Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Performance of Prediction Models for Contrast-Associated Acute Kidney Injury After Percutaneous Coronary Intervention.

BACKGROUND Identifying patients at increased risk of contrast-associated acute kidney injury (CA-AKI) can help target risk mitigation strategies toward these individuals during percutaneous coronary intervention. Illuminating which risk models best stratify risk is an important foundation for such quality improvement efforts. METHODS AND RESULTS Seven previously published risk prediction models for CA-AKI and 3 models for kidney injury requiring dialysis were validated using 2 definitions for CA-AKI (the Kidney Disease: Improving Global Outcomes definition of ≥0.3 mg/dL within 48 hours or ≥50% increase in serum creatinine from baseline within 7 days and the historical definition of ≥0.5 mg/dL or ≥25% increase in serum creatinine from baseline within 48 hours), and AKI requiring dialysis within 30 days of percutaneous coronary intervention. Model performance was compared based on discrimination, calibration, and categorical net reclassification index before and after model recalibration. Among 7888 patients who underwent percutaneous coronary intervention in Alberta Canada, CA-AKI occurred in 330 patients (4.2%) when CA-AKI was defined using the Kidney Disease: Improving Global Outcomes definition and 571 (7.3%) when using the historical definition. CA-AKI requiring dialysis occurred in 42 (0.6%) patients. When validated using the Kidney Disease: Improving Global Outcomes definition for CA-AKI, the 2 most recently published models for CA-AKI showed better discrimination (C statistics, 0.75-0.76) than older models (C statistics, 0.61-0.68). C statistics of models for kidney injury requiring dialysis ranged from 0.70 to 0.86. The calibration of all models for CA-AKI deviated from ideal, and the proportion of patients classified into different risk categories for CA-AKI differed substantially for the 2 most recent models. Recalibration significantly improved risk stratification of patients into clinical risk categories for some models. CONCLUSIONS Recent prediction models for CA-AKI show better discrimination compared with older models; however, model recalibration should be examined in external cohorts to improve the accuracy of predictions, particularly if predicted risk strata are used to guide management approaches.
Keratin 18 is an integral part of the intermediate filament network in murine skeletal muscle.

Intermediate filaments (IFs) contribute to force transmission, cellular integrity and signaling in skeletal muscle. We previously identified keratin 19 (Krt19) as muscle IF protein. We now report the presence of a second type I muscle keratin, Krt18. Krt18 mRNA levels are about half those for Krt19, and only 1:1000th those for desmin; the protein was nevertheless detectable in immunoblots. Muscle function, measured by maximal isometric force in vivo, was moderately compromised in Krt18 knockout (Krt18 KO) or dominant negative mutant mice (Krt18 DN), but structure was unaltered. Exogenous Krt18, introduced by electroporation, localized in a reticulum around the contractile apparatus in wild type muscle and to a lesser extent in muscle lacking Krt19 or desmin, or both proteins. Exogenous Krt19, which was either reticular or aggregated in controls, became reticular more frequently in Krt19-null than in Krt18-null, desmin-null or double-null muscles. Desmin assembled into the reticulum normally in all genotypes. Notably, all three IF proteins appeared in overlapping reticular structures. We assessed the effect of Krt18 on susceptibility to injury in vivo by electroporating siRNA into TA muscles of control and Krt19 KO mice and testing 2 weeks later. Results showed a 33% strength deficit (reduction in maximal torque after injury) compared to siRNA-treated controls. Conversely, electroporation of siRNA to Krt19 into Krt18-null TA yielded a strength deficit of 18% after injury compared to controls. Our results suggest that Krt18 plays a complementary role to Krt19 in skeletal muscle both in assembling keratin-based filaments and transducing contractile force.
Anti-inflammatory drugs with more penetration into the central nervous system may contribute to the treatment of trigeminal neuralgia.

