Miracle-dz/UniFAR-FTUs huggingface dataset:
Etiologic Subtypes of Ischemic Stroke in SARS-COV-2 Virus patients

Objective: To describe the ischemic stroke etiopathogenesis related to COVID-19 in a cohort of NYC hospitals. Background: Extra-pulmonary involvement of COVID-19 has been reported in the hepatic, renal and hematological systems. Most neurological manifestations are non-focal but few have reported the characteristics of ischemic strokes or investigated its pathophysiology. Methods: Over the last 6 weeks, data from four centers in New York City were collected to review the possible ischemic stroke types seen in COVID-19 positive patients. Their presentation, demographics, other related vascular risk factors, associated laboratory and coagulation markers, as well as imaging and outcomes were collected. Results: In our study, age range of patients was 25-75 with no significant male preponderance. 70% presented for acute hospitalization due the stroke. About a fifth did not have common risk factors for ischemic stroke like diabetes and hypertension. None had history of atrial fibrillation or smoking. 50% had poor outcome with four ending in mortality and one in a critical condition due ARDS. All had high Neutrophil/Lymphocyte ratio except one who demonstrated some neurological recovery. In 70% of our cases, D-dimer levels were collected, and all showed mild to severe elevation. None of the emergent large vessel occlusion (LVO) cases had known cardiac risk factors but two out of five were found to have cardiac abnormalities during the course of their hospitalization. All LVOs had hypercoagulable lab markers especially elevated D-dimer and/or Fibrinogen. The LVO patients were younger and sicker with a median age of 46 and mean NIHSS of 24 as opposed to non-LVOs with a median age of 62 and mean NIHSS of 6 respectively. Conclusion: COVID-19 related ischemic events can be small vessel, branch emboli or large vessel occlusions. The latter is often associated with either a hypercoagulable state or cardio-embolism. Patient outcomes were worse when multi-organ or pulmonary system failure prevailed. Keywords: COVID-19, Acute Ischemic strokes, Emergent Large Vessel Occlusion, Mechanical Thrombectomy
Risk of Secondary Infection Waves of COVID-19 in an Insular Region: The Case of the Balearic Islands, Spain

The Spanish government declared the lockdown on March 14th, 2020 to tackle the fast-spreading of COVID-19. As a consequence, the Balearic Islands remained almost fully isolated due to the closing of airports and ports, these isolation measures and the home-based confinement have led to a low prevalence of COVID-19 in this region. We propose a compartmental model for the spread of COVID-19 including five compartments (Susceptible, Exposed, Presymptomatic Infective, Diseased, and Recovered), and the mobility between municipalities. The model parameters are calibrated with the temporal series of confirmed cases provided by the Spanish Ministry of Health. After calibration, the proposed model captures the trend of the official confirmed cases before and after the lockdown. We show that the estimated number of cases depends strongly on the initial dates of the local outbreak onset and the number of imported cases before the lockdown. Our estimations indicate that the population has not reached the level of herd immunization necessary to prevent future outbreaks. While the low prevalence, in comparison to mainland Spain, has prevented the saturation of the health system, this low prevalence translates into low immunization rates, therefore facilitating the propagation of new outbreaks that could lead to secondary waves of COVID-19 in the region. These findings warn about scenarios regarding after-lockdown-policies and the risk of second outbreaks, emphasize the need for widespread testing, and could potentially be extrapolated to other insular and continental regions.
An Experimental Model: Bacterial Specialists and Generalists Competing in Chemostats

