Miracle-dz/UniFAR-FTUs huggingface dataset:
The Ins and Outs of Central Nervous System Inflammation-Lessons Learned from Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic disease that is characterized by the inappropriate invasion of lymphocytes and monocytes into the central nervous system (CNS), where they orchestrate the demyelination of axons, leading to physical and cognitive disability. There are many reasons immunologists should be interested in MS. Aside from the fact that there is still significant unmet need for patients living with the progressive form of the disease, MS is a case study for how immune cells cross CNS barriers and subsequently interact with specialized tissue parenchymal cells. In this review, we describe the types of immune cells that infiltrate the CNS and then describe interactions between immune cells and glial cells in different types of lesions. Lastly, we provide evidence for CNS-compartmentalized immune cells and speculate on how this impacts disease progression for MS patients. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
New Model for Predicting the Presence of Coronary Artery Calcification

Coronary artery calcification (CAC) is a feature of coronary atherosclerosis and a well-known risk factor for cardiovascular disease (CVD). As the absence of CAC is associated with a lower incidence rate of CVD, measurement of a CAC score is helpful for risk stratification when the risk decision is uncertain. This was a retrospective study with an aim to build a model to predict the presence of CAC (i.e., CAC score = 0 or not) and evaluate the discrimination and calibration power of the model. Our data set was divided into two set (80% for training set and 20% for test set). Ten-fold cross-validation was applied with ten times of interaction in each fold. We built prediction models using logistic regression (LRM), classification and regression tree (CART), conditional inference tree (CIT), and random forest (RF). A total of 3302 patients from two cohorts (Soonchunhyang University Cheonan Hospital and Kangbuk Samsung Health Study) were enrolled. These patients’ ages were between 40 and 75 years. All models showed acceptable accuracies (LRM, 70.71%; CART, 71.32%; CIT, 71.32%; and RF, 71.02%). The decision tree model using CART and CIT showed a reasonable accuracy without complexity. It could be implemented in real-world practice.
Diabetes predicts severity of COVID‐19 infection in a retrospective cohort: A mediatory role of the inflammatory biomarker C‐reactive protein

Diabetes is a risk factor for developing severe COVID‐19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID‐19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID‐19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%–6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID‐19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID‐19 outcome was analyzed by cox regression. Adjusted mediation analysis of C‐reactive protein (CRP) on the relationship between diabetes and severe COVID‐19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID‐19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID‐19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54–17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92–8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22–4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID‐19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID‐19 infection, confirming that inflammation is important in the pathogenesis of severe COVID‐19 in diabetes.
Sulfaquinoxaline Oxidation and Toxicity Reduction by Photo-Fenton Process

Sulfaquinoxaline (SQX) has been detected in environmental water samples, where its side effects are still unknown. To the best of our knowledge, its oxidation by Fenton and photo-Fenton processes has not been previously reported. In this study, SQX oxidation, mineralization, and toxicity (Escherichia coli and Staphylococcus aureus bacteria) were evaluated at two different setups: laboratory bench (2 L) and pilot plant (15 L). The experimental design was used to assess the influence of the presence or absence of radiation source, as well as different H2O2 concentrations (94.1 to 261.9 mg L−1). The experimental conditions of both setups were: SQX = 25 mg L−1, Fe(II) = 10 mg L−1, pH 2.8 ± 0.1. Fenton and photo-Fenton were suitable for SQX oxidation and experiments resulted in higher SQX mineralization than reported in the literature. For both setups, the best process was the photo-Fenton (178.0 mg L−1 H2O2), for which over 90% of SQX was removed, over 50% mineralization, and bacterial growth inhibition less than 13%. In both set-ups, the presence or absence of radiation was equally important for sulfaquinoxaline oxidation; however, the degradation rates at the pilot plant were between two to four times higher than the obtained at the laboratory bench.
Intact HIV reservoir estimated by the intact proviral DNA assay correlates with levels of total and integrated DNA in the blood during suppressive antiretroviral therapy.

