Miracle-dz/UniFAR-FTUs huggingface dataset:
Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.
Benefit and Risk of Prolonged Dual Antiplatelet Therapy After Percutaneous Coronary Intervention With Drug-Eluting Stents in Patients With Elevated Lipoprotein(a) Concentrations

Background: Lipoprotein(a) is positively related to cardiovascular events in patients with coronary artery disease (CAD). Given that lipoprotein(a) has a prothrombotic effect, prolonged dual antiplatelet therapy (DAPT) might have a beneficial effect on reducing ischemic events in patients with elevated lipoprotein(a) levels after percutaneous coronary intervention (PCI). We performed this study to assess the efficacy and safety of prolonged DAPT (>1 year) in this population. Methods: We evaluated a total of 3,025 CAD patients with elevated lipoprotein(a) levels who were event-free at 1 year after PCI from the prospective Fuwai PCI Registry, of which 913 received DAPT ≤ 1 year and 2,112 received DAPT>1 year. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction or stroke. Results: After a median follow-up of 2.4 years, patients who received DAPT>1 year were associated with lower risks of MACCE compared with DAPT ≤ 1 year (1.6 vs. 3.8%; hazard ratio [HR] 0.383, 95% confidence interval [CI] 0.238–0.616), which was primarily driven by the lower all-cause mortality (0.2 vs. 2.3%; HR 0.078, 95% CI 0.027–0.227). In addition, DAPT>1 year was also associated with lower risks of cardiac death, and definite/probable stent thrombosis than those who received DAPT ≤ 1 year (P < 0.05). Conversely, no difference was found between the two groups in terms of clinically relevant bleeding. Similar results were observed in multivariate Cox regression analysis and inverse probability of treatment weighting analysis. Conclusions: In patients with elevated lipoprotein(a) concentrations after PCI, prolonged DAPT (>1 year) reduced ischemic cardiovascular events, including MACCE, all-cause mortality, cardiac mortality, and definite/probable stent thrombosis, without increase in clinically relevant bleeding risk compared with ≤ 1-year DAPT. Lipoprotein(a) levels might be a new important consideration when deciding the duration of DAPT after PCI.
Challenges and Opportunities in Coastal Shoreline Prediction

Sandy beaches comprise approximately 31% of the world's ice-free coasts. Sandy coastlines around the world are continuously adjusting in response to changing waves and water levels at both short (storm) and long (climate-driven, from El-Nino Southern Oscillation to sea level rise) timescales. Managing this critical zone requires robust, advanced tools that represent our best understanding of how to abstract and integrate coastal processes. However, this has been hindered by (1) a lack of long-term, large-scale coastal monitoring of sandy beaches and (2) a robust understanding of the key physical processes that drive shoreline change over multiple timescales. This perspectives article aims to summarize the current state of shoreline modeling at the sub-century timescale and provides an outlook on future challenges and opportunities ahead.
Exploring K v 1.2 Channel Inactivation Through MD Simulations and Network Analysis

The KCNA2 gene encodes the K v 1.2 channel, a mammalian Shaker-like voltage-gated K+ channel, whose defections are linked to neuronal deficiency and childhood epilepsy. Despite the important role in the kinetic behavior of the channel, the inactivation remained hereby elusive. Here, we studied the K v 1.2 inactivation via a combined simulation/network theoretical approach that revealed two distinct pathways coupling the Voltage Sensor Domain and the Pore Domain to the Selectivity Filter. Additionally, we mutated some residues implicated in these paths and we explained microscopically their function in the inactivation mechanism by computing a contact map. Interestingly, some pathological residues shown to impair the inactivation lay on the paths. In summary, the presented results suggest two pathways as the possible molecular basis of the inactivation mechanism in the K v 1.2 channel. These pathways are consistent with earlier mutational studies and known mutations involved in neuronal channelopathies.
Impact of COVID-19 Pandemic and Lockdown Measures on the Mental Health of the General Population in the Gulf Cooperation Council States: A Cross-Sectional Study

