Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic Sub-Classification of Ovarian Clear Cell Carcinoma Revealed by Distinct Mutational Signatures

Simple Summary It is well-known that ovarian clear cell carcinoma presents unique molecular traits in comparison to other ovarian cancer subtypes, partially reflecting on chemotherapy resistance. Here, by investigating a panel of cancer-associated genes in a Danish population, our data showed that patients were further stratified into four different molecular subgroups: “PIK3CA”, “ARID1A”, “PIK3CA-ARID1A” and “Undetermined”, in regard to the presence of mutation on these genes. Somatic signature investigation further revealed that those subgroups share common features, such as ageing and defective MMR, whilst also bearing unique signatures. These findings suggest that different groups possess specific molecular backgrounds, indicating that such individuals could better benefit from more individualized therapy regimens. Abstract Ovarian clear cell carcinoma (OCCC) is characterized by dismal prognosis, partially due to its low sensitivity to standard chemotherapy regimen. It is also well-known for presenting unique molecular features in comparison to other epithelial ovarian cancer subtypes. Here, we aim to identify potential subgroups of patients in order to (1) determine their molecular features and (2) characterize their mutational signature. Furthermore, we sought to perform the investigation based on a potentially clinically relevant setting. To that end, we assessed the mutational profile and genomic instability of 55 patients extracted from the Gynecologic Cancer Database (DGCD) by using a panel comprised of 409 cancer-associated genes and a microsatellite assay, respectively; both are currently used in our routine environment. In accordance with previous findings, ARID1A and PIK3CA were the most prevalent mutations, present in 49.1% and 41.8%, respectively. From those, the co-occurrence of ARID1A and PIK3CA mutations was observed in 36.1% of subjects, indicating that this association might be a common feature of OCCC. The microsatellite instability frequency was low across samples. An unbiased assessment of signatures identified the presence of three subgroups, where “PIK3CA” and “Double hit” (with ARID1A and PIK3CA double mutation) subgroups exhibited unique signatures, whilst “ARID1A” and “Undetermined” (no mutations on ARID1A nor PIK3CA) subgroups showed similar profiles. Those differences were further indicated by COSMIC signatures. Taken together, the current findings suggest that OCCC presents distinct mutational landscapes within its group, which may indicate different therapeutic approaches according to its subgroup. Although encouraging, it is noteworthy that the current results are limited by sample size, and further investigation on a larger group would be crucial to better elucidate them.
MicroRNAs in the Onset of Schizophrenia

Mounting evidence implicates microRNAs (miRNAs) in the pathology of schizophrenia. These small noncoding RNAs bind to mRNAs containing complementary sequences and promote their degradation and/or inhibit protein synthesis. A single miRNA may have hundreds of targets, and miRNA targets are overrepresented among schizophrenia-risk genes. Although schizophrenia is a neurodevelopmental disorder, symptoms usually do not appear until adolescence, and most patients do not receive a schizophrenia diagnosis until late adolescence or early adulthood. However, few studies have examined miRNAs during this critical period. First, we examine evidence that the miRNA pathway is dynamic throughout adolescence and adulthood and that miRNAs regulate processes critical to late neurodevelopment that are aberrant in patients with schizophrenia. Next, we examine evidence implicating miRNAs in the conversion to psychosis, including a schizophrenia-associated single nucleotide polymorphism in MIR137HG that is among the strongest known predictors of age of onset in patients with schizophrenia. Finally, we examine how hemizygosity for DGCR8, which encodes an obligate component of the complex that synthesizes miRNA precursors, may contribute to the onset of psychosis in patients with 22q11.2 microdeletions and how animal models of this disorder can help us understand the many roles of miRNAs in the onset of schizophrenia.
Difference in Body Weight at Breeding Affects Reproductive Performance in Replacement Beef Heifers and Carries Consequences to Next Generation Heifers