Letter to Editor: We read with great interest the article by Ericson et al. in a recent issue of the journal. One of the crucial findings is that the levels of inflammatory markers in the cerebrospinal fluid from patients with trigeminal neuralgia (TN) changed after surgery compared with healthy controls, indicating that inflammation in the central nervous system might serve as a promising target for the treatment of TN. This topic is of heightened interest to pain management in TN. However, we express some concerns about missing detailed information, which may affect the validity of the conclusions. First, the authors should provide detailed data on the consumption of anti-inflammatory drugs (which they referred to as second-line drugs) that study participants were taking rather than simply reporting the first-line drugs (carbamazepine and gabapentin) they were taking. Second, research suggests that a neurovascular conflict can exist in 17% of healthy trigeminal nerves. Thus, we are curious about whether there are differences in inflammation levels between TN patients with and without a neurovascular conflict. Third, for their future work, we suggest the authors could go a step further to compare the differences between central and peripheral inflammation in different TN settings. In closing, we thank Ericson et al. for their innovative study, which may spur researchers to reconsider the mechanisms of TN and seeking more promising strategies to the pain management of TN. If arachnoiditis in the region of the trigeminal nerve does indeed contribute to the etiology of TN, in the future, administration of anti-inflammatory drugs with more penetration into the central nervous systemmay become an alternative compared with current drugs. In addition, for anti-inflammatory drugs with limitations in passing the blood– brain barrier, an intranasal route of delivery may yield better therapeutic effects with a lower dose and reduced peripheral side effects.
G-quadruplex structures trigger RNA phase separation

Abstract Liquid–liquid phase separation plays an important role in a variety of cellular processes, including the formation of membrane-less organelles, the cytoskeleton, signalling complexes, and many other biological supramolecular assemblies. Studies on the molecular basis of phase separation in cells have focused on protein-driven phase separation. In contrast, there is limited understanding on how RNA specifically contributes to phase separation. Here, we described a phase-separation-like phenomenon that SHORT ROOT (SHR) RNA undergoes in cells. We found that an RNA G-quadruplex (GQ) forms in SHR mRNA and is capable of triggering RNA phase separation under physiological conditions, suggesting that GQs might be responsible for the formation of the SHR phase-separation-like phenomenon in vivo. We also found the extent of GQ-triggered-phase-separation increases on exposure to conditions which promote GQ. Furthermore, GQs with more G-quartets and longer loops are more likely to form phase separation. Our studies provide the first evidence that RNA can adopt structural motifs to trigger and/or maintain the specificity of RNA-driven phase separation.
Identification of gene–environment interactions with marginal penalization

Gene–environment (G–E) interaction analysis has been extensively conducted for complex diseases. In marginal analysis, the common practice is to conduct likelihood‐based (and other “standard”) estimation with each marginal model, and then select significant G–E interactions and main effects based on p values and multiple comparisons adjustment. One limitation of this approach is that the identification results often do not respect the “main effects, interactions” hierarchy, which has been stressed in recent G–E interaction analyses. There is some recent effort tackling this problem, however, with very complex formulations. Another limitation of the common practice is that it may not perform well when regularization is needed, for example, because of “non‐normal” distributions. In this article, we propose a marginal penalization approach which adopts a novel penalty to directly tackle the aforementioned problems. The proposed approach has a framework more coherent with that of the recently developed joint analysis methods and an intuitive formulation, and can be effectively realized. In simulation, it outperforms the popular significance‐based analysis and simple penalization‐based alternatives. Promising findings are made in the analysis of a single‐nucleotide polymorphism and a gene expression data.
Dementia screening in Brazil: a systematic review of normative data for the mini-mental state examination

The Mini-Mental State Examination (MMSE) is the most widely used instrument for the screening of older adults with suspected cognitive impairment; the MMSE has been translated and validated in numerous languages and countries. The cultural and sociodemographic characteristics of the sample can influence performance on the test; therefore, applying the MMSE in different populations usually requires adjustments of those variables. From this perspective, the present study aims to review the normative data for the MMSE in the Brazilian older population, including those adaptations to the original test. Database searches were performed in Medline, Web of Knowledge, Scielo and Pepsic for articles assessing healthy elderly Brazilian samples using the MMSE. Heterogeneity across and within the studies was analyzed. Of a total of 1,085 retrieved articles, 14 were included. Significant differences across studies were identified for the characteristics of the samples, the presence of alterations to the MMSE subtests and the presentation of the results. The risk of biases was relevant for all the studies. Considering the large methodological heterogeneity among studies, the generalization of the available normative data for the MMSE may not be appropriate for the general elderly Brazilian population.
Gene microarray integrated with iTRAQ-based proteomics for the discovery of NLRP3 in LPS-induced inflammatory response of bovine mammary epithelial cells

