Miracle-dz/UniFAR-FTUs huggingface dataset:
The ovarian reserve as measured by the anti-Müllerian hormone is not diminished in patients with rheumatoid arthritis compared to the healthy population.

OBJECTIVES Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyse the relationship between fertility in RA female patients and AMH. The aim of present study is to determine the AMH serum concentrations in a long-standing RA patient group and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs. METHODS Serum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynaecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student's t-test or Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. p-values <0.005 were considered significant. RESULTS The median age was similar in AR and control groups (37.4±6.23 vs. 37.3±6.27 p=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of AMH was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (p=0.608). Neither disease activity (p=0.862), nor current or previous bDMARDs treatments (p=0.871) were associated with AMH levels. However, a negative linear correlation was observed between AMH and IL-10 levels (p=0.033). CONCLUSIONS Our study shows that ovarian reserve determined by AMH serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, AMH levels were not affected by disease activity, however, a significant correlation was observed between AMH and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have been recommended in RA pregnant patients.
THERMAL MODELLING OF SMALL BIRDS EXPOSED TO MICROWAVE RADIATION (2.45 GHz CW)

(2) The model was created from physiological and biophysical energy-exchange data from the published literature and was calibrated with the body temperature responses of restrained birds exposed to microwave irradiances of 250 and 500 W m-2. (3) The model predicts that tolerance to microwave radiation for a bird should be positively correlated with its mass and that ambient temperature is the environmental variable that has most influence on the level of tolerance for microwave radiation. (4) Other predictions are that tolerance to microwave radiation should be dependent on ambient relative humidity at high ambient temperatures, that 2.45 GHz CW radiation is absorbed by a small bird with an average solar absorptance at approximately twice the rate that solar radiation is absorbed, and that a small change in wind speed will have considerable effect on tolerance when wind speeds are low (< 10 km h-').
HOXC10 promotes tumour metastasis by regulating the EMT-related gene Slug in ovarian cancer

The mortality rate of ovarian cancer is the highest among gynaecological cancers, primarily due to metastatic symptoms. Recent studies have shown that HOX genes are crucial in tumour progression, but the underlying mechanisms remain unclear. Here, HOXC10 expression was examined in ovarian cancer tissues. The function of HOXC10 in ovarian cancer metastasis was investigated in vitroand via intraperitoneal injection in vivo. A total of 158 ovarian cancer patients with adequate records were enrolled for analysis. HOXC10 was associated with metastasis and poor prognosis in ovarian cancer. In vitro, HOXC10 overexpression promoted ovarian cancer cell migration. Moreover, HOXC10 positively regulated Slug expression, altering the migration ability of cancer cells. Furthermore, our study showed that miR-222-3p was a suppressor of HOXC10. In vivo, a decrease in hepatic metastasis was seen in xenograft mice harbouring tumours with stable HOXC10 overexpression after miR-222-3p agomir (an overexpression reagent) injection. This study provides the first evidence that HOXC10 promotes ovarian cancer metastasis by regulating the transcription of the EMT-related gene Slug. Moreover, we found that HOXC10 is regulated by miR-222-3p. These data highlight the crucial role of HOXC10 in enhancing ovarian cancer metastasis and may provide a therapeutic target for ovarian cancer.
Cellrox deep red® for the detection of oxidative stress in ram sperm by in vitro induction

The sperm cell is highly susceptible to damage caused by oxidative stress (OS). It is one of the factors that are associated with male infertility. Therefore, it is very important to find new analyses methods that are easier to perform and read. The CellROX Deep Red Reagent® fluorescent probe (CAT 10422, Life Technologies, New York, USA) presents a number of advantages, but there are no published studies of its use on sperm. Thus, the aim of the present study is to evaluate the effectiveness of this method in samples of ram semen induced to in vitro OS. The analyses were conducted in four ejaculates of three White Dorper rams (n=12) that were between 14 and 24 months of age. Semen was collected by artificial vagina. The ejaculates were treated in T0, T50 and T100. T0 corresponded to the control semen sample that was not submitted to OS induction, T50 corresponded to the semen sample content 50% without OS induction and 50% inducted to OS, and T100 corresponded to the semen sample that was entire submitted to OS induction. The OS induction was performed by adding iron sulfate (4 mM) and ascorbic acid (20 mM). For the preparation of the technique, 200 μL (25x106 spermatozoa/mL) of each semen sample (T0, T50 and T100) was used and 0.5 μL of CellROX® (1 mM) and 2 μL of Hoechst 33342 (2.5 mg/mL, Life Technologies) were added. The semen sample was incubated at 37° C/30 minutes. After incubation, the sample was centrifuged at 2,000g/5 minutes, the supernatant was removed and the pellet was resuspended in 200 μL of TALP sperm. The cells were classified as sperm under mild or no OS (unstained midpiece), sperm under moderate OS (midpiece stained pale red), and sperm under intense OS (midpiece stained strong red). Data obtained from T0, T50 and T100 treatments were evaluated by analysis of variance (ANOVA) and the means were compared using Fisher's LSD test. OS data in T0, T50 and T100 treatments were subjected to linear regression analysis by Statview software (Stat View 1998, SAS Institute Inc., Cary, NC, USA). The experimental model used was: Y = a + bX, wherein Y is the estimative of OS due to treatment, a is the linear regression coefficient corresponding to the value of Y when X is 0, b is the regression coefficient for the percent of X on the response Y and X is the treatment. A significant difference (p<0.0001) in OS was observed between T0 (0.25±0.11%a), T50 (16.37±1.75%b) and T100 (30.83±3.57%c) treatments. As there were differences between the treatments, the results were submitted to linear regression analysis, resulting in the equation Y=12.33+2.381x and determination coefficient was of 0.728. Thus, it is possible to conclude that the CellROX® Deep Red probe is able to detect ROS production in spermatozoa, using the ovine species as the experimental model and the OS induction model with iron sulfate and ascorbic acid.
Variation in Fusarium graminearum and cultivar resistance to wheat scab

