Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting B cells in multiple sclerosis

Purpose of review Treatments targeting B cells are increasingly used for patients with multiple sclerosis (MS). We review the mechanisms of action, clinical effectiveness and safety of treatment, with emphasis on recently published studies. Recent findings Several monoclonal antibodies targeting the surface molecule CD20 on B cells are approved or being developed for treatment of MS. Overall, they seem comparable in terms of strongly suppressing radiological disease activity and relapse biology. Novel approaches include anti-CD19 antibody therapy and treatment with oral drugs targeting Bruton's tyrosine kinase (BTK). The main safety issue with persistent B cell depletion is an increased risk of infections – possibly including an increased risk of severe COVID-19. Vaccine responses are also blunted in patients treated with anti-CD20 antibodies. Lower doses or longer infusion intervals may be sufficient for control of disease activity. Whether this might also improve the safety of treatment and increase vaccination responses remains to be determined. Summary Available data support the widespread use of therapies targeting B cells in MS. Whether novel approaches targeting CD19 or BTK will have advantages compared to anti-CD20 antibody therapy remains to be established. Furthermore, trials investigating alternative dosing regimens for anti-CD20 antibody treatment are warranted.
A preliminary study of the reduction of Np(VI) by formohydroxamic acid using stopped-flow near-infrared spectrophotometry

The kinetics of the reduction of NpO22+ to NpO2+ in nitric acid aqueous solution by formohydroxamic acid (FHA) were studied to allow more accurate flow sheet modelling of neptunium separation from uranium and plutonium in an Advanced PUREX process. The rate of the reaction was monitored using stopped-flow spectrophotometry with near-infrared detection. The conditional reduction rate in 2 M nitric acid at 22°C could be described by the following equation: -d [NpO22+]/dt = k [NpO22+][FHA](M/s) with k = 1.17×103 M-1 s-1 at [H+] = 2.0 M. Comparison with other data available in the literature, indicates that formohydroxamic acid is an unusually strong reducing agent for NpO22+.
High-density MIM capacitors using Al 2 O 3 and AlTiO x dielectrics

We have investigated the electrical characteristics of Al/sub 2/O/sub 3/ and AlTiO/sub x/ MIM capacitors from the IF (100 KHz) to RF (20 GHz) frequency range. Record high capacitance density of 0.5 and 1.0 /spl mu/F/cm/sup 2/ are obtained for Al/sub 2/O/sub 3/ and AlTiO/sub x/ MIM capacitors, respectively, and the fabrication process is compatible to existing VLSI backend integration. However, the AlTiO/sub x/ MIM capacitor has very large capacitance reduction at increasing frequencies. In contrast, good device integrity has been obtained for the Al/sub 2/O/sub 3/ MIM capacitor as evidenced from the small frequency dependence, low leakage current, good reliability, small temperature coefficient, and low loss tangent.
Multivessel Disease Patients' Outcome and Second Generation Stent: Is Syntax Still a Valid Score? A Real-World Study from a Tertiary Center.

OBJECTIVE The SYNTAX trial was designed to evaluate whether multivessel disease patients could benefit from percutaneous or surgical revascularization using a paclitaxel eluting stents, but after the introduction of second generation stents, this score needs to be reevaluated. The aim of our study was to analyze the association between SYNTAX score and the prognosis of multivessel patients submitted to percutaneous coronary intervention (PCI) and second generation everolimus eluting stents (EES) implantation. MATERIALS AND METHODS Data on 289 patients with multivessel coronary artery disease submitted to PCI with EES were stored in a dedicated database and retrospectively analyzed. During a mean follow-up period of 14.4±6.4 months, major adverse cardiac and cerebrovascular events (MACCE) including death from any cause, myocardial infarction, target lesion revascularization (TLR) and stroke, were systematically assessed. RESULTS The incidence of MACCE at follow-up was 13.1%; death from any cause occurred in 19 patients (6.6%) and myocardial infarction in 9 patients (3.1%). TLR was detected in 2.7% of patients and stroke was observed in 2 patients. The SYNTAX score did not prove to be an independent predictor of overall death at multivariable analysis. CONCLUSION At mid-term follow-up, the incidence of MACCE in multivessel disease patients submitted to PCI and EES implantation was low; no significant association was found between SYNTAX score severity and MACCE at follow-up, suggesting that it should be modified after the introduction of EES.
C9orf72-associated arginine-rich dipeptide repeats induce RNA-dependent nuclear accumulation of Staufen in neurons