Accurate characterization of the HIV reservoir is imperative to develop an effective cure. HIV was measured in antiretroviral therapy-suppressed individuals using the intact proviral DNA assay (IPDA), along with assays for total or integrated HIV DNA, and inducible HIV RNA or p24. Intact provirus correlated with total and integrated HIV.
Indirect Atomic Absorption Spectrometric Determination of Ammonia, Thiosulfate and Cyanide in an Unsegmented Flow System

Abstract A flow injection analysis method (FIA), has been developed for the determination of cyanide, thiosulfate and ammonia by atomic absorption spectrometry (AAS). Aqueous solution of the analyte was injected into an on-line column containing glass beads and packed with silver chloride and deionized water was used as the carrier. The analyte dissolves the silver chloride and the dissolved silver complex is introduced to the nebulizer of the AAS. This method has proved to be sensitive, simple and precise. Detection limits of 1.0 × 10−7 M, 5.0×10−7 M and 5.0x10−6M were obtained for thiosulfate, cyanide and ammonia, respectively. The precision of the technique was 2.0%, 2.4% and 1.4% in case of thiosulfate, cyanide and ammonia, respectively. The effects of flow rate and sample volume on the FIA/AAS signals are presented.
MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1

Simple Summary Prostate cancer is one of the leading causes of death among men worldwide. Advanced prostate cancer is an incurable disease whose mechanisms of action are still not fully understood. Secretion of the matrix protein MINDIN has been associated with prostate tumor development towards advanced prostate cancer. We aimed to study the mechanisms whereby MINDIN promotes prostate cancer progression. Evaluation of human and mouse prostate cancer samples showed increased MINDIN expression associated with decreased expression of the adaptor protein Na+/H+ exchanger regulatory factor 1 (NHERF-1). We found that NHERF-1 was downregulated by MINDIN in prostate cancer, causing an increase in tumor cell migration and proliferation. These observations point to NHERF-1 as a key modulator of MINDIN actions on prostate cancer progression and suggest that both proteins could be potential targets for the development of future prostate cancer therapies. Abstract Advanced prostate cancer preferential metastasis to bone is associated with osteomimicry. MINDIN is a secreted matrix protein upregulated in prostate tumors that overexpresses bone-related genes during prostate cancer progression. Na+/H+ exchanger regulatory factor (NHERF-1) is a scaffold protein that has been involved both in tumor regulation and osteogenesis. We hypothesize that NHERF-1 modulation is a mechanism used by MINDIN to promote prostate cancer progression. We analyzed the expression of NHERF-1 and MINDIN in human prostate samples and in a premetastatic prostate cancer mouse model, based on the implantation of prostate adenocarcinoma TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) cells in immunocompetent C57BL/6 mice. The relationship between NHERF-1 and MINDIN and their effects on cell proliferation, migration, survival and osteomimicry were evaluated. Upregulation of MINDIN and downregulation of NHERF-1 expression were observed both in human prostate cancer samples and in the TRAMP-C1 model. MINDIN silencing restored NHERF-1 expression to control levels in the mouse model. Stimulation with MINDIN reduced NHERF-1 expression and triggered its mobilization from the plasma membrane to the cytoplasm in TRAMP-C1 cells. MINDIN-dependent downregulation of NHERF-1 promoted tumor cell migration and proliferation without affecting osteomimicry and adhesion. We propose that MINDIN downregulates NHERF-1 expression leading to promotion of processes involved in prostate cancer progression.
Druggability modification strategies of the diarylpyrimidine‐type non‐nucleoside reverse transcriptase inhibitors