Simple Summary The effect of prebreeding feeding to attain 55% vs. 65% of mature cow body weight (MBW; 545 kg) at breeding on the reproductive performance of beef heifers and its offspring was investigated. Angus-cross dam heifers from weaning were randomly fed to attain 55% (n = 1622) vs. 65% (n = 1578) of MBW and off-spring (F1) heifers born to dam heifers in both 55% (n = 1285) vs. 65% (n = 1324) groups were fed to attain 65% of MBW. Results showed that restricted feeding negatively affected puberty, breeding season pregnancy and 21-day calving rates. F1 generation heifers that were fed normal diets but were born to dams that were fed restricted diets also had reduced puberty, breeding season pregnancy and 21-day calving rates. In conclusion, restricted feeding during the prebreeding period of dam heifers reduced post-pubertal fertility and fertility of their heifer offspring that were fed normal prebreeding diets. Abstract Nutrition imprinting carries consequences across generations. The effect of 55% vs. 65% of mature cow body weight (MBW; 545 kg) at breeding on the reproductive performance of heifers and their offspring was investigated. Angus-cross dam heifers were randomly fed to attain 55% (n = 1622) vs. 65% (n = 1578) of MBW, and offspring (F1) heifers born to dam heifers [55% (n = 1285) vs. 65% (n = 1324)] were fed to attain 65% of MBW. Bodyweight and reproductive indices were recorded throughout the study. In dam heifers, puberty (44% vs. 53%), breeding season pregnancy (86.4% vs. 90.6%) and 21-day calving rates (55.2% vs. 65.4%) did vary, but dystocia rate (8.7% vs. 9.0%) did not differ between 55% and 65% MBW groups. Puberty (49.2% vs. 58.2%), breeding season pregnancy (87.2% vs. 92.8%) and 21-day calving rates (53.8% vs. 64.1%) did differ (p < 0.05), but dystocia rate (8.4 vs. 9.2%) did not differ between F1 heifer groups. In conclusion, 55% of MBW at breeding negatively affected the reproductive performance of heifers and its offspring heifers. The recommendation is to feed heifers a balanced diet to reach 65% of MBW at breeding with consideration of production traits.
Chronic Lithium Treatment Affects Anxious Behaviors and theExpression of Serotonergic Genes in Midbrain Raphe Nuclei of Defeated Male Mice

There is experimental evidence that chronic social defeat stress is accompanied by the development of an anxiety, development of a depression-like state, and downregulation of serotonergic genes in midbrain raphe nuclei of male mice. Our study was aimed at investigating the effects of chronic lithium chloride (LiCl) administration on anxiety behavior and the expression of serotonergic genes in midbrain raphe nuclei of the affected mice. A pronounced anxiety-like state in male mice was induced by chronic social defeat stress in daily agonistic interactions. After 6 days of this stress, defeated mice were chronically treated with saline or LiCl (100 mg/kg, i.p., 2 weeks) during the continuing agonistic interactions. Anxiety was assessed by behavioral tests. RT-PCR was used to determine Tph2, Htr1a, Htr5b, and Slc6a4 mRNA expression. The results revealed anxiolytic-like effects of LiCl on social communication in the partition test and anxiogenic-like effects in both elevated plus-maze and social interaction tests. Chronic LiCl treatment upregulated serotonergic genes in midbrain raphe nuclei. Thus, LiCl effects depend on the treatment mode, psycho-emotional state of the animal, and experimental context (tests). It is assumed that increased expression of serotonergic genes is accompanied by serotonergic system activation and, as a side effect, by higher anxiety.
Pembrolizumab in endometrial cancer: Where we stand now

Recently, immunotherapy has shown promising results in solid tumors. To the best of our knowledge, this is the first systematic review of published literature synthesizing all the available data and evaluating both the efficacy and safety of pembrolizumab in endometrial cancer. The present study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by searching the MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms ‘endometrial cancer’ and ‘pembrolizumab’. Overall, nine articles incorporating data from 712 patients were eligible. Pembrolizumab was demonstrated to be an effective and safe therapeutic option for the management of advanced/metastatic endometrial cancer. Results of ongoing trials evaluating either pembrolizumab alone or in combination with other antineoplastic regimens are expected to confirm its efficacy in this setting of patients. Pembrolizumab appears to be both durable and robust in endometrial cancer. However, there is an emerging need for novel predictive biomarkers to guide clinical practice.
The Impact of Sex on the Neurocognitive Functions of Patients with Parkinson’s Disease

