Miracle-dz/UniFAR-FTUs huggingface dataset:
Sodium–Glucose Cotransporter-2 Inhibitors in Patients With Heart Failure

BACKGROUND Randomized controlled trials established the cardiac protection of sodium-glucose cotransporter-2 (SGLT2) inhibitors among adults with type 2 diabetes. New evidence suggests that these results could extend to people without diabetes. PURPOSE To evaluate the effect of SGLT2 inhibitors in patients with heart failure, regardless of the presence of type 2 diabetes. DATA SOURCES PubMed, Web of Science, Cochrane Library, and Embase (OVID interface). STUDY SELECTION Eligible trials randomly assigned adults with heart failure to SGLT2 inhibitors or control. DATA EXTRACTION Time-to-event individual patient data were reconstructed from published Kaplan-Meier plots; time-varying risk ratios (RRs) were calculated in half-, 1-, and 2-year time frames; and anticipated absolute benefits were calculated using simple models applying relative effects to baseline risks. DATA SYNTHESIS Sodium-glucose cotransporter-2 inhibitors reduce hospitalization for heart failure by 37% (95% CI, 25% to 47%) at 6 months, 32% (CI, 20% to 42%) at 1 year, and 26% (CI, 10% to 40%) at 2 years (all high certainty) and reduce cardiovascular death by 14% (CI, 1% to 25%) at 1 year (high certainty). Nevertheless, low-certainty evidence did not indicate protection against all-cause death, kidney disease progression, or kidney failure. Anticipated absolute benefits are greater for patients treated in the first year and for those with poorer prognoses, such as those newly diagnosed with heart failure in the hospital. In addition, SGLT2 inhibitors doubled the risk for genital infections (RR, 2.69 [CI, 1.61 to 4.52]; high certainty). LIMITATION Covariates were unavailable in meta-analyses with reconstructed individual patient data. CONCLUSION Among people with heart failure, SGLT2 inhibitors reduce hospitalizations for heart failure regardless of the presence of diabetes; absolute benefits are most pronounced in first-year treatment and vary with prognostic factors. Clinicians should note the increased risk for genital infection in patients receiving SGLT2 inhibitors. PRIMARY FUNDING SOURCE 1.3. 5 Project for Disciplines of Excellence, West China Hospital of Sichuan University. (PROSPERO: CRD42021255544).
Bisphenol-A/Radiation mediated inflammatory response activates EGFR/KRAS/ERK1/2 signaling pathway leads to lung carcinogenesis incidence

Background Bisphenol (BPA) and ionizing radiation exposure (IR) are potent oxidants that cause free radical induction, leading to signaling pathway activation that alters cell growth. Due to the insufficient knowledge of the impact of BPA and IR on the lungs, the current study determined the impact of BPA and IR on the lung tissue of adult female Wistar rats. Methods Forty Wister female rats were used in this study and were randomly divided into four groups. The rats received BPA (150 mg/kg body weight/day for 6 weeks) and were exposed to IR at 2 Gy/week up to 12 Gy for 6 weeks. Results It was found that BPA and IR possess a harmful effect on the lungs via induction of oxidative stress, confirmed by increasing levels of malondialdehyde (MDA), nitric oxide, myeloperoxidase (MPO), and lactate dehydrogenase (LDH). Exposure to BPA and IR activates inflammatory cytokines TNF-α, IL-6, IL-1β, growth factors such as TGF-β, and gastrin-releasing peptides. BPA/IR exposures induced phosphorylated expression p-ERK1/2 and p-MEK1/2 associated with triggering of the GPER/EGFR/KRAS signaling factors, resulting in matrix metalloproteinase-2 and 9 overexpression and the development of lung tumors. Our findings support the causal role of two deleterious environmental pollutants BPA and IR, via the cytotoxicity in the respiratory system in the form of severe lung damage resulting in cancerous cells.
Genome Sequences of 14 Siphophages That Infect Serratia marcescens

