the malaria parasite. In an alternative strategy, Wang et al. engineered mosquitoes' gut bacteria. A strain of nonpathogenic bacteria, AS1, was both sexually and transgenerationally transmitted. The strain infected a laboratory population of mosquitoes and persisted for at least three generations. AS1 engineered to inhibit malaria parasite development in the midgut could do so without handicapping the mosquitoes. Science, this issue p. 1396, p. 1399 An engineered bacterial symbiont supplied to mosquitoes effectively spreads combinations of antimalaria parasite genes. The huge burden of malaria in developing countries urgently demands the development of novel approaches to fight this deadly disease. Although engineered symbiotic bacteria have been shown to render mosquitoes resistant to the parasite, the challenge remains to effectively introduce such bacteria into mosquito populations. We describe a Serratia bacterium strain (AS1) isolated from Anopheles ovaries that stably colonizes the mosquito midgut, female ovaries, and male accessory glands and spreads rapidly throughout mosquito populations. Serratia AS1 was genetically engineered for secretion of anti-Plasmodium effector proteins, and the recombinant strains inhibit development of Plasmodium falciparum in mosquitoes.
Population genetic structure of cotton pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae) using mitochondrial cytochrome oxidase I (COI) gene sequences from India

Abstract Pink bollworm (PBW), Pectinophora gossypiella is one of the most destructive pest’s globally inflicting huge economic losses in cotton even during later stages of crop growth. In the present investigation, the population genetic structure, distribution, and genetic diversity of P. gossypiella in cotton growing zones of India using partial mitochondrial DNA cytochrome oxidase-I (COI) gene was addressed. The overall haplotype (Hd), number of nucleotide differences (K), and nucleotide diversity (π) were 0.3028, 0.327, and 0.00047, respectively which suggest that entire population exhibited low level of genetic diversity. Zone-wise clustering of population revealed that central zone recorded low level of Hd (0.2730) as compared to north (0.3619) and south (0.3028) zones. The most common haplotype (H1) reported in all 19 locations could be proposed as ancestral/original haplotype. This haplotype with one mutational step formed star-like phylogeny connected with 11 other haplotypes. The phylogenetic relationship studies revealed that most haplotypes of populations are closely related to each other. Haplotype 5 was exclusively present in Dharwad (South zone) shared with populations of Hanumangarh and Bathinda (North zone). The result indicated that there is no isolation by distance effect among the Indian populations of PBW. The present study reports a low genetic diversity among PBW populations of India and H1, as ancestral haplotype from which other haplotypes have evolved suggests that the migration and dispersal over long distance and invasiveness are major factors.