Miracle-dz/UniFAR-FTUs huggingface dataset:
ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

Prevention and overcoming castration resistance of prostate cancer (PC) remains one of the main unsolved problems in modern oncology. Hence, many studies are focused on the investigation of novel androgen receptor (AR) regulators that could serve as potential drug targets in disease therapy. Among such factors, inhibitor of growth (ING) proteins were identified. Some ING proteins act as AR transcriptional coregulators, indicating their relevance for PC research. The ING family consists of five protein-coding genes from ING1 to ING5 and pseudogene INGX. The ING genes were revealed through their sequence homology to the first identified ING1 from an in vivo screen. ING factors are a part of histone modification complexes. With the help of the conserved plant homeodomain (PHD) motif, ING factors bind to Histone 3 Lysine 4 (H3K4) methylation mark with a stronger affinity to the highest methylation grade H3K4me3 and recruit histone acetyltransferases (HAT) and histone deacetylases (HDAC) to chromatin. ING1 and ING2 are core subunits of mSIN3a-HDAC corepressor complexes, whereas ING3–5 interact with different HAT complexes that serve as coactivators. ING members belong to type II tumour suppressors and are frequently downregulated in many types of malignancies, including PC. As the family name indicates, ING proteins are able to inhibit cell growth and tumour development via regulation of cell cycle and cancer-relevant pathways such as apoptosis, cellular senescence, DNA repair, cell migration, invasion, and angiogenesis. Many ING splice variants that enhance the diversity of ING activity were discovered. However, it seems that the existence of multiple ING splice variants is underestimated, since alternative splice variants, such as the AR coregulators ING1 and ING3, counteract full-length ING and thus play an opposite functional role. These results open a novel prospective investigation direction in understanding ING factors biology in PC and other malignancies.
Transcriptome Analysis of In Vitro Fertilization and Parthenogenesis Activation during Early Embryonic Development in Pigs

Parthenogenesis activation (PA), as an important artificial breeding method, can stably preserve the dominant genotype of a species. However, the delayed development of PA embryos is still overly severe and largely leads to pre-implantation failure in pigs. The mechanisms underlying the deficiencies of PA embryos have not been completely understood. For further understanding of the molecular mechanism behind PA embryo failure, we performed transcriptome analysis among pig oocytes (meiosis II, MII) and early embryos at three developmental stages (zygote, morula, and blastocyst) in vitro fertilization (IVF) and PA group. Totally, 11,110 differentially expressed genes (DEGs), 4694 differentially expressed lincRNAs (DELs) were identified, and most DEGs enriched the regulation of apoptotic processes. Through cis- and trans-manner functional prediction, we found that hub lincRNAs were mostly involved in abnormal parthenogenesis embryonic development. In addition, twenty DE imprinted genes showed that some paternally imprinted genes in IVF displayed higher expression than that in PA. Notably, we identified that three DELs of imprinted genes (MEST, PLAGL1, and DIRAS3) were up regulated in IVF, and there was no significant change in PA group. Disordered expression of key genes for embryonic development might play key roles in abnormal parthenogenesis embryonic development. Our study indicates that embryos derived from different production techniques have varied in vitro development to the blastocyst stage, and they also affect the transcription level of corresponding genes, such as imprinted genes. This work will help future research on these genes and molecular-assisted breeding for pig parthenotes.
1,8-Cineole Affects Agonists-Induced Platelet Activation, Thrombus Formation and Haemostasis

