Miracle-dz/UniFAR-FTUs huggingface dataset:
Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Background: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammation-related genes with non–muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression. Methods: We considered 822 NMIBC included in the SBC/EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures. Results: While no SNP was found to be associated with risk-of-recurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of-progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 × 10−5) and two SNPs in MASP1 and AIRE, showed a posterior probability ≥80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively. Conclusions: Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC. Impact: This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases. Cancer Epidemiol Biomarkers Prev; 25(7); 1144–50. ©2016 AACR.
One Basic Blueprint, Many Different Motors

The cytoplasmic C ring of the bacterial flagellum is known as the switch complex. It binds the response regulator phospho-CheY to control the direction of flagellar rotation. ABSTRACT The cytoplasmic C ring of the bacterial flagellum is known as the switch complex. It binds the response regulator phospho-CheY to control the direction of flagellar rotation. The C ring of enteric bacteria is well characterized. However, no Gram-positive switch complex had been modeled. Ward et al. (E. Ward, E. A. Kim, J. Panushka, T. Botelho, et al., J Bacteriol 201:e00626-18, 2019, https://doi.org/10.1128/JB.00626-18) propose a structure for the Bacillus subtilis switch complex based on extensive biochemical studies. The work demonstrates that a similar architecture can accommodate different proteins and a reversed signaling logic.
DEAD box helicases as promising molecular tools for engineering abiotic stress tolerance in plants

Abstract Diverse abiotic stresses constitute one of the major factors which adversely affect the normal plant growth and development which results worldwide in decreased agricultural productivity. At present, utilization of new molecular tools to achieve improved stress tolerance and increased crop productivity is highly desirable. Abiotic stress in plants induces expression of a wide range of genes like transcription factors, defense related genes and so on, and the products of these genes are important in combating stress conditions. Helicases are one such category of proteins that play a key role in maintaining the genomic integrity of the cell by participating in nucleic acid mediated processes such as recombination, replication, and repair of DNA as well as the unwinding of misfolded RNA structures that are formed during stress conditions. The DEAD box helicases are a subgroup of helicases which contain the amino acids Asp-Glu-Ala-Asp (DEAD) and are involved in the above molecular functions that mediate adaptation to stress. Overexpression of DEAD box helicases is known to provide stress tolerance in various plants and thus their use in developing stress tolerant plants is gaining importance. The plausible physiological mechanisms of helicases in bestowing abiotic stress tolerance of plants include ROS scavenging, enhanced photosynthesis, ion homeostasis and regulation of various stress responsive genes. In this review, the characteristics of plant DEAD box helicases and the stress conditions under which they express are discussed. We have provided a detailed description on the transgenic plants overexpressing DEAD box helicases with an emphasis on their stress tolerance abilities.
Treatment Options for Osteoarthritis: Considerations for Older Adults

Abstract Osteoarthritis (OA) is the most common form of arthritis and the leading cause of disability among older adults in the United States. Treatment options such as acetaminophen and nonsteroidal anti-inflammatory drugs are the most widely used agents to manage mild-to-moderate pain. Treatment with tramadol or opioids is usually reserved for severe pain associated with OA. These agents do not come without risk, especially for older adults. Patient-specific parameters and comorbid conditions must be considered when evaluating treatment options for older adults. This article reviews pharmacological and nonpharmacological approaches to the management of OA in older adults.
Tandem Affinity Purification and Mass Spectrometry (TAP‐MS) for the Analysis of Protein Complexes

Affinity purification followed by mass spectrometry has become the technique of choice to identify binding partners in biochemical complexes isolated from a physiologic cellular context. In this report we detail our protocol for tandem affinity purification (TAP) primarily based on the use of the FLAG and HA peptide epitopes, with a particular emphasis on factors affecting yield and specificity, as well as steps to implement an automated version of the TAP procedure. © 2019 by John Wiley & Sons, Inc.
Modulation of Lipid Metabolism by Celastrol.