Drug discovery of human immunodeficiency virus (HIV) is a hot field in medicinal chemistry community for many years. The diarylpyrimidines (DAPYs) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTIs) targeting reverse transcriptase, playing a great irreplaceable role in HIV transcriptional therapy. However, fast‐growing drug‐resistant mutations as nonnegligible challenge are still unpredictably appeared in the clinical practice, leading to deactivate or reduce the existing drugs. In the last 20 years, more and more novel DAPY derivatives have developed with the purpose to counter the mutants. Nevertheless, most of them have dissatisfactory pharmacokinetics (PK) or poor antiviral activity toward resistant mutant strains. In this article, we will analyze the NNRTI derivatives with promising druggability, and summarize a series of druggability modification strategies to improve the antiviral activity, reduce toxicity and improve the PK properties in recent years. The prospects of DAPYs and the directions for future efforts will be discussed.
Low frequency noise in heavily doped polysilicon thin film resistors

Low frequency noise and current–voltage measurements in several heavily doped polysilicon resistors of varying geometry and both p and n type, and over a limited range of temperatures from −60 to 50 °C were conducted for the first time. We found that the noise in p-type polysilicon was independent of temperature, but not the n-type polysilicon. For the p-type resistors, linear current–voltage characteristics were observed, and the relative noise spectral density was independent of bias and inversely proportional to frequency. For the n-type resistors, linear current–voltage characteristics were observed, and the relative noise spectral density was independent of bias. Finally, the normalized noise level in the linear n-type resistors was almost an order of magnitude lower than for the p-type resistors. We believe that this difference is because n-type dopants segregate to the grain boundaries, thus passivating some of the traps there. Boron (p-type dopant), on the other hand, does not segregate to the grain boundaries, leaving more unpassivated grain-boundary traps which capture and emit more carriers, resulting in more low frequency noise.Low frequency noise and current–voltage measurements in several heavily doped polysilicon resistors of varying geometry and both p and n type, and over a limited range of temperatures from −60 to 50 °C were conducted for the first time. We found that the noise in p-type polysilicon was independent of temperature, but not the n-type polysilicon. For the p-type resistors, linear current–voltage characteristics were observed, and the relative noise spectral density was independent of bias and inversely proportional to frequency. For the n-type resistors, linear current–voltage characteristics were observed, and the relative noise spectral density was independent of bias. Finally, the normalized noise level in the linear n-type resistors was almost an order of magnitude lower than for the p-type resistors. We believe that this difference is because n-type dopants segregate to the grain boundaries, thus passivating some of the traps there. Boron (p-type dopant), on the other hand, does not segregate to the gra.
Survival after Laparoscopic versus Abdominal Radical Hysterectomy in Early Cervical Cancer: A Randomized Controlled Trial

Background: Previous studies have reported the safety of laparoscopic radical hysterectomy for treatment of early cervical cancer, as option to laparotomy. This study aims to compare overall survival between laparoscopic versus abdominal radical hysterectomy for early cervical cancer. Methods: A single-center randomized controlled trial enrolled 30 patients with clinically staged IA2 cervical cancer and lymphovascular invasion, IB and IIA, who underwent laparoscopic radical hysterectomy (16) or abdominal radical hysterectomy (14). Result: The mean overall survival time was 74.74 months (CI 95%: 54.15-95.33) for LRH 91.67 months (CI 95%: 74.97-108.37) for ARH (log-rank test = 0.30). The mean disease-free survival time was 81.07 months (CI 95%: 60.95-101.19) for LRH and 95.82 months (CI 95%: 80.18-111.47) for ARH (log-rank test = 0.371). The overall survival hazard ratio was 2.05 (CI 95%: 0.51-8.24), and the disease-free hazard ratio was 2.13 (CI 95%: 0.39-11.7). Conclusion: Our study suggests a non-significant trend of worse outcomes for LRH. In light of recent controversy and need for prospective studies, further studies in different populations are required for definite conclusions and until then, patients should be aware of risks and benefits, survival data and quality of life outcomes related to both surgical techniques.
Summary of the Available Molecular Methods for Detection of SARS-CoV-2 during the Ongoing Pandemic

