Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear PKR in retinal neurons in the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats

Retinal neuron apoptosis is a key component of diabetic retinopathy (DR), one of the most common complications of diabetes. Stress due to persistent hyperglycaemia and corresponding glucotoxicity represents one of the primary pathogenic mechanisms of diabetes and its complications. Apoptosis of retinal neurons serves a critical role in the pathogenesis of DR observed in patients with diabetes and streptozotocin (STZ)-induced diabetic rats. Retinal neuron apoptosis occurs one month after STZ injection, which is considered the early stage of DR. The molecular mechanism involved in the suppression of retinal neuron apoptosis during the early stage of DR remains unclear. RNA-dependent protein kinase (PKR) is a stress-sensitive pro-apoptotic kinase. Our previous study indicated that PKR-associated protein X, a stress-sensitive activator of PKR, is upregulated in the early stage of STZ-induced diabetes. In order to assess the role of PKR in DR prior to apoptosis of retinal neurons, immunofluorescence and western blotting were performed to investigate the cellular localization and expression of PKR in the retina in the early stage of STZ-induced diabetes in rats. PKR activity was indirectly assessed by expression levels of phosphorylated eukaryotic translation initiation factor 2α (p-eIF2-α) and the presence of apoptotic cells in the retina was investigated by TUNEL assay. The findings revealed that PKR was localized in the nucleus of retinal ganglion and inner nuclear layer cells from normal and diabetic rats. To the best of our knowledge, the present study is the first to demonstrate nuclear localization of PKR in retinal neurons. Immunofluorescence analysis demonstrated that PKR was expressed in the nuclei of retinal neurons at 3 and 6 days and its expression was decreased at 15 days after STZ treatment. In addition, p-eIF2-α expression and cellular localization followed the trend of PKR, suggesting that this pro-apoptotic kinase was active in the nuclei of retinal neurons. These findings are consistent with the hypothesis that nuclear translocation of PKR may be a mechanism to sequester active PKR, thus preventing upregulation of cytosolic signalling pathways that induce apoptosis in retinal neurons. Apoptotic cells were not detected in the retina in the early stage of DR. A model was proposed to explain the mechanism by which apoptosis of retinal neurons by PKR is suppressed in the early stage of DR. The possible role of mitochondrial RNA (mtRNA) and Alu RNA in this phenomenon is also discussed since it was demonstrated that the cellular stress due to prolonged hyperglycaemia induces the release of mtRNA and transcription of Alu RNA. Moreover, it mtRNA activates PKR, whereas Alu RNA inhibits the activation of this protein kinase.
Variation awaiting bias: Substantively biased learning of vowel harmony variation

Abstract This article examines whether children alter a variable phonological pattern in an artificial language towards a phonetically-natural form. We address acquisition of a variable rounding harmony pattern through the use of two artificial languages; one with dominant harmony pattern, and another with dominant non-harmony pattern. Overall, children favor harmony pattern in their production of the languages. In the language where harmony is non-dominant, children's subsequent production entirely reverses the pattern so that harmony predominates. This differs starkly from adults. Our results compare to the regularization found in child learning of morphosyntactic variation, suggesting a role for naturalness in variable phonological learning.
Hydrogen Sulphide (H2S) Exposure Hazard Assessment: An Algorithm for Generating Exposure Index Based on Direct Instrument Readings

Abstract Objectives Increased use of small affordable alarm sensors with logging or network capabilities has improved the ability to monitor exposure. The large datasets generated from these monitors calls for development of a computer algorithm to assess these data. Methods We examined 88 time series of hydrogen sulphide (H2S) from wastewater works previously used for developing the exposure index. The time series covered 331 h, where 16 h had readings different from zero. Results The developed algorithm reproduced the manual assessed index almost perfectly (linear regression β = 1.02, R2 = 0.97, P < 0.001). Time-weighted average (TWA) values of the 88 time series showed a mean value of 0.04 ppm (range 0.0–0.9). The mean index value was 18 (range 0–337), with a good linear fit (β = 0.002, R2 = 0.93, and P < 0.001). The index gave us a better resolution and basis for risk assessment than the TWA, and managed to combine evaluation of TWA and exceedance of ceiling value in one number. Conclusions As long as peaks above ceiling value occur, we find alarm tools with an H2S sensor to be an essential personal protective equipment against H2S. The proposed method has been verified, and it removes some common human errors in graph evaluation. Use of the index is a possible way of quantifying risk level in exposure to H2S in one single number and provides better understanding of the risk of exposure, as it eases the analysis and evaluation of large numbers of time series.
Evaluation of curved root canals filled with a new bioceramic sealer: A microcomputed tomographic study using images with different voxel sizes and segmentation methods