Hyperlipidemia, characterized by high serum lipids, is a risk factor for cardiovascular disease. Recent studies have identified an important role for celastrol, a proteasome inhibitor isolated from Tripterygium wilfordii Hook. F. , in obesity-related metabolic disorders. However, the exact influences of celastrol on lipid metabolism remain largely unknown. Celastrol inhibited the terminal differentiation of 3T3-L1 adipocytes and decreased the levels of triglycerides in wild-type mice. Lipidomics analysis revealed that celastrol increased the metabolism of lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), sphingomyelins (SMs), and phosphatidylethanolamines (PEs). Further, celastrol reversed the tyloxapol-induced hyperlipidemia induced associated with increased plasma LPCs, PCs, SMs, and ceramides (CMs). Among these lipids, LPC(16:0), LPC(18:1), PC(22:2/15:0), and SM(d18:1/22:0) were also decreased by celastrol in cultured 3T3-L1 adipocytes, mice, and tyloxapol-treated mice. The mRNAs encoded by hepatic genes associated with lipid synthesis and catabolism, including Lpcat1, Pld1, Smpd3, and Sptc2, were altered in tyloxapol-induced hyperlipidemia, and significantly recovered by celastrol treatment. The effect of celastrol on lipid metabolism was significantly reduced in Fxr-null mice, resulting in decreased Cers6 and Acer2 mRNAs compared to wild-type mice. These results establish that FXR was responsible in part for the effects of celastrol in controlling lipid metabolism and contributing to the recovery of aberrant lipid metabolism in obesity-related metabolic disorders.
Screening for insomnia in primary care: using a two-item version of the Sleep Condition Indicator.

Insomnia, defined as difficulty falling asleep, staying asleep, or waking up too early for 3 or more nights per week for 3 months or more with significant daytime effects,1 is the most common sleep problem presenting in general practice: 10 to 12% of the population meet formal diagnostic criteria for insomnia disorder, and up to 40% express complaints of insomnia.2 For those suffering from sleep problems, the GP is often the first point of contact, with previous research suggesting 79% of GPs see someone with a sleep complaint at least once a week.3 GPs are often unaware of patients’ sleep problems, and, even when they are, fewer than 8% of doctors use validated sleep questionnaires or sleep diaries.4 Despite both GPs and patients believing that a detailed sleep assessment is important, this lack of assessment may be due to time pressure …
Association of Electronic Cigarette Use With Subsequent Initiation of Tobacco Cigarettes in US Youths

Key Points Question Is electronic cigarette (e-cigarette) use among tobacco-naive youths associated with subsequent risk of cigarette initiation? Findings In this cohort study using data from the Population Assessment of Tobacco and Health Study (2013-2016), youths whose first tobacco product was an e-cigarette were more likely to initiate cigarettes over 2 years of follow-up. At the population level, approximately 180 000 new ever smokers and 45 000 current smokers in the United States over 2 years may have started smoking combustible cigarettes after initiating e-cigarette use. Meaning Tobacco-naive youths who initiate e-cigarettes may be at greater risk of subsequently initiating cigarette smoking.
The education of nurses working in care homes for older people: An Appreciative Inquiry.

AIM To explore the education and developmental needs of care home nursing staff. BACKGROUND With an increasing ageing population, the need for high-quality care provision is set to rise and will require nursing staff with the desired knowledge, skills and values. However, multiple concerns have been identified when considering the development of nurses working in care homes. Moreover, challenges in the care home sector have also contributed to a situation where some nurses view care home work as being of low status and choose this work to fit around other commitments, rather than viewing it as a viable career pathway. METHOD A qualitative approach based on the principles of Appreciative Inquiry. Fifteen participants working in five care homes with nursing, based in England (UK), took part in this study. Data were collected during 2016-2017 and involved managerial, qualified and unqualified staff. RESULTS Data analysis revealed three distinct themes: an effective learning environment; the care home as a nursing student placement; and the need for financial investment. These themes were found to have the most influence on the development and education of care home nursing staff. CONCLUSION This research provides important insights into the care home as an educational environment, not only for nursing students but also for those employees already working in such settings. Exploration of the ways in which higher education organisations and care home teams could collaborate more closely could be mutually beneficial to the quality of care and to raising the profile of care home work. IMPLICATIONS FOR PRACTICE Care homes can provide a rich learning environment for both staff and nursing students. Collaboration and appreciative ways of working enhance opportunities for developing practice and care.
Repeated Transcranial Magnetic Stimulation-Induced Motor Evoked Potentials Correlate With the Subject-Specific Serum Metabolic Profile of Creatine.