Understanding variation in pathogen virulence and cultivar resistance is important for development of effective strategies for breeding wheat cultivars resistant to scab. Six isolates of Fusarium graminearum from China and the United States were compared for variation in cultural characteristics and virulence on nine wheat cultivars with different degrees of resistance to scab. The isolates varied in their cultural characteristics and ability to cause scab, but there was no consistent specificity of cultivar resistance or pathogen virulence. Therefore, a mixture of local isolates is an appropriate inoculum to screen for scab resistance. Subculturing the fungus on potato dextrose agar for eight generations did not reduce virulence. In the greenhouse, eight cultivars were tested five times over 3 years by inoculating one central floret in a spike with an Indiana isolate of the fungus. Cultivars Ning 7840, Sumai 49, Fu 5114, and Sumai 3 were consistently resistant. The fungus spread from the inoculated spikelet to noninoculated spikelets of resistant cultivars in less than 20% of the plants, and spread was not evident until 12 days after inoculation. All plants of susceptible cultivar Clark showed spread of infection, and symptoms appeared on noninoculated spikelets by 8 days after inoculation. Sudden blight on the top part of the spike may be an important characteristic of highly susceptible cultivars. Measurement of spread of scab within a spike is a stable and reliable estimate of cultivar resistance.
Neural and molecular mechanisms underlying female mate choice decisions in vertebrates

ABSTRACT Female mate choice is a dynamic process that allows individuals to selectively mate with those of the opposite sex that display a preferred set of traits. Because in many species males compete with each other for fertilization opportunities, female mate choice can be a powerful agent of sexual selection, often resulting in highly conspicuous traits in males. Although the evolutionary causes and consequences of the ornamentation and behaviors displayed by males to attract mates have been well studied, embarrassingly little is known about the proximate neural mechanisms through which female choice occurs. In vertebrates, female mate choice is inherently a social behavior, and although much remains to be discovered about this process, recent evidence suggests the neural substrates and circuits underlying other fundamental social behaviors (such as pair bonding, aggression and parental care) are likely similarly recruited during mate choice. Notably, female mate choice is not static, as social and ecological environments can shape the brain and, consequently, behavior in specific ways. In this Review, we discuss how social and/or ecological influences mediate female choice and how this occurs within the brain. We then discuss our current understanding of the neural substrates underlying female mate choice, with a specific focus on those that also play a role in regulating other social behaviors. Finally, we propose several promising avenues for future research by highlighting novel model systems and new methodological approaches, which together will transform our understanding of the causes and consequences of female mate choice. Summary: Current knowledge about how female mate choice occurs within the brain is discussed along with future avenues of research that will broaden our current knowledge of this process.
Deep Learning for Automatic Segmentation of Hybrid Optoacoustic Ultrasound (OPUS) Images

The highly complementary information provided by multispectral optoacoustics and pulse-echo ultrasound have recently prompted development of hybrid imaging instruments bringing together the unique contrast advantages of both modalities. In the hybrid optoacoustic ultrasound (OPUS) combination, images retrieved by one modality may further be used to improve the reconstruction accuracy of the other. In this regard, image segmentation plays a major role as it can aid improving the image quality and quantification abilities by facilitating modeling of light and sound propagation through the imaged tissues and surrounding coupling medium. Here, we propose an automated approach for surface segmentation in whole-body mouse OPUS imaging using a deep convolutional neural network (CNN). The method has shown robust performance, attaining accurate segmentation of the animal boundary in both optoacoustic and pulse-echo ultrasound images, as evinced by quantitative performance evaluation using Dice coefficient metrics.
Sleep duration and risk of overall and 22 site‐specific cancers: A Mendelian randomization study