The aim of this study was to investigate the filling ability of a new premixed bioceramic sealer in comparison with an epoxy resin‐based sealer in curved root canals using different segmentation methods and voxel sizes in micro‐CT images. Twelve curved mesial roots of mandibular molars with two separated canals were selected. All root canals were prepared by using HyFlex EDM files size 25/. 08 and filled by the single cone technique and Bio‐C Sealer or AH Plus (n = 12). The samples were scanned by micro‐CT at 5 μm. The images were analyzed at 5, 10, and 20 μm for the volumetric analysis of voids in filling. Visual image segmentation was performed by two examiners, and the automatic segmentation was accomplished for comparison. Radiopacity of the sealers was evaluated by radiographic analysis. Data were submitted to the two‐way ANOVA and non‐paired t tests at a significance level of 5%. AH Plus had the highest radiopacity (p < .05). Root canals filled with AH Plus or Bio‐C had similar low percentage of voids (p > .05). There was no difference interobserver, which had similar results to those obtained with automatic segmentation for all voxel sizes evaluated (p > .05). Bio‐C Sealer had appropriate filling ability. Visual and automatic segmentation can be applied to micro‐CT images with voxel sizes from 5 to 20 μm to evaluate the filling of sealers with adequate radiopacity. Automatic segmentation should be used as a faster method.
Improved Brain MR Imaging from a Compact, Lightweight 3T Scanner with High‐Performance Gradients

A low‐cryogen, compact 3T (C3T) MRI scanner with high‐performance gradients capable of simultaneously achieving 80 mT/m gradient amplitude and 700 T/m/second slew rate has been in use to study research patients since March 2016 but has not been implemented in the clinical practice.
Effects of social-distancing on infectious disease dynamics: an evolutionary game theory and economic perspective

We propose two models inspired by the COVID-19 pandemic: a coupled disease-human behaviour (or disease-game theoretic), and a coupled disease-human behaviour-economic model, both of which account for the impact of social-distancing on disease control and economic growth. The models exhibit rich dynamical behaviour including multistable equilibria, a backward bifurcation, and sustained bounded periodic oscillations. Analyses of the first model suggests that the disease can be eliminated if everybody practices full social-distancing, but the most likely outcome is some level of disease coupled with some level of social-distancing. The same outcome is observed with the second model when the economy is weaker than the social norms to follow health directives. However, if the economy is stronger, it can support some level of social-distancing that can lead to disease elimination.
Replacement of Sedentary Behavior by Various Daily-Life Physical Activities and Structured Exercises: Genetic Risk and Incident Type 2 Diabetes

OBJECTIVE To prospectively analyze the association of sedentary behavior time with type 2 diabetes (T2D) risk and perform the isotemporal substitution analyses to estimate the effect of substitution of sedentary behaviors by equal time of different types of daily-life physical activities and structured exercise. We also examined modifications by the genetic predisposition to T2D. RESEARCH DESIGN AND METHODS We included 475,502 participants free of T2D in the UK Biobank. Sedentary time was quantified by summing up the time spent on television watching, computer use, and driving. RESULTS During a median follow-up of 11 years, we documented 18,169 incident T2D cases. In comparison of the extreme categories (≥6 vs. <2 h/day), the hazard ratio for T2D was 1.58 (95% CI 1.47, 1.71) after adjustment for age, race, sex, lifestyle factors, and other covariates. Replacing 30 min of sedentary behavior per day with an equal amount of time of different types of daily-life activities and structured exercise was significantly associated with a 6–31% risk reduction of T2D, with strenuous sports showing the strongest (31%, 95% CI 24, 37) benefit. Moreover, we found a significant interaction between sedentary behavior and genetic predisposition for the risk of T2D (Pinteraction = 0.0008). The association was more profound among participants with a lower genetic risk of T2D. CONCLUSIONS Our study indicates that sedentary behavior time is associated with an increased risk of T2D; replacing sedentary behavior with a short duration (30 min/day) of daily-life physical activities or structured exercise is related to a significant reduction in T2D risk. Furthermore, such association was stronger among those with a lower genetic risk of T2D.
Presymptomatic transmission of SARS-CoV-2 infection: a secondary analysis using published data