We announce the complete genome sequences of 14 Serratia bacteriophages isolated from wastewater treatment plants. These phages define two previously undescribed types which we call the Carrot-like phage cluster (phages Carrot, BigDog, LittleDog, Niamh, Opt-148, Opt-169, PhooPhighters, Rovert, Serratianator, Stoker, Swain, and Ulliraptor) and Tlacuache-like phage cluster (Tlacuache and Opt-155). ABSTRACT We announce the complete genome sequences of 14 Serratia bacteriophages isolated from wastewater treatment plants. These phages define two previously undescribed types which we call the Carrot-like phage cluster (phages Carrot, BigDog, LittleDog, Niamh, Opt-148, Opt-169, PhooPhighters, Rovert, Serratianator, Stoker, Swain, and Ulliraptor) and Tlacuache-like phage cluster (Tlacuache and Opt-155).
Co-circulation of Chikungunya Virus during the 2015–2017 Zika Virus Outbreak in Pernambuco, Brazil: An Analysis of the Microcephaly Epidemic Research Group Pregnancy Cohort

ABSTRACT. Co-circulation of arthropod-borne viruses, particularly those with shared mosquito vectors like Zika (ZIKV) and Chikungunya (CHIKV), is increasingly reported. An accurate differential diagnosis between ZIKV and CHIKV is of high clinical importance, especially in the context of pregnancy, but remains challenging due to limitations in the availability of specialized laboratory testing facilities. Using data collected from the prospective pregnancy cohort study of the Microcephaly Epidemic Research Group, which followed up pregnant persons with rash during the peak and decline of the 2015–2017 ZIKV epidemic in Recife, Pernambuco, Brazil, this study aims to describe the geographic and temporal distribution of ZIKV and CHIKV infections and to investigate the extent to which ZIKV and CHIKV infections may be clinically differentiable. Between December 2015 and June 2017, we observed evidence of co-circulation with laboratory confirmation of 213 ZIKV mono-infections, 55 CHIKV mono-infections, and 58 sequential ZIKV/CHIKV infections (i.e., cases with evidence of acute ZIKV infection with concomitant serological evidence of recent CHIKV infection). In logistic regressions with adjustment for maternal age, ZIKV mono-infected cases had lower odds than CHIKV mono-infected cases of presenting with arthralgia (aOR, 99% CI: 0.33, 0.15–0.74), arthritis (0.35, 0.14–0.85), fatigue (0.40, 0.17–0.96), and headache (0.44, 0.19–1.00). However, sequential ZIKV/CHIKV infections complicated discrimination, as they did not significantly differ in clinical presentation from CHIKV mono-infections. These findings suggest clinical symptoms alone may be insufficient for differentiating between ZIKV and CHIKV infections during pregnancy and therefore laboratory diagnostics continue to be a valuable tool for tailoring care in the event of arboviral co-circulation.
The Effect of Surgeon Experience on Short- to Medium-Term Complication Rate Following Operative Fixation of Acetabular Fractures

Objectives: Operative management of acetabular fractures is technically challenging, but there is little data regarding how surgeon experience affects outcomes. Previous efforts have focused only on reduction quality in a single surgeon series. We hypothesized that increasing surgeon experience would be associated with improved acetabular surgical outcomes in general. Design: Retrospective cohort study. Setting: Urban academic level-I trauma center. Patients/Participants: Seven hundred ninety-five patients who underwent an open reduction internal fixation for an acetabular fracture. Results: There was a significant association between surgeon experience and certain outcomes, specifically reoperation rate (16.9% overall), readmission rate (13.9% overall), and reduction quality. Deep infection rate (9.7% overall) and secondary displacement rate (3.7% overall) were not found to have a significant association with surgeon experience. For reoperation rate, the time until 50% peak performance was 2.4 years in practice. Conclusion: Surgeon experience had a significant association with reoperation rate, quality of reduction, and readmission rate after open reduction internal fixation of acetabular fractures. Other patient outcomes were not found to be associated with surgeon experience. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
A conditional gene-based association framework integrating isoform-level eQTL data reveals new susceptibility genes for schizophrenia