Studies of sleep duration in relation to the risk of site‐specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site‐specific cancers using the Mendelian randomization (MR) design. Single‐nucleotide polymorphisms associated with the sleep traits identified from a genome‐wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site‐specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short‐sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15‐4.30; P = .018), pancreas (OR, 2.18; 95% CI, 1.32‐3.62; P = .002) and colorectum (OR, 1.48; 95% CI, 1.12‐1.95; P = .006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22‐0.99; P = .047). Suggestive evidence of association of genetic liability to long‐sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25‐0.79; P = .005) and kidney cancer (OR, 0.44; 95% CI, 0.21‐0.90; P = .025) was observed. However, none of these associations passed the multiple comparison threshold and two‐sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site‐specific cancers. Further MR studies are required.
Do visual and auditory stimulus‐specific response modulation reflect different mechanisms of neocortical plasticity?

Stimulus response modulation (SRM) of sensory evoked potentials represents a promising method as a non‐invasive index of long‐term potentiation (LTP)‐like synaptic plasticity in the human sensory cortices. As of today, however, no consensus exists regarding which experimental parameters elicit the most robust SRM response. The aim of the current study was twofold; firstly, we aimed to replicate former studies demonstrating visual SRM in healthy adults. Second, we integrated visual and auditory stimuli within the same SRM recording session to assay potential cross‐modal associations. Such an association between modalities would strengthen the assumption that the SRM effect reflects common mechanisms underlying synaptic plasticity rather than reflecting modality‐specific phenomena. A replication of previous findings showing robust potentiation of the visual evoked potential was evident, supporting the majority of previous work using similar paradigms, lending further support to the notion that high‐frequent visual stimulation is a viable probe into LTP‐like synaptic plasticity in the human visual cortex. The auditory evoked potentials (AEPs) did not, however, fully replicate previous work, though a significant increase of temporally later AEP components was found. In contrast to our hypothesis, there were no significant within‐subject cross‐modality correlations between the visual and auditory SRM. This lack of significant association might suggest that auditory and visual SRM depend on different mechanisms, and that further SRM studies on non‐invasive LTP‐like synaptic plasticity should focus on optimizing paradigms within the visual modality.
Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease

Abstract The study aims to evaluate the potency of two hundred natural antiviral phytocompounds against the active site of the Severe Acquired Respiratory Syndrome - Coronavirus − 2 (SARS-CoV-2) Main-Protease (Mpro) using AutoDock 4.2. 6. The three- dimensional crystal structure of the Mpro (PDB Id: 6LU7) was retrieved from the Protein Data Bank (PDB), the active site was predicted using MetaPocket 2.0. Food and Drug Administration (FDA) approved viral protease inhibitors were used as standards for comparison of results. The compounds theaflavin-3-3’-digallate, rutin, hypericin, robustaflavone, and (-)-solenolide A with respective binding energy of −12.41 (Ki = 794.96 pM); −11.33 (Ki = 4.98 nM); −11.17 (Ki = 6.54 nM); −10.92 (Ki = 9.85 nM); and −10.82 kcal/mol (Ki = 11.88 nM) were ranked top as Coronavirus Disease − 2019 (COVID-19) Mpro inhibitors. The interacting amino acid residues were visualized using Discovery Studio 3.5 to elucidate the 2-dimensional and 3-dimensional interactions. The study was validated by i) re-docking the N3-peptide inhibitor-Mpro and superimposing them onto co-crystallized complex and ii) docking decoy ligands to Mpro. The ligands that showed low binding energy were further predicted for and pharmacokinetic properties and Lipinski’s rule of 5 and the results are tabulated and discussed. Molecular dynamics simulations were performed for 50 ns for those compounds using the Desmond package, Schrödinger to assess the conformational stability and fluctuations of protein-ligand complexes during the simulation. Thus, the natural compounds could act as a lead for the COVID-19 regimen after in-vitro and in- vivo clinical trials. Communicated by Ramaswamy H. Sarma Graphical Abstract
An interferon lambda 4-associated variant in the hepatitis C virus RNA polymerase affects viral replication in infected cells