Objective To estimate the proportion of presymptomatic transmission of SARS-CoV-2 infection that can occur, and the timing of transmission relative to symptom onset. Setting/design Secondary analysis of international published data. Data sources Meta-analysis of COVID-19 incubation period and a rapid review of serial interval and generation time, which are published separately. Participants Data from China, the Islamic Republic of Iran, Italy, Republic of Korea, Singapore and Vietnam from December 2019 to May 2020. Methods Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset, and the proportion of presymptomatic transmission, were estimated. Outcome measures Transmission time of SARS-CoV-2 relative to symptom onset and proportion of presymptomatic transmission. Results Based on 18 serial interval/generation time estimates from 15 papers, mean transmission time relative to symptom onset ranged from −2.6 (95% CI −3.0 to –2.1) days before infector symptom onset to 1.4 (95% CI 1.0 to 1.8) days after symptom onset. The proportion of presymptomatic transmission ranged from 45.9% (95% CI 42.9% to 49.0%) to 69.1% (95% CI 66.2% to 71.9%). Conclusions There is substantial potential for presymptomatic transmission of SARS-CoV-2 across a range of different contexts. This highlights the need for rapid case detection, contact tracing and quarantine. The transmission patterns that we report reflect the combination of biological infectiousness and transmission opportunities which vary according to context.
Evaluation of Commercial Rapid Lateral Flow Tests, Alone or in Combination, for SARS-CoV-2 Antibody Testing

ABSTRACT. Antibody tests can be tools for detecting current or past severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 [coronavirus disease 2019 (COVID-19)]) infections. Independent test evaluations are needed to document the performance with different sample sets. We evaluated six lateral flow assays (LFAs) and two laboratory-based tests (EUROIMMUN-SARS-CoV-2 ELISA and Abbott-Architect-SARS-CoV-2-IgG). We tested 210 plasma samples from 89 patients diagnosed with acute COVID-19. These samples were collected at different time points after the onset of symptoms. In addition, 80 convalescent plasma samples, and 168 pre-pandemic samples collected from adults in the United States and in Africa were tested. LFA performance varied widely, and some tests with high sensitivity had low specificity. LFA sensitivities were low (18.8–40.6%) for samples collected 0 to 3 days after symptom onset, and were greater (80.3–96.4%) for samples collected > 14 days after symptom onset. These results are similar to those obtained by ELISA (15.6% and 89.1%) and chemiluminescent microparticle assay (21.4% and 93.1%). The range of test specificity was between 82.7% and 97%. The combined use of two LFAs can increase specificity to more than 99% without a major loss of sensitivity. Because of suboptimal sensitivity with early COVID-19 samples and background reactivity with some pre-pandemic samples, none of the evaluated tests alone is reliable enough for definitive diagnosis of COVID-19 infection. However, antibody testing may be useful for assessing the status of the epidemic or vaccination campaign. Some of the LFAs had sensitivities and specificities that were comparable to those of more expensive laboratory tests, and these may be useful for seroprevalence surveys in resource-limited settings.
Effects of a minimal‐guided on‐line intervention for alcohol misuse in Estonia: a randomized controlled trial