Linkage disequilibrium and disease-associated variants in the non-coding regions make it difficult to distinguish the truly associated genes from the redundantly associated genes for complex diseases. In this study, we proposed a new conditional gene-based framework called eDESE that leveraged an improved effective chi-squared statistic to control the type I error rates and remove the redundant associations. eDESE initially performed the association analysis by mapping variants to genes according to their physical distance. We further demonstrated that the isoform-level eQTLs could be more powerful than the gene-level eQTLs in the association analysis using a simulation study. Then the eQTL-guided strategies, that is, mapping variants to genes according to their gene/isoform-level variant-gene cis-eQTLs associations, were also integrated with eDESE. We then applied eDESE to predict the potential susceptibility genes of schizophrenia and found that the potential susceptibility genes were enriched with many neuronal or synaptic signaling-related terms in the Gene Ontology knowledgebase and antipsychotics-gene interaction terms in the drug-gene interaction database (DGIdb). More importantly, seven potential susceptibility genes identified by eDESE were the target genes of multiple antipsychotics in DrugBank. Comparing the potential susceptibility genes identified by eDESE and other benchmark approaches (i.e., MAGMA and S-PrediXcan) implied that strategy based on the isoform-level eQTLs could be an important supplement for the other two strategies (physical distance and gene-level eQTLs). We have implemented eDESE in our integrative platform KGGSEE (http://pmglab.top/kggsee/#/) and hope that eDESE can facilitate the prediction of candidate susceptibility genes and isoforms for complex diseases in a multi-tissue context.
Transcending Dimensions in Apicomplexan Research: from Two-Dimensional to Three-Dimensional In Vitro Cultures

Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by the immune system, and cause acute and chronic illness. SUMMARY Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by the immune system, and cause acute and chronic illness. In this phylum, we can find parasites of human and veterinary health relevance, such as Toxoplasma, Plasmodium, Cryptosporidium, and Eimeria. There are still many unknowns about the biology of these pathogens due to the ethical and practical issues of performing research in their natural hosts. Animal models are often difficult or nonexistent, and as a result, there are apicomplexan life cycle stages that have not been studied. One recent alternative has been the use of three-dimensional (3D) systems such as organoids, 3D scaffolds with different matrices, microfluidic devices, organs-on-a-chip, and other tissue culture models. These 3D systems have facilitated and expanded the research of apicomplexans, allowing us to explore life stages that were previously out of reach and experimental procedures that were practically impossible to perform in animal models. Human- and animal-derived 3D systems can be obtained from different organs, allowing us to model host-pathogen interactions for diagnostic methods and vaccine development, drug testing, exploratory biology, and other applications. In this review, we summarize the most recent advances in the use of 3D systems applied to apicomplexans. We show the wide array of strategies that have been successfully used so far and apply them to explore other organisms that have been less studied.
Experimental investigation of the spatial variability of the steel weight loss and corrosion cracking of reinforced concrete members: novel X-ray and digital image processing techniques

Abstract The material properties of concrete structures and their structural dimensions are known to be random due to the spatial variability associated with workmanship and various other factors. This randomness produces spatially variable corrosion damages, such as steel weight loss and corrosion cracks. The structural capacity of reinforced concrete (RC) members strongly depends on the local conditions of their reinforcements. Modelling the spatial variability of steel corrosion is important, but steel corrosion in RC members can only be observed after severely damaging the concrete members. To understand the steel corrosion growth process and the change in the spatial variability of steel corrosion with time, continuous monitoring is necessary. In this study, X-ray photography is applied to observe steel corrosion in RC beams. The steel weight loss is estimated by the digital image processing of the X-ray photograms. The non-uniform distribution of steel weight loss along rebars inside RC beams determined using X-ray radiography and its correlation with longitudinal crack widths are experimentally investigated.
Prediction Error Determines Whether NMDA Receptors in the Basolateral Amygdala Complex Are Involved in Pavlovian Fear Conditioning