1,8-cineole, a monoterpenoid is a major component of eucalyptus oil and has been proven to possess numerous beneficial effects in humans. Notably, 1,8-cineole is the primary active ingredient of a clinically approved drug, Soledum® which is being mainly used for the maintenance of sinus and respiratory health. Due to its clinically valuable properties, 1,8-cineole has gained significant scientific interest over the recent years specifically to investigate its anti-inflammatory and antioxidant effects. However, the impact of 1,8-cineole on the modulation of platelet activation, thrombosis and haemostasis was not fully established. Therefore, in this study, we demonstrate the effects of 1,8-cineole on agonists-induced platelet activation, thrombus formation under arterial flow conditions and haemostasis in mice. 1,8-cineole largely inhibits platelet activation stimulated by glycoprotein VI (GPVI) agonists such as collagen and cross-linked collagen-related peptide (CRP-XL), while it displays minimal inhibitory effects on thrombin or ADP-induced platelet aggregation. It inhibited inside-out signalling to integrin αIIbβ3 and outside-in signalling triggered by the same integrin as well as granule secretion and intracellular calcium mobilisation in platelets. 1,8-cineole affected thrombus formation on collagen-coated surface under arterial flow conditions and displayed a minimal effect on haemostasis of mice at a lower concentration of 6.25 µM. Notably, 1,8-cineole was found to be non-toxic to platelets up to 50 µM concentration. The investigation on the molecular mechanisms through which 1,8-cineole inhibits platelet function suggests that this compound affects signalling mediated by various molecules such as AKT, Syk, LAT, and cAMP in platelets. Based on these results, we conclude that 1,8-cineole may act as a potential therapeutic agent to control unwarranted platelet reactivity under various pathophysiological settings.
Assessment of the Knowledge and Approach of General Dentists Who Treat Children and Pediatric Dentists Regarding the Proper Use of Antibiotics for Children

Background: Antibiotics are widely used in dentistry. Dentists often provide antibiotics unnecessarily. Excessive use can induce resistant bacterial strains. There are certain indications for the proper use of antibiotics for pediatric dentistry according to the European and American Pediatric Dentistry (EAPD and AAPD). Very often dentists do not follow these guidelines. Objectives: This study aims to examine the level of knowledge among general dentists (who also treat children) and pediatric dentists on proper use of antibiotics. In addition, we examined whether there is unjustified use of antibiotics, if dentists are aware of the new and conservative approach of administering antibiotics to patients, and whether there is a relationship between years of professional seniority and dentist’s knowledge level of proper use of antibiotics. Methods: One hundred general dentists (GD) who treat children in addition to 100 pediatric dentists (PD) completed the study questionnaires which measured knowledge, practice and attitudes regrading using antibiotics during dental treatment among children. Results: The general average of level of knowledge on proper use of antibiotics among general dentists was relatively low for both GD (60.7%) and PDs (65%). PDs demonstrated a relatively greater knowledge of correct use of antibiotics, especially in cases of endodontics and trauma. PDs also showed higher awareness to latest guidelines for the admission of “prophylactic antibiotics” according to the American Association (AAPD) and/or the European Union (EAPD) compared with GDs (86.2% vs. 66.3%). Conclusion: The level of knowledge of both general dentists and pediatric dentists is poor, with a large percentage of dentists from both groups not knowing whether antibiotics are needed in a specific dental case or not. Compliance with the EAPD/AAPD guidelines is also low and inadequate. The method of prescribing antibiotics given by dentists can be improved by increasing awareness, educational initiatives, and postgraduate courses among dentists regarding the recommended indications.
Presence of the Human Cytomegalovirus in Glioblastomas—A Systematic Review