Abstract Background and Aims Estonia has one of the highest alcohol‐attributable mortality rates within the European Union. The aim of this study was to estimate the efficacy of an on‐line self‐help intervention to reduce problem drinking at the population level. Design On‐line open randomized controlled trial with an 8‐week intervention and an active control group (intervention n = 303, control n = 286). Assessments took place at baseline and at 6 months follow‐up. Setting On‐ and offline channels were used for population‐based recruitment within a nation‐wide prevention campaign in Estonia. Participants Inclusion criteria were age ≥ 18 years, heavy drinking [Alcohol Use Disorders Identification (AUDIT) test score ≥ 8], literacy in Estonian and at least weekly access to the internet; n = 589 participants were randomized (50% male, 1% other; mean age 37.86 years; 45% with higher level of education). Intervention and comparator The intervention consisted of 10 modules based on principles of cognitive–behavioral therapy and motivational interviewing. The active control group received access to a website with a self‐test including personalized normative feedback and information for standard alcohol treatment. Measurements The primary outcome was AUDIT scores at 6 months follow‐up adjusted for baseline scores. Findings Intention‐to‐treat analyses were applied. Missing data were addressed by using baseline observation carried forward (BOCF) and multiple imputation by chained equations (MI); 175 completed follow‐up in the intervention group and 209 in the control group. AUDIT score at follow‐up was significantly smaller in the intervention [BOCF mean = 13.91, standard deviation (SD) = 7.61, MI mean = 11.03, SD = 6.55] than control group (BOCF mean = 15.30, SD = 7.31; MI mean = 14.30, SD = 7.21), with a group difference of −1.38 [95% confidence interval (CI) = –2.58, –0.18], P = 0.02 for BOCF and −3.26 (95% CI = –2.01, –4.51), P < 0.001 for MI. Conclusions A randomized controlled trial has found that an on‐line self‐help intervention with minimal guidance was effective at reducing problem drinking in Estonia.
Proton pump inhibitors versus histamine-2 receptor blockers for stress ulcer prophylaxis in patients with sepsis: a retrospective cohort study

Objective We aimed to compare the efficacy and risks of proton pump inhibitor (PPI) versus histamine-2 receptor blocker (H2B) use for stress ulcer prophylaxis (SUP) in critically ill patients with sepsis and risk factors for gastrointestinal bleeding (GIB). Methods In this retrospective cohort study, we used the Medical Information Mart for Intensive Care III Clinical Database to identify critically ill adult patients with sepsis who had at least one risk factor for GIB and received either an H2B or PPI for ≥48 hours. Propensity score matching (PSM) was conducted to balance baseline characteristics. The primary outcome was in-hospital mortality. Results After 1:1 PSM, 1056 patients were included in the H2B and PPI groups. The PPI group had higher in-hospital mortality (23.8% vs. 17.5%), GIB (8.9% vs. 1.6%), and pneumonia (49.6% vs. 41.6%) rates than the H2B group. After adjusting for risk factors of GIB and pneumonia, PPI use was associated with a 1.28-times increased risk of in-hospital mortality, 5.89-times increased risk of GIB, and 1.32-times increased risk of pneumonia. Conclusions Among critically ill adult patients with sepsis at risk for GIB, SUP with PPIs was associated with higher in-hospital mortality and higher risk of GIB and pneumonia than H2Bs.
Effects of the methanol fraction of modified Seonghyangjeongki-san water extract on transient ischaemic brain injury in mice

Abstract Context Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. However, studies on the specific mechanisms of action of SHJKS for the treatment of ischaemic stroke are still lacking. Objective This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury. Materials and methods C57BL/6 male mice were orally administered SHJKSmex (30, 100, or 300 mg/kg) for 3 consecutive days (2 days, 1 day, and 1 h, respectively) before middle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volumes were measured, brain edoema indices were calculated, and neurological deficit scores were determined. Inflammation-related substances in the ipsilateral hemisphere were determined by western blotting, dichlorofluorescin diacetate, thiobarbituric acid-reactive substances assay, and enzyme-linked immunosorbent assay. Results SHJKSmex pre-treatment at 300 mg/kg decreased infarct volume by 87% and mean brain water content by 90% of the MCAO control group. Moreover, SHJKSmex effectively suppressed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and −9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MCAO control group. Discussion and conclusions SHJKSmex protected the brain from ischaemic stroke in mice through its antioxidant, anti-inflammatory, and antiapoptotic activities. Our findings suggest that SHJKSmex is a promising therapeutic candidate for the development of a new formulation for ischaemia-induced brain damage.
Vitamin D in critical care: where are we now and what is next?