Abstract Mastitis, a major infectious disease in dairy cows, is characterized by an inflammatory response to pathogens such as Escherichia coli and Staphylococcus aureus. To better understand the immune and inflammatory response of the mammary gland, we stimulated bovine mammary gland epithelial cells (BMECs) with E. coli-derived lipopolysaccharide (LPS). Using transcriptomic and proteomic analyses, we identified 1019 differentially expressed genes (DEGs, fold change ≥2 and P-value < 0.05) and 340 differentially expressed proteins (DEPs, fold change ≥1.3 and P-value < 0.05), of which 536 genes and 162 proteins were upregulated and 483 genes and 178 proteins were downregulated following exposure to LPS. These differentially expressed genes were associated with 172 biological processes; 15 Gene Ontology terms associated with response to stimulus, 4 associated with immune processes, and 3 associated with inflammatory processes. The DEPs were associated with 51 biological processes; 2 Gene Ontology terms associated with response to stimulus, 1 associated with immune processes, and 2 associated with inflammatory processes. Meanwhile, several pathways involved in mammary inflammation, such as Toll-like receptor, NF-κB, and NOD-like receptor signaling pathways were also represented. NLRP3 depletion significantly inhibited the expression of IL-1β and PTGS2 by blocking caspase-1 activity in LPS-induced BMECs. These results suggest that NLR signaling pathways works in coordination with TLR4/NF-κB signaling pathways via NLRP3-inflammasome activation and pro-inflammatory cytokine secretion in LPS-induced mastitis. The study highlights the function of NLRP3 in an inflammatory microenvironment, making NLRP3 a promising therapeutic target in Escherichia coli mastitis.
Enhancement in Particulate Organic Nitrogen and Light Absorption of Humic-like Substances over Tibetan Plateau due to Long-Range Transported Biomass Burning Emissions.

To elucidate the influence of long-range transported biomass burning organic aerosols (BBOA) on the Tibetan Plateau, the molecular compositions and light absorption of HUmic-Like Substances (HULIS), major fractions of brown carbon, were characterized during the pre-monsoon season. Under the significant influence of biomass burning, HULIS concentrations increased to as high as 26 times of the background levels, accounting for 54% of water soluble organic carbon (WSOC) and 50% of organic carbon (OC). The light absorption of HULIS also enhanced up to 42 times of the background levels, contributing 61% of the WSOC absorption and 50% of OC absorption. Meanwhile, elevated nitrogen-containing compounds (NOCs) among HULIS were observed. The NOCs from fresh and aged BBOA were unambiguously identified on the molecular level, through comparing with the molecular compositions of NOCs from lab-controlled and field burning experiments. N-heterocyclic bases represent major fractions in the reduced nitrogen compounds from fresh BBOA, and nitroaromatic compounds are important groups among the oxidized nitrogen compounds from aged BBOA. The nitrogen-containing compounds, including nitroaromatics and N-heterocyclic compounds, were also important chromophores, which contributed to the enhanced light absorption of extracted HULIS during biomass burning-influenced periods.
Acceptance of illness mediate the effects of health literacy on self-management behaviour