Host IFNL4 haplotype status contributes to the development of chronic hepatitis C virus infection in individuals who are acutely infected with the virus. In silico studies revealed that specific amino acid variants at multiple sites on the HCV polyprotein correlate with functional single nucleotide polymorphisms (SNPs) in the IFNL4 locus. Thus, SNPs at the IFNL4 locus may select variants that influence virus replication and thereby outcome of infection. Here, we examine the most significantly IFNL4-associated amino acid variants that lie in the ‘Lambda (L) 2 loop’ of the HCV NS5B RNA polymerase. L2 loop variants were introduced into both sub-genomic replicon and full-length infectious clones of HCV and viral replication examined in the presence and absence of exogenous IFNλ4. Our data demonstrate that while mutation of NS5B L2 loop affects replication, individual IFNL4-associated variants have modest but consistent effects on replication both in the presence and absence of IFNλ4. Given the strong genetic association between these variants and IFNL4, these data suggest a nuanced effect of each individual position on viral replication, the combined effect of which might mediate resistance to the effects of IFNλ4.
Aspects of the development of yolk spheres in the hen's oöcyte, studied by electron microscopy

The yolk of the hen9s egg is composed mainly of proteins, lipids and water (see reviews by Bellairs, 1964; Williams, 1966). It consists essentially of yolk spheres floating in an aqueous protein medium (Grodzinski, 1939; Bellairs, 1961). The raw materials from which the yolk is formed are synthesized in the liver of the laying hen and pass from there in the blood to the ovary (see reviews by Romanoff, 1960; Bellairs, 1964). Each oocyte is enclosed in a capsule of follicle cells, and all the raw materials pass through this capsule before they enter the oocyte. The morphological changes that take place within the oocyte as the yolk spheres form have been described previously by light microscopists who have produced a variety of theories to explain their observations. Formerly, it was supposed that yolk arose in the so-called ‘yolk nucleus’, or Balbiani body, which lies alongside the cell nucleus, but few would subscribe to this theory now.
An inverted CAV1 (caveolin 1) topology defines novel autophagy-dependent exosome secretion from prostate cancer cells

ABSTRACT CAV1 (caveolin 1) expression and secretion is associated with prostate cancer (PCa) disease progression, but the mechanisms underpinning CAV1 release remain poorly understood. Numerous studies have shown CAV1 can be secreted within exosome-like vesicles, but antibody-mediated neutralization can mitigate PCa progression; this is suggestive of an inverted (non-exosomal) CAV1 topology. Here we show that CAV1 can be secreted from specific PCa types in an inverted vesicle-associated form consistent with the features of bioactive CAV1 secretion. Characterization of the isolated vesicles by electron microscopy, single-molecule fluorescence microscopy and proteomics reveals they represent a novel class of exosomes ~40 nm in diameter containing ~50-60 copies of CAV1 and, strikingly, are released via a non-canonical secretory macroautophagy/autophagy pathway. This study provides novel insights into a mechanism whereby CAV1 translocates from a normal plasma membrane distribution to an inverted secreted form implicated in PCa disease progression. Abbreviations: 3-MA: 3-methyladenine; APEX: a modified soybean ascorbate peroxidase; ATG5: autophagy related 5; ATG9A: autophagy related 9A; ATG12: autophagy related 12; BHK: baby hamster kidney; C-exosomes: caveolin-exosomes; CAMKK2/CAMKKβ: calckum/calmodulin dependent protein kinase kinase 2; CAV1: caveolin 1; DAB: 3,3′-diaminobenzidine; DAPK: death associated protein kinase; EEA1: early endosome antigen 1; EM: electron microscopy; FCS: fluorescence correlation spectroscopy; GBP: GFP/YFP-binding peptide; GFP: green fluorescent protein; GOLGA2: golgin A2; ILVs: intralumenal vesicles; LC3: microtubule-associated protein 1 light chain 3; MBP: maltose binding protein; MTORC1: mechanistic target of rapamycin kinase complex 1; MVBs: multivesicular bodies; PBS: phosphate-buffered saline; PCa: prostate cancer; PI3K: phosphoinositide 3-kinase; PM: plasma membrane; SFM: serum-free medium; TSG101: tumor susceptibility 101; WCL: whole cell lysates; WT: wild type; YFP: yellow fluorescent protein; βoG: β-octylglucoside
Protective Role of Glutathione Against Peroxynitrite-Mediated DNA Damage During Acute Inflammation.

Inflammation is an immune response to protect against various types of infections. When unchecked, acute inflammation can be life-threatening, as seen with the current corona virus pandemic. Strong oxidants, such as peroxynitrite produced by immune cells, are major mediators of the inflammation-associated pathogenesis. Cellular thiols play important roles in mitigating inflammation-associated macromolecular damage including DNA. Herein, we have demonstrated a role of glutathione (GSH) and other thiols in neutralizing the effect of peroxynitrite-mediated DNA damage through stable GSH-DNA adduct formation. Our observation supports the use of thiol supplements as a potential therapeutic strategy against severe Covid-19 cases and a Phase II (NCT04374461) open-label clinical trial launched in early May 2020 by the Memorial Sloan Kettering Cancer Center.