Miracle-dz/UniFAR-FTUs huggingface dataset:
Cutting Edge: CXCR3 Escapes X Chromosome Inactivation in T Cells during Infection: Potential Implications for Sex Differences in Immune Responses

Key Points A bicistronic dual-reporter mouse enables visualization of allelic CXCR3 expression. CXCR3 escapes X chromosome inactivation (XCI) in T cells in vivo during infection. XCI escape by CXCR3 potentially contributes to enhanced Th1 responses in females. CXCR3, an X-linked gene, is subject to X chromosome inactivation (XCI), but it is unclear whether CXCR3 escapes XCI in immune cells. We determined whether CXCR3 escapes XCI in vivo, evaluated the contribution of allelic CXCR3 expression to the phenotypic properties of T cells during experimental infection with Leishmania, and examined the potential implications to sex differences in immune responses. We used a bicistronic CXCR3 dual-reporter mouse, with each CXCR3 allele linked to a green or red fluorescent reporter without affecting endogenous CXCR3 expression. Our results show that CXCR3 escapes XCI, biallelic CXCR3-expressing T cells produce more CXCR3 protein than monoallelic CXCR3-expressing cells, and biallelic CXCR3-expressing T cells produce more IFN-γ, IL-2, and CD69 compared with T cells that express CXCR3 from one allele during Leishmania mexicana infection. These results demonstrate that XCI escape by CXCR3 potentially contributes to the sex-associated bias observed during infection.
Eye-tracking the dual-screen experience

, as well as identify with a suﬃcient temporal resolution, when people switched their attention between devices. The data collected has given us some insight into the nature of the second screen experience, and revealed some of the factors that might be involved in triggering attention shifts. From these results, we hypothesise that attention shifts to the tablet are generally visually driven (e.g., noticing an automatic update in peripheral vision) while shifts to the TV are audio driven (e.g., hearing an exclamation). These results are only the tentative conclusions of a single pilot
Walking increases pain tolerance in humans: an experimental cross-over study

Abstract Background and aims Exercise is commonly used as treatment for chronic pain with positive long-term effects on pain and pain-related disability. In pain-free subjects, hypoalgesia following an acute bout of exercise compared with a control condition has consistently been demonstrated also known as exercise-induced hypoalgesia (EIH). Walking exercise, a low intensity aerobic exercise, is frequently used in clinical practice as an easily applicable intervention for patients with chronic pain. Walking exercise is furthermore recommended as an effective treatment for patients with chronic musculoskeletal pain conditions to alleviate pain and reduce disability, however, the effect of walking on pain sensitivity is currently unknown. The aims of the present study were to investigate (1) the acute effect of walking on pain sensitivity, and (2) the relative (between-subjects) and absolute (within-subject) test-retest reliability of the hypoalgesic response across two sessions separated by 1 week. Methods In this randomised experimental cross-over study including two identical sessions, 35 pain-free subjects performed a standardized 6 min walking test and a duration-matched quiet rest condition in a randomized and counterbalanced order in each session. Before and after both conditions, handheld pressure pain thresholds (PPTs) were assessed at the thigh and shoulder, and pressure pain thresholds (cPPT) and pain tolerance (cPTT) were assessed with computer-controlled cuff algometry at the lower leg. Change in the pain sensitivity measures were analysed with repeated-measures ANOVAs, and test-retest reliability with intraclass correlation coefficients (ICC) and agreements in classification of EIH responders/non-responders between the two sessions. Results All subjects completed the walking conditions in both session 1 and session 2. The perceived intensity of walking assessed with rating of perceived exertion (RPE) and walking distance did not differ significantly between session 1 (distance: 632.5 ± 75.2 meters, RPE: 10.9 ± 1.9) and session 2 (distance: 642.1 ± 80.2 meters, RPE: 11.0 ± 2.4) (p > 0.11). Moreover, RPE showed excellent relative reliability with an ICC value of 0.95 [95%CI: 0.90–0.97]. Walking increased pain tolerance (mean difference: 2.6 kPa [95%CI: 0.5–4.9 kPa; p = 0.02]), but not pain thresholds compared with rest in both sessions. Hypoalgesia after walking demonstrated fair to good relative reliability (ICC = 0.61), however the agreement in classification of EIH responders/non-responders (absolute reliability) across sessions was low and not significant (κ = 0.19, p = 0.30). Conclusions Walking consistently increased pain tolerance but not pain thresholds compared with a duration-matched control condition with fair to good relative reliability between sessions. Based on classification of EIH responders/non-responders the absolute reliability between the two sessions was low indicating individual variance in the EIH response. Future studies should investigate the hypoalgesic effect of a walking exercise in a clinical pain population.
Augmenting subnetwork inference with information extracted from the scientific literature