Background: Self-management is crucial for blood pressure control and subsequent disease prevention. Health literacy and acceptance of illness may contribute to self-management behaviour; in addition, acceptance of illness may mediate the effects of health literacy on self-management behaviour among patients with hypertension. Objective: The aims of the research were to examine whether health literacy and acceptance of illness were associated with both pharmacological and non-pharmacological management behaviour and examine the possible mediating effects of the acceptance of illness in patients with hypertension. Methods: Hierarchical regression analysis was conducted to analyse the relationships between health literacy, acceptance of illness, pharmacological and non-pharmacological management behaviours. Mediation effects were examined by the PROCESS macro. Results: This was a cross-sectional study. A total of 478 hypertensive patients completed measures of health literacy, acceptance of illness, self-management, social support, depression, physical function and demographic and clinical characteristics. Functional, communicative, critical health literacy and acceptance of illness showed positive associations to pharmacological and non-pharmacological management behaviour. Acceptance of illness mediated the relationships between three types of health literacy, pharmacological and non-pharmacological management but the effects size and pathway differed. In detail, functional health literacy influenced pharmacological and non-pharmacological management behaviour mainly by indirect effects mediated by the acceptance of illness, but communicative and critical health literacy influenced pharmacological and non-pharmacological management behaviour mainly by direct effects. Conclusions: Acceptance of illness mediated the relationships between three types of health literacy and self-management. Health literacy and acceptance of illness should be addressed when taking measures to improve patients’ self-management behaviour.
Heterogeneity in Economic and Carbon Benefits of Electric Technology Vehicles in the U.S.

To broadly contribute to sustainable mobility, electric technology vehicles (hybrid, electric and plug-in-hybrid) must become more price competitive with internal combustion vehicles. This study assesses the economic and carbon benefits of electric technology vehicles in the U.S., accounting for household-by-household behavioral variability and geographical differences in fuel and electricity prices. This finer resolution provides insight into subsets of the population for whom adoption is economically or environmentally favorable, allowing us to construct Marginal Abatement Cost Curves for CO2 that account for geographic, behavioral and stock heterogeneities. Currently, low gasoline prices and high initial expense means that, without subsidies, few consumers benefit financially from electric technology vehicles (1.7% of drivers). However, improved technology dramatically and non-linearly increases both the number of consumers that benefit and corresponding carbon emissions that could be abated without government subsidy. Our results clarify cost targets that electric vehicle technology must achieve in order to deliver net financial and subsidy-free environmental benefits.
Association among blood BPDE-DNA adduct, serum interleukin-8 (IL-8) and DNA strand breaks for children with pulmonary diseases

ABSTRACT Exposure to benzo[a]pyrene (B[a]P) may be a risk factor for pulmonary diseases. To investigate the correlations among B[a]P exposure level, DNA strand breaks and pulmonary inflammation, we recruited 83 children diagnosed with pulmonary diseases and 63 healthy children from Guangzhou, China. Results showed that the levels of Benzo[a]pyrene diol epoxide (BPDE) DNA adduct in blood and IL-8 in serum in case group were significantly higher than those in control group (p < 0.01). Moreover, levels of atmospheric B[a]P in case group was about twice of those in control group, which was consistent with the levels of BPDE-DNA adduct in blood. Significant positive correlations were observed among the levels of BPDE-DNA adduct, IL-8 and DNA strand breaks (p < 0.05). Our findings indicate that environmental air is an important exposure source of B[a]P and higher B[a]P exposure may contribute to the occurrence of pulmonary inflammation and lead to high health risks.
Highly active oxygen evolution integrated with efficient CO2 to CO electroreduction

