Miracle-dz/UniFAR-FTUs huggingface dataset:
Narcolepsy type 1: what have we learned from genetics?

Abstract Type-1 narcolepsy is a severe neurological disorder with distinct characteristic of loss of hypocretin neurotransmitter. Genetic analysis in type-1 narcolepsy have revealed a unique signal pointing toward autoimmune, rather than psychiatric origin. While type-1 narcolepsy has been intensively studied, the other subtypes of hypersomnolence, narcolepsy, and hypersomnia are less thoroughly understood. This review summarizes the latest breakthroughs in the field in narcolepsy. The goal of this article is to help the reader to understand better the risk from genetic factors and their interplay with immune, genetic, and epidemiological aspects in narcolepsy.
Nervous system of the earthworm, lumbricus terrestris L.

A study of the peripheral nerves of the earthworm shows that one pair of nerve trunks arise from the lateral regions of the cerebral ganglion, one pair from near the lateral, and two pairs from the ventral region of the circumpharyngeal connectives. These supply, in the order given, the prostomium, segment 1 and segment 2. Segment 3 and each succeeding segment, except the last, are supplied with three pairs of nerve trunks which arise from the nerve cord in the segment concerned. None of the nerve trunks of the body was observed to send branches to more than one segment, which shows that they are segmental in origin and distribution.
Metabolomic analysis reveals differences in evolution between maize and rice.

Metabolites are the intermediate and final products of metabolism, which play essential roles in plant growth, evolution and adaptation to changing climates. However, it is unclear how evolution contributes to metabolic variation in plants. Here, we investigated the metabolomics data from leaf and seed tissues in maize and rice. By a principal component analysis (PCA) based on leaf metabolites but not seed metabolites, it was able to be clearly separated for rice Indica and Japonica accessions, while two maize subgroups, temperate and tropical, showed more visible admixture. Rice and maize seed exhibited significant interspecific differences in metabolic variation, while within rice, leaf and seed displayed similar metabolic variations. Among 10 metabolic categories, flavonoids had higher variation in maize than rice, indicating flavonoids are a key constituent of interspecific metabolic divergence. Interestingly, metabolic regulation was additionally found to be dramatically reshaped from positive to negative correlations, indicative of the differential evolutionary processes in maize and rice. Moreover, perhaps due to this divergence significantly more metabolic interactions were identified in rice than maize. Furthermore, in rice, the leaf was found to harbor much more intense metabolic interactions than the seed. Our result suggests that metabolomes are valuable for tracking evolutionary history, thereby complementing and extending genomic insights concerning which features are responsible for interspecific differentiation in maize and rice.
Cell response to substrate rigidity is regulated by active and passive cytoskeletal stress

Significance The observation that cells sense and adapt to the physical stiffness of their environment is consistent across many different cell types and has profound implications in the final biological phenotype. In a diseased state or transformed cell, the substrate rigidity sensing and adaptation machinery is perturbed or outright abolished, which leads to progression of the disease, thus fully understanding this process is vital. Here, we found that the organization of the actin cytoskeleton in fibroblasts was governed by active and passive cross-linkers and the relative cell-to-substrate elasticity, and we present a phenomenological model detailing this. As cell rigidity sensing is a robust mechanism observed in various contexts, a generalized physics-based understanding such as presented here will yield universal insights. Morphogenesis, tumor formation, and wound healing are regulated by tissue rigidity. Focal adhesion behavior is locally regulated by stiffness; however, how cells globally adapt, detect, and respond to rigidity remains unknown. Here, we studied the interplay between the rheological properties of the cytoskeleton and matrix rigidity. We seeded fibroblasts onto flexible microfabricated pillar arrays with varying stiffness and simultaneously measured the cytoskeleton organization, traction forces, and cell-rigidity responses at both the adhesion and cell scale. Cells adopted a rigidity-dependent phenotype whereby the actin cytoskeleton polarized on stiff substrates but not on soft. We further showed a crucial role of active and passive cross-linkers in rigidity-sensing responses. By reducing myosin II activity or knocking down α-actinin, we found that both promoted cell polarization on soft substrates, whereas α-actinin overexpression prevented polarization on stiff substrates. Atomic force microscopy indentation experiments showed that this polarization response correlated with cell stiffness, whereby cell stiffness decreased when active or passive cross-linking was reduced and softer cells polarized on softer matrices. Theoretical modeling of the actin network as an active gel suggests that adaptation to matrix rigidity is controlled by internal mechanical properties of the cytoskeleton and puts forward a universal scaling between nematic order of the actin cytoskeleton and the substrate-to-cell elastic modulus ratio. Altogether, our study demonstrates the implication of cell-scale mechanosensing through the internal stress within the actomyosin cytoskeleton and its coupling with local rigidity sensing at focal adhesions in the regulation of cell shape changes and polarity.
Comparison of multiplicative and additive hyperbolic and hyperboloid discounting models in delayed lotteries involving gains and losses

