Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety of Ovaleap® (Follitropin Alfa) in Infertile Women Undergoing Superovulation for Assisted Reproductive Technologies: A Multinational Comparative, Prospective Cohort Study

Background Ovaleap® (follitropin alfa), a recombinant human follicle stimulating hormone, is a biosimilar medicinal product to Gonal-f® and is used for ovarian stimulation. The main objective of this study was to assess the safety and effectiveness of Ovaleap® compared to Gonal-f® in one treatment cycle in routine clinical practice. Methods Safety of Ovaleap® Follitropin alfa in Infertile women undergoing superovulation for Assisted reproductive technologies (SOFIA) was a prospective cohort study conducted in six European countries. Eligible patients were infertile women undergoing superovulation for assisted reproductive technology, who were administered Ovaleap® or Gonal-f® for ovarian stimulation and were naïve to follicle stimulating hormone treatment. The recruitment ratio was 1:1. The primary endpoint was incidence proportion of ovarian hyperstimulation syndrome (OHSS) and the secondary endpoint was OHSS severity (Grades I, II, III). The effect of risk factors or potential confounders on the odds ratio for OHSS incidence as well as treatment effect on OHSS incidence was explored using univariate logistic regression. Pregnancy and live birth rates were also assessed. Results A total of 408 women who were administered Ovaleap® and 409 women who were administered Gonal-f® were eligible for analysis. The incidence proportion of OHSS was 5.1% (95% CI: 3.4, 7.7) in the Ovaleap® cohort and 3.2% (95% CI: 1.9, 5.4) in the Gonal-f® cohort. This difference in OHSS incidence proportion between the two cohorts was not statistically significant neither before (p = 0.159) nor after univariate adjustment for each potential confounder (p > 0.05). The incidence proportion of OHSS severity grades was similar in the two treatment groups (3.4% versus 2.0% for Grade I, 1.2% versus 1.0% for Grade II, and 0.5% versus 0.2% for Grade III, in the Ovaleap® and Gonal-f® cohorts, respectively), without a significant statistical difference (p = 0.865, for each grade). Among patients who had embryo transfer, clinical pregnancy rates were 33% and 31% and live birth rates were 27% and 26%, in the two cohorts, respectively. Conclusions Findings from the SOFIA study indicate that the incidence proportions of OHSS and OHSS severity, as well as pregnancy and live birth rates, are similar between Ovaleap® and Gonal-f® treatments and corroborate the safety and effectiveness of Ovaleap® as a biosimilar to Gonal-f®.
Monocytes From Patients With Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis Are Hyperresponsive to Interferon Gamma

Objective To investigate the activation of the IFNγ signaling pathway in monocytes of patients with secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS) and to evaluate whether levels of phosphorylated STAT1 represent a biomarker for the identification of patients at early stages of the disease. Methods Fresh whole blood samples from pediatric patients with active sHLH/MAS, not receiving (n=10) and receiving glucocorticoids (n=14) at time of sampling, were prospectively collected. As disease control groups, patients with active systemic juvenile idiopathic arthritis (sJIA) without MAS, patients with sHLH/MAS in remission and patients with other rheumatic diseases were also sampled. Whole blood cells were left unstimulated or stimulated with increasing concentrations of IFNγ for 10 minutes and the intracellular Tyrosine (701)-phosphorylated STAT1 (pSTAT1) levels were evaluated in monocytes by flow cytometry. Results Monocytes from untreated sHLH/MAS patients showed significantly higher basal levels of pSTAT1 compared to those observed in monocytes from glucocorticoid-treated sHLH/MAS patients and from all the other disease controls. In addition, a significant increase in responsiveness to IFNγ, as assessed by increased levels of pSTAT1 following ex vivo stimulation, was observed in monocytes from untreated sHLH/MAS patients. pSTAT1 levels in monocytes distinguished patients with sHLH/MAS not treated with glucocorticoids from patients with active sJIA or with other rheumatic diseases [AUC, 0.93; 95% confidence interval 0.85-1.00, p<0.001]. Statistically significant correlations between IFNG mRNA levels in whole blood cells, circulating IFNγ levels and pSTAT1 levels in sHLH/MAS monocytes were found. Conclusion Our data demonstrating higher basal levels of pSTAT1 as well as a hyperreactivity to IFNγ stimulation in monocytes from patients with sHLH/MAS point to perturbations in the activation of downstream IFNγ signaling pathway as a contributor to the hyperinflammation occurring in these patients. Finally, the observation that glucocorticoids affect pSTAT1 levels in vivo, makes it difficult to consider the measurement of pSTAT1 levels as a biomarker to identify patients at early stages of sHLH/MAS in clinical practice.
Plant Associated Rhizobacteria for Biocontrol and Plant Growth Enhancement