It is widely accepted that activation of NMDA receptors (NMDAR) is necessary for the formation of fear memories in the basolateral amygdala complex (BLA). This acceptance is based on findings that blockade of NMDAR in the BLA disrupts Pavlovian fear conditioning in rodents when initially innocuous stimuli are paired with aversive and unexpected events (surprising foot shock). The present study challenges this acceptance by showing that the involvement of NMDAR in Pavlovian fear conditioning is determined by prediction errors in relation to aversive events. In the initial experiments, male rats received a BLA infusion of the NMDAR antagonist, D-AP5 and were then exposed to pairings of a novel target stimulus and foot shock. This infusion disrupted acquisition of fear to the target when the shock was surprising (experiments 1a, 1b, 2a, 2b, 3a, and 3b) but spared fear to the target when the shock was expected based on the context, time and other stimuli that were present (experiments 1a and 1b). Under the latter circumstances, fear to the target required activation of calcium-permeable AMPAR (CP-AMPA; experiments 4a, 4b, and 4c), which, using electrophysiology, were shown to regulate the activity of interneurons in the BLA (experiment 5). Thus, NMDAR activation is not required for fear conditioning when danger occurs as expected given the context, time and stimuli present, but is required for fear conditioning when danger occurs unexpectedly. These findings are related to current theories of NMDAR function and ways that prediction errors might influence the substrates of fear memory formation in the BLA. SIGNIFICANCE STATEMENT It is widely accepted that NMDA receptors (NMDAR) in the basolateral amygdala complex (BLA) are activated by pairings of a conditioned stimulus (CS) and an aversive unconditioned (US) stimulus, leading to the synaptic changes that underlie formation of a CS-US association. The present findings are significant in showing that this theory is incomplete. When the aversive US is unexpected, animals encode all features of the situation (context, time and stimuli present) as a new fear/threat memory, which is regulated by NMDAR in the BLA. However, when the US is expected based on the context, time and stimuli present, the new fear memory is assimilated into networks that represent those features, which occurs independently of NMDAR activation in the BLA.
Effect of Interleukin 6 on Scleral Fibroblast Proliferation, Differentiation, and Apoptosis Involved in Myopic Scleral Remodeling

Introduction: Scleral hypoxia (HO) is present in myopic eyes, and interleukin (IL)-6 is increased in the aqueous humor of patients with high myopia. The aim of this study was to investigate the effects of IL-6 on scleral fibroblast proliferation, differentiation, and apoptosis under conditions of HO and the possible role of IL-6 in myopic scleral remodeling. Methods: Primary human scleral fibroblasts (HSFs) were cultured using a tissue mass adherent method. First, cells were cultured under conditions of HO (2% O2) or normoxia (NO, 20% O2) for different times. A quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence were used to detect the expression of IL-6 in HSFs. Next, cells were divided into five groups: NO, HO, HO plus IL-6, HO plus IL-6 receptor inhibitor (IL6RI), and HO plus IL-6 and IL6RI. The groups were treated separately for 72 h. Cell counting kit-8 assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Western blotting and qRT-PCR were used to detect the expression of various genes in the transforming growth factor-β1/Smad2/matrix metalloproteinase-2 pathway; these methods and immunofluorescence were also used to detect transdifferentiation of HSFs. Results: HO resulted in upregulation of IL-6 expression in HSFs. Compared with NO, HO resulted in diminished cell proliferation and increased apoptosis and differentiation in HSFs; the above trend was further enhanced by the addition of IL6RI. Compared with the HO group, the addition of IL-6 led to a decrease in cell proliferation and an increase in apoptosis and differentiation of HSFs; the above trends showed opposite changes after the addition of both IL-6 and IL6RI. Additionally, IL-6 and IL6RI exerted opposite regulatory effects on the transforming growth factor-β1/Smad2/matrix metalloproteinase-2 pathway under conditions of HO. Conclusion: HO caused HSFs to overexpress IL-6. IL-6 has a role in scleral remodeling in myopic eyes through affecting the proliferation, differentiation, and apoptosis of HSFs.
Examination of Genetic Susceptibility in Radiation-Associated Meningioma