Abstract RNA-binding proteins (RBPs) play essential roles in diverse cellular processes through post-transcriptional regulation of RNAs. The subcellular localization of RBPs is thus under tight control, the breakdown of which is associated with aberrant cytoplasmic accumulation of nuclear RBPs such as TDP-43 and FUS, well-known pathological markers for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Here, we report in Drosophila model for ALS/FTD that nuclear accumulation of a cytoplasmic RBP Staufen may be a new pathological feature. We found that in Drosophila C4da neurons expressing PR36, one of the arginine-rich dipeptide repeat proteins (DPRs), Staufen accumulated in the nucleus in Importin- and RNA-dependent manner. Notably, expressing Staufen with exogenous NLS—but not with mutated endogenous NLS—potentiated PR-induced dendritic defect, suggesting that nuclear-accumulated Staufen can enhance PR toxicity. PR36 expression increased Fibrillarin staining in the nucleolus, which was enhanced by heterozygous mutation of stau (stau+/−), a gene that codes Staufen. Furthermore, knockdown of fib, which codes Fibrillarin, exacerbated retinal degeneration mediated by PR toxicity, suggesting that increased amount of Fibrillarin by stau+/− is protective. stau+/− also reduced the amount of PR-induced nuclear-accumulated Staufen and mitigated retinal degeneration and rescued viability of flies expressing PR36. Taken together, our data show that nuclear accumulation of Staufen in neurons may be an important pathological feature contributing to the pathogenesis of ALS/FTD.
Rapid optimization of processes for the integrated purification of biopharmaceuticals

Straight‐through chromatography, wherein the eluate from one column passes directly onto another column without adjustment, is one strategy to integrate and intensify manufacturing processes for biologics. Development and optimization of such straight‐through chromatographic processes is a challenge, however. Conventional high‐throughput screening methods optimize each chromatographic step independently, with limited consideration for the connectivity of steps. Here, we demonstrate a method for the development and optimization of fully integrated, multi‐column processes for straight‐through purification. Selection of resins was performed using an in silico tool for the prediction of processes for straight‐through purification based on a one‐time characterization of host‐cell proteins combined with the chromatographic behavior of the product. A two‐step optimization was then conducted to determine the buffer conditions that maximized yield while minimizing process‐ and product‐related impurities. This optimization of buffer conditions included a series of range‐finding experiments on each individual column, similar to conventional screening, followed by the development of a statistical model for the fully integrated, multi‐column process using design of experiments. We used this methodology to develop and optimize integrated purification processes for a single‐domain antibody and a cytokine, obtaining yields of 88% and 86%, respectively, with process‐ and product‐related variants reduced to phase‐appropriate levels for nonclinical material.
Neofusicoccum caryigenum, a new species causing leaf dieback disease of pecan (Carya illinoinensis)