Simple Summary Whether the human cytomegalovirus (HCMV) is present in samples obtained from patients with glioblastoma (GBM) has been a matter under debate during the last two decades. Many investigators have demonstrated the presence of HCMV proteins and nucleic acids in GBM tumors, while some have not been able to detect it. It is important to evaluate current data and resolve these issues to clarify the possible role of the HCMV in GBM tumorigenesis and if this virus can serve as a potential target of therapy for these patients. In the present systematic review, we aim to review published research studies with a focus to identify differences and similarities in methods used for the detection of the HCMV in GBM samples found to be positive or negative for HCMV. Our data suggest that the HCMV is highly prevalent in glioblastomas and that optimized immunohistochemistry techniques are required to detect it. Abstract Glioblastoma is a malignant brain tumor with a dismal prognosis. The standard treatment has not changed in the past 15 years as clinical trials of new treatment protocols have failed. A high prevalence of the human cytomegalovirus (HCMV) in glioblastomas was first reported in 2002. The virus was found only in the tumor and not in the surrounding healthy brain tissue. Many groups have confirmed the presence of the HCMV in glioblastomas, but others could not. To resolve this discrepancy, we systematically reviewed 645 articles identified in different databases. Of these, 81 studies included results from 247 analyses of 9444 clinical samples (7024 tumor samples and 2420 blood samples) by different techniques, and 81 articles included 191 studies that identified the HCMV in 2529 tumor samples (36% of all tumor samples). HCMV proteins were often detected, whereas HCMV nucleic acids were not reliably detected by PCR methods. Optimized immunohistochemical techniques identified the virus in 1391 (84,2%) of 1653 samples. These data suggest that the HCMV is highly prevalent in glioblastomas and that optimized immunohistochemistry techniques are required to detect it.
Efficacy and Safety of Filgrastim and Its Biosimilars to Prevent Febrile Neutropenia in Cancer Patients: A Prospective Study and Meta-Analysis

Simple Summary Febrile neutropenia is the serious side-effect associated with myelosuppressive chemotherapy. Filgrastim, the first granulocyte colony-stimulating factor (G-CSF) was approved by the Food and Drug Administration for the treatment of neutropenia. Subsequently, pegfilgrastim (long-acting G-CSF) and filgrastim biosimilars were developed to have comparable efficacy to filgrastim. Therefore, it is necessary to produce a systematic review and meta-analysis that provides evidence that filgrastim is more efficacious than placebo/no-treatment, as it provides evidence on the comparable efficacy of filgrastim versus pegfilgrastim and biosimilar filgrastim. Abstract Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrophil count ANC recovery, depth of ANC nadir (lowest ANC), neutropenia-related hospitalization and other neutropenia-related complications. For filgrastim versus biosimilar filgrastim comparison, the primary efficacy endpoint was the mean difference in duration of severe neutropenia DSN. Results: A total of 56 studies were considered that included data from 13,058 cancer patients. The risk of febrile neutropenia in filgrastim versus placebo/no treatment was not statistically different. The risk ratio for febrile neutropenia was 0.58, a 42% reduction in favor of filgrastim. The most reported adverse event with FIL was bone pain. For pegfilgrastim versus filgrastim, no statistically significant difference was noted. The risk ratio was 0.90 (95% CI 0.67 to 1.12). The overall difference in duration of severe neutropenia between filgrastim and biosimilar filgrastim was not statistically significant. The risk ratio was 1.03 (95% CI 0.93 to 1.13). Conclusions: Filgrastim was effective and safe in reducing febrile neutropenia and related complications, compared to placebo/no treatment. No notable differences were found between pegfilgrastim and filgrastim in terms of efficacy and safety. However, a similar efficacy profile was observed with FIL and its biosimilars.
The Soluble Urokinase-Type Plasminogen Activator Receptor as a Biomarker for Survival and Early Treatment Effect in Metastatic Colorectal Cancer