Crop disease remains a major problem to global food production. Excess use of pesticides through chemical disease control measures is a serious problem for sustainable agriculture as we struggle for higher crop productivity. The use of plant growth promoting rhizobacteria (PGPR) is a proven environment friendly way of controlling plant disease and increasing crop yield. PGPR suppress diseases by directly synthesizing pathogen-antagonizing compounds, as well as by triggering plant immune responses. It is possible to identify and develop PGPR that both suppress plant disease and more directly stimulate plant growth, bringing dual benefit. A number of PGPR have been registered for commercial use under greenhouse and field conditions and a large number of strains have been identified and proved as effective biocontrol agents (BCAs) under environmentally controlled conditions. However, there are still a number of challenges before registration, large-scale application, and adoption of PGPR for the pest and disease management. Successful BCAs provide strong theoretical and practical support for application of PGPR in greenhouse production, which ensures the feasibility and efficacy of PGPR for commercial horticulture production. This could be pave the way for widespread use of BCAs in agriculture, including under field conditions, to assist with both disease management and climate change conditions.
Early-Onset Sepsis in Neonates - A Population-Based Study in South-West Norway From 1996 to 2018

Background: The epidemiology of early-onset sepsis (EOS) may change over time. Longitudinal surveillance of causative pathogens, antibiotic susceptibility patterns and antibiotic therapy is important for optimal therapy strategies. Objectives: To describe the incidence of culture-confirmed EOS, causative pathogens, antibiotic susceptibility patterns and antibiotic therapy over a 23-year period. Methods: Retrospective population-based study from a single-center neonatal intensive care unit at Stavanger University Hospital, Norway, covering a population in South-West Norway, during the 23-year period 1996–2018. Results: Of 104,377 live born infants, 101 infants (0.97/1,000) had culture-confirmed EOS; 89 with Gram positive and 12 with Gram-negative bacteria. The EOS-attributable mortality was 6/101 (5.8%). For the three most prevalent pathogens the incidences were; Group B streptococcus (GBS) 0.57/1,000, Escherichia coli 0.11/1,000 and viridans group streptococci (VGS) 0.10/1,000. GBS was the most common pathogen (59/93; 63%) in infants with gestational age (GA) ≥ 28 weeks. In contrast, among extremely preterm infants (GA <28 weeks) the incidence of E. coli infection was higher than for GBS infection. The second most common bacterial pathogens causing EOS among term infants were VGS. There was no change in the incidence of EOS for the entire study period, but from 2000 to 2018 there was a mean decline in EOS by 6% per year (95% CI 1%−10%) (p = 0.019). The incidences of GBS and E. coli did not change during the study period. The initial empirical antibiotic regimen for EOS was in all cases a combination of benzylpenicillin or ampicillin and an aminoglycoside, but in 21/101 (21%) of cases a broad-spectrum antibiotic was either added or substituted this regimen. In 2/101 (2%) EOS cases, the pathogens were nonsusceptible to the empirical antibiotic regimen. All E. coli isolates were susceptible to aminoglycosides. Conclusion: GBS was the most common causative pathogens in EOS, but E. coli dominated in infants with GA <28 weeks. There was no change in the incidence of EOS during the entire study period. The current empiric regimen with benzylpenicillin and gentamicin provides a very high coverage for EOS in our setting.
Antimicrobial Susceptibility and Genomic Analysis of Aliarcobacter cibarius and Aliarcobacter thereius, Two Rarely Detected Aliarcobacter Species

