Miracle-dz/UniFAR-FTUs huggingface dataset:
Ratios of neutrophil-to-lymphocyte and platelet-to-lymphocyte predict all-cause mortality in inpatients with coronavirus disease 2019 (COVID-19): a retrospective cohort study in a single medical centre

Abstract The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56–71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911–1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563–0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.
Evaluation of COVID-19 Surveillance Strategy in Ecuador

ABSTRACT Objectives: Evaluate the relevance of the coronavirus disease 2019 (COVID-19) positive case detection policy or model implemented by the Ministry of Public Health (MPH) of Ecuador and to compare it with the experiences of other countries. Methods: Data contained the daily reports publicized by the MPH. The formulations were carried out under the Conditioned Probability modality applying Bayes’ Theorem. All the COVID-19 tests applied in relation to the confirmed cases per million inhabitants were considered to obtain their level of positivity, and compared with the experience of Iceland and South Korea. Results: The probability of detecting positive cases of COVID-19 in Ecuador was higher than Iceland and South Korea, because the diagnostic tests were aimed at symptomatic patients, without identifying asymptomatic or mild symptomatic, who play an important role in the transmission of the disease. In addition, many symptomatic patients were examined but will remain undiagnosed due to the unavailability of tests and the low quality of many of them. Conclusions: The daily reports on the behavior of the COVID-19 issued by the Ecuadorian government do not adequately represent the growth in the number of those infected each day, nor the actual behavior of the epidemic, affecting possible control measures.
Elucidating the Role of Ezh2 in Tolerogenic Function of NOD Bone Marrow-Derived Dendritic Cells Expressing Constitutively Active Stat5b

Tolerogenic dendritic cells (toDCs) are crucial to controlling the development of autoreactive T cell responses and the prevention of autoimmunity. We have reported that NOD.CD11cStat5b-CA transgenic mice expressing a constitutively active (CA) form of Stat5b under the control of a CD11c promoter are protected from diabetes and that Stat5b-CA-expressing DCs are tolerogenic and halt ongoing diabetes in NOD mice. However, the molecular mechanisms by which Stat5b-CA modulates DC tolerogenic function are not fully understood. Here, we used bone marrow-derived DCs (BMDCs) from NOD.CD11cStat5b-CA transgenic mice (Stat5b-CA.BMDCs) and found that Stat5b-CA.BMDCs displayed high levels of MHC class II, CD80, CD86, PD-L1, and PD-L2 and produced elevated amounts of TGFβ but low amounts of TNFα and IL-23. Stat5b-CA.BMDCs upregulated Irf4 and downregulated Irf8 genes and protein expression and promoted CD11c+CD11b+ DC2 subset differentiation. Interestingly, we found that the histone methyltransferase Ezh2 and Stat5b-CA bound gamma-interferon activated site (GAS) sequences in the Irf8 enhancer IRF8 transcription, whereas Stat5b but not Ezh2 bound GAS sequences in the Irf4 promoter to enhance IRF4 transcription. Injection of Stat5b-CA.BMDCs into prediabetic NOD mice halted progression of islet inflammation and protected against diabetes. Importantly, inhibition of Ezh2 in tolerogenic Stat5b-CA.BMDCs reduced their ability to prevent diabetes development in NOD recipient mice. Taken together, our data suggest that the active form of Stat5b induces tolerogenic DC function by modulating IRF4 and IRF8 expression through recruitment of Ezh2 and highlight the fundamental role of Ezh2 in Stat5b-mediated induction of tolerogenic DC function.
Acetylcholine ameliorated TNF-α-induced primary trophoblast malfunction via muscarinic receptors†

Abstract Oxidative stress and apoptosis of trophoblasts are involved in preeclampsia (PE). Numerous studies have shown that acetylcholine (ACh), the principal vagal neurotransmitter, plays a crucial role in attenuating oxidative stress, inflammation, and apoptosis in a variety of human diseases. However, the role of ACh in PE management remains unclear. Here, we aimed to determine the effects of ACh on TNF-α-treated human primary trophoblast cells. Western blotting, CCK-8, DHE, TUNEL immunofluorescence staining, transwell assays, and wound-healing assays were performed to evaluate the role of ACh in vitro. We found that both TNF-α expression and the apoptotic index were higher in placentas from preeclamptic women than in normal placentas. TNF-α enhanced oxidative stress and increased the number of TUNEL-positive nuclei, Bax/Bcl-2 ratio, and the cleaved caspase-3/caspase-3 ratio while decreasing cell viability in primary human trophoblast cells. TNF-α promoted cell migration and invasion. PDTC, a selective NF-κB inhibitor, significantly blunted TNF-α-induced effects. ACh treatment attenuated oxidative stress and apoptosis while further promoting migration and invasion of TNF-α-treated primary trophoblast cells. The effects of ACh could be reversed by the muscarinic receptor antagonist atropine. Overall, our findings indicate that ACh significantly ameliorates TNF-α-induced oxidative stress and apoptosis of human primary trophoblast cells via muscarinic receptors. This is the first time that the improvement of vagal activity served as a therapeutic strategy for PE-like trophoblasts, suggesting its potential value in clinical practice. Summary Sentence: TNF-α is increased in the placentas from preeclamptic women and acetylcholine significantly ameliorates TNF-α-induced oxidative stress and apoptosis of human primary trophoblast cells via muscarinic receptors. Graphical Abstract
Longevity, Fecundity, and Searching Ability of Trichogramma pretiosum Reared by Three Methods