Simple Summary Patients with metastatic colorectal cancer are likely to have a poor outcome. Chemotherapy is the primary treatment, but because of toxicity and a lack of benefit for a large group of patients, it is important to monitor the treatment effect. The only tool for evaluating treatment effect currently is imaging. Biomarkers associated with disease progression could therefore be important for treatment monitoring in the future. The biomarker suPAR is prognostic for the overall survival in colorectal cancer. This study aimed to investigate if plasma suPAR levels before and during treatment were prognostic of survival and predictive for treatment effect. Our study confirmed that higher plasma suPAR levels before initiation of palliative chemotherapy were prognostic of shorter survival. Abstract The soluble urokinase-type plasminogen activator receptor (suPAR) is prognostic for overall survival (OS) in colorectal cancer (CRC). Our study explored the association between baseline suPAR and OS and progression-free survival (PFS) in metastatic CRC (mCRC). It is also the first study to explore the association between the initial change in suPAR level and OS, PFS and the first CT response evaluation. The study included 132 patients with mCRC treated with chemotherapy (FOLFIRI) with or without an EGFR-inhibitor. Blood samples were drawn before the first treatment cycle and in between the first and second treatment cycle. suPAR levels were determined using an ELISA assay. Using the Kaplan-Meyer method, we demonstrated a significantly shorter OS for patients with suPAR levels above the median (HR = 1.79, 95%CI = 1.10–2.92, p = 0.01). We also showed association between plasma suPAR level, gender and performance status (PS). However, we could not show any association with PFS, and analysis on the change in suPAR level provided no significant results. The results showing association between baseline suPAR and OS are in line with previous findings.
A Review of Methods for Sleep Arousal Detection Using Polysomnographic Signals

Multiple types of sleep arousal account for a large proportion of the causes of sleep disorders. The detection of sleep arousals is very important for diagnosing sleep disorders and reducing the risk of further complications including heart disease and cognitive impairment. Sleep arousal scoring is manually completed by sleep experts by checking the recordings of several periods of sleep polysomnography (PSG), which is a time-consuming and tedious work. Therefore, the development of efficient, fast, and reliable automatic sleep arousal detection system from PSG may provide powerful help for clinicians. This paper reviews the automatic arousal detection methods in recent years, which are based on statistical rules and deep learning methods. For statistical detection methods, three important processes are typically involved, including preprocessing, feature extraction and classifier selection. For deep learning methods, different models are discussed by now, including convolution neural network (CNN), recurrent neural network (RNN), long-term and short-term memory neural network (LSTM), residual neural network (ResNet), and the combinations of these neural networks. The prediction results of these neural network models are close to the judgments of human experts, and these methods have shown robust generalization capabilities on different data sets. Therefore, we conclude that the deep neural network will be the main research method of automatic arousal detection in the future.
Muscular Echovariation as a New Biomarker for the Classification of Soleus Muscle Pathology: A Cross-Sectional Study

Background: Soleus injury is one of the most common soft tissue tears during sport activities. Current classifications of muscle tears are based on symptoms and tear size and they do not contribute suitable evidence-based treatment protocols. The objective of this study was to analyze the most frequent echotexture findings of patients with soleus muscle injury, located in the central intramuscular tendon (IMT), and healthy people to determine whether they behave differently and to propose an ultrasound (US)-based classification. Methods: eighty-four athletes, who played in sport activities comprising lower limbs. Echotexture characteristics of soleus muscle were reviewed for 84 subjects. They were divided based on the muscle echogenicity in three groups (Injury Type 1 group, Injury type 2 group and healthy group). Echointensity (EI) and Echovariation (EV) were taken in all groups like quantitative US variable. Results. The Injury Type 1 group was identified by a hypoechoic area and characterized by a higher EV; and Injury Type 2 group was identified by a fibrotic area and characterized by a lower EV. The echogenic pattern of healthy people obtained an intermediate value of EV between both injured soleus types. Conclusions. EV may be useful to classify different types of soleus muscle pathology according to the echogenicity pattern. An innovative proposed US-based classification system for soleus tears may be used to guide treatment decisions for patients with central tendon injury of soleus muscle.
Impact of Heat Waves on Hospitalisation and Mortality in Nursing Homes: A Case-Crossover Study