Aliarcobacter cibarius and Aliarcobacter thereius are two rarely detected Aliarcobacter species. In the study, we analyzed the antimicrobial susceptibility and provide detailed insights into the genotype and phylogeny of both species using whole-genome sequencing. Thermophilic Campylobacter species are the most common bacterial foodborne pathogens causing gastroenteritis in humans worldwide. The genus Aliarcobacter is part of the Campylobacteraceae family and includes the species Aliarcobacter butzleri, Aliarcobacter cryaerophilus, Aliarcobacter skirrowii, and the rarely described Aliarcobacter cibarius, Aliarcobacter faecis, Aliarcobacter lanthieri, Aliarcobacter thereius, and Acrobarter trophiarum. Aliarcobacter are emergent enteropathogens and potential zoonotic agents. Here, we generated, analyzed, and characterized whole-genome sequences of Aliarcobacter cibarius and Aliarcobacter thereius. They were isolated from water poultry farms in Germany, cultured and identified by MALDI-TOF MS. With PCR the identity was verified. Antibiotic susceptibility testing was carried out with erythromycin, ciprofloxacin, doxycycline, tetracycline, gentamicin, streptomycin, ampicillin, and cefotaxime using the gradient strip method (E-test). Whole-genome sequences were generated including those of reference strains. Complete genomes for six selected strains are reported. These provide detailed insights into the genotype. With these, we predicted in silico known AMR genes, virulence-associated genes, and plasmid replicons. Phenotypic analysis of resistance showed differences between the presence of resistance genes and the prediction of phenotypic resistance profiles. In Aliarcobacter butzleri, the nucleotide sequence of the gyrA gene (DQ464331) can show a signature mutation resulting in an amino acid change T85>I. Acrobarter cibarius and Acrobarter thereius showed the same gene as assessed by similarity annotation of the mutations 254C>G. Most of the isolates were found to be sensitive to ciprofloxacin. The ciprofloxacin-resistant Aliarcobacter thereius isolate was associated with the amino acid change T85>I. But this was not predicted with antibiotic resistance databases, before. Ultimately, a phylogenetic analysis was done to facilitate in future outbreak analysis.
Autobiographical Memory and Social Identity in Autism: Preliminary Results of Social Positioning and Cognitive Intervention

Autobiographical memory (AM) is closely linked to the self-concept, and fulfills directive, identity, social, and adaptive functions. Individuals with autism spectrum disorder (ASD) are now known to have atypical AM, which may be closely associated with social communication difficulties. This may result in qualitatively different autobiographical narratives, notably regarding social identity. In the present study, we sought to investigate this concept and develop a cognitive intervention targeting individuals with ASD. First, 13 adolescents with ASD and 13 typically developing adolescents underwent an AM interview featuring an original coding system designed to analyze the social self. We observed that the narratives produced by the ASD group focused more on the family than on extended social spheres, compared with those of the comparison group. Moreover, participants with ASD did not include themselves in the social groups they mentioned, and produced more references to others, compared with typically developing participants. Second, we designed a cognitive intervention program consisting of individual and group sessions that targeted AM. We conducted a pilot study among three adolescents with ASD aged 12, 16, and 17 years. Preliminary results showed that the program increased extra-family narrative references by the two youngest adolescents, who produced more social integration markers. Our study of autobiographical narratives yielded interesting findings about social positioning in ASD and showed how AM can be targeted in rehabilitation programs as a vector of social interaction.
Naturalistic and Uncontrolled Pilot Study on the Efficacy of Vortioxetine in Binge Eating Disorder With Comorbid Depression

