Miracle-dz/UniFAR-FTUs huggingface dataset:
The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies.

Meningiomas are the most common primary intracranial tumor with current classification offering limited therapeutic guidance. Here, we interrogated meningioma enhancer landscapes from 33 tumors to stratify patients based upon prognosis and identify novel meningioma-specific dependencies. Enhancers robustly stratified meningiomas into three biologically distinct groups (adipogenesis/cholesterol, mesodermal and neural crest) distinguished by distinct hormonal lineage transcriptional regulators. Meningioma landscapes clustered with intrinsic brain tumors and hormonally-responsive systemic cancers with meningioma subgroups reflecting progesterone or androgen hormonal signaling. Enhancer classification identified a subset of tumors with poor prognosis, irrespective of histological grading. Super enhancer signatures predicted drug dependencies with superior in vitro efficacy to treatment based upon the NF2 genomic profile. Inhibition of DUSP1, a novel and druggable meningioma target, impaired tumor growth in vivo. Collectively, epigenetic landscapes empower meningioma classification and identification of novel therapies.
NIRS-derived skeletal muscle oxidative capacity is correlated with aerobic fitness and independent of sex.

Near-infrared spectroscopy (NIRS) provides a simple and reliable measure of skeletal muscle oxidative capacity; however, its relationship to aerobic fitness and sex are unclear. We hypothesized that NIRS-derived oxidative capacity in the vastus lateralis (VL) and medial gastrocnemius (MG) would be correlated to indices of aerobic fitness and independent of sex. Twenty-six participants (13 males, 13 females) performed ramp- and step-incremental tests to volitional exhaustion on separate days to establish maximal oxygen uptake (V̇O2max), peak power output (PPO), lactate threshold (LT), gas exchange threshold (GET), respiratory compensation point (RCP), and maximal fat oxidation (MFO). Data were normalized to lean body mass to account for sex-based differences in body composition. Exercise tests were preceded by duplicate measurements of NIRS-derived oxidative capacity on the VL and MG muscles (i.e., repeated arterial occlusions following a brief set of muscle contractions). Skeletal muscle oxidative capacity for the VL (mean±SD: 21.9±4.6s) and MG (22.5±6.1s) were similar but unrelated (r2=0.03, p=0.39). Skeletal muscle oxidative capacity for the VL, but not the MG (p>0.05 for all variables), was significantly correlated with V̇O2max (r2=0.24; p=0.01), PPO (r2=0.23; p=0.01), LT (r2=0.23; p=0.01), GET (r2=0.23; p=0.01), and RCP (r2=0.27; p=0.006). MFO was not correlated with VL or MG skeletal muscle oxidative capacity (p>0.05). Females (54.9±4.5mL/kg LBM/min) and males (56.0±6.2mL/kg LBM/min), matched for V̇O2max (p=0.62), had similar NIRS-derived oxidative capacities for VL (20.7±4.4s vs. 23.2±4.6s; p=0.18) and MG (24.4±6.8s vs. 20.5±4.8; p=0.10). Overall, NIRS-derived skeletal muscle oxidative capacity in VL is indicative of aerobic fitness and independent of sex in humans.
Affective traits, states, and breathlessness.

PURPOSE OF REVIEW Breathlessness is a prevalent and aversive symptom in various conditions and closely related to affect. Here, we review recent literature from the previous 18 months examining the interactions between affective traits and states with breathlessness. RECENT FINDINGS Available studies used various qualitative, quantitative, and experimental research designs in diverse samples of patients with breathlessness and in healthy individuals. Most studies clearly demonstrated that nonspecific forms of negative affective personality traits such as anxiety and depression, disease or symptom-specific forms such as fear-of-dyspnea and fear-of-physical activity as well as short-lasting negative affective states such as experimentally induced fear were associated with greater breathlessness. Moreover, breathlessness was shown to evoke negative affect, whereas positive affect reduced breathlessness. Different treatment approaches demonstrated concurrent beneficial effects on both negative affect and breathlessness and several potential mechanisms underlying these interactions were suggested. SUMMARY Negative affect is common in diverse patient groups suffering from breathlessness and is related to increased burden because of breathlessness. Future research is required to improve our understanding of the mechanisms underlying these associations together with increased clinical efforts for improved detection and treatment of negative affect in breathless patients.
Intralesional immunotherapy for the treatment of anogenital warts in pediatric population