Climate change leads to more days with extremely hot temperatures. Previous analyses of heat waves have documented a short-term rise in mortality. The results on the relationship between high temperatures and hospitalisations, especially in vulnerable patients admitted to nursing homes, are inconsistent. The objective of this research was to examine the discrepancy between heat-related mortality and morbidity in nursing homes. A time-stratified case-crossover study about the impact of heat waves on mortality and hospitalisations between 1 January 2013 and 31 December 2017 was conducted in 10 nursing homes over 5 years in Flanders, Belgium. In this study, the events were deaths and hospitalisations. We selected our control days during the same month as the events and matched them by day of the week. Heat waves were the exposure. Conditional logistic regression models were applied. The associations were reported as odds ratios at lag 0, 1, 2, and 3 and their 95% confidence intervals. In the investigated time period, 3048 hospitalisations took place and 1888 residents died. The conditional logistic regression showed that odds ratios of mortality and hospitalisations during heat waves were 1.61 (95% confidence interval 1.10–2.37) and 0.96 (95% confidence interval 0.67–1.36), respectively, at lag 0. Therefore, the increase in mortality during heat waves was statistically significant, but no significant changes in hospitalisations were obtained. Our result suggests that heat waves have an adverse effect on mortality in Flemish nursing homes but have no significant effect on the number of hospitalisations.
Methanogenesis and Salt Tolerance Genes of a Novel Halophilic Methanosarcinaceae Metagenome-Assembled Genome from a Former Solar Saltern

Anaerobic archaeal methanogens are key players in the global carbon cycle due to their role in the final stages of organic matter decomposition in anaerobic environments such as wetland sediments. Here we present the first draft metagenome-assembled genome (MAG) sequence of an unclassified Methanosarcinaceae methanogen phylogenetically placed adjacent to the Methanolobus and Methanomethylovorans genera that appears to be a distinct genus and species. The genome is derived from sediments of a hypersaline (97–148 ppt chloride) unrestored industrial saltern that has been observed to be a significant methane source. The source sediment is more saline than previous sources of Methanolobus and Methanomethylovorans. We propose a new genus name, Methanosalis, to house this genome, which we designate with the strain name SBSPR1A. The MAG was binned with CONCOCT and then improved via scaffold extension and reassembly. The genome contains pathways for methylotrophic methanogenesis from trimethylamine and dimethylamine, as well as genes for the synthesis and transport of compatible solutes. Some genes involved in acetoclastic and hydrogenotrophic methanogenesis are present, but those pathways appear incomplete in the genome. The MAG was more abundant in two former industrial salterns than in a nearby reference wetland and a restored wetland, both of which have much lower salinity levels, as well as significantly lower methane emissions than the salterns.
The Neural Markers of Self-Caught and Probe-Caught Mind Wandering: An ERP Study

Mind-wandering (MW) is a common phenomenon, defined as task-unrelated thoughts. This study is based on event-related potentials (ERPs), using modified sustained attention to response task (modified SART, mSART) to discuss the neural patterns of different types of MW. In the current study, we defined the MW realized by participants as self-caught MW, and the MW measurement acquired by probes as probe-caught MW. The behavioral results showed that the reaction times (RTs) during self-caught MW were greater than those during non-self-caught MW. The ERP results showed that during self-caught MW, the mean amplitudes of N1 decreased significantly, indicating that the participants’ attention had deviated from the current task. The increase in the mean amplitudes of P2 during self-caught MW indicated lower vigilance. We also found that the mean amplitudes of N300 reduced during self-caught MW, which indicated that cognitive control or monitoring might be affected by self-caught MW. The average amplitudes of P300 were significantly lower during probe-caught MW than during on-task, indicating the impact on high-level cognitive processing. In addition, the amplitudes of N1, P2, and N300 in anterior regions were greater than those in posterior regions. P300 amplitudes during probe-caught MW in the right hemisphere were greater than those of the left hemisphere. In summary, our research results demonstrated that alertness and cognitive processing decreased during both self-caught MW and probe-caught MW. ERPs were statistically different under the conditions of self-caught MW and probe-caught MW. The current study provided new insights into the relationship between MW and neural markers. It was the first study exploring the ERP correlates between self-caught MW and probe-caught MW based on mSART.