Since early 2020, the COVID-19 pandemic has caused an excess in morbidity and mortality rates worldwide. Containment strategies rely firstly on rapid and sensitive laboratory diagnosis, with molecular detection of the viral genome in respiratory samples being the gold standard. The reliability of diagnostic protocols could be affected by SARS-CoV-2 genetic variability. In fact, mutations occurring during SARS-CoV-2 genomic evolution can involve the regions targeted by the diagnostic probes. Following a review of the literature and an in silico analysis of the most recently described virus variants (including the UK B 1.1.7 and the South Africa 501Y.V2 variants), we conclude that the described genetic variability should have minimal or no effect on the sensitivity of existing diagnostic protocols for SARS-CoV-2 genome detection. However, given the continuous emergence of new variants, the situation should be monitored in the future, and protocols including multiple targets should be preferred.
Synthesis of ceramic nanocomposite powders with in situ formation of nanowires/nanobelts

A significant challenge in synthesizing nanowire/nanobelt-reinforced ceramic nanocomposites is to uniformly disperse these reinforcements. Here, we report the synthesis of amorphous silicon carbonitride powders containing in situ-formed single-crystal Si3N4 nanowires and nanobelts via the catalyst-assisted pyrolysis of a polymeric precursor. The nanowires/nanobelts are uniformly dispersed within the powder matrix. The ratio of nanomaterials to powder can be controlled by tailoring the experimental conditions. The novel powders could be useful for fabricating nanowire/nanobelt-reinforced ceramic nanocomposites.
Registered Nurses’ Experiences Taking Breaks on Night Shift: A Qualitative Analysis

Background: Fatigue mitigation strategies among night shift workers can include deliberate use of restful work breaks, taking naps, and consuming caffeine. However, nurses have frequently reported missing break opportunities, and the rationale for missed breaks remains unclear. The purpose of this study was to describe and interpret the lived experience of hospital night shift nurses taking breaks and the meaning of this phenomenon as it relates to the workplace. Methods: Registered nurses (n = 16) from a U.S. community hospital were interviewed about how they took rest breaks during their shift. Data were analyzed with methods consistent to interpretive phenomenology. Findings: Identified themes about the breaks included (a) breaks are a time to eat, (b) breaks are inconsistently supported by unit-level structures and processes, and (c) breaks are a luxury, not a right. Conclusions/Applications to Practice: Nurses in this study reported an absence of consistent and restorative breaks. Organizations should analyze gaps within systems and processes to optimize a consistent, restorative nature of the break experience among nurses working night shift.
Orc4 spatiotemporally stabilizes centromeric chromatin

The establishment of centromeric chromatin and its propagation by the centromere-specific histone CENPA is mediated by epigenetic mechanisms in most eukaryotes. DNA replication origins, origin binding proteins, and replication timing of centromere DNA are important determinants of centromere function. The epigenetically regulated regional centromeres in the budding yeast Candida albicans have unique DNA sequences that replicate earliest in every chromosome and are clustered throughout the cell cycle. In this study, the genome-wide occupancy of the replication initiation protein Orc4 reveals its abundance at all centromeres in C. albicans. Orc4 is associated with four different DNA sequence motifs, one of which coincides with tRNA genes (tDNA) that replicate early and cluster together in space. Hi-C combined with genome-wide replication timing analyses identify that early replicating Orc4-bound regions interact with themselves stronger than with late replicating Orc4-bound regions. We simulate a polymer model of chromosomes of C. albicans and propose that the early replicating and highly enriched Orc4-bound sites preferentially localize around the clustered kinetochores. We also observe that Orc4 is constitutively localized to centromeres, and both Orc4 and the helicase Mcm2 are essential for cell viability and CENPA stability in C. albicans. Finally, we show that new molecules of CENPA are recruited to centromeres during late anaphase/telophase, which coincides with the stage at which the CENPA-specific chaperone Scm3 localizes to the kinetochore. We propose that the spatiotemporal localization of Orc4 within the nucleus, in collaboration with Mcm2 and Scm3, maintains centromeric chromatin stability and CENPA recruitment in C. albicans.
Hierarchical Human Semantic Parsing With Comprehensive Part-Relation Modeling