Background: Binge eating disorder (BED) is clinically relevant by virtue of the global impairment, poor quality of life, and increased overall medical morbidity. The high comorbidity with psychiatric disorders, particularly depression, has received attention as a possible mediator of the poor outcome. Further, BED and depression share cognitive dysfunctions. This naturalistic and uncontrolled pilot study aimed at evaluating the efficacy of vortioxetine (VTX) on depressive symptoms in patients with BED, secondly the efficacy in improving a broad array of executive functions, and third to explore the effect on eating behavior and body weight. Methods: This pilot study involved 30 patients with BED and comorbid MDD, treated with VTX for 24 weeks. Assessments were run at baseline (t0), 4 (t1), 8 (t2), 12 (t3), and 24 (t4) weeks. Changes in depressive symptoms (HDRS and BDI), executive functions, eating behaviors (binge frequency and severity, night eating, food addiction), and body weight were estimated after treatment with VTX through GLM. Results: Significant improvements emerged after treatment with VTX in: depression (HDRS p < 0.001; BDI p = 0.002) regardless the dose of VTX and first diagnosis (BED/MDD), working memory (RAVLT acquisition p = 0.01, delay recall p < 0.001, RCFT percentage of recall p = 0.01, and Attentional Matrices p = 0.05), binge days frequency (p < 0.001), binge eating severity (BES p < 0.001), night eating (p = 0.001), food addiction (YFAS 2.0 p = 0.039), and body weight (p = 0.039). The improvement in depressive symptoms was associated with the concurrent improvement in night eating as assessed by the I-NEQ. Conclusions: VTX can be a valid therapeutic choice for patients with BED with comorbid depression in controlling the depressive symptoms, working memory, and eating behavior. Indeed, by acting on affective symptoms, neurocognitive functioning, and eating behaviors, it confirms the results already obtained with VTX in other disorders, expanding them to BED.
Phenotypic Changes in T Cell and Macrophage Subtypes in Perivascular Adipose Tissues Precede High-Fat Diet-Induced Hypertension

Perivascular adipose tissue (PVAT) may connect adiposity to hypertension because of its vasoactive functions and proximity to blood vessels. We hypothesized that immune cell changes in PVATs precede the development of high fat diet (HFD)-induced hypertension. Both sexes of Dahl S rat become equally hypertensive when fed a HFD. Further, both sexes would have similar immune cell composition in PVATs with the development and progression of hypertension. Male and female Dahl S rats were fed a regular (10% calories from fat; CD) diet or a HFD (60%) from weaning. PVATs from around the thoracic aorta (APVAT) and small mesenteric vessels (MRPVAT) were harvested at 10 weeks (pre-hypertensive), 17 weeks (onset), or 24 (hypertensive) weeks on diet. RNA-sequencing in MRPVAT at 24 weeks indicated sex-differences with HFD (>CD) and diet-differences in males (>females). The top 2 out of 7 immune processes with the maximum number of differentially expressed genes (DEGs) were associated with immune effector processes and leukocyte activation. Macrophages and T cells (and their activation status), neutrophils, mast, B and NK cells were measured by flow cytometry. Sex-specific changes in the number of CD4 memory T cells (males > females) and M2-like macrophages (females > males) in PVATs occur with a HFD before hypertension developed. Sex-differences became more prominent with the development and progression of hypertension, driven by the diet (HFD > CD). These findings suggest that though the magnitudes of increased blood pressure were equivalent in both sexes, the associated phenotypic changes in the immune subsets within the PVATs were different in the male vs. the female with the development and progression of hypertension. Graphical Abstract Sex-differences in immune cell activation status (numbers/mean fluorescence intensity) in MRPVAT (A) and APVAT (B). (Key: e.g., at 10 weeks, higher density/MFI of M1-like macrophages occur in CD females vs. CD males in MRPVAT.) Differences in mean arterial pressure between HFD and respective CD-fed rats are presented as mm Hg [Supplementary Figure 1 and as measured by radiotelemetry (Fernandes et al., 2018)] with 10, 17, and 24 weeks on diet.
Studies on hydrothermally synthesised zinc oxide nanorod arrays for their enhanced visible light photocatalysis

Photocatalytic activities of hydrothermally synthesised ZnO nanorod films in synergism with visible light have been studied. Influence of each of the synthesis parameters, like concentration of precursor solution, relative concentration of hexamine and zinc nitrate, growth time, growth temperature, pre-growth seeding, post-growth annealing, concentration and pH of the contaminant suspension, and light source have been investigated. Appraisal of photocatalytic efficiencies of all the synthesised samples have been done on degradation of aqueous Methylene Blue (MB) solution under artificial/ambient light. Maximum photocatalytic activities were obtained when ZnO nanorods were synthesised with equimolar concentration of 10 mM hexamine and zinc nitrate grown for 15 hr at 90°C with post-synthesis annealing at 250°C in air. Solar irradiation was found more effective than artificial white light while the activity increased exponentially with pH value of the contaminant suspension.
Modeling in situ phytoplankton absorption from total absorption spectra in productive inland marine waters