An experimental model was used to test the ecological axiom that a generalist is less efficient than a specialist. The generalists in this model were strains of Escherichia coli which can use both maltose and lactose. The specialists were strains of E. coli which can use only maltose because of a deletion of the lactose genes. These generalists and specialists competing for maltose in energy-limited chemostats containing both sugars achieved coexistence under certain conditions. The equilibrium frequency depended upon the pair of strains used and the percentage of the sugar which is lactose. A genetic change was important in the outcome of these experiments: a lac constitutive mutation replaced the lac + of the generalist. (Cells with a lactose constitutive mutation produce lactose enzyme whether or not lactose is present.) This allowed the generalist to coexist on lower amounts of lactose than it would have been able to otherwise. We propose that the lactose constitutive is selected for over the wild-type in a lactose-limited chemostat because the concentration of lactose required for growth, if the operon is constitutively derepressed, is less than that required for continued derepres- sion of the lactose operon. The equilibrium frequency predicted by chemostat competition theory gave a much higher fre- quency of the generalist than seen in the experiments. When only the generalist was added to a chemostat containing both maltose and lactose, an equilibrium of both lac + and lac constitutive cells was established. This implies that there exists "resource interference. " Resource interference hap- pens when an organism is not as efficient at using a resource when it is using other resources as when it was using that resource alone. When a constant for resource interference was incorporated into the equations, the theoretical predictions agreed with the experimental results. We hypothesize that this resource interference is due to competition for permease sites.
Lower Limb Kinematics Trajectory Prediction Using Long Short-Term Memory Neural Networks

This study determined whether the kinematics of lower limb trajectories during walking could be extrapolated using long short-term memory (LSTM) neural networks. It was hypothesised that LSTM auto encoders could reliably forecast multiple time-step trajectories of the lower limb kinematics, specifically linear acceleration (LA) and angular velocity (AV). Using 3D motion capture, lower limb position–time coordinates were sampled (100 Hz) from six male participants (age 22 ± 2 years, height 1.77 ± 0.02 m, body mass 82 ± 4 kg) who walked for 10 min at 5 km/h on a 0% gradient motor-driven treadmill. These data were fed into an LSTM model with a sliding window of four kinematic variables with 25 samples or time steps: LA and AV for thigh and shank. The LSTM was tested to forecast five samples (i.e., time steps) of the four kinematic input variables. To attain generalisation, the model was trained on a dataset of 2,665 strides from five participants and evaluated on a test set of 1 stride from a sixth participant. The LSTM model learned the lower limb kinematic trajectories using the training samples and tested for generalisation across participants. The forecasting horizon suggested higher model reliability in predicting earlier future trajectories. The mean absolute error (MAE) was evaluated on each variable across the single tested stride, and for the five-sample forecast, it obtained 0.047 m/s2 thigh LA, 0.047 m/s2 shank LA, 0.028 deg/s thigh AV and 0.024 deg/s shank AV. All predicted trajectories were highly correlated with the measured trajectories, with correlation coefficients greater than 0.98. The motion prediction model may have a wide range of applications, such as mitigating the risk of falls or balance loss and improving the human–machine interface for wearable assistive devices.
Magnesium Salt, a Simple Strategy to Improve Methadone Analgesia in Chronic Pain: An Isobolographic Preclinical Study in Neuropathic Mice

Analgesic efficacy of methadone in cancer and chronic non-cancer pains is greater than that of other opioids, probably because of its unique pharmacokinetics properties and also because it targets glutamatergic receptors in addition to µ-opioid receptors. However, methadone has drawbacks which are clearly related to dosing and treatment duration. The authors hypothesized that the antinociceptive efficacy of methadone could be synergistically potentiated by magnesium and copper salts in a preclinical mouse model of chronic pain, using the intraplantar formalin test as algesimetric tool. The spared nerve injury mice model was used to generate mononeuropathy. A low dose (0.25%) formalin was injected in the neuropathic limb in order to give rise only to Phase I response, resulting from direct activation by formalin of nociceptive primary afferents. Licking/biting of the formalin-injected limb was evaluated as nociceptive behavior during a 35-min observation period. Dose-response curves for intraperitoneal magnesium sulfate (10, 30, 100, and 300 mg/kg i.p.), copper sulfate (0.1, 0.3, 1, and 3 mg/kg i.p.) and methadone (0.1, 0.3, 1, and 3 mg/kg i.p.) allowed to combine them in equieffective doses and to determine their interaction by isobolographic analysis. Magnesium sulfate, copper sulfate and methadone dose-dependently decreased the nociceptive response evoked by formalin injection, the respective ED50 being 76.38, 1.18, and 0.50 mg/kg i.p. Isobolographic analysis showed a superadditive interaction for magnesium and methadone. Indeed, despite that both ED50 are obviously equieffective, the ED50 for the MgSO4/methadone combination contained less than one third of the methadone having the ED50 for methadone alone. For the CuSO4/methadone combination, the interaction was only additive. Extrapolated to clinical settings, the results suggest that magnesium salts might be used to improve synergistically the efficacy of methadone in neuropathy, which would allow to reduce the dose of methadone and its associated side effects.
Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling

Stenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Adenia stenodactyla Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactive oxygen species. We analyzed the effect of stenodactylin on Raji and Ramos (Human Burkitt’s lymphoma cells) and MOLM-13 (acute myeloid leukemia cells). Moreover, we focused on the early events in MOLM-13 cells that characterize the cellular response to the toxin by whole-genome microarray analysis of gene expression. Treatment with stenodactylin induced the depurination of 28S rRNA within 4 h and increased the phosphorylation of p38 and JNK. A time-dependent activation of caspase 1, 2, 8, 9, 3/7 was also observed. Genome-wide gene expression microarray analysis revealed early changes in the expression of genes involved in the regulation of cell death, inflammation and stress response. After 4 h, a significant increase of transcript level was detectable for ATF3, BTG2, DUSP1, EGR1, and JUN. Increased upstream JUN signaling was also confirmed at protein level. The early response to stenodactylin treatment involves inflammatory and apoptotic signaling compatible with the activation of multiple cell death pathways. Because of the above described properties toward acute myeloid leukemia cells, stenodactylin may be a promising candidate for the design of new immunoconjugates for experimental cancer treatment.
Immune Defect in Adults With Down Syndrome: Insights Into a Complex Issue

Children with Down syndrome (DS) suffer from recurrent respiratory infections, which represent the leading cause of mortality during childhood. This susceptibility to infections is usually considered multifactorial and related to both impaired immune function and non-immunological factors. Infections are also one of the top causes of death in DS at adulthood. DS is considered an immunodeficiency with syndromic features by some researchers because of this high rate of infection and the immunological characteristics observed in children with DS. Little is known about the immune status of adult patients. Herein, we report the clinical and immune phenotype of 44 adults with DS, correlated with their infectious history. We observed that these adults had an aberrant lymphocyte phenotype with decreased naïve/memory T cell ratios and reduced numbers of switched memory B cells. The lower incidence of infectious events at adulthood distinguish DS from other inborn errors of immunity. Primary immunodeficiency-related features in DS could explain the increased risk of developing autoimmunity, malignancies, and infections. During adulthood, this immune dysfunction may be compensated for in mid-life, and infection-related mortality observed in older patients might be favored by multiple factors such as neurological impairment or nosocomial antigen exposure. Clinical Trial Registration: www.ClinicalTrials. gov, identifier NCT01663675 (August 13, 2012).
The Draft Genome Dataset of the Asian Cricket Teleogryllus occipitalis for Molecular Research Toward Entomophagy

1 School of Advanced Science and Engineering, Waseda University, Tokyo, Japan, Department of BioScience, Nagahama Institute of Bio-Science and Technology, Shiga, Japan, Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), National Institute of Advanced Industrial Science and Technology, Tokyo, Japan, Global Consolidated Research Institute for Science Wisdom, Waseda University, Tokyo, Japan, 5 Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, Tokyo, Japan, 6 Research Organization for Nano & Life Innovation, Waseda University, Tokyo, Japan, Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Hyogo, Japan, Graduate School of Bio-Applications and Systems Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan
Doxycycline: From Ocular Rosacea to COVID-19 Anosmia. New Insight Into the Coronavirus Outbreak