ABSTRACT Neofusicoccum species are endophytes and pathogens of woody hosts and members of the Botryosphaeriaceae. Leaf dieback is a new disease resulting in death of compound leaves and extensive defoliation of pecan trees (Carya illinoinensis) throughout the southeastern United States. Currently, the disease is consistently most severe on trees that are not managed with fungicides for pecan scab. Preliminary observations of the fungus isolated from symptomatic leaves indicated that it was a member of the genus Neofusicoccum. Our objectives were to confirm that this is the causal organism of leaf dieback disease of pecan and to determine whether this disease is caused by a new or previously described species of Neofusicoccum. Morphological observations of pure cultures, conidiomata, conidiogenous cells, and conidia were consistent with members of the genus Neofusicoccum. Using Koch’s postulates, we established that Neofusicoccum sp. isolated from symptomatic leaves caused the disease. We sequenced the internal transcribed spacer of the rDNA (ITS), elongation factor 1-α (EF1-α), the second largest subunit of RNA polymerase II (RPB2), and β-tubulin (TUB2) of 11 isolates collected from Georgia and Texas. Phylogenetic and network analyses of these sequences combined with publicly available sequences of 40 members of the N. parvum–N. ribis species complex and the outgroup N. australe revealed that this fungus is a member of the species complex but is genetically distinct from previously described species. We determined that leaf dieback of pecan is caused by a novel species, named herein N. caryigenum.
Normal-tension glaucoma is associated with cognitive impairment

Background/aims Recent research suggests an association between normal-tension glaucoma (NTG) and dementia. This study investigated whether cognitive impairment is more strongly associated with NTG than high tension glaucoma (HTG) using cognitive screening within an Australiasian Glaucoma Disease Registry. Methods The authors completed a case–control cross-sectional cognitive screening involving 290 age-matched and sex-matched NTG participants and HTG controls aged ≥65 randomly sampled from the Australian and New Zealand Registry of Advanced Glaucoma. Cognitive screening was performed using the Telephone Version of the Montreal Cognitive Assessment (T-MoCA). The T-MoCA omits points requiring visual interpretation, accounting for confounding factors related to vision loss in visually impaired participants. Cognitive impairment was defined by a T-MoCA score of <11/22. Cognition was compared between NTG and HTG participants using predetermined thresholds and absolute screening scores. Results A total of 290 participants completed cognitive assessment. There were no differences in NTG (n=144) and HTG (n=146) cohort demographics or ocular parameters at baseline. Cognitive impairment was more prevalent in the NTG cohort than the HTG cohort (OR=2.2; 95% CI 1.1 to 6.7, p=0.030). Though a linear trend was also observed between lower absolute T-MoCA scores in the NTG cohort when compared with the HTG cohort, this association was not statistically significant (p=0.108). Conclusion This study demonstrated an association between NTG status and poor cognition, supporting the hypothesis that there exists a disease association and shared pathoaetiological features between NTG and dementia.
An open label, randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia

Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DEC plus albendazole (DA, 27 subjects). Participants were actively monitored for adverse events (AE) for two days after treatment by nurses and physicians who were masked regarding treatment assignments. Passive monitoring was performed by clinical teams that visited participant’s home villages for an additional five days. Microfilaremia was assessed by membrane filtration of 1 ml night blood at baseline, at 24h and one year after treatment. IDA was more effective than DA for completely clearing Mf at 24 hours (25/28, 89% vs. 8/27, 30%, P < 0.001). By 12 months after treatment, only one of 27 IDA recipients had Mf in their blood (4%) vs. 10 of 25 (40%) in persons treated with DA (P = 0.002). Approximately 90% of participants had antibodies to recombinant filarial antigen BmR1 at baseline. Antibody prevalence decreased to approximately 30% in both treatment groups at 12 months. About 45% of persons in both treatment groups experienced AE such as fever, muscle aches, lower back, joint and abdominal pain. These were mostly mild and most common during the first two days after treatment. No participant experienced a severe or serious AE. This study showed that IDA was well-tolerated and significantly more effective for clearing B. timori Mf from the blood than DA. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis. Trial Registration: NCT02899936.
Use of Machine Learning to Develop and Evaluate Models Using Preoperative and Intraoperative Data to Identify Risks of Postoperative Complications