Abstract Background The prevalence of anogenital warts is increasing in adults as well as in pediatric population. The treatment of anogenital warts is challenging, particularly in children as most conventional modalities are painful and associated with high recurrence rates. Objectives To evaluate the efficacy and safety of intralesional immunotherapy for the treatment of anogenital warts in pediatric patients. Methods Forty child presenting with multiple anogenital warts were randomly assigned into 3 groups. The first group (15 patients) received intralesional MMR vaccine, the second group (15 patients) received intralesional Candida antigen and the third group (10 patients) received intralesional saline as a control. Each modality was injected into the largest wart at 2-week intervals until complete clearance or for a maximum of 5 sessions. Results Highly significant difference was found between the therapeutic response of anogenital warts to both MMR vaccine and Candida antigen compared to intralesional saline (p = .005). No significant difference was observed between MMR vaccine and Candida antigen groups (p = .885). Side effects were mild and no recurrence was detected in the 6 month follow-up period. Conclusions Intralesional immunotherapy is a promising effective and well-tolerated treatment modality for multiple anogenital warts in children.
Image Co-Segmentation via Examples Guidance

Given a collection of images which contains objects from the same category, the co-segmentation methods aim at simultaneously segmenting such common objects in each image. Most of existing co-segmentation approaches rely on comput-ing similarities inter-regions representing foregrounds in these images. However, region similarity measurement is challenging due to the large appearance variations among objects in the same category. In addition, for real-world images which have cluttered backgrounds, the existing co-segmentation approaches miss sufficient robustness to extract the common object from the background. In this paper, we propose a new co-segmentation method which takes advantage of the reliable segmentation of few selected images, in order to guide the segmentation of the remaining images in the collection. A random sample of images is first selected from the image collection. Then, the selected images are segmented using an interactive segmentation method. These segmentation results are used to construct positive/negative samples of the targeted common object and background regions respectively. Finally, these samples are propagated to the remain-ing images in the collection through computing both local and global consistency. The experiments on the iCoseg and MSRC datasets demonstrate the performance and robustness of the proposed method.
COVID-19: Exposing and addressing health disparities among ethnic minorities and migrants

COVID-19: Exposing and addressing health disparities among ethnic minorities and migrants Christina Greenaway, MD, MSc1,2,3,*, Sally Hargreaves, PhD4, Sapha Barkati, MD, MSc3,5, Christina M. Coyle, MD, MS6, Federico Gobbi, MD, PhD7, Apostolos Veizis, MD8 and Paul Douglas, MD9 1Division of Infectious Diseases, Jewish General Hospital, McGill University, Montreal, Canada, 2Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Canada, 3JD MacLean Centre for Tropical Diseases, McGill University Health Centre, McGill University, Montreal, Canada, 4Institute for Infection and Immunity, St George’s University of London, London, UK, 5Department of Medicine, Division of Infectious Diseases, McGill University Health Center, McGill University, Montreal, Canada, 6Department of Medicine, Division of Infectious Disease, Albert Einstein College of Medicine, Bronx, NY, USA, 7Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy, 8Médecins Sans Frontières, Athens, Greece and 9Migration Health Division, International Organization for Migration, Geneva, Switzerland
PROVISIONING RATE AND ATTENDANCE PATTERNS OF WANDERING ALBATROSSES AT BIRD ISLAND, SOUTH GEORGIA

Abstract We investigated foraging behavior of Wandering Albatrosses (Diomedea exulans) breeding at South Georgia to assess how sex and season-specific foraging patterns relate to provisioning performance. We estimated Wandering Albatross chicks require 60–65 kg of food over the chick-rearing period; males deliver 54% of this total. Meal size delivered by both sexes remained essentially constant throughout the post-brooding chick-rearing period, but foraging trip duration varied considerably. Females made consistently longer foraging trips and delivered smaller meals but transported an average load that was 20% heavier in proportion to their body mass than males. We suggest that chick-rearing places greater demands on females compared with males and Wandering Albatrosses work hard to deliver food during the first half of chick rearing (at the expense of their own condition), thereafter reduce their work rate, presumably so as not to compromise their survival.
Spinal caspase-6 regulates AMPA receptor trafficking and dendritic spine plasticity via netrin-1 in postoperative pain following orthopedic surgery for tibial fracture in mice.