Significance Electrochemical reduction of CO2 to useful chemicals or fuels is critical to closing the carbon cycle and preventing further deterioration of the environment/climate. This work addresses the low-energy-efficiency problem of CO2 reduction limited by sluggish oxygen evolution reaction (OER) on the anode side. The only active OER catalysts for coupling CO2 reduction in neutral conditions are based on noble metals such as Ir, Ru, and gold. Herein, we developed a nonprecious-metal-based OER anode with higher activity and stability than those based on noble-metal catalysts IrO2 and Ir/C. We integrated our anode with a selective CO2 reduction cathode to achieve >97% conversion of CO2 to CO and a record-setting high energy efficiency for CO2 conversion. Electrochemical reduction of CO2 to useful chemicals has been actively pursued for closing the carbon cycle and preventing further deterioration of the environment/climate. Since CO2 reduction reaction (CO2RR) at a cathode is always paired with the oxygen evolution reaction (OER) at an anode, the overall efficiency of electrical energy to chemical fuel conversion must consider the large energy barrier and sluggish kinetics of OER, especially in widely used electrolytes, such as the pH-neutral CO2-saturated 0.5 M KHCO3. OER in such electrolytes mostly relies on noble metal (Ir- and Ru-based) electrocatalysts in the anode. Here, we discover that by anodizing a metallic Ni–Fe composite foam under a harsh condition (in a low-concentration 0.1 M KHCO3 solution at 85 °C under a high-current ∼250 mA/cm2), OER on the NiFe foam is accompanied by anodic etching, and the surface layer evolves into a nickel–iron hydroxide carbonate (NiFe-HC) material composed of porous, poorly crystalline flakes of flower-like NiFe layer-double hydroxide (LDH) intercalated with carbonate anions. The resulting NiFe-HC electrode in CO2-saturated 0.5 M KHCO3 exhibited OER activity superior to IrO2, with an overpotential of 450 and 590 mV to reach 10 and 250 mA/cm2, respectively, and high stability for >120 h without decay. We paired NiFe-HC with a CO2RR catalyst of cobalt phthalocyanine/carbon nanotube (CoPc/CNT) in a CO2 electrolyzer, achieving selective cathodic conversion of CO2 to CO with >97% Faradaic efficiency and simultaneous anodic water oxidation to O2. The device showed a low cell voltage of 2.13 V and high electricity-to-chemical fuel efficiency of 59% at a current density of 10 mA/cm2.
The changing paradigm of intron retention: regulation, ramifications and recipes

Abstract Intron retention (IR) is a form of alternative splicing that has long been neglected in mammalian systems although it has been studied for decades in non-mammalian species such as plants, fungi, insects and viruses. It was generally assumed that mis-splicing, leading to the retention of introns, would have no physiological consequence other than reducing gene expression by nonsense-mediated decay. Relatively recent landmark discoveries have highlighted the pivotal role that IR serves in normal and disease-related human biology. Significant technical hurdles have been overcome, thereby enabling the robust detection and quantification of IR. Still, relatively little is known about the cis- and trans-acting modulators controlling this phenomenon. The fate of an intron to be, or not to be, retained in the mature transcript is the direct result of the influence exerted by numerous intrinsic and extrinsic factors at multiple levels of regulation. These factors have altered current biological paradigms and provided unexpected insights into the transcriptional landscape. In this review, we discuss the regulators of IR and methods to identify them. Our focus is primarily on mammals, however, we broaden the scope to non-mammalian organisms in which IR has been shown to be biologically relevant.
Multidisciplinary protocol for the management of fibromyalgia associated with imbalance. Our experience and literature review.

OBJECTIVE We reported our multidisciplinary protocol for the management of fibromyalgia associated with imbalance. Our aim was to verify the effectiveness of a proprioceptive training program as a complementary therapy for a traditional protocol of education, mindfulness, and exercise training for the management of fibromyalgia associated with imbalance. METHODS Retrospective cohort study on 84 women, with primary fibromyalgia associated to imbalance. A group of patients performed traditional exercise training; in a second group the training was supplemented with proprioception exercises. Each session lasted from 40 to 60 minutes and was performed three times a week for 12 weeks. RESULTS After three months of training and eight months after the end of the training, the balance evaluation revealed signiﬁcant differences in the comparison of the Timed Up and Go test, Berg Balance Scale, and Tinetti scale with the baseline, there was a better improvement in the proprioceptive training group (p<0.05). A reduction in pain and improvement in functional and muscular performance and quality of life were observed in both groups (p<0.05), but with no significant differences between them in the Numeric Pain Rating Scale, Fibromyalgia Impact Questionnaire, and Short Form Health Survey (p>0.05). Fifteen months after the end of the program, the effects of training were not maintained. CONCLUSION The present study revealed that training supplemented with proprioception exercises has beneficial effects on clinical ﬁndings and improves balance in patients with fibromyalgia, even if the positive results did not persist after the interruption of the rehabilitative program in the long term.