This study aimed to understand the impact of sex on the neurocognitive function of patients with Parkinson’s disease (PD). Ninety-four participants with idiopathic PD and 167 age-matched healthy individuals as normal controls (NCs) were recruited and underwent comprehensive neuropsychological assessments. Sex differences were found in NCs, but not in patients with PD. Among male participants, patients with PD showed worse performance on the Digit Symbol Substitution (DSS) (p < 0.001) test and Symbol Search (SS) (p < 0.001) than NCs. Among female participants, patients with PD showed worse performance on the category score of the Modified Wisconsin Card Sorting Test (p < 0.001), SS (p < 0.001), and pentagon copying (p < 0.001) than NCs. After controlling for the effects of age and years of education, Hoehn and Yahr stage was found to predict the performance of the Color Trails Test part A (βA = 0.241, pA = 0.036), Stroop Color and Word Test (β = −0.245, p = 0.036), and DSS (β = −0.258, p = 0.035) in men with PD. These results indicate the differential effect of sex on the neurocognitive function among healthy aging and PD populations. The disappearance of sex differences, which is present in healthy aging, in patients with PD suggests a gradual loss of the neuroprotective effect of estrogen after the initiation of the neurodegenerative process. This study also found mental flexibility and visuospatial function to be the susceptible cognitive domains in women with PD, while the disease severity could predict the working memory and processing speed in men with PD.
Increased wood biomass growth is associated with lower wood density in Quercus petraea (Matt.) Liebl. saplings growing under elevated CO2

Atmospheric carbon dioxide (CO2) has increased substantially since the industrial revolution began, and physiological responses to elevated atmospheric CO2 concentrations reportedly alter the biometry and wood structure of trees. Additionally, soil nutrient availability may play an important role in regulating these responses. Therefore, in this study, we grew 288 two-year-old saplings of sessile oak (Quercus petraea (Matt.) Liebl. ) in lamellar glass domes for three years to evaluate the effects of CO2 concentrations and nutrient supply on above- and belowground biomass, wood density, and wood structure. Elevated CO2 increased above- and belowground biomass by 44.3% and 46.9%, respectively. However, under elevated CO2 treatment, sapling wood density was markedly lower (approximately 1.7%), and notably wider growth rings—and larger, more efficient conduits leading to increased hydraulic conductance—were observed. Moreover, despite the vessels being larger in saplings under elevated CO2, the vessels were significantly fewer (p = 0.023). No direct effects of nutrient supply were observed on biomass growth, wood density, or wood structure, except for a notable decrease in specific leaf area. These results suggest that, although fewer and larger conduits may render the xylem more vulnerable to embolism formation under drought conditions, the high growth rate in sessile oak saplings under elevated CO2 is supported by an efficient vascular system and may increase biomass production in this tree species. Nevertheless, the decreased mechanical strength, indicated by low density and xylem vulnerability to drought, may lead to earlier mortality, offsetting the positive effects of elevated CO2 levels in the future.
Emerging Landscape of Immunotherapy for Primary Central Nervous System Lymphoma

Simple Summary Primary central nervous system lymphoma (PCNSL) is characterized by its location in the central nervous system comprising the brain, the eye, the cerebrospinal fluid and the spinal cord and a poor prognosis with the current chemotherapies. Immunotherapies represent a new paradigm in the care of patients with B-cell lymphoma, but, till recently, immunotherapies studies excluded patients with PCNSL because of the lack of knowledge on the immune network in the brain. Recent studies shed a new light on the origin and characteristics of the CNS immune cells. We review the current experimental preclinical and clinical developments of immunotherapies in CNS lymphoma as well as the effects of targeted therapies on the brain microenvironment. We provide perspectives for improving the efficacy of immunotherapies in the specific setting of PCNSL for a better prognosis of this disease. Abstract Primary central nervous system lymphoma (PCNSL) is, mainly, a diffuse large B-cell lymphoma (DLBCL) with a non-germinal center B-cell (non-GCB) origin. It is associated with a poor prognosis and an unmet medical need. Immunotherapy has emerged as one of the most promising areas of research and is now part of the standard treatment for many solid and hematologic tumors. This new class of therapy generated great enthusiasm for the treatment of relapsed/refractory PCNSL. Here, we discuss the challenges of immunotherapy for PCNSL represented by the lymphoma cell itself and the specific immune brain microenvironment. We review the current clinical development from the anti-CD20 monoclonal antibody to CAR-T cells, as well as immune checkpoint inhibitors and targeted therapies with off-tumor effects on the brain microenvironment. Perspectives for improving the efficacy of immunotherapies and optimizing their therapeutic role in PCNSL are suggested.
Coordination Study on Ecological and Economic Coupling of the Yellow River Basin

