Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of urbanization on vulnerability to heat-related mortality in urban and rural areas in South Korea: a nationwide district-level time-series study.

BACKGROUND Although urbanization is often an important topic in climate change studies, the complex effect of urbanization on heat vulnerability in urban and rural areas has rarely been studied. We investigated the disparate effects of urbanization on heat vulnerability in urban and rural areas, using nationwide data. METHODS We collected daily weather data for all 229 administrative districts in South Korea (2011-17). Population density was applied as an urbanization indicator. We calculated the heat-mortality risk using a distributed lag nonlinear model and analysed the relationship with population density. We also examined district characteristics that can be related to the spatial heterogeneity in heat-mortality risk. RESULTS We found a U-shaped association between population density and heat-mortality risk, with the highest risk for rural populations; in urban areas, risk increases with increasing population density. Higher heat-mortality risk was associated with a lower number of hospital beds per person and higher percentage of people requiring recuperation. The association between hospital beds and heat-mortality risk was prominent in high-density urban areas, whereas the association between the percentage of people requiring recuperation and heat-mortality risk was pronounced in rural areas. CONCLUSIONS Our findings indicate that the association between population density and heat-mortality risk is different in urban and rural areas, and that district characteristics related to heat-mortality risk also differ by urbanicity. These results can contribute to understanding the complex role of urbanization on heat vulnerability and can provide evidence to policy makers for prioritizing resources.
Atomically dispersed Fe atoms anchored on S and N–codoped carbon for efficient electrochemical denitrification

Significance Denitrification by electrochemistry is a mild and efficient technique to reduce nitrate pollution in water. The urgency of finding a wastewater treatment has accelerated electrode material development. Here, (S) N-modified, carbon-supported Fe or Cu single-atom catalysts (SACs) were prepared using the anchoring effect of a defect-rich carbon basal plane with high activity and atom economy. Fe-CNS exhibits the highest Fe utilization in electrodenitrification among all reported studies. The coordination environment of Fe atoms was optimized by S-doping with asymmetric charge distribution and electron redistribution, resulting in higher activity of nitrate reduction. The atomic-level structure–activity relationship and reaction mechanism were investigated. The unique structure of Fe SACs renders them promising for the practical removal of pollutants in water. Nitrate, a widespread contaminant in natural water, is a threat to ecological safety and human health. Although direct nitrate removal by electrochemical methods is efficient, the development of low-cost electrocatalysts with high reactivity remains challenging. Herein, bifunctional single-atom catalysts (SACs) were prepared with Cu or Fe active centers on an N-doped or S, N–codoped carbon basal plane for N2 or NH4+ production. The maximum nitrate removal capacity was 7,822 mg N ⋅ g−1 Fe, which was the highest among previous studies. A high ammonia Faradic efficiency (78.4%) was achieved at a low potential (−0.57 versus reversible hydrogen electrode), and the nitrogen selectivity was 100% on S-modified Fe SACs. Theoretical and experimental investigations of the S-doping charge-transfer effect revealed that strong metal–support interactions were beneficial for anchoring single atoms and enhancing cyclability. S-doping altered the coordination environment of single-atom centers and created numerous defects with higher conductivity, which played a key role in improving the catalyst activity. Moreover, interactions between defects and single-atom sites improved the catalytic performance. Thus, these findings offer an avenue for high active SAC design.
Characterization of cross-species transcription and splicing from Penicillium to Saccharomyces cerevisiae

Abstract Heterologous expression of eukaryotic gene clusters in yeast has been widely used for producing high-value chemicals and bioactive secondary metabolites. However, eukaryotic transcription cis-elements are still undercharacterized, and the cross-species expression mechanism remains poorly understood. Here we used the whole expression unit (including original promoter, terminator, and open reading frame with introns) of orotidine 5′-monophosphate decarboxylases from 14 Penicillium species as a showcase, and analyzed their cross-species expression in Saccharomyces cerevisiae. We found that pyrG promoters from the Penicillium species could drive URA3 expression in yeast, and that inefficient cross-species splicing of Penicillium introns might result in weak cross-species expression. Thus, this study demonstrates cross-species expression from Penicillium to yeast, and sheds light on the opportunities and challenges of cross-species expression of fungi expression units and gene clusters in yeast without refactoring for novel natural product discovery.
miR-122–based therapies select for three distinct resistance mechanisms based on alterations in RNA structure