Many day-to-day decisions may involve risky outcomes that occur at some delay after a decision has been made. We refer to such scenarios as delayed lotteries. Despite human choice often involves delayed lotteries, past research has primarily focused on decisions with delayed or risky outcomes. Comparatively, less research has explored how delay and probability interact to influence decisions. Within research on delayed lotteries, rigorous comparisons of models that describe choice from the discounting framework have not been conducted. We performed two experiments to determine how gain or loss outcomes are devalued when delayed and risky. Experiment 1 used delay and probability ranges similar to past research on delayed lotteries. Experiment 2 used individually calibrated delay and probability ranges. Ten discounting models were fit to the data using a genetic algorithm. Candidate models were derived from past research on discounting delayed or probabilistic outcomes. We found that participants' behavior was best described primarily by a three-parameter multiplicative model. Measures based on information criteria pointed to a solution in which only delay and probability were psychophysically scaled. Absolute measures based on residuals pointed to a solution in which amount, delay, and probability are simultaneously scaled. Our research suggests that separate scaling parameters for different discounting factors may not be necessary with delayed lotteries.
Utility of Liver Function Tests and Fatty Liver Index to Categorize Metabolic Phenotypes in a Mediterranean Population

The aim of this study was to analyze the utility of liver function tests (LFT) and fatty liver index (FLI), a surrogate marker of non-alcoholic fatty liver disease, in the categorization of metabolic phenotypes in a Mediterranean population. A cross-sectional study was performed on a random representative sample of 2233 adults assigned to a health center in Málaga, Spain. The metabolic phenotypes were determined based on body mass index (BMI) categorization and the presence or absence of two or more cardiometabolic abnormalities (high blood pressure, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, pre-diabetes) or type 2 diabetes. No difference was observed between metabolically healthy and metabolically abnormal phenotypes on LFT. The mean FLI of the population was 41.1 ± 28.6. FLI was significantly higher (p < 0.001) in the metabolically abnormal phenotypes in all BMI categories. The proportion of individuals with pathological FLI (≥60) was significantly higher in the metabolically abnormal overweight and obese phenotypes (p < 0.001). On a multivariate model adjusted for sex, age, and waist circumference, a significant correlation was found between pathological FLI and metabolically abnormal phenotypes in the overweight and obese BMI categories. Area under the curve (AUC) of FLI as a biomarker was 0.76, 0.74, and 0.72 for the metabolically abnormal normal-weight, overweight, and obese groups, respectively. Liver biochemistry is poorly correlated with metabolic phenotypes. Conversely, a good correlation between FLI, as a marker of non-alcoholic fatty liver disease (NAFLD), and metabolically abnormal phenotypes in all BMI ranges was found. Our study suggests that FLI may be a useful marker for characterizing metabolically abnormal phenotypes in individuals who are overweight or obese.
Cytomegalovirus inhibition of extrinsic apoptosis determines fitness and resistance to cytotoxic CD8 T cells

Significance CD8+ T lymphocytes protect from intracellular pathogens by recognizing pathogen's antigenic peptides presented on MHC-I molecules. Many viruses evade T cell control by using genes that subvert MHC-I presentation on infected cells. Here we shift this paradigm and show that viral proteins that block the effector branch of T cells are more efficient for T cell evasion than MHC-I downregulation. The block of signaling in infected target cells at the level of caspase-8 as a crucial convergence point of death-receptor and perforine/granzyme pathways in the viral evasion of cytotoxic T cells. We show that these principles apply in the clinically relevant HCMV infection and in the biologically relevant in vivo context, using the MCMV experimental model. Viral immune evasion is currently understood to focus on deflecting CD8 T cell recognition of infected cells by disrupting antigen presentation pathways. We evaluated viral interference with the ultimate step in cytotoxic T cell function, the death of infected cells. The viral inhibitor of caspase-8 activation (vICA) conserved in human cytomegalovirus (HCMV) and murine CMV (MCMV) prevents the activation of caspase-8 and proapoptotic signaling. We demonstrate the key role of vICA from either virus, in deflecting antigen-specific CD8 T cell-killing of infected cells. vICA-deficient mutants, lacking either UL36 or M36, exhibit greater susceptibility to CD8 T cell control than mutants lacking the set of immunoevasins known to disrupt antigen presentation via MHC class I. This difference is evident during infection in the natural mouse host infected with MCMV, in settings where virus-specific CD8 T cells are adoptively transferred. Finally, we identify the molecular mechanism through which vICA acts, demonstrating the central contribution of caspase-8 signaling at a point of convergence of death receptor-induced apoptosis and perforin/granzyme-dependent cytotoxicity.
Effects of Linagliptin on Cardiovascular and Kidney Outcomes in People With Normal and Reduced Kidney Function: Secondary Analysis of the CARMELINA Randomized Trial