Many biological studies involve either (i) manipulating some aspect of a cell or its environment and then simultaneously measuring the effect on thousands of genes, or (ii) systematically manipulating each gene and then measuring the effect on some response of interest. A common challenge that arises in these studies is to explain how genes identified as relevant in the given experiment are organized into a subnetwork that accounts for the response of interest. The task of inferring a subnetwork is typically dependent on the information available in publicly available, structured databases, which suffer from incompleteness. However, a wealth of potentially relevant information resides in the scientific literature, such as information about genes associated with certain concepts of interest, as well as interactions that occur among various biological entities. We contend that by exploiting this information, we can improve the explanatory power and accuracy of subnetwork inference in multiple applications. Here we propose and investigate several ways in which information extracted from the scientific literature can be used to augment subnetwork inference. We show that we can use literature-extracted information to (i) augment the set of entities identified as being relevant in a subnetwork inference task, (ii) augment the set of interactions used in the process, and (iii) support targeted browsing of a large inferred subnetwork by identifying entities and interactions that are closely related to concepts of interest. We use this approach to uncover the pathways involved in interactions between a virus and a host cell, and the pathways that are regulated by a transcription factor associated with breast cancer. Our experimental results demonstrate that these approaches can provide more accurate and more interpretable subnetworks. Integer program code, background network data, and pathfinding code are available at https://github.com/Craven-Biostat-Lab/subnetwork_inference
Histone deacetylase activity is required for Botrylloides leachii whole-body regeneration

ABSTRACT The colonial tunicate Botrylloides leachii is exceptional at regenerating from a piece of vascular tunic after loss of all adults from the colony. Previous transcriptome analyses indicate a brief period of healing before regeneration of a new adult (zooid) in as little as 8–10 days. However, there is little understanding of how the resulting changes to gene expression, required to drive regeneration, are initiated and how the overall process is regulated. Rapid changes to transcription often occur in response to chromatin changes, mediated by histone modifications such as histone acetylation. Here, we investigated a group of key epigenetic modifiers, histone deacetylases (HDAC), which are known to play an important role in many biological processes such as development, healing and regeneration. Through our transcriptome data, we identified and quantified the expression levels of HDAC and histone acetyltransferase enzymes during whole-body regeneration (WBR). To determine whether HDAC activity is required for WBR, we inhibited its action using valproic acid and trichostatin A. HDAC inhibition prevented the final morphological changes normally associated with WBR and resulted in aberrant gene expression. Botrylloides leachii genes including Slit2, TGF-β, Piwi and Fzd4 all showed altered mRNA levels upon HDAC inhibition in comparison with the control samples. Additionally, atypical expression of Bl_Piwi was found in immunocytes upon HDAC inhibition. Together, these results show that HDAC function, specifically HDAC I/IIa class enzymes, are vital for B. leachii to undergo WBR successfully. Summary: Histone deacetylases are key epigenetic modifiers in Botrylloides leachii, a tunicate capable of whole-body regeneration. HDAC activity is required for regeneration and correct gene expression in this novel model system.
Number needed to treat: A primer for neurointerventionalists