Previous research with different species of Trichogramma has indicated that the size or species of the host egg in which the parasite develops may alter its efficiency (Salt 1940, Marston and Ertle 1973). Also, storing of Trichogramma pupae at reduced temperatures weakens the emerging parasites (Schread and Garman1934). Since the host used to rear Trichogramma may greatly affect the rearing costs, and since cold storage of pupae may ease handling of the parasites for field use(Stinner and Ridgway, unpublished data), information was needed about the effects of these factors on Trichogramma . Therefore, we conducted laboratory and field studies on the longevity, fecundity, and searching ability of Trichogramma reared on 2 hosts and stored at reduced temperatures.
Numerical Mesoscale Analysis of Textile Reinforced Concrete

This contribution presents a framework for Numerical Material Testing (NMT) of textile reinforced concrete based on the mesomechanical analysis of a Representative Volume Element (RVE). Hence, the focus of this work is on the construction of a proper RVE representing the dominant mechanical characteristics of Textile Reinforced Concrete (TRC). For this purpose, the RVE geometry is derived from the periodic mesostructure. Furthermore, sufficient constitutive models for the individual composite constituents as well as their interfacial interactions are considered, accounting for the particular mechanical properties. The textile yarns are modeled as elastic transversal isotropic unidirectional layers. For the concrete matrix, an advanced gradient enhanced microplane model is utilized considering the complex plasticity and damage behavior at multiaxial loading conditions. The mechanical interactions of the constituents are modeled by an interface formulation considering debonding and friction as well as contact. These individual constitutive models are calibrated by corresponding experimental results. Finally, the damage mechanisms as well as the load bearing behavior of the constructed TRC-RVE are analyzed within an NMT procedure based on a first-order homogenization approach. Moreover, the effective constitutive characteristics of the composite at macroscale are derived. The numerical results are discussed and compared to experimental results.
Nomogram-Based Preoperative Score for Predicting Clinical Outcome in Unilateral Primary Aldosteronism.

CONTEXT More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy. OBJECTIVE To develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA. DESIGN AND SETTING The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort. PARTICIPANTS Patients with UPA achieving complete biochemical success after unilateral adrenalectomy. MAIN OUTCOME MEASURE the predictive performance of NBPS compared with two previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score. RESULTS Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone to renin ratio and target organ damage. The nomogram showed good concordance indices and calibration curves in both Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to ARS [0.745(0.667-0.812), p=0.019] and PASO score [0.747(0.670-0.815), p=0.012]. The AUC of NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than ARS [0.745 (95% CI 0.672-0.810), p=0.045], but not significantly different from PASO score [0.825 (95% CI 0.758-0.880), p=0.911]. CONCLUSION The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.
Delay-period activity in frontal, parietal, and occipital cortex tracks noise and biases in visual working memory

Working memory is imprecise, and these imprecisions can be explained by the combined influences of random diffusive error and systematic drift toward a set of stable states (“attractors”). However, the neural correlates of diffusion and drift remain unknown. Here, we investigated how delay-period activity in frontal and parietal cortex, which is known to correlate with the decline in behavioral memory precision observed with increasing memory load, might relate to diffusion and drift. We analyzed data from an existing experiment in which subjects performed delayed recall for line orientation, at different loads, during functional magnetic resonance imaging (fMRI) scanning. To quantify the influence of drift and diffusion, we modeled subjects’ behavior using a discrete attractor model and calculated within-subject correlation between frontal and parietal delay-period activity and whole-trial estimates of drift and diffusion. We found that although increases in frontal and parietal activity were associated with increases in both diffusion and drift, diffusion explained the most variance in frontal and parietal delay-period activity. In comparison, a subsequent whole-brain regression analysis showed that drift, rather than diffusion, explained the most variance in delay-period activity in lateral occipital cortex. These results are consistent with a model of the differential recruitment of general frontoparietal mechanisms in response to diffusive noise and of stimulus-specific biases in occipital cortex.
Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).
The methylome is altered for plants in a high CO2 world: Insights into the response of a wild plant population to multigenerational exposure to elevated atmospheric [CO2]