PURPOSE Transcranial magnetic stimulation-induced motor responses have been considered to mainly reflect the electrophysiological characteristics of the central motor system. However, certain motor phenomena, such as the magnitude of repetition suppression measured with motor evoked potentials (MEPs), could also in part be influenced by metabolic processes in the peripheral muscles and in both the peripheral and central nervous system. Repetition suppression is an inhibitory phenomenon in which the amplitude of MEP decreases in comparison to that of the first MEP in a train of transcranial magnetic stimulation pulses. This study aimed to identify possible metabolic processes influencing repetition suppression. METHODS The metabolic profiles from serum samples and repetition suppression from the right abductor pollicis brevis muscle were measured in 73 subjects (37 female subjects). Repetition suppression was measured using trains of transcranial magnetic stimulation stimuli consisting of 4 identical single pulses at 1-second intervals. The trains were repeated every 20 seconds, and 30 trains were given with a stimulation intensity of 120% of the resting motor threshold of the abductor pollicis brevis. Thus, a total of 120 stimuli were administered. RESULTS The main finding was a significant negative relationship between serum creatine levels and the magnitude of repetition suppression (standardized β coefficient (β) = -0.43; P < 0.001). In other words, higher creatine levels corresponded to a smaller decrement in the MEP amplitude in response to repetition. When MEPs were not repeated, no relationship was observed (β = 0.09; P = 0.454). Creatine is used to form phosphocreatine, which in turn is needed to resynthesize adenosine triphosphate from adenosine diphosphate in situations requiring high amounts of energy in muscles and neural cells. CONCLUSIONS For the first time, this study demonstrated a connection between repeated MEPs and peripheral serum metabolites linked to muscle function. These findings could explain some of the intersubject variability commonly observed in MEPs when the pulses are repeated.
Deciphering the essentiality and function of the anti‐σM factors in Bacillus subtilis

Bacteria use alternative sigma factors to adapt to different growth and stress conditions. The Bacillus subtilis extracytoplasmic function sigma factor SigM regulates genes for cell wall synthesis and is crucial for maintaining cell wall homeostasis under stress conditions. The activity of SigM is regulated by its anti‐sigma factor, YhdL, and the accessory protein YhdK. Here, we show that dysregulation of SigM caused by the absence of either component of the anti‐sigma factor complex leads to toxic levels of SigM and severe growth defects. High SigM activity results from a dysregulated positive feedback loop, and can be suppressed by overexpression of the housekeeping sigma, SigA. Using a sigM merodiploid strain, we selected for suppressor mutations that allow survival of yhdL depletion strain. The recovered suppressor mutations map to the beta and beta‐prime subunits of RNA polymerase core enzyme and selectively reduce SigM activity, and in some cases increase the activity of other alternative sigma factors. This work highlights the ability of mutations in RNA polymerase that remodel the sigma‐core interface to differentially affect sigma factor activity, and thereby alter the transcriptional landscape of the cell.
Muscle stem cells: what’s new in orthopedics?

Background and aim of the work: Adult stem cells were studied as a source of potentially useful development for tissue engineering and repair techniques. The aim of this review is to clarify the actual and possible uses of muscle stem cells in orthopedics. Methods: A selection of studies was made to obtain a homogeneous and up to date overview on the muscle stem cells applications. Results: In recent years muscle was studied as a good source of adult stem cells that can differentiate into different cell lineages. Muscle stem cells are a heterogeneous population of cells, which demonstrated in vitro a great potential for the regeneration and repair of muscle, bone and cartilage tissue. Among muscle stem cells, satellite stem cells are the most known progenitor cells: they can differentiate in osteoblasts, adipocytes, chondrocytes and myocytes. Conclusions: Although muscle stem cells are a promising field of research, more pre-clinical studies in animal models are still needed to determine the safety and efficiency of the transplant procedures in humans. (www.actabiomedica.it)
Involvement of M1 and M3 receptors in isolated pancreatic islets function during weight cycling in ovariectomized rats.

We investigate structural and functional adaptations of the pancreas during weight cycling in animals submitted to hypoestrogenism. Female Wistar groups: ShamAL (AL: ad libitum), OVXAL (ovariectomized), and OVXcycle (dietary restriction with weight cycling). The ShamAL and OVXAL received ad libitum commercial feed, while the OVXcycle received 21 days of ad libitum commercial feed and 21 days of caloric restriction with 40% of the amount of feed consumed by the OVXAL. The tolerance tests for glucose and insulin were applied. After euthanasia, the pancreas and adipose tissue were collected. A higher rate of disappearance of glucose during the insulin assay was observed for the OVXcycle, compared to the OVXAL. Fasting glycemia and perirenal adipose tissue were lower for the OVXcycle. In comparison with the ShamAL and OVXAL, the OVXcycle showed higher protein expression of the M1 and M3 receptors, SOD1-2 as well as higher carbachol-induced insulin secretion. Under highly stimulatory conditions with 16.7 mM glucose, the OVXAL and OVXcycle presented lower insulin secretion versus ShamAL. Morphological analysis revealed higher iron deposition in the OVXAL islets versus OVXcycle. The results showed that ovariectomy accelerated the loss of pancreatic islet function, while weight cycling was able to restore the characteristics of the islets.
The influence of environmental enrichment and stocking density on the plumage and health conditions of laying hen pullets