Significance MicroRNA (miRNA)–based drugs are quickly taking the clinic by storm. Herein, we analyzed resistance-associated variants (RAVs) to the first miRNA inhibitors to make it to the clinic, namely miR-122 inhibitors for chronic hepatitis C virus (HCV) infection. We uncovered three distinct resistance mechanisms based on unique alterations to the structure of the viral RNA. Specifically, RAVs altered the structure of the viral RNA in a manner that promotes riboswitch activity, genome stability, or positive-strand viral RNA synthesis. Our findings support recent models of miR-122–mediated HCV RNA accumulation and provide mechanism(s) of resistance to antiviral therapy. These early insights into the mechanism(s) of resistance to miRNA-based therapies may be of importance as more miRNA-targeted therapies enter into the clinic. Hepatitis C virus (HCV) is a positive-sense RNA virus that interacts with a liver-specific microRNA called miR-122. miR-122 binds to two sites in the 5′ untranslated region of the viral genome and promotes HCV RNA accumulation. This interaction is important for viral RNA accumulation in cell culture, and miR-122 inhibitors have been shown to be effective at reducing viral titers in chronic HCV-infected patients. Herein, we analyzed resistance-associated variants that were isolated in cell culture or from patients who underwent miR-122 inhibitor–based therapy and discovered three distinct resistance mechanisms all based on changes to the structure of the viral RNA. Specifically, resistance-associated variants promoted riboswitch activity, genome stability, or positive-strand viral RNA synthesis, all in the absence of miR-122. Taken together, these findings provide insight into the mechanism(s) of miR-122–mediated viral RNA accumulation and provide mechanisms of antiviral resistance mediated by changes in RNA structure.
Comparison of lumbopelvic stability, low back pain and well-being of women who have overactive bladder syndrome to asymptomatic controls: cut-off points

Abstract Aims Overactive bladder (OAB) syndrome has been associated with core muscles weakness, which is important in aetiology of low back pain (LBP) and affects general well-being. This study aimed to compare the lumbopelvic stability, LBP and well-being of women with OAB to asymptomatic controls and to determine the cut-off points. Methods Women with (OAB group, n = 36) and without OAB syndrome (control group, n = 36) were included. The lumbopelvic stability with the Sahrmann and McGill trunk muscle endurance tests, LBP intensity with the Visual Analogue Scale were assessed. As for general well-being, sleep quality with the Pittsburgh Sleep Quality Index (PSQI), fatigue severity with the Fatigue Severity Index (FSI), anxiety and depression levels with the Hospital Anxiety Depression Scale (HADS-A, HADS-D) were evaluated. Results In the OAB group compared to the control group, the lumbopelvic stability scores were lower (p < 0.001) while LBP prevalence (p < 0.001), pain intensity (p = 0.020), and PSQI, FSI, HADS-A, and HADS-D scores (p < 0.001) were higher. The cut-off points for trunk extension, flexion, right and left lateral flexion endurance tests and Sahrmann test were ≤9.42 sec, ≤8.62 sec, ≤19.26 sec, ≤5.16 sec, and ≤2 level, respectively. The cut-off points for PSQI, FSI, HADS-D, HADS-A were >5, >5.22, >6 and >6 scores, respectively. Conclusions Women with OAB syndrome had lower lumbopelvic stability, higher LBP prevalence and intensity, lower sleep quality, and more fatigue, anxiety, and depression levels compared to asymptomatic women. The cut-off values were detected between the occurrence of OAB and lumbopelvic stability and general well-being parameters.
Improving the efficacy and reliability of rTMS language mapping by increasing the stimulation frequency