Dissolved and suspended materials in the ocean modify the in‐water light field by absorbing and scattering photons. Direct measurement of inherent optical properties of individual optical constituents is difficult since the constituents themselves cannot all be separated. A model was developed to resolve in situ phytoplankton absorption from a measured in situ total absorption spectrum which includes water, dissolved organics, particulate detritus, and phytoplankton. The model was tested on a set of absorption spectra obtained from the productive waters around the San Juan Islands, Washington. Results indicate that the model can predict the spectral shape of phytoplankton absorption (r2 > 0.9) and total photon absorption by phytoplankton with <27% error. Total photon absorption can be used to estimate phytoplankton absorption of light energy for improved primary production predictions, given submarine light field measurements or model calculations. Although developed for high chlorophyll waters, the model parameters are easily modified for various Case 1 optical domains.
Assessment of The Stretched Laminar Flamelet Approach For Nonpremixed Turbulent Combustion

Abstract An assessment is sought of the stretched laminar flamelet approach, in particular as far as its capability to account for finite-rate chemistry effects in nonpremixed turbulent combustion is concerned. It is used here with the k - e - 9 turbulence model, in order to obtain a computational model which can easily be implemented on current codes. A particularly convenient form is adopted, which limits the computational overhead over nonreacting computations to a minimum. An appropriate plane is identified to check the combustion regime in the different regions of the flame. Test cases are reported which involve quantities most directly affected by finite-rate chemistry, namely mean and variance of OH, CO and NO concentration in different flames. Numerical predictions worked out with the present model are compared to experimental results and predictions by other authors. Results confirm the potentialities of the proposed approach, which in addition can beextended to include insofar neglected effects.
ANTINOCICEPTIVE AND GASTROPROTECTIVE EFFECT OF THE CRUDE ETHANOLIC EXTRACTS OF EXCOECARIA AGALLOCHA LINN.

The effect of alcoholic extracts of bark from Excoecaria. agallocha Linn. (Family: Euphorbiaceae) was evaluated in experimental models of pain and ulceration. Crude extracts of Excoecaria agallocha (300 mg/kg dose) showed maximum time needed for the response against thermal stimuli (6.72±0.43 seconds) which is comparable to diclofenac sodium (8.20±0.21seconds) in the hot plate test. Hot tail immersion test also showed similar results as in hot plate test. The bark extracts at 500 and 250 mg/kg showed significant reduction in acetic acid induced writhings in mice with a maximum effect of 53.87% reduction at 500 mg/kg dose. The effect produced by the alcoholic extract at the highest dose was comparable to that of diclofenac sodium at 100 mg/kg (70.56%). It has also been seen anti-ulcerogenic activity compared to acetylsalicylic acid, which may be due to the protective effect of the extract. The result suggest that the analgesic effect of the extract as claimed in folklore medicine, which may be mediated via both peripheral and central mechanism having gastro-protective effect.
Safe Approximation - An Efficient Solution for a Hard Routing Problem

The Disjoint Connecting Paths problem and its capacitated generalization, called Unsplittable Flow problem, play an important role in practical applications such as communication network design and routing. These tasks are NP-hard in general, but various polynomial-time approximations are known. Nevertheless, the approximations tend to be either too loose (allowing large deviation from the optimum), or too complicated, often rendering them impractical in large, complex networks. Therefore, our goal is to present a solution that provides a relatively simple, efficient algorithm for the unsplittable flow problem in large directed graphs, where the task is NP-hard, and is known to remain NP-hard even to approximate up to a large factor. The efficiency of our algorithm is achieved by sacrificing a small part of the solution space. This also represents a novel paradigm for approximation. Rather than giving up the search for an exact solution, we restrict the solution space to a subset that is the most important for applications, and excludes only a small part that is marginal in some well-defined sense. Specifically, the sacrificed part only contains scenarios where some edges are very close to saturation. Since nearly saturated links are undesirable in practical applications, therefore, excluding near saturation is quite reasonable from the practical point of view. We refer the solutions that contain no nearly saturated edges as safe solutions, and call the approach safe approximation. We prove that this safe approximation can be carried out efficiently. That is, once we restrict ourselves to safe solutions, we can find the exact optimum by a randomized polynomial time algorithm.