Coronavirus Disease 19 (COVID-19) caused by Severe Acute Respiratory Syndrome-Coronavirus2 (SARS-CoV-2) it usually manifests with respiratory symptoms (1). Similarly, to other human respiratory Coronaviruses (HCoV), it seems to have a neuroinvasive and neurotropic activity (1, 2). In the retrospective case series study conducted by Mao et al. three categories of neurological symptoms COVID19-related included central nervous system (CNS) manifestations, peripheral nervous system (PNS) symptoms and musculoskeletal disorders (2). Hyposmia has been reported as a possible peripheral nervous system (PNS) symptom caused by COVID-19 infection (2). In our experience, the smell alteration (hyposmia, anosmia) seems to be one of the first manifestations of COVID-19 disease, with or without the loss of taste (dysgeusia). Sometimes it remains the only symptom; more often, it comes with fatigue, fever, and cough. We provide a commentary on how COVID-19 could affect the sense of smell and the reason why doxycycline (Dox) could play a role in its recover.
Pangolins Lack IFIH1/MDA5, a Cytoplasmic RNA Sensor That Initiates Innate Immune Defense Upon Coronavirus Infection

Zoonotic infections are an imminent threat to human health. Pangolins were recently identified as carriers and intermediate hosts of coronaviruses. Previous research has shown that infection with coronaviruses activates an innate immune response upon sensing of viral RNA by interferon-induced with helicase C domain 1 (IFIH1), also known as MDA5. Here, we performed a comparative genomics study of RNA sensor genes in three species of pangolins. DDX58/RIG-I, a sensor of cytoplasmic viral RNA and toll-like receptors (TLR) 3, 7, and 8, which bind RNA in endosomes, are conserved in pangolins. By contrast, IFIH1 a sensor of intracellular double-stranded RNA, has been inactivated by mutations in pangolins. Likewise, Z-DNA-binding protein (ZBP1), which senses both Z-DNA and Z-RNA, has been lost during the evolution of pangolins. These results suggest that the innate immune response to viruses differs significantly between pangolins and other mammals, including humans. We put forward the hypothesis that loss of IFIH1 and ZBP1 provided an evolutionary advantage by reducing inflammation-induced damage to host tissues and thereby contributed to a switch from resistance to tolerance of viral infections in pangolins.
Genome-Wide Analysis of WRKY Genes and Their Response to Salt Stress in the Wild Progenitor of Asian Cultivated Rice, Oryza rufipogon

The WRKY gene family is widespread in plants, which plays key roles in plant development and stress response. Although WRKY transcription factors have been widely characterized in many plants, a genome-wide analysis of the WRKY gene family is lacking in Oryza rufipogon. In this study, we identified 101 O. rufipogon WRKY (OrWRKY) transcription factors, which were further classified into eight subgroups. Phylogenetic analysis showed that OrWRKY transcription factors were supported by highly conserved motifs and gene structures. Chromosomal distribution of OrWRKYs indicated that most genes were dispersed on all 12 chromosomes, especially enriched on Chromosome 1. Syntenic analysis revealed that 69 (68.3%) genes were derived from either segmental (49) or tandem duplication events (20), suggesting a pivotal role of segmental duplications. We totally characterized 39 orthologous gene pairs between Oryza sativa ssp. japonica WRKY (OsjWRKY) and OrWRKY genes. We performed quantitative real-time polymerase chain reaction (qRT-PCR) experiments to validate tissue-specific and differential expression of the OrWRKYs and corresponsive expression of the OrWRKYs in response to salt stresses in leaves and roots. This study provides a new insight on the evolution of the WRKY gene family in O. rufipogon and will help further functional characterization of candidate genes toward wild rice germplasm exploration for rice genetic improvement programs.
The Genomic Characteristics of ALK Fusion Positive Tumors in Chinese NSCLC Patients