Background The number needed to treat is a commonly used statistical term in modern neurointerventional practice. It represents the number of patients that need to be treated for one patient to benefit from an intervention. Given its growing popularity in reflecting study results, understanding the basics behind this statistic is of practical value to the neurointerventionalist. Methods Here, we review the basic theory and calculation of the number needed to treat, its application to stroke interventions, and its limitations. In addition, we demonstrate several simple methods of calculating the number needed to treat utilizing recent thrombectomy trial results. By presenting the number needed to treat as a universal metric, we provide a comprehensive comparative of the number needed to treat for key stroke therapies, including mechanical thrombectomy, tissue plasminogen activator, carotid endarterectomy, and prevention with antiplatelet and statin drugs. Conclusions In comparison with available stroke therapies, mechanical thrombectomy stands out as the most effective acute intervention in patients with emergent large-vessel occlusions. Understanding how the number needed to treat is derived and its implications helps provide perspective to clinical trial data, identify health-care resource priorities, and improve communication with patients, health-care providers, and additional key stakeholders.
An emerging ribosomopathy affecting the skeleton due to biallelic variations in NEPRO

Cartilage hair hypoplasia (CHH), anauxetic dysplasia 1, and anauxetic dysplasia 2 are rare metaphyseal dysplasias caused by biallelic pathogenic variants in RMRP and POP1, which encode the components of RNAse‐MRP endoribonuclease complex (RMRP) in ribosomal biogenesis pathway. Nucleolus and neural progenitor protein (NEPRO), encoded by NEPRO (C3orf17), is known to interact with multiple protein subunits of RMRP. We ascertained a 6‐year‐old girl with skeletal dysplasia and some features of CHH. RMRP and POP1 did not harbor any causative variant in the proband. Parents‐child trio exomes revealed a candidate biallelic variant, c.435G>C, p.(Leu145Phe) in NEPRO. Two families with four affected individuals with skeletal dysplasia and a homozygous missense variant, c.280C>T, p.(Arg94Cys) in NEPRO, were identified from literature and their published phenotype was compared in detail to the phenotype of the child we described. All the five affected individuals have severe short stature, brachydactyly, skin laxity, joint hypermobility, and joint dislocations. They also have short metacarpals, broad middle phalanges, and metaphyseal irregularities. Protein modeling and stability prediction showed that the mutant protein has decreased stability. Both the reported variants are in the same domain of the protein. Our report delineates the clinical and radiological characteristics of an emerging ribosomopathy caused by biallelic variants in NEPRO.
Trichome regulator SlMIXTA‐like directly manipulates primary metabolism in tomato fruit

Summary Trichomes are storage compartments for specialized metabolites in many plant species. In trichome, plant primary metabolism is significantly changed, providing substrates for downstream secondary metabolism. However, little is known of how plants coordinate trichome formation and primary metabolism regulation. In this report, tomato (Solanum lycopersicum) trichome regulator SlMIXTA‐like is indicated as a metabolic regulation gene by mGWAS analysis. Overexpression of SlMIXTA‐like in tomato fruit enhances trichome formation. In addition, SlMIXTA‐like can directly bind to the promoter region of gene encoding 3‐deoxy‐7‐phosphoheptulonate synthase (SlDAHPS) to activate its expression. Induction of SlDAHPS expression enhances shikimate pathway activities and provides substrates for downstream secondary metabolism. Our data provide direct evidence that trichome regulator can directly manipulate primary metabolism, in which way plants can coordinate metabolic regulation and the formation of storage compartments for specialized metabolites. The newly identified SlMIXTA‐like can be used for future metabolic engineering.
Plant seed protease inhibitors differentially affect innate immunity in a tumor microenvironment to control hepatocarcinoma.