Previous epidemiological studies have demonstrated elevated susceptibility to ionizing radiation in some families, thus suggesting the presence of genetic components that conferred increased rate of radiation-associated meningioma (RAM). In this study, we exome-sequenced and investigated the segregation pattern of rare deleterious variants in 11 RAM pedigrees. In addition, we performed a rare-variant association analysis in 92 unrelated familial cases of RAM that were ancestry-matched with 88 meningioma-free controls. In the pedigree analysis, we found that each family carried mostly a unique set of rare deleterious variants. A follow-up pathway analysis of the union of the genes that segregated within each of the 11 pedigrees identified a single statistically significant (q value = 7.90E-04) “ECM receptor interaction” set. In the case-control association analysis, we observed no statistically significant variants or genes after multiple testing correction; however, examination of ontological categories of the genes that associated with RAM at nominal P values <0.01 identified biologically relevant pathways such as DNA repair, cell cycle and apoptosis. These results suggest that it is unlikely that a small number of highly penetrant genes are involved in the pathogenesis of RAM. Substantially larger studies are needed to identify genetic risk variants and genes in RAM.
Prevention of Typhoid by Vi Conjugate Vaccine and Achievable Improvements in Household Water, Sanitation, and Hygiene: Evidence From a Cluster-Randomized Trial in Dhaka, Bangladesh

Abstract Background Typhoid fever contributes to approximately 135 000 deaths annually. Achievable improvements in household water, sanitation, and hygiene (WASH) combined with vaccination using typhoid conjugate vaccines (TCVs) may be an effective preventive strategy. However, little is known about how improved WASH and vaccination interact to lower the risk of typhoid. Methods A total of 61 654 urban Bangladeshi children aged 9 months to <16 years, residing in 150 clusters with a baseline population of 205 760 residents, were randomized 1:1 by cluster to Vi-tetanus toxoid TCV or Japanese encephalitis (JE) vaccine. Surveillance for blood culture–confirmed typhoid fever was conducted over 2 years. Existing household WASH status was assessed at baseline as Better or Not Better using previously validated criteria. The reduction in typhoid risk among all residents associated with living in TCV clusters, Better WASH households, or both was evaluated using mixed-effects Poisson regression models. Results The adjusted reduced risk of typhoid among all residents living in the clusters assigned to TCV was 55% (95% confidence interval [CI], 43%–65%; P < .001), and that of living in Better WASH households, regardless of cluster, was 37% (95% CI, 24%–48%; P < .001). The highest risk of typhoid was observed in persons living in households with Not Better WASH in the JE clusters. In comparison with these persons, those living in households with Better WASH in the TCV clusters had an adjusted reduced risk of 71% (95% CI, 59%–80%; P < .001). Conclusions Implementation of TCV programs combined with achievable and culturally acceptable household WASH practices were independently associated with a significant reduction in typhoid risk. Clinical Trials Registration ISRCTN11643110.
The Influence of Emotion Regulation on the Association Between Depression and Heart Rate Variability in Cardiac Patients

ABSTRACT Objective Poor vagally mediated heart rate variability (vmHRV) is a mechanism linking depression to coronary heart disease (CHD). Reduced vmHRV is also considered an index of emotion dysregulation—the frequent use of maladaptive emotion regulation strategies, one of the most important being expressive suppression—which is a key component of depression. Therefore, this study aimed to investigate the moderating role of expressive suppression in the relation between depression and vmHRV in patients with CHD. Methods The sample included 235 patients with CHD (mean [standard deviation] age = 61.6 [9.8] years; 12% women) admitted to cardiac rehabilitation after a cardiac intervention. The Beck Depression Inventory-II was administered to assess depressive symptoms. Emotion regulation strategies based on either expressive suppression or cognitive reappraisal were assessed through the Emotion Regulation Questionnaire. Resting electrocardiographic recordings were collected for 5 minutes to compute HRV indices. Results Expressive suppression moderated the relation between depressive symptoms and vmHRV (b = −0.03, p = .012). Patients with lower expressive suppression scores showed no association between depressive symptoms and vmHRV (b = −0.00, p = .94), whereas those with higher expressive suppression scores showed a significant negative association between depressive symptoms and vmHRV (b = −0.05, p = .015). Conclusions The use of expressive suppression is likely to potentiate the relation between depressive symptoms and poor vmHRV, which could increase the cardiac risk in these patients. Targeting emotion regulation skills in cardiac rehabilitation programs may be useful for reducing the impact of depression in cardiac patients.