Repetitive TMS (rTMS) with a frequency of 5–10 Hz is widely used for language mapping. However, it may be accompanied by discomfort and is limited in the number and reliability of evoked language errors. We, here, systematically tested the influence of different stimulation frequencies (i.e., 10, 30, and 50 Hz) on tolerability, number, reliability, and cortical distribution of language errors aiming at improved language mapping. 15 right‐handed, healthy subjects (m = 8, median age: 29 yrs) were investigated in two sessions, separated by 2–5 days. In each session, 10, 30, and 50 Hz rTMS were applied over the left hemisphere in a randomized order during a picture naming task. Overall, 30 Hz rTMS evoked significantly more errors (20 ± 12%) compared to 50 Hz (12 ± 8%; p <.01), whereas error rates were comparable between 30/50 and 10 Hz (18 ± 11%). Across all conditions, a significantly higher error rate was found in Session 1 (19 ± 13%) compared to Session 2 (13 ± 7%, p <.05). The error rate was poorly reliable between sessions for 10 (intraclass correlation coefficient, ICC = .315) and 30 Hz (ICC = .427), whereas 50 Hz showed a moderate reliability (ICC = .597). Spatial reliability of language errors was low to moderate with a tendency toward increased reliability for higher frequencies, for example, within frontal regions. Compared to 10 Hz, both, 30 and 50 Hz were rated as less painful. Taken together, our data favor the use of rTMS‐protocols employing higher frequencies for evoking language errors reliably and with reduced discomfort, depending on the region of interest.
Bias and fairness assessment of a natural language processing opioid misuse classifier: detection and mitigation of electronic health record data disadvantages across racial subgroups

Abstract Objectives To assess fairness and bias of a previously validated machine learning opioid misuse classifier. Materials & Methods Two experiments were conducted with the classifier’s original (n = 1000) and external validation (n = 53 974) datasets from 2 health systems. Bias was assessed via testing for differences in type II error rates across racial/ethnic subgroups (Black, Hispanic/Latinx, White, Other) using bootstrapped 95% confidence intervals. A local surrogate model was estimated to interpret the classifier’s predictions by race and averaged globally from the datasets. Subgroup analyses and post-hoc recalibrations were conducted to attempt to mitigate biased metrics. Results We identified bias in the false negative rate (FNR = 0.32) of the Black subgroup compared to the FNR (0.17) of the White subgroup. Top features included “heroin” and “substance abuse” across subgroups. Post-hoc recalibrations eliminated bias in FNR with minimal changes in other subgroup error metrics. The Black FNR subgroup had higher risk scores for readmission and mortality than the White FNR subgroup, and a higher mortality risk score than the Black true positive subgroup (P < .05). Discussion The Black FNR subgroup had the greatest severity of disease and risk for poor outcomes. Similar features were present between subgroups for predicting opioid misuse, but inequities were present. Post-hoc mitigation techniques mitigated bias in type II error rate without creating substantial type I error rates. From model design through deployment, bias and data disadvantages should be systematically addressed. Conclusion Standardized, transparent bias assessments are needed to improve trustworthiness in clinical machine learning models.
Development of functional network architecture explains changes in children's altruistically motivated helping.

Childhood is marked by profound changes in prosocial behaviour. The underlying motivational mechanisms remain poorly understood. We investigated the development of altruistically motivated helping in middle childhood and the neurocognitive and -affective mechanisms driving this development. 127 6-12 year-old children performed a novel gustatory costly helping task designed to measure altruistic motivations of helping behaviour. Neurocognitive and -affective mechanisms including emotion regulation, emotional clarity and attentional reorienting were assessed experimentally through an extensive task-battery while functional brain activity and connectivity were measured during an empathy for taste paradigm and during rest. Altruistically motivated helping increased with age. Out of all mechanisms probed for, only emotional clarity increased with age and accounted for altruistically motivated helping. This was associated with greater functional integration of the empathy-related network with fronto-parietal brain regions at rest. We isolate a highly specific neuroaffective mechanism as the crucial driver of altruistically motivated helping during child development. This article is protected by copyright. All rights reserved.
The associations of incarceration and depression with healthcare experiences and utilization among Black men who have sex with men in HPTN 061