Identifying tolerance responses to ingested foodstuff over life is essential for understanding dysfunction in metabolic diseases. This study presents a comparative structural and functional analysis of serine-type protease inhibitors (STPIs) from Chenopodium quinoa, Salvia hispanica L. , Avena sativa and Triticum durum. It also evaluates their influence on an in vivo hepatocarcinoma (HCC) model. STPIs are found in all samples with significant differences in protease inhibitory capacity: C. quinoa = S. hispanica < A. sativa = T. durum. STPIs in C. quinoa and S. hispanica appear as heterologous complexes, while those in A. sativa are present as homologous complexes. T. durum provides different subunits with STPI capacity. HPLC-RP-ESI analyses revealed homology between STPIs in the different samples and the partial resistance of those to simulated gastrointestinal digestion. In vivo, STPIs from S. hispanica showed the most positive effects, increasing F4/80+ cells normalizing the expression (mRNA) of CD36 and the innate immune 'Toll-like' receptor (TLR)-4. Only STPIs from C. quinoa and S. hispanica did not impair the production of inflammatory mediators (granulocyte-monocyte colony stimulating factor, stem cell factor and TNFα), contributing to maintaining the polarization of the antitumoral M1 macrophage phenotype. These structural and functional features of STPIs from C. quinoa and S. hispanica can be used to control HCC aggressiveness.
Acute effects of kinesio taping on muscular strength and endurance parameters of the finger flexors in sport climbing: A randomised, controlled crossover trial

Abstract Kinesio taping (KT) is a commonly used intervention in sports and, recently, KT has become popular among athletes competing in sport climbing and bouldering events. However, evidence on the effect of KT on grip strength and endurance is still controversial. Therefore, the purpose of this study was to evaluate immediate effects of KT on muscular strength and endurance of the finger flexor muscles in sport climbers. Twenty recreationally-trained active sport climbers (10 men, 10 women) aged 28.5 ± 10.6 years performed one familiarisation trial and subsequently, in a randomised crossover design, two test trials either with (TAPE) or without (CONTROL) KT over the finger flexor muscles. Test trials consisted of three performance measurements (hand grip strength and endurance, finger hang, and lap climbing) at intervals of 48 h in a randomised order. We observed no significant differences in the parameters of hand grip peak force, fatigue index, finger hang time, lap climbing distance and time, or maximum blood lactate values after lap climbing between the TAPE and CONTROL trials (p > 0.05). The participants’ climbing ability was significantly correlated with the intra-individual performance changes between the TAPE and CONTROL conditions for the fatigue index (r = −0.598, p = 0.005), but not in any of the other performance-related parameters. Therefore, KT over the finger flexor muscles neither enhanced hand grip strength and endurance nor the sport climbing performance parameters of finger hang, lap climbing distance and time, and maximum blood lactate values after lap climbing.
A novel group parenting intervention to reduce emotional and behavioural difficulties in young autistic children: protocol for the Autism Spectrum Treatment and Resilience pilot randomised controlled trial

Introduction The majority of young autistic children display impairing emotional and behavioural difficulties that contribute to family stress. There is some evidence that behavioural parenting interventions are effective for reducing behavioural difficulties in autistic children, with less evidence assessing change in emotional difficulties. Previous trials have tended to use unblinded parent-report measures as primary outcomes and many do not employ an active control, limiting the conclusions that can be drawn. Methods and analysis The Autism Spectrum Treatment and Resilience study is a pilot randomised controlled trial (RCT) testing the specific effect of a 12-week group parenting intervention (Predictive Parenting) on primary and secondary outcomes, in comparison to an attention control condition consisting of psychoeducation parent groups. Following a feasibility study to test research procedures and the interventions, the pilot RCT participants include 60 parents of autistic children aged 4–8 years who are randomised to Predictive Parenting versus the attention control. Measures are administered at baseline and post intervention to assess group differences in child and parent outcomes, costs and service use and adverse events. The primary outcome is an objective measure of child behaviours that challenge during interactions with their parent and a researcher. The trial aims to provide data on recruitment, retention, completion of measures and acceptability of the intervention and research protocol, in addition to providing a preliminary indication of potential efficacy and establishing an effect size that could be used to power a larger-scale efficacy trial. We will also provide preliminary estimates of the cost-effectiveness of the interventions. Ethics and dissemination Ethical approval was granted from NHS Camden and Kings Cross Research Ethics Committee (ref: 16/LO/1769) along with NHS R&D approval from South London and Maudsley, Guy’s and St Thomas', and Croydon Health Services NHS Trusts. The findings will be disseminated through publication in peer-reviewed journals and presentations at conferences. Trial registration number ISRCTN91411078
Backstepping Based Adaptive Control of Magnetic Levitation System