Chronic postoperative pain hinders functional recovery after bone fracture and orthopedic surgery. Recently reported evidence indicates that caspase-6 is important in excitatory synaptic plasticity and pathological pain. Meanwhile, netrin-1 controls post-synaptic recruitment of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and synaptogenesis. The present work aimed to examine whether caspase-6 and netrin-1 contribute to fracture-induced postoperative allodynia. A mouse model of tibial fracture by intramedullary pinning was generated for inducing postoperative pain. Then, paw withdrawal threshold, spinal caspase-6 activity, netrin-1 secretion, AMPAR trafficking, and spine morphology were examined. Caspase-6 inhibition and netrin-1 knockdown by shRNA were performed to elucidate the pathogenetic mechanism of allodynia and its prevention. Whole-cell patch-clamp recording was carried out to assess caspase-6's function in spinal AMPAR-induced current. Tibial fractures after orthopedic operation initiated persistent postsurgical mechanical and cold allodynia, accompanied by increased spinal active caspase-6, netrin-1 release, GluA1-containing AMPAR trafficking, spine density and AMPAR-induced current in dorsal horn neurons. Caspase-6 inhibition reduced fracture-associated allodynia, netrin-1 secretion and GluA1 trafficking. Netrin-1 deficiency impaired fracture-caused allodynia, post-synaptic GluA1 recruitment and spine plasticity. The specific GluA2-lacking AMPAR antagonist NASPM also dose-dependently prevented postoperative pain. The reduction of fracture-mediated postoperative excitatory synaptic AMPAR current in the dorsal horn by caspase-6 inhibition was compromised by recombinant netrin-1. Exogenous caspase-6 induced pain hypersensitivity, reversing by netrin-1 knockdown or co-application of NASPM. Thus, spinal caspase-6 modulation of GluA1-containing AMPAR activation and spine morphology through netrin-1 secretion is important in the development of fracture-related postsurgical pain in the mouse.
Long-term consequences of early development on personality traits: a study in European rabbits

Early-life parameters such as litter size and growth are frequently associated with an animal's behavioral performance or motor skills as well as with its stress responsiveness. All these traits can be involved in the ontogeny of behavioral phenotypes, and therefore, we wanted to know whether features such as early growth also show long-term correlations with the animals' behavioral responses to challenges around maturity. We collected data on the early postnatal development of individually marked European rabbits living in a field enclosure and conducted 2 standardized behavioral tests shortly before the animals matured. In small enclosures, we experimentally tested their behavioral responses 1) in this novel environment and 2) to the confrontation with predator odor. Animals, which were more exploratory during the novel environment test, showed lower behavioral signs of anxiety during the predator test. Both responses were correlated with individual pup body mass, with subjects with higher body mass being more exploratory in the first test and showing lower levels of anxiety in the second. The animals' current body mass or age when being tested were not correlated with any of their responses. First, the correlated responses of the animals during the different contexts of the applied tests strongly suggest the existence of behavioral phenotypes in European rabbits. Second, and most importantly, our study provides evidence that an animal's early development can exert long-term effects on its personality type, although it is not clear whether body mass per se or some correlated physiological features drive the observed relationships. Copyright 2011, Oxford University Press.
PKAN neurodegeneration and residual PANK2 activities in patient erythrocytes

Pantothenate kinase 2‐associated neurodegeneration (PKAN) is a rare neurodegenerative disease caused by mutations in the pantothenate kinase 2 (PANK2) gene. PKAN is associated with iron deposition in the basal ganglia and, occasionally, with the occurrence of misshaped erythrocytes (acanthocytes). The aim of this study was to assess residual activity of PANK2 in erythrocytes of PKAN patients and to correlate these data with the type of PANK2 mutations and the progression of neurodegeneration.
Managing sickle cell disease in pregnancy, the success and the challenges: Our experience in a semi-urban tertiary health-care facility, Southwest, Nigeria