ABSTRACT Associations of incarceration with healthcare access and utilization among Black sexual minority men (BSMM) and differences in association among those with and without pre-incarceration symptoms of depression were measured. Secondary analysis using survey data from the longitudinal cohort HIV Prevention Trials Network 061 study was conducted among 1553 BSMM from six major U.S. cities from 2009 to 2011. We used modified log-binomial regression with robust standard errors to estimate associations of incarceration (reported at 6 month follow-up) on next six-month healthcare utilization and access (reported at the 12 month follow-up). We tested the significance of baseline depressive symptoms by incarceration interaction and reported differences in associations when observed. Participants with a history of incarceration were more likely to have depressive symptoms at baseline compared to those without. Recent incarceration was associated with almost twice the risk of mistrust in healthcare providers and emergency room utilization. Among men reporting depressive symptoms, a history of incarceration was associated with almost tripled risk of reporting providers do not communicate understandably. Among those with depression, one in five reported a missed visit regardless of incarceration status.
Role of microRNAs as biomarkers of cervical carcinogenesis: a systematic review

We performed a systematic review to identify the role of microRNAs (miRNAs) as biomarkers in the progression of cervical precancerous lesions. A comprehensive search of the Cochrane Controlled Register of Trials, PubMed, ScienceDirect, and Embase databases was performed for articles published between January 2010 and June 2020. The following Medical Subject Headings (MeSH) terms were searched: “microRNA” and “cervical” and “lesion. ” All study designs that aimed to evaluate the correlation of miRNA expression with different precancerous cervical staging and/ or cervical cancer were included, except for case reports and case series. Approximately 82 individual miRNAs were found to be significant in differentiating the stages of cervical carcinogenesis. Among the miRNAs, miR-21 is the most prevalent, and it is consistently upregulated progressively from normal cervical to worsening cervical lesion stages in both cell and serum samples. miR-205 has been shown to have a higher specificity than human papilloma virus testing in predicting the absence of high-grade squamous intraepithelial lesions (HSILs) in exfoliated cell samples. The tumor suppressor miRNAs miR-34, let-7, miR-203 miR-29, and miR-375 were significantly downregulated in low-grade squamous intraepithelial lesions, HSILs, and cervical cancer. We found significant dysregulated miRNAs in cervical carcinogenesis with their dynamic expression changes and ability to detect viral persistency, risk prediction of low-grade lesions (cervical intraepithelial neoplasia [CIN] 2) to high-grade lesions (CIN 3), and progression of CIN 3 to cancer. Their ability to discriminate HSILs from non-dysplastic lesions has potential implications in early diagnosis and reducing overtreatment of otherwise regressive early preinvasive lesions.
Gene Differential Co-Expression Networks Based on RNA-Seq: Construction and Its Applications

Gene co-expression network (GCN) becomes an increasingly important tool in omics data analysis. A great challenge for GCN construction is that the sample size is far lower than the number of genes. Traditional methods rely on considerable samples. Moreover, association signals are likely weak, nonlinear and stochastic, which are difficult to be identified among thousands of candidates. In this paper, the gray correlation coefficient (GCC) is introduced, and a novel method to construct gene differential co-expression networks (GDCNs) is proposed. Based on the GDCNs, three measures are proposed to explore informative genes. The proposed method can make full use of the information provided by a handful of samples and overcome the shortages of GCNs, which can evaluate the changes of co-expression relationships that are possibly triggered by treatments. Based on RNA-seq data of Brassica napus, GDCNs under multiple experimental conditions are constructed and investigated. It is found that the GCC-based method is very robust to data processing. The GDCNs facilitate the inference of gene functions and the identification of informative genes that are responsible for stress responsiveness. The GDCN-based approaches integrate the ‘guilt by association’ and the ‘guilt by rewiring’ rules, which provide alternative tools for omics data analysis.
Neural-Network-Based Set-Membership Fault Estimation for 2-D Systems Under Encoding–Decoding Mechanism