Background: In the Gulf Cooperation Council (GCC) countries (Kuwait, Qatar, Saudi Arabia, Bahrain, United Arab Emirates, and Oman), as in the rest of the world, the COVID-19 has been spreading since 2019, and it had a significant impact on various aspects of life. The outbreak and the restrictive measures imposed by countries to stop the spread of the virus could harm the mental health condition of the general population. This cross-sectional study aims to assess the impact of the pandemic on mental health and investigate the potential risk factors. Methods: An online survey was collected from individuals in GCC countries from May to October 2020. The final sample included 14,171 participants, 67.3% females and 60.4% younger than 35 years old. The survey consisted of depression, Anxiety, Insomnia, and post-traumatic stress questionnaires. Crude and adjusted Odds ratios are calculated using simple and multivariable logistic regressions to investigate the association between risk factors and mental health issues. Results: Endorsement rates for depression were 11,352 (80.1%), 9,544 (67.3%) for anxiety, 8,845 (63.9%) for insomnia and 9,046 (65.2%) for post-traumatic stress. Being female and younger age were associated with a higher likelihood of developing depression, anxiety, insomnia, and post-traumatic stress. In addition, participants with underlying psychological problems were three times more likely to develop depressive and post-traumatic stress symptoms. Conclusion: According to the findings, women, youth, singles, divorced individuals, and individuals with pre-existing psychological and medical conditions are subject to a higher risk of mental health problems during the pandemic, which policy-makers should consider when imposing restrictive measures.
The Roles of Cardiovascular H2-Histamine Receptors Under Normal and Pathophysiological Conditions

This review addresses pharmacological, structural and functional relationships among H2-histamine receptors and H1-histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential clinical role of cardiac H2-histamine-receptors in cardiac diseases will be examined. The use of H2-histamine receptor agonists to acutely increase the force of contraction will be discussed. Special attention will be paid to the potential role of cardiac H2-histamine receptors in the genesis of cardiac arrhythmias. Moreover, novel findings on the putative role of H2-histamine receptor antagonists in treating chronic heart failure in animal models and patients will be reviewed. Some limitations in our biochemical understanding of the cardiac role of H2-histamine receptors will be discussed. Recommendations for further basic and translational research on cardiac H2-histamine receptors will be offered. We will speculate whether new knowledge might lead to novel roles of H2-histamine receptors in cardiac disease and whether cardiomyocyte specific H2-histamine receptor agonists and antagonists should be developed.
Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma

Introduction: tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs, are divided into two categories: tRNA-related fragments (tRFs) and tRNA halves (tiRNAs). Abnormal expression of tsRNAs has been found in diverse cancers, which indicates that further understanding of the function of tsRNAs will help identify new biomarkers and potential therapeutic targets. Until now, the underlying roles of tsRNAs in primary nasopharyngeal carcinoma (NPC) are still unknown. Methods: tRF and tiRNA sequencing was performed on four pairs of NPC tissues and healthy controls. Thirty pairs of NPC samples were used for quantitative real-time polymerase chain reaction (qRT-PCR) verification, and the ROC analysis was used to evaluate the diagnostic efficiency initially. Target prediction and bioinformatics analysis of validated tRFs and tiRNAs were conducted to explore the mechanisms of tsRNAs in NPC’s pathogenesis. Results: A total of 158 differentially expressed tRFs and tiRNAs were identified, of which 88 are upregulated and 70 are downregulated in NPC. Three validated tRFs in the results of qRT-PCR were consistent with the sequencing data: two upregulations (tRF-1:28-Val-CAC-2 and tRF-1:24-Ser-CGA-1-M3) and one downregulation (tRF-55:76-Arg-ACG-1-M2). The GO and KEGG pathway enrichment analysis showed that the potential target genes of validated tRFs are widely enriched in cancer pathways. The related modules may play an essential role in the pathogenesis of NPC. Conclusions: The tsRNAs may become a novel class of biological diagnostic indicators and possible targets for NPC.
Prenatal and Postnatal Manifestations of Congenital Chloride Diarrhea Due to a Heterozygote Variant of the SLC26A3 Gene: A Case Report