Background: Pregnancy complicated by sickle cell disease (SCD) is known to be associated with poor maternal and fetal outcomes. However, the challenges encountered in managing these patients in the rural and semi-urban areas are yet to be evaluated by many of these studies. Objectives: The objective of the study is to determine the maternal and fetal outcomes of pregnancy complicated by SCD, the importance of the pregestational counseling and care and the challenges faced by the health-care givers in giving them optimal care in Nigeria, especially in rural and semi-urban settings. Materials and Methods: This is a prospective study. All diagnosed SCD pregnant women seen between May 2013 and April 2016 were recruited into the study, after taking informed consent from them. They were all subjected to the standard management of sickle disease in pregnancy. The antenatal, intrapartum, immediate postdelivery and the puerperal events were documented in structured obstetric data sheets. The information obtained from these data sheets were used to generate a database for analysis. Results: The total number of the patients recruited into this study was 54. They were all booked patients or those referred from other centers with adequate antenatal records. The incidence of SCD in this study was 1.15% (HBSS; 0.49%, HBSC; 0.55%, and HBCC; 0.11%). The mean maternal ages at booking were 26.35 ± 5.76, 27.12 ± 3.28, and 27.004 ± 0.69 years for HBSS, HBSC, and HBCC, respectively. The mean gestational ages at delivery were 37.43 ± 1.36, 38.58 ± 1.21, and 35.80 ± 0.84 weeks for HBSS, HBSC, and HBCC, respectively. The antenatal bookings were all in the second and third trimesters. Similarly, only 10 (39.96%) had pregestational counseling and care before pregnancy. The patients were mostly middle social class status and with poor antenatal clinic visits. Discussion: Poor maternal and fetal outcomes were seen more in HBSS than HBSC and HBCC. However, statistical analysis showed statistically significant differences only in the prematurity, preterm labor, and the mean fetal weights. Factors such as pregestational counseling and care, social class, parity, and early antenatal booking play important roles in achieving optimal care and excellent outcomes. Conclusion: Many authors documented poor maternal and fetal outcomes in pregnancies complicated by SCD. The focus now should be identifying factors that may militate against achieving excellent results from the optimal care of these patients. This we have initiated in this study.
The distribution and environmental requirements of large brown seaweeds in the British Isles

Kelps, fucoids and other large brown seaweeds are common and important features of temperate coastal zones. The British Isles is a centre for seaweed diversity in the NE Atlantic, but, despite numerous surveys, an incomplete picture of the distribution remains. Survey data and herbarium specimens were used to examine the environmental preference of 15 species of large brown seaweeds, covering the orders Laminariales (kelps), Fucales (wracks) and one species of Tilopteridales. Habitat suitability models were developed to estimate broad-scale distribution and area of habitat created by these species around the British Isles. Topographic parameters were important factors limiting distributions. Generally, temperature did not appear to be a limiting factor, probably because the British Isles lies in the centre of the NE Atlantic distribution for most species, and not at climatic tolerance limits. However, for the recent migrant Laminaria ochroleuca, temperature was found to be important for the model, thus range expansion could continue northwards provided dispersal is possible. In contrast, the widespread Alaria esculenta showed a negative association with warmer summer temperatures. The total potential habitat around the British and Irish coastline is more than 19,000 km2 for kelps and 11,000 km2 for wracks, which represents a significant habitat area similar in scale to British broadleaf forest. We conclude that large brown algal species need to be managed and conserved in a manner that reflects their scale and importance.
A review of the effects of forage condensed tannins on ruminal fermentation and bloat in grazing cattle

Condensed tannins (CT) are polyphenolic secondary plant products that are widespread in the plant kingdom. By definition, CT bind to protein and are regarded as "antinutritional" compounds which reduce protein digestibility. Variations in CT chemistry alter protein binding capacities among polymers from different plant species and developmental stages. Condensed tannins interact with proteins in feed, saliva and microbial cells, with microbial exoenzymes, and with endogenous proteins or other feed components, which alters digestive processes as compared with diets free of CT. Tannin levels exceeding 40 to 50 g kg−1 DM in forages may reduce protein and DM digestibility of the forages by ruminants. At low to moderate levels, CT increase the quantity of dietary protein, especially essential amino acids, flowing to the small intestine. Unlike alfalfa, legumes that contain CT do not cause bloat. Dietary CT may provide a means to beneficially manipulate protein digestion and/or prevent pasture bloat in ruminant.
Utility of cervical pap smears in screening of postmenopausal women