The coupling and coordination relationship between ecology and the economy in the Yellow River Basin is a hot topic in sustainable development research. Said research has important guiding significance for the ecological security and comprehensive development of the Yellow River Basin. Taking the Yellow River Basin as the object of our study, based on the data of the economy, energy consumption data, ecology data and water resources data, we construct an indicator system of the economic development and ecological status of the Yellow River Basin and use the principal component analysis method to calculate the economic development and ecological status index. Then, we use the evaluation method, the coupling degree model and the coupling coordination degree model to analyze the time and space evolution trends of economic development and ecological state, coupling degree and coupling coordination degree. The results show that: (1) From 2000 to 2018, the economic development index of the Yellow River Basin rose steadily; the ecological status index showed a slow rise and then a downward trend. (2) The degree of coupling between economic development and ecological state has been considered as intensity coupling after 2005. The coupling trend slowly increased and then decreased, indicating that the interaction effect between the economy and ecology was first significantly enhanced and then slowly weakened. (3) The degree of coupling coordination increased from 0.2994 to 0.6266 and then decreased to 0.5917, reflecting the continuous improvement of the relationship between the regional economy and the ecological environment and the trend toward coordination. From 2015 to 2018, due to the gradual increase in the difference between economic development and ecological conditions, the coupling and coordination between the two decreased. Studies have shown that ecological construction and protection should be strengthened to ease the contradiction between the economy and ecology and achieve coordinated development.
Retinal Vascular Response to Hyperoxia in Patients with Diabetes Mellitus without Diabetic Retinopathy

Purpose To evaluate the retinal vascular response to hyperoxia in patients with diabetes at the preclinical stage of diabetic retinopathy (DR) and to quantify the changes in comparison with normal subjects using optical coherence tomography angiography (OCTA). Methods In this prospective study, 40 eyes of 20 participants comprising 10 diabetic patients with no diabetic retinopathy (NDR) and 10 normal subjects were recruited. OCTA images were acquired in the resting position and were repeated after a hyperoxic challenge using a nasal mask connected to a reservoir bag supplying 100% oxygen at the rate of 15 L per minute for 5 minutes. The changes of mean parafoveal vessel density (VD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the foveal avascular zone (FAZ) size, and the outer retina flow index were compared between two conditions in each group and between the two study groups. The statistical significance of differences in the means was evaluated using Student's t-test for unpaired samples with consideration of the generalized estimating equations (GEE) for intereye correlation. Results At baseline, the mean parafoveal VD of SCP and DCP were significantly lower in the NDR participants compared to the healthy subjects (P < 0.001 and P = 0.006, respectively). After induction of the hyperoxic challenge in healthy participants, mean parafoveal VD reduced at both the SCP and DCP, but reached a statistical significance only in DCP (P = 0.006). However, following induction of hyperoxic challenge in patients with NDR, no significant decline was noticed in mean parafoveal VD of SCP and DCP. The degree of change in mean parafoveal VD of DCP was statistically significantly more pronounced in healthy subjects compared to the NDR group (P = 0.034). The change in FAZ size and the outer retina flow index were comparable between the two study groups. Conclusion Retinal capillary layers responded differently to hyperoxia-induced challenge, and in normal subjects, the autoregulatory mechanism was mostly effective in the parafoveal DCP. Retinal vascular reactivity was impaired in SCP and DCP at the preclinical stage of DR. OCTA as a noninvasive modality was able to quantify the retinal vascular response to the hyperoxic challenge.
Counseling in Vape Shops: A Survey of Vape Shop Managers in Switzerland