Modeling the human structure is central for human parsing that extracts pixel-wise semantic information from images. We start with analyzing three types of inference processes over the hierarchical structure of human bodies: direct inference (directly predicting human semantic parts using image information), bottom-up inference (assembling knowledge from constituent parts), and top-down inference (leveraging context from parent nodes). We then formulate the problem as a compositional neural information fusion (CNIF) framework, which assembles the information from the three inference processes in a conditional manner, i.e., considering the confidence of the sources. Based on CNIF, we further present a part-relation-aware human parser (PRHP), which precisely describes three kinds of human part relations, i.e., decomposition, composition, and dependency, by three distinct relation networks. Expressive relation information can be captured by imposing the parameters in the relation networks to satisfy specific geometric characteristics of different relations. By assimilating generic message-passing networks with their edge-typed, convolutional counterparts, PRHP performs iterative reasoning over the human body hierarchy. With these efforts, PRHP provides a more general and powerful form of CNIF, and lays the foundation for more sophisticated and flexible human relation patterns of reasoning. Experiments on five datasets demonstrate that our two human parsers outperform the state-of-the-arts in all cases.
Treatment of Anaemia in Patients with Acute Burn Injury: A Study of Blood Transfusion Practices †

Objective: To determine blood transfusion practices, risk factors, and outcomes associated with the use of blood products in the setting of the acute management of burn patients at the Victorian Adult Burn Service. Background: Patients with burn injuries have variable transfusion requirements, based on a multitude of factors. We reviewed all acute admissions to the Victorian Adult Burns Service (VABS) between 2011 and 2017: 1636 patients in total, of whom 948 had surgery and were the focus of our analysis. Method and results: Patient demographics, surgical management, transfusion details, and outcome parameters were collected and analyzed. A total of 175 patients out of the 948 who had surgery also had a blood transfusion, while 52% of transfusions occurred in the perioperative period. The median trigger haemoglobin in perioperative was 80mg/dL (IQR = 76–84.9 mg/dL), and in the non-perioperative setting was 77 mg/dL (IQR = 71.61–80.84 mg/dL). Age, gender, % total body surface area (TBSA) burn, number of surgeries, and intensive care unit and hospital length of stay were associated with transfusion. Conclusions: The use of blood transfusions is an essential component of the surgical management of major burns. As observed in our study, half of these transfusions are related to surgical procedures and may be influenced by the employment of blood conserving strategies. Furthermore, transfusion trigger levels in stable patients may be amenable to review and reduction. Risk adjusted analysis can support the implementation of blood transfusion as a useful quality indicator in burn care.
Selective Serotonin Reuptake-Inhibitors for Symptom-Based Treatment of Borderline Personality Disorders in Older Adults: An International Delphi Study

Objective International guidelines on symptom-based treatment of borderline personality disorders (BPD) in older adults are lacking. The number of older adults (≥ 65 years) with borderline personality disorder is rising. Effectiveness of Selective Serotonin Reuptake Inhibitors (SSRIs) on symptoms of BPD has only been investigated in younger adults and results are ambiguous. During life, serotonergic function changes, which can influence the indication and effectiveness of SSRIs in older adults with BPD. Aim of this study is to reach consensus on the suitability of SSRIs for the treatment of older adults with BPD. Methods A Delphi study was conducted among eighteen international experts. In three successive rounds, a total of 16 statements addressing the treatment with SSRI’s in older adults with BPD were assessed. Consensus on specific statements was reached if at least two-third of these experts agreed. Results Consensus was reached on 11 statements related to the indication and effectiveness of SSRIs in the treatment of older adults with BPD. Conclusion The results of this study suggest a valuable role for SSRIs in the treatment of affective instability, and to a lesser extent impulsive behavior, in older adults with BPD. Sertraline or citalopram are suggested to be the first-choice medication but should be prescribed with some caution. Treatment recommendations have been suggested (presented in a flowchart), but still have to be investigated in clinical practice.