Introduction: Cervical cancer is one of the most preventable and curable cancer. The papanicolaou cervical cytology test is capable of detecting cervical cancer at an early stage and is widely used in developed countries, where it has decreased both the incidence and mortality of cervical cancer. Therefore, it is important to investigate the significance of screening in postmenopausal women. Objectives of the study: To study the cytomorphology of different cervical lesions among postmenopausal women. To determine the significance of cervical cancer screening in symptomatic and asymptomatic postmenopausal women. Materials and Methods: A prospective study of one year duration from January 2017 to December 2017 was conducted in the department of pathology of our institution. The conventional cervical pap smears of postmenopausal women were obtained from the department of gynaecology and reported according to the 2014 Bethesda system. Results: Out of the 198 smears of postmenopausal women screened, 17 (8.6%) were normal smears, 12 (6.1%) were atropic, 97(48.9%) were inflammatory smears. Atypical squamous cells of undetermined significance (ASC-US) were 31(15.7%) cases, 10(5.1%) were reactive cellular changes associated with inflammation, 06 (3.0%) were low grade squamous intraepithelial lesion (LSIL), 08 (4.0%) were high grade squamous intraepithelial lesion (HSIL) and 01 (0.5%) case of squamous cell carcinoma was observed in our study. 16(8.1%) smears were unsatisfactory for evaluation. Conclusion: The risk of cervical cancer increases as the age advances, therefore postmenopausal women should be screened with cervical Pap smears for early detection and better management. Keywords: Pap smear, Postmenopausal women, Screening.
Moderate warm temperature improves shoot growth, affects carbohydrate status and stimulates photosynthesis of sweet orange plants

Citrus plants were grown under two thermal conditions for evaluating carbon metabolism acclimation to moderate warm temperature (30/20oC, day/night), and its likely impact on plant growth. As reference, plants were grown at 25/20oC, in which they were subjected to optimum temperature for photosynthesis during the diurnal period (25oC). Higher photosynthetic rates were found at 30/20oC as compared to 25/20oC in both mature and young leaves, being this response associated with higher stomatal conductance. After 30 days of thermal treatment, plants grown at 30/20oC presented higher shoot growth as compared to those at 25/20oC. The carbohydrate concentration decreased in stem and root tissues, while it increased in leaf tissues under moderate warm conditions. Both mature and young leaves showed higher photoassimilate consumption/exportation at 30/20oC than at 25/20oC. In this paper, we have proven that citrus plants present a positive balance in carbon metabolism as an acclimation mechanism to temperature changes, with plants presenting increased photosynthesis. Such photosynthetic acclimation was associated with improved vegetative growth, being both mature and young tissues sensitive to changes in thermal regimen.
Probabilisitic forecasts in hierarchical time series

Forecast reconciliation involves adjusting forecasts to ensure coherence with aggregation constraints. We extend this concept from point forecasts to probabilistic forecasts by redefining forecast reconciliation in terms of linear functions in general, and projections more specifically. New theorems establish that the true predictive distribution can be recovered in the elliptical case by linear reconciliation, and general conditions are derived for when this is a projection. A geometric interpretation is also used to prove two new theoretical results for point forecasting; that reconciliation via projection both preserves unbiasedness and dominates unreconciled forecasts in a mean squared error sense. Strategies for forecast evaluation based on scoring rules are discussed, and it is shown that the popular log score is an improper scoring rule with respect to the class of unreconciled forecasts when the true predictive distribution coheres with aggregation constraints. Finally, evidence from a simulation study shows that reconciliation based on an oblique projection, derived from the MinT method of Wickramasuriya, Athanasopoulos and Hyndman (2018) for point forecasting, outperforms both reconciled and unreconciled alternatives.