Purpose of review To summarize the recent evidence on the role of vitamin D deficiency in critically ill patients and emerging data claiming a role of vitamin D in COVID-19. Recent findings Vitamin D is a strong predictor for worse outcomes in critically ill patients, and as well in COVID-19. The vitamin D content in typical nutrition regimes is lower than what is recommended for the general population. Although its supplementation has been shown to reduce respiratory tract infections, asthma exacerbations and mortality risk in noncritically ill patients, its role in the acute setting is not yet clear. Several small intervention trials have shown interesting results in COVID-19, and larger studies are ongoing. Summary Although research on this topic is still ongoing, it appears reasonable to recommend at least the standard vitamin dose for the healthy population (600--800 IU of native vitamin D3). Many questions remain on the actual role, the best metabolite, regime, and so forth. However, the role for vitamin D in bone health is clear. Elderly ICU survivors have a high risk for osteoporosis/fractures, so at least in this population, an optimal vitamin D status should be targeted.
Numerical Simulation of Industrial Opposed Multiburner Coal–Water Slurry Entrained Flow Gasifier

A comprehensive three-dimensional numerical model is developed for simulation of the industrial opposed multiburner (OMB) coal–water slurry (CWS) entrained flow gasifier. The CWS gasification process is divided into several submodels, including water evaporation, coal pyrolysis, and homogeneous and heterogeneous char reactions. The “effectiveness factor” method is used to extrapolate the intrinsic char reactivity data to industrial CWS gasifier conditions. Numerical simulations with the proposed models are performed on the industrial OMB gasifier, and the predicted temperature and gas compositions at the outlet of the gasifier are in good agreement with industrial operating data. The profiles of flow field, temperature, and gas composition in the gasifier are described. In addition, the effects of the slurry concentration and oxygen/coal ratio on the gasifier performance are also studied, which reveal that the lower oxygen/coal ratio or higher slurry concentration leads to higher cold gas efficiency, whil.
Is stem cell transplantation still needed for adult Philadelphia chromosome-positive acute lymphoblastic leukemia receiving tyrosine kinase inhibitors therapy?: A systematic review and meta-analysis

Background Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, tyrosine kinase inhibitors (TKI) also play a significant role in the treatment of these patients. We conducted this systematic review and meta-analysis to compare the efficacy of allogeneic (allo-) HSCT, autologous (auto-) HSCT, and chemotherapy (CMT) alone–all in combination with TKIs in adult Ph+ ALL patients. Materials and methods This systematic review identified studies from the EMBASE and MEDLINE databases from inception to April 2021 using search terms related to “ALL” and “HSCT. ” Eligible studies could be randomized controlled trials or cohort studies that included adult Ph+ ALL patients who received a TKI and either allo-HSCT, auto-HSCT, or CMT alone, and that reported the number of patients in each group for each of our primary outcomes of interest: overall survival (OS) or disease-free survival (DFS). Point estimates and associated 95% confidence intervals (CI) from each study were combined using the Hantel-Maenszel method. Results After two rounds of review, 26 cohort studies were determined to be eligible for the meta-analysis. Adult Ph+ ALL patients who received HSCT had better survival outcomes than those who did not receive any HSCT (pooled odds ratio [OR] for OS of 1.61, 95%CI: 1.08–2.40; I2 = 59%, and for DFS of 3.23, 95%CI: 2.00–5.23; I2 = 62% for allo-HSCT; and, pooled OR for OS of 7.04, 95%CI: 1.97–25.15; I2 = 0%, and for DFS of 5.78, 95%CI: 1.04–32.19; I2 = 42% for auto-HSCT). Allo-HSCT recipients had comparable OS and DFS, but lower relapse rate compared to auto-HSCT recipients. Funnel plot generally demonstrated no presence of publication bias. Conclusions This systematic review and meta-analysis demonstrated superior results of HSCT in Ph+ ALL patients compared to CMT alone. Moreover, auto-HSCT could be implemented with comparable survival outcomes to allo-HSCT in patients with no available donor or when haploidentical HSCT is not feasible.