Unravelling plant responses to rising atmospheric CO2 concentration ([CO2]) has largely focussed on plastic functional attributes to single generation [CO2] exposure. Quantifying the consequences of long‐term, decadal multigenerational exposure to elevated [CO2] and the genetic changes that may underpin evolutionary mechanisms with [CO2] as a driver remain largely unexplored. Here, we investigated both plastic and evolutionary plant responses to elevated [CO2] by applying multi‐omic technologies using populations of Plantago lanceolata L. , grown in naturally high [CO2] for many generations in a CO2 spring. Seed from populations at the CO2 spring and an adjacent control site (ambient [CO2]) were grown in a common environment for one generation, and then offspring were grown in ambient or elevated [CO2] growth chambers. Low overall genetic differentiation between the CO2 spring and control site populations was found, with evidence of weak selection in exons. We identified evolutionary divergence in the DNA methylation profiles of populations derived from the spring relative to the control population, providing the first evidence that plant methylomes may respond to elevated [CO2] over multiple generations. In contrast, growth at elevated [CO2] for a single generation induced limited methylome remodelling (an order of magnitude fewer differential methylation events than observed between populations), although some of this appeared to be stably transgenerationally inherited. In all, 59 regions of the genome were identified where transcripts exhibiting differential expression (associated with single generation or long‐term natural exposure to elevated [CO2]) co‐located with sites of differential methylation or with single nucleotide polymorphisms exhibiting significant inter‐population divergence. This included genes in pathways known to respond to elevated [CO2], such as nitrogen use efficiency and stomatal patterning. This study provides the first indication that DNA methylation may contribute to plant adaptation to future atmospheric [CO2] and identifies several areas of the genome that are targets for future study.
Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti-Interleukin 12/23p40 Antibody Ustekinumab.

Importance Ustekinumab, a monoclonal antibody targeting interleukin 12/23p40 (IL-12/23p40), is effective in the treatment of moderate to severe psoriasis, psoriatic arthritis, and Crohn disease. In 2011, a meta-analysis of randomized clinical trials reported a potential risk of severe cardiovascular events (SCEs) within the first few months after the initiation of anti-IL-12/23p40 antibodies. Objective To assess whether the initiation of ustekinumab treatment is associated with increased risk of SCEs. Design, Setting, and Participants This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018. Exposure The initiation of ustekinumab treatment was screened during the risk and reference periods. Main Outcomes and Measures Odds ratios for the risk of SCE after the initiation of ustekinumab treatment were calculated. Results Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke). Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59). Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13). Conclusions and Relevance This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk. In line with the current mechanistic models for atherosclerotic disease, the period after the initiation of anti-IL-12/23p40 may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17. Although the study interpretation is limited by its observational design, these results suggest that caution may be needed in the prescription of ustekinumab to patients at high cardiovascular risk.
Porphyra tanegashimensis, a New Species of Rodophyceae from Tanegashima Island in Southern Japan

Since September 1971, the present writer has been studying the genus Porphyra in the north-eastern coast of Tanegashima Island, Kagoshima Prefecture, and of these species of Porphyra, one is ascertained to be a new species. In the present paper, Porphyra tanegashimensis sp. nov. is proposed and discussed in comparison with some other related species of Porphyra. The main morphological and ecological characters of this new species are as follows:1) The present plants are found during all seasons of the year in the form of leaf-like fronds, and well grown ones, reaching 10-15 cm in height, though chiefly found from September to November. The most noticeable characteristic of these plants is that the fronds issue many linear lateral branches.2) Sexual reproductive organs are found from late September to early April.3) Monosporangia are formed at the upper marginal part of the frond through all seasons, and the monospores are mostly liberated from March to September.4) Both germinating monospore and conchospore grow into similar plants with the lateral branches mentioned above.5) The adequate water temperatures for growth of the plants are recognized to be higher by 3-5°C than those for some other species of the cultivated Porphyra.
Pan-Echinocandin-Resistant Candida glabrata Bloodstream Infection Complicating COVID-19: A Fatal Case Report

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, but coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly due to multidrug-resistant Gram-negative bacteria, and lastly due to a possibly fatal Candida glabrata. The development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.
Long-Term Prognosis of Endodontic Microsurgery—A Systematic Review and Meta-Analysis

Background and objectives: The long-term outcome of endodontic microsurgery (EMS) performed on root-filled teeth affected by post-treatment apical periodontitis (AP) has been a matter of debate, re-launched by the introduction of novel root-end filling materials which have been proven to improve the short-term outcome of EMS. The purpose of this systematic review and meta-analysis is to evaluate the clinical and radiographic long-term outcome of endodontic microsurgery in teeth diagnosed with secondary AP through radiographic evaluation. Materials and Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion and exclusion criteria were defined a priori to select the best longitudinal evidence. Only randomized clinical trials (RCT) and prospective clinical studies (PCS), with a follow-up ≥ 2-year, and exhibiting well-established clinical and radiographic outcome criteria, were selected. Results: A total of 573 articles were obtained, from which 10 fulfill inclusion criteria: 6 PCS and 4 RCT. Meta-analysis showed a pooled proportion of success rate of 91.3%, from an overall amount of 453 treated teeth included in RCT; from overall 839 included teeth in PCS, a pooled success rate of 78.4% was observed, with the follow-up time ranging from 2 to 13-years. Survival rate outcomes varied from 79 to 100% for the same follow-up period. Five prognostic factors with influence on the outcome were disclosed: smoking habits, tooth location and type, absence/presence of dentinal defects, interproximal bone level, and root-end filling material. Conclusions: High success rates and predictable results can be expected when EMS is performed by trained endodontists, allowing good prognosis and preservation of teeth affected by secondary AP.