In this article, the simultaneous state and fault estimation problem is investigated for a class of nonlinear 2-D shift-varying systems, where the sensors and the estimator are connected via a communication network of limited bandwidth. With the purpose of relieving the communication burden and enhancing the transmission security, a new encoding–decoding mechanism is put forward so as to encode the transmitted data with a finite number of bits. The aim of the addressed problem is to develop a neural-network (NN)-based set-membership estimator for jointly estimating the system states and the faults, where the estimation errors are guaranteed to reside within an optimized ellipsoidal set. With the aid of the mathematical induction technique and certain convex optimization approaches, sufficient conditions are derived for the existence of the desired set-membership estimator, and the estimator gains and the NN tuning scalars are then presented in terms of the solutions to a set of optimization problems subject to ellipsoidal constraints. Finally, an illustrative example is given to demonstrate the effectiveness of the proposed estimator design method.
Mulberry fruit extract alleviates the intracellular amyloid‐β oligomer‐induced cognitive disturbance and oxidative stress in Alzheimer’s disease model mice

Intracellular amyloid‐β (Aβ) oligomers are key therapeutic targets because they are strongly cytotoxic and play crucial roles in the cognitive function in Alzheimer's disease (AD). Anthocyanins, polyphenolic flavonoids with antioxidant and neuroprotective properties, are potential therapeutic candidates for AD. Here, we investigated the effects of anthocyanin‐enriched extracts from fruits of mulberry (Morus alba Linn.) in Thailand against the neurotoxicity of Aβ oligomers. Using the monitoring system for Aβ aggregation, we showed that the extract induced the dissociation of Aβ in cultured HEK293T cells. To investigate the effects on cognitive function, we orally administered the extract to Aβ‐GFP transgenic mice (Aβ‐GFP Tg), a mouse model that expresses Aβ oligomers inside neurons, and performed the novel object recognition test and passive avoidance test. Aβ‐GFP Tg usually showed deficits in novel object recognition memory and reference memory compared with non‐Tg, but administration of the extract improved both compared with vehicle‐treated Aβ‐GFP Tg. Aβ‐GFP Tg exhibited lower superoxide dismutase (SOD) activity than non‐Tg. However, after the administration of the extract, the SOD activity was restored. These results suggest that Thai mulberry fruit extract ameliorates cytotoxicity induced by the intracellular Aβ oligomers and may be an effective therapeutic or preventive candidate for AD.
Functional and Clinical Outcomes of Combined Simultaneous Bilateral Anterior Distal Femoral Plate Hemiepiphysiodesis and Hamstrings Release in Management of Knee Flexion Contractures in Children With Neuromuscular Disorders

Background: We examined the clinical and functional outcomes of the simultaneous anterior distal femoral 8-plate hemiepiphysiodesis (ADF8PH) and hamstring release, for fixed knee flexion deformity in children with neuromuscular disease. To our knowledge, no published evidence is available that reports the outcomes of this combined techniques. Methods: Electronic medical records were retrospectively reviewed for 19 consecutive children who underwent bilateral ADF8PH and concomitant hamstrings release in our institution from 2012 to 2019. Relevant demographics, Gross Motor Functional Classification Score and preoperative and postoperative knee flexion contractures and popliteal angles were documented. Results: The average age at the time of operation was 12±2.1 years. There were 15 males and 4 females. Diagnoses included cerebral palsy (n=16), Cornelia de Lange syndrome (n=1), hereditary spastic paraplegia type 56 (n=1) and fructose-1,6 bisphosphonate aldose B deficiency (n=1). Mean length of follow-up was 3.8 years (range: 1.5 to 7 y). Mean fixed knee flexion deformity improved from 28.9 to 13.4 degrees (P<0.001) at an average correction rate of 0.94 degrees per month. Mean popliteal angle improved from 81.8 to 44.4 degrees (P<0.001) in the early postoperative phase and to 51.8 degrees (P<0.001) in latest clinic review. Mean time to correction was 18.9 months. The agreed treatment goals of maintaining or promoting the use of standing frame and spinal/postural symmetry was attained in 18 patients (94.7%). Postoperative knee pain was reported in 2 cases (10.5%). We report 2 complications; 1 case of neurapraxia and 1 case of sepsis because of respiratory infection. Conclusion: Simultaneous bilateral ADF8PH with hamstrings release is a promising effective technique for correction of knee flexion contractures in skeletally immature individuals with neuromuscular disabilities. Our findings demonstrate improvement in clinical outcomes and maintaining functional outcomes, indicating the validity of this approach as a satisfactory, less invasive alternative in the management of this deformity. Level of Evidence: Level IV—therapeutic study.