ABSTRACT In this study, the effects of environmental enrichment, stocking density, and microclimate on feather condition, skin injuries, and other health parameters were investigated. During 2 rearing periods (RP), non-beak-trimmed Lohmann Brown hybrid pullets were housed in an aviary system for rearing with cages and from week 5 of age onwards with access to a litter area. All pullets were reared in the same barn and under practical conditions. In total, 9,187 (RP 1) and 9,090 (RP 2) pullets were distributed in 9 units, and each unit was assigned to 1 of 3 experimental groups (EG). In the control group (EG 1), the pullets were kept without environmental enrichment and at a commonly used stocking density (22 to 23 pullets per m²). Each unit of the 2 treatment groups was provided with 3 types of environmental enrichment simultaneously (pecking stones, pecking blocks, and lucerne bales), and the pullets were kept at a lower than usual (18 pullets per m²) (EG 2) or commonly used stocking density (EG 3). In each RP, the plumage condition, injuries and health of the pullets, and the microclimate of the housing system were examined 5 times. The statistical relationships of enrichment, stocking density, and microclimate with animal health were estimated via regression models. We found that the provision of environmental enrichment had a significant increasing effect on the plumage quality in week 17. Furthermore, significant relationships were found between several predictors (temperature in the housing system, dust concentration, and age of the pullets) and response variables (plumage condition, body injuries, head injuries, bodyweight, difference to the target weight and uniformity). The results of this study showed that increasing temperature in the housing system and increasing age of the pullets are significantly associated with the occurrence of feather damage and skin injuries during rearing. With stocking densities as high as we used (all > 17 pullets per m²), no significant positive effect of a reduced stocking density could be observed.
Critical Outcomes in Longitudinal Observational Studies and Registries in Patients with Rheumatoid Arthritis: An OMERACT Special Interest Group Report

Objective. Outcomes important to patients are those that are relevant to their well-being, including quality of life, morbid endpoints, and death. These outcomes often occur over the longterm and can be identified in prospective longitudinal observational studies (PLOS). There are no standards for which outcome domains should be considered. Our overarching goal is to identify critical longterm outcome domains for patients with rheumatic diseases, and to develop a conceptual framework to measure and classify them within the scope of OMERACT Filter 2.0. Methods. The steps of this initiative primarily concern rheumatoid arthritis (RA) and include (1) performing a systematic review of RA patient registries and cohorts to identify previously collected and reported outcome domains and measurement instruments; (2) developing a conceptual framework and taxonomy for identification and classification of outcome domains; (3) conducting focus groups to identify domains considered critical by patients with RA; and (4) surveying patients, providers, and researchers to identify critical outcomes that can be evaluated through the OMERACT filter. Results. In our initial evaluation of databases and registries across countries, we found both commonalities and differences, with no clear standardization. At the initial group meeting, participants agreed that additional work is needed to identify which critical outcomes should be collected in PLOS, and suggested several: death, independence, and participation, among others. An operational strategy for the next 2 years was proposed. Conclusion. Participants endorsed the need for an initiative to identify and evaluate critical outcome domains and measurement instruments for data collection in PLOS.
‘Taking the lid off the box’: The value of extended clinical assessment for adolescents presenting with gender identity difficulties

As the number of young people referred to specialist gender identity clinics in the western world increases, there is a need to examine ways of making sense of the range and diversity of their developmental pathways and outcomes. This article presents a joint case review of the authors caseloads over an 18-month period, to identify and describe those young people who presented to the Gender Identity Development Service (GIDS) with gender dysphoria (GD) emerging in adolescence, and who, during the course of assessment, ceased wishing to pursue medical (hormonal) interventions and/or who arrived at a different understanding of their embodied distress. From the 12 cases identified, 2 case vignettes are presented. Implications for the development of clinical practice, service delivery and research are considered.
Separability and Compactness Network for Image Recognition and Superresolution

Convolutional neural networks (CNNs) have wide applications in pattern recognition and image processing. Despite recent advances, much remains to be done for CNNs to learn a better representation of image samples. Therefore, constant optimizations should be provided on CNNs. To achieve a good performance on classification, intuitively, samples’ interclass separability, or intraclass compactness should be simultaneously maximized. Accordingly, in this paper, we propose a new network, named separability and compactness network (SCNet) to rectify this problem. SCNet minimizes the softmax loss and the distance between features of samples from the same class under a jointly supervised framework, resulting in simultaneous maximization of interclass separability and intraclass compactness of samples. Furthermore, considering the convenience and the efficiency of the cosine similarity in face recognition tasks, we incorporate it into SCNet’s distance metric to enable sample features from the same class to line up in the same direction and those from different classes to have a large angle of separation. We apply SCNet to three different tasks: visual classification, face recognition, and image superresolution. Experiments on both public data sets and real-world satellite images validate the effectiveness of our SCNet.