Vaporizers (e-cigarettes) are the most common smoking cessation aids in Switzerland, but we do not know what information customers receive in vape shops. We surveyed vape-shop managers to find out what recommendations they make to their customers. An interdisciplinary group developed the questionnaire. Respondents self-reported their smoking history, demographics, and the recommendations they thought they would give to hypothetical customers in clinical vignettes. We also queried if they collaborated with health care professionals. Of those contacted, 53.8% (70/130) of vape-shop managers responded, and 52.3% (68/130) were included in the final analysis. Managers were mostly male and ex-smokers who switched to vaporizers; 60.3% would encourage a hypothetical smoker with high nicotine dependence to start with the highest possible nicotine concentration when switching to vaporizers. For this smoker, 36.9% would recommend high (≥15 mg/mL), 32.3% medium (6–14 mg/mL), and 3.1% low (1–5 mg/mL) nicotine concentrations. The rest adapted their recommendations to fit the customer or device; 76.5% reported that physicians referred customers to them, and 78.8% would attend a course given by experts in the field of vaporizers and smoking cessation. Vape-shop managers varied widely in the recommendations they gave customers. Most reported ongoing collaboration with health care professionals and were interested in improving their counselling skills through training.
Effects of Probiotics, Prebiotics and Synbiotics Injected in Ovo on the Microstructure of the Breast Muscle in Different Chicken Genotypes

Simple Summary Probiotics, prebiotics and synbiotics are defined as biologically active food ingredients or food supplements. They promote higher growth performance but also have a positive effect on animal health by reducing the incidence of intestinal diseases and the risk of contamination of poultry products. These substances can be an alternative to recently banned antibiotics, used mainly to prevent infections, treat sick animals and promote growth. The present study compared the effects of different bioactive substances on the histological features of muscles from chickens representing two genotypes: Ross 308 broilers and GP native chickens. The results obtained clearly indicate that the microstructural features of pectoral muscles depend not only on the type of the injected bioactive substance but also on the genotype of the chickens. Abstract The aim of the study was to analyse the effect of probiotics, prebiotics and synbiotics injected in ovo on day 12 of embryonic development on the microstructure of the superficial pectoral muscle (musculus pectoralis superficialis) from 42-day-old chickens of different genotypes: broilers (Ross 308) and general-purpose type (green-legged partridge (GP) chickens Zk-11, native chickens). Incubated eggs were divided into four groups (each genotype separately) depending on the substance injected in ovo: normal saline (C, control); Lactococcus lactis subsp. cremoris (PRO); galactooligosaccharides, GOS (PRE) or GOS + L. lactis (SYN). After hatching, chicks were placed in eight replicated pens (four pens/genotype group). There were eight birds per pen. In total, 64 birds were used in the experiment. Birds were slaughtered at the age of 42 days, and samples of superficial pectoral muscles were taken for analysis. The microstructure of the pectoral muscles was evaluated using the cryosectioning (frozen tissue sectioning) technique and staining with haematoxylin and eosin. Statistical analysis revealed that the in ovo injection of probiotics, prebiotics and synbiotics had no significant effect on the diameter of muscle fibres from chickens of the two genotypes. The number of fibres in the muscles from green-legged partridge chickens was about three-fold higher than the fibre density in the muscles from broiler chickens, with the fibre diameter being two-fold smaller. This fact may indicate a greater tenderness of meat from GP chickens compared to the meat from Ross 308 broilers. In the case of broilers, a prebiotic (GOS) was the most effective bioactive substance in reducing the number of histopathological changes. Considering muscles from GP chickens, the number of normal fibres was highest in birds treated with the probiotic. These findings indicate that the microstructural features of pectoral muscles depend not only on the type of the injected bioactive substance but also on the genotype of chickens.