OBJECTIVE Type 2 diabetes is a leading cause of kidney failure, but few outcome trials proactively enrolled individuals with chronic kidney disease (CKD). We performed secondary analyses of cardiovascular (CV) and kidney outcomes across baseline estimated glomerular filtration rate (eGFR) categories (≥60, 45 to <60, 30 to <45, and <30 mL/min/1.73 m2) in Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA), a cardiorenal placebo-controlled outcome trial of the dipeptidyl peptidase 4 inhibitor linagliptin (NCT01897532). RESEARCH DESIGN AND METHODS Participants with CV disease and/or CKD were included. The primary outcome was time to first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke (three-point major adverse CV event [3P-MACE]), with a secondary outcome of renal death, end-stage kidney disease, or sustained ≥40% decrease in eGFR from baseline. Other end points included progression of albuminuria, change in HbA1c, and adverse events (AEs) including hypoglycemia. RESULTS A total of 6,979 subjects (mean age 65.9 years; eGFR 54.6 mL/min/1.73 m2; 80.1% albuminuria) were followed for 2.2 years. Across eGFR categories, linagliptin as compared with placebo did not affect the risk for 3P-MACE (hazard ratio 1.02 [95% CI 0.89, 1.17]) or the secondary kidney outcome (1.04 [0.89, 1.22]) (interaction P values >0.05). Regardless of eGFR, albuminuria progression was reduced with linagliptin, as was HbA1c, without increasing risk for hypoglycemia. AEs were balanced among groups overall and across eGFR categories. CONCLUSIONS Across all GFR categories, in participants with type 2 diabetes and CKD and/or CV disease, there was no difference in risk for linagliptin versus placebo on CV and kidney events. Significant reductions in risk for albuminuria progression and HbA1c and no difference in AEs were observed.
Association between Breast Milk Mineral Content and Maternal Adherence to Healthy Dietary Patterns in Spain: A Transversal Study

The composition of breast milk is influenced by many factors, some of which dependent on the mother and others on the child. Changes in lactation and other factors depending on the mother’s physiology and anthropometric characteristics, as well as her nutritional status and diet, are of key importance. Breast milk minerals have been extensively studied with highly uneven results. In this work, a comparison will made with data across the world. To understand the factors that might explain the disparity, several minerals (Na, K, Ca, P, Mg, Fe, Se and I) have been analyzed using ICP-MS in a set of human milk samples (n = 75). The samples had an identical geographical origin (Galicia, in northwestern Spain) but different lactation circumstances, including maternal anthropometric data, lactating time, newborn sex and maternal adherence to healthy dietary patterns (Mediterranean Diet, MD, or Atlantic Diet, AD). The required concentrations of essential elements reported in the literature are similar to those found in these Spanish women. A univariate approach revealed that factors such as lactating time, body mass index (BMI) and newborn sex have a significant influence in breastmilk mineral content. According to multivariate linear regression analysis, minerals in milk are particularly associated with lactating time, but also with newborn sex, maternal BMI, age and diet pattern in some cases. More precisely, these results suggest that the iron and selenium concentrations in the milk of Galician donors may be positively influenced by maternal adherence to AD and MD, respectively.
The mating behaviour of tsetse flies (Glossina): a review

Abstract. The mode of reproduction of tsetse flies, by adenotrophic viviparity, is unusual among the Diptera and is associated with many unique aspects of the tsetse's mating system. Tsetse exist at relatively low densities in the environment but a combination of olfactory and visual stimuli brings males and virgin females together on or around host animals. The behavioural repertoire associated with mate location and identification, courtship and copulation is regulated by external physical and chemical stimuli as well as by internal physiological mechanisms. With a view to identifying stimuli that could be used to manipulate tsetse behaviour and exploited for control purposes, much progress has been made in recent years in elucidating the mating behaviour of tsetse and its regulatory mechanisms. This progress and the current state of understanding of tsetse mating behaviour is reviewed.
The Role of TRM Cells in the Pathogenesis of Vitiligo—A Review of the Current State-Of-The-Art

Vitiligo is the most common hypopigmentation disease affecting both the skin and mucous membranes. The pathogenesis of this disorder is complex and involves the influence of genetic and environmental factors, oxidative stress, and autoimmune responses. Recent studies have indicated that skin lesions observed in vitiligo tend to recur in the same places where they were found before treatment. This phenomenon is explained by the presence of recently discovered tissue-resident memory T cells (TRM), whose primary function is to provide antiviral and antibacterial protection in non-lymphoid tissues. TRM cells show the presence of CD49a, CD69, and CD103 markers on their surface, although not all of them express these particles. Due to their ability to produce and secrete perforin, IFN-γ, and granzyme B, TRM cells demonstrate a cytotoxic effect on melanocytes, thus inducing depigmented lesions in the course of the vitiligo. It has been proved that the occurrence of TRM cells largely depends on IL-15, which promotes the TRM function ex vivo. The findings above, as well as their reference to the pathogenesis of autoimmune skin diseases will have a considerable influence on the development of new therapeutic strategies in the near future. This article presents an up-to-date review of information regarding the role of TRM cells in the development and progression of vitiligo.
Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis

BACKGROUND: The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections. METHODS: In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study (n = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza (n = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference −1.62, 95% CI −3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence). INTERPRETATION: Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.
Prevalence and Clinical Picture of Sleep Paralysis in a Polish Student Sample

Sleep paralysis (SP) is a psychobiological phenomenon caused by temporary desynchrony in the architecture of rapid eye movement (REM) sleep. It affects approximately 7.6% of the general population during their lifetime. The aim of this study was to assess (1) the prevalence of SP among Polish students in Lublin (n = 439) using self-reported online surveys, (2) the frequency of SP-related somatic and psychopathologic symptoms, and (3) the factors potentially affecting the occurrence of symptoms among people experiencing SP. We found that the incidence of SP in the Polish student population was slightly higher (32%) than the average prevalence found in other student populations (28.3%). The SP clinical picture was dominated by somatic symptomatology: 94% of respondents reported somatic symptoms (most commonly tachycardia, 76%), 93% reported fear (most commonly fear of death, 46%), and 66% reported hallucinations (most commonly visual hallucinations, 37%). The number of SP episodes was related to sleep duration and supine position during sleep. The severity of somatic symptoms correlated with lifestyle variables and anxiety symptomatology. Our study shows that a significant proportion of students experience recurrent SP and that this phenomenon is associated with fear and physical discomfort. The scale of the phenomenon requires a deeper analysis.
Factors regulating the downstream migration of mature eels (Anguilla spp.) at Aniwhenua Dam, Bay of Plenty, New Zealand

Abstract The downstream migrations of mature longfinned eels (Anguilla dieffenbachii Gray, 1842) and shortfinned eels (Anguilla australis Richardson, 1848) were investigated at Aniwhenua Dam on the Rangitaiki River between 1992 and 1998. Migrants were mostly females over 1000 mm total length (TL) with otoliths indicating rapid growth rates. Migrations, which occurred on a few nights each autumn, generally began once water temperatures began to decline and ended when temperatures dropped below c. 11 °C. Rainfall and flow increases were found to be key factors triggering migration events. Rainfall exceeding a cumulative total of 40 mm over 3 days accounted for 60% of migrant eels arriving at Aniwhenua. It is proposed that such rainfall triggers could be used as predictors to instigate mitigation activities that would allow mature eels to proceed uninjured past barriers such as hydro‐electric dams.
Clinicopathological characteristics of primary central nervous system lymphoma with low 18F-fludeoxyglucose uptake on brain positron emission tomography

Abstract Primary central nervous system lymphoma (PCNSL) typically shows a strong uptake of 18F-fludeoxyglucose (FDG) imaged by positron emission tomography (PET). Uncommonly, PCNSL demonstrates a low uptake on FDG PET. We investigated the clinicopathological characteristics of the unusual cases of PCNSL with low FDG uptake. We retrospectively enrolled 104 consecutive patients with newly diagnosed PCNSL who underwent baseline brain FDG PET. The degree of FDG uptake of PCNSL was visually scored by 4 grades (0, ≤contralateral white matter; 1, >contralateral white matter and contralateral gray matter). Grades 0–2 were considered as PCNSL with low uptake. We investigated association of low uptake of PCNSL with the following clinicopathological factors: age, sex, steroid treatment, lactate dehydrogenase level, cerebrospinal fluid protein level, condition of PET scanning, immunohistochemical markers (cluster of differentiation 10 [CD10], B-cell lymphoma 6 [BCL-6], B-cell lymphoma 2 [BCL-2], multiple myeloma oncogene 1 [MUM1], Epstein-Barr virus [EBV] protein, and Ki67), location of lesions, tumor size, multiplicity of lesions, involvement of deep brain structures, and cystic or necrotic appearance of lesions. Of the 104 patients with PCNSL, 14 patients (13.5%) showed PCNSL with low FDG uptake on PET. Among various clinicopathological factors, MUM1 negativity was the only factor associated with low FDG uptake PCNSL by univariate (P = .002) and multivariate analysis (P = .007). This study suggests that the different clinicopathological characteristics between patients with high uptake and low uptake of PCNSL on FDG PET is closely associated with lack of MUM1, a protein known to be a crucial regulator of B-cell development and tumorigenesis.