Key Points Question Can machine learning models predict patient risks of postoperative complications related to pneumonia, acute kidney injury, deep vein thrombosis, delirium, and pulmonary embolism? Findings In a cohort study of 111 888 operations at a large academic medical center, machine learning algorithms exhibited high areas under the receiver operating characteristic curve for predicting the risk of postoperative complications related to pneumonia, acute kidney injury, deep vein thrombosis, pulmonary embolism, and delirium. Meaning These findings suggest that machine learning models using preoperative and intraoperative data can predict postoperative complications and generate reliable and clinically meaningful interpretations for supporting clinical decisions along the perioperative care continuum.
Temporal course of net N mineralization and immobilization in topsoil following incorporation of crop residues of winter oilseed rape, peas and oats in a northern climate

The impact of incorporated residues of winter oilseed rape, peas and oats on soil N availability and the risk of N leaching during autumn and winter in a northern climate is not clear. Therefore, the aim was to determine the influence of incorporated residues on net N mineralization–immobilization in topsoil during autumn and winter. A field experiment carried out at three sites in South Sweden provided soil samples and crop residues for an interpretive, in situ incubation study. Topsoil corresponding to a 7‐cm soil layer from each site used for the field experiment was incubated with and without aboveground residues under natural temperature conditions at a single field location. On the basis of the incubation study, we concluded that in the field experiment, soil N dynamics during autumn and winter trials were the combined outcome of net N mineralization in the topsoil fraction not affected by aboveground residues and net N immobilization in the fraction in contact with aboveground crop residues. In the absence of aboveground residues, the net rate of N mineralization during early autumn was similar after both oilseed rape and peas, but values were larger than that after oats. After incorporation, aboveground residues of winter oilseed rape and peas made no contribution to soil mineral N in late autumn and thus did not increase the risk of N losses during winter. In fact, the residues of oilseed rape, peas and oats reduced the amount of soil mineral N by 7–14 kg N/ha during the main drainage period (October–March). Therefore, incorporating chopped aboveground residues should be encouraged before sowing winter wheat after peas and winter oilseed rape.
Measurement of Water Adsorption Layers on Metal Surfaces

Following some theoretical considerations of water adsorption on metal surfaces, a description is given of the measuring devices. The mass of the water adsorption layer is determined by weighing, with due regard to the following influencing parameters: material, roughness, oxide layers and impurities as a function of the humidity of air. In addition, results obtained for various metal surfaces (coated and uncoated) will be discussed.
Factors affecting anaemia among women of reproductive age in Nepal: a multilevel and spatial analysis

Objective The main objective of this study was to explore the factors affecting anaemia among women of reproductive age (WRA) in Nepal using spatial and multilevel epidemiological analysis. Design This cross-sectional study analysed data from the 2016 Nepal Demographic and Health Survey. Spatial analysis was performed using ArcGIS software V.10. 8 to identify the hot and cold spots of anaemia among WRA (15–49 years). Data were analysed using multilevel mixed-effect logistic regression analysis. Setting Nepal. Participants A total of 6414 WRA were included in the analysis. Main outcome measure Anaemia defined by WHO as haemoglobin level less than 120 g/L in non-pregnant women and less than 110 g/L in pregnant women. Results The spatial analysis showed that statistically significant hotspots of anaemia were in the southern Terai region (four districts in province 1, eight districts in province 2, one district in Bagmati province, two districts in province 5 and one district in Sudurpaschim province) of Nepal. At the individual level, women who underwent female sterilisation (adjusted OR, aOR: 3.61, 95% CI 1.10 to 11.84), with no education (aOR: 1.99, 95% CI: 1.17 to 3.39), and from middle socioeconomic class families (aOR: 1.65, 95% CI: 1.02 to 2.68) were more likely to be anaemic, whereas, older women (>35 years) (aOR: 0.51, 95% CI: 0.26 to 0.97) and those women who were using hormonal contraceptives (aOR: 0.63, 95% CI: 0.43 to 0.90) were less likely to be anaemic. At the community level, women from province 2 (aOR=2.97, 95% CI: 1.52 to 5.82) had higher odds of being anaemic. Conclusion WRA had higher odds of developing anaemia, and it varied by the geographical regions. Nutrition-specific and nutrition-sensitive interventions can be tailored based on the factors identified in this study to curb the high burden of anaemia.
Views on ethical issues in research labs: A university-wide survey