In view of parameter uncertainty in the magnetic levitation system, the adaptive controller design problem is investigated for the system. Nonlinear adaptive controller based on backstepping is proposed for the design of the actual system with parameter uncertainty. The controller can estimate the uncertainty parameter online so as to improve control accuracy. Theoretical analysis shows that the closed-loop system is stable regardless of parameter uncertainty. Simulation results demonstrate the effectiveness of the presented method.
Comparison between a commercial blend of functional oils and monensin on the performance and microbiota of coccidiosis-challenged broilers.

The aim of the study was to evaluate the effects of a cashew nut shell oil and commercial castor oil blend (CNSL-Castor oil) on the performance and microbiota of broiler chickens with and without coccidiosis challenge. A total of 864 one-day-old male chicks (Cobb) were randomly distributed to receive 6 treatments (8 pens/treatment; 18 chicks/pen) in a 3 × 2 factorial, with 3 additives (control [non-additives], 100 ppm sodium monensin, or 0.15% CNSL-Castor oil blend), and 2 levels of coccidiosis challenge at 14 D of age (unchallenged or inoculated by gavage with 1 mL of solution containing oocysts sporulated with Eimeria tenella, Eimeria acervulina, and Eimeria maxima). No differences in productive performance were observed among treatments in the pre-challenge period and in unchallenged birds (P > 0.05). Seven-days post-challenge, birds receiving monensin performed better than birds in the positive control group (non-additive and challenge) or in the CNSL-Castor oil group (P > 0.05). However, 14 D post-challenge, birds supplemented with CNSL-Castor oil presented higher weight gain and better feed conversion (P > 0.05), without any change in feed intake (P > 0.05). During the accumulated period (1 to 42 D of age), the live weight, weight gain, and feed intake did not differ between the CNSL-Castor oil and monensin groups, both of which presented higher values than the positive control. Lactobacillus spp. and Clostridium perfringens numbers were increased in the challenged birds (P < 0.05). CNSL-Castor oil supplementation reduced Clostridium cluster XIV, C. perfringens, and S. aureus, compared with the monensin and control groups (P > 0.05). In addition, the CNSL-Castor oil group presented the highest number of Lactobacillus spp. copies, followed by the monensin and positive control groups (P > 0.05). Thus, monensin and CNSL-Castor oil effectively minimized the impact of coccidiosis at different times. While monensin acts as an antimicrobial, CNSL-Castor oil modulates the intestinal microbiota with antimicrobial action against gram-positive bacteria, mainly C. perfringens and S. aureus.
A systematic review of strategies to increase drinking‐water access and consumption among 0‐ to 5‐year‐olds

The objective of this study is to identify promising strategies for improving drinking‐water access and consumption among children aged 0 to 5 years. MEDLINE/PubMed, Embase, ERIC, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched in this review. Studies included peer‐reviewed, full‐text studies from high‐income countries, published in English between January 1, 2000, and January 12, 2018, that evaluated interventions to increase water access or consumption in children aged 0 to 5 years. Twenty‐five studies met inclusion criteria; 19 used an effective intervention strategy to increase water access or water consumption. Three studies addressed both water access and consumption. Frequently used strategies included policy and practice changes, increasing water access and convenience, and education, training, or social support for caregivers. Studies were of fair methodological quality (average score: 18.8 of 26) for randomized studies and of moderate quality (5.1 of 9) for non‐randomized studies. To date, few high‐quality studies with objectively measured outcomes have clearly demonstrated strategies that may influence water intake and consumption among young children aged 0 to 5 years.