Anaplastic lymphoma kinase (ALK) fusion events account for ~3–7% genetic alterations in patients with non-small cell lung cancer (NSCLC). In this study, we identified the ALK fusion patterns and a novel ALK fusion partner in 44 ALK positive NSCLC patients using a customized HapOncoCDx panel, and identified ALK fusion partners. The most common partner is EML4, forming the variant 1 (v1, E13:A20, 18/44), variant 2 (v2, E20:A20, 5/44), and variant 3 (v3, E6:A20, 13/44). Moreover, we detected a new ALK fusion partner HMBOX1. At the mutation level, TP53 is the most frequently mutated gene (24%), followed by ALK (12%) and STED2 (12%). The median tumor mutation burden (TMB) of these samples is 2.29 mutations/Mb, ranging from 0.76 mut/Mb to 16.79 muts/Mb. We further elaborately portrayed the TP53 mutation sites on the peptide sequence of the encoded protein by lollipop. The mutational signature and copy number alterations (CNAs) of the samples were also analyzed. The CNA events were found in 13 (13/44) patients, and the most commonly amplified genes were MDM2 (n = 4/13) and TERT (n = 4/13). Together, these results may guide personalized clinical management of patients with ALK fusion in the era of precision medicine.
Cumulative Live Birth Rates After the First ART Cycle Using Flexible GnRH Antagonist Protocol vs. Standard Long GnRH Agonist Protocol: A Retrospective Cohort Study in Women of Different Ages and Various Ovarian Reserve

Objective: To compare the cumulative live birth rates (cLBRs) after the first assisted reproductive technology (ART) cycle using flexible gonadotropin releasing hormone (GnRH)-antagonist protocol vs. standard long GnRH agonist protocol for controlled ovarian stimulation (COS) in infertile women with different ages and ovarian reserve. Methods: Women who underwent ART treatment at our center between June 1st, 2015 and December 31st, 2018 were screened. Among them, only women who underwent their first COS cycle with flexible GnRH antagonist protocol or standard long GnRH agonist protocol were included in this study. The main outcome measurement was cLBR. Results: A total of 4,402 patients were eligible for the analysis, of whom, 2,762 patients used the GnRH agonist protocol and 1,640 patients used the GnRH antagonist protocol. The cLBRs of women in the antagonist protocol group and long agonist protocol group were 45.3 and 50.0%, respectively. Subgroup multivariable regression analysis showed that, in patients with low ovarian reserve (AFC ≤ 7), the cLBR was significantly lower in the antagonist group than in the long agonist protocol group [OR (95% CI) 0.62 (0.41, 0.94)], which effect was more robust in younger patients (<30 y) [OR (95% CI) 0.29 (0.11, 0.74)]. The analysis also revealed remarkably lower cLBR in patients above 40 years regardless of their AFC, although the difference was not statistically significant. However, in patients with high ovarian reserve (AFC >24), the cLBR was higher in cycles with antagonist protocol than with the long agonist protocol [OR (95% CI) 1.43 (0.96, 2.12)], and the effect was of statistical significance in younger patients (< 30 y) [OR (95% CI) 1.78 (1.07, 2.96)]. Conclusion: The present study suggests that the flexible GnRH antagonist protocol might not be suitable for patients with low ovarian reserve (AFC ≤ 7) or patients aged over 40 years. However, flexible GnRH antagonist protocol might be strongly recommended for patients under 30 years old and with high ovarian reserve (AFC > 24). For the rest groups of patients in the present cohort, antagonist protocol was slightly favored because it had lower OHSS in general and in patients with poly-cystic ovarian syndrome (PCOS) according to previous publications.
“Mitochondrial Toolbox” – A Review of Online Resources to Explore Mitochondrial Genomics

Mitochondria play a significant role in many biological systems. There is emerging evidence that differences in the mitochondrial genome may contribute to multiple common diseases, leading to an increasing number of studies exploring mitochondrial genomics. There is often a large amount of complex data generated (for example via next generation sequencing), which requires optimised bioinformatics tools to efficiently and effectively generate robust outcomes from these large datasets. Twenty-four online resources dedicated to mitochondrial genomics were reviewed. This ‘mitochondrial toolbox’ summary resource will enable researchers to rapidly identify the resource(s) most suitable for their needs. These resources fulfil a variety of functions, with some being highly specialised. No single tool will provide all users with the resources they require; therefore, the most suitable tool will vary between users depending on the nature of the work they aim to carry out. Genetics resources are well established for phylogeny and DNA sequence changes, but further epigenetic and gene expression resources need to be developed for mitochondrial genomics.