ABSTRACT In this article, we summarize the key findings of an exploratory study in which students and faculty completed a survey that sought to identify the most important ethical issues in STEM fields, how often these issues are discussed in research groups, and how often these ethical issues come up in the daily practice of research. Participants answered a series of open-ended and Likert-scale questions to provide a detailed look at the current ethical landscape at a private research university in the Midwest. The survey also looked at potential differences between faculty and undergraduate and graduate students’ perceptions in answering these questions. The results indicate that while all community members tended to view issues that can be classified as research misconduct as the most important activities to avoid in STEM-related research, the level of discussion and actual witnessing of these practices was relatively low. The study points to a consensus among students and faculty about the important ethical issues in STEM and the need for more discussion and attention to be paid to communication, collaboration, and interpersonal relationships in the research environment.
Patterns of Athlete Medication Use at the 2018 PyeongChang Paralympic Games

Objective Medication use among elite athletes has received growing attention over the past decades. However, only limited studies have focused on para athletes, and trends in medication use among this cohort remain unclear. The aims of this study were (1) to describe the pattern of medication use in elite Paralympic athletes, with a particular focus on analgesics, (2) to analyze whether medications declared by athletes were included in the 2018 World Anti-Doping Agency’s prohibited list and monitoring program, (3) to report on a variety of novel supplements, and (4) to review whether athlete analgesic needs will be met by the new Olympic & Paralympic Model Formulary. Design This is a retrospective, descriptive cohort study. Results Of all athletes who underwent doping control, 21% declared the use of an analgesic medication. Athletes with limb deficiency and para snowboarders declared the most analgesic medications in their respective categories. It was determined that 84% of the athletes’ analgesic medication needs were provided from the new Olympic & Paralympic Model Formulary. Conclusions Analgesic use among athletes who participated at the 2018 PyeongChang Winter Paralympics was high. Para snowboarders and athletes with limb deficiency declared the most analgesics. The new Olympic & Paralympic Model Formulary adequately addressed the medication needs of the athletes attending the 2018 games.
Incorporating Information on Control Diseases Across Space and Time to Improve Estimation of the Population-level Impact of Vaccines

Supplemental Digital Content is available in the text. Background: The synthetic control method evaluates the impact of vaccines while adjusting for a set of control time series representing diseases that are unaffected by the vaccine. However, noise in control time series, particularly in areas with small counts, can obscure the association with the outcome, preventing proper adjustments. To overcome this issue, we investigated the use of temporal and spatial aggregation methods to smooth the controls and allow for adjustment of underlying trends. Methods: We evaluated the impact of pneumococcal conjugate vaccine on all-cause pneumonia hospitalizations among adults ≥80 years of age in 25 states in Brazil from 2005 to 2015. Pneumonia hospitalizations in this group indicated a strong increasing secular trend over time that may influence estimation of the vaccine impact. First, we aggregated control time series separately by time or space before incorporation into the synthetic control model. Next, we developed distributed lags models (DLMs) to automatically determine what level of aggregation was most appropriate for each control. Results: The aggregation of control time series enabled the synthetic control model to identify stronger associations between outcome and controls. As a result, the aggregation models and DLMs succeeded in adjusting for long-term trends even in smaller states with sparse data, leading to more reliable estimates of vaccine impact. Conclusions: When synthetic control struggles to identify important prevaccine associations due to noise in control time series, users can aggregate controls over time or space to generate more robust estimates of the vaccine impact. DLMs automate this process without requiring prespecification of the aggregation level.