Congenital chloride diarrhea (CCD) is caused by a recessive mutation in the SLC26A3 gene and characterized mainly by watery diarrhea, hypochloremia and metabolic alkalosis. Various different mutations in SLC26A3 are responsible for the disease. In the prenatal period, the symptoms of CCD may include polyhydramnios, preterm labor and abdominal distension. The main feature of CCD is chloride-rich diarrhea, which leads to excessive loss of fluid and salt immediately after birth and is followed by weight loss and dehydration. Hyponatremia and hypochloremia are soon accompanied by hypokalemia and metabolic alkalosis. Untreated CCD is fatal even in the first weeks of life. Diagnosis is made by high fecal chloride concentrations in patients with serum electrolytes corrected by salt substitution and confirmed using genetic testing of peripheral blood samples. Here, we detail prenatal and postnatal manifestations of a preterm infant, born via Caesarian section, who was suspected to suffer intrauterine bowel obstruction. Upper median laparotomy was performed and no intestinal abnormalities found. The course of the neonatal period was complicated by severe diarrhea with hypochloremia, hyponatremia and metabolic alkalosis. Based on the patient's clinical picture and stool examination, a diagnosis of CCD was established. Mutation of the SLC26A3 gene was confirmed using genetic testing.
Organic Anion Transporting Polypeptide 2B1 in Human Fetal Membranes: A Novel Gatekeeper for Drug Transport During Pregnancy?

Current intervention strategies have not been successful in reducing the risks of adverse pregnancy complications nor maternal and fetal morbidities associated with pregnancy complications. Improving pregnancy and neonatal outcomes requires a better understanding of drug transport mechanisms at the feto-maternal interfaces, specifically the placenta and fetal membrane (FM). The role of several solute carrier uptake transporter proteins (TPs), such as the organic anion transporting polypeptide 2B1 (OATP2B1) in transporting drug across the placenta, is well-established. However, the mechanistic role of FMs in this drug transport has not yet been elucidated. We hypothesize that human FMs express OATP2B1 and functions as an alternate gatekeeper for drug transport at the feto-maternal interface. We determined the expression of OATP2B1 in term, not-in-labor, FM tissues and human FM cells [amnion epithelial cell (AEC), chorion trophoblast cell (CTC), and mesenchymal cells] using western blot analyses and their localization using immunohistochemistry. Changes in OATP2B1 expression was determined for up to 48 h after stimulation with cigarette smoke extract (CSE), an inducer of oxidative stress. The functional role of OATP2B1 was determined by flow cytometry using a zombie violet dye substrate assay. After OATP2B1 gene silencing, its functional relevance in drug transport through the feto-maternal interface was tested using a recently developed feto-maternal interface organ-on-a-chip (OOC) system that contained both FM and maternal decidual cells. Propagation of a drug (Rosuvastatin, that can be transported by OATP2B1) within the feto-maternal interface OOC system was determined by mass spectrometry. FMs express OATP2B1 in the CTC and AEC layers. In FM explants, OATP2B1 expression was not impacted by oxidative stress. Uptake of the zombie violet dye within AECs and CTCs showed OATP2B1 is functionally active. Silencing OATP2B1 in CTCs reduced Rosuvastatin propagation from the decidua to the fetal AEC layer within the feto-maternal interface-OOC model. Our data suggest that TPs in FMs may function as a drug transport system at the feto-maternal interface, a function that was previously thought to be performed exclusively by the placenta. This new knowledge will help improve drug delivery testing during pregnancy and contribute to designing drug delivery strategies to treat adverse pregnancy outcomes.
Incorporation of Partially Hydrolyzed Polyacrylamide With Zwitterionic Units and Poly(Ethylene Glycol) Units Toward Enhanced Tolerances to High Salinity and High Temperature

Partially hydrolyzed polyacrylamide (HPAM) was widely implemented to improve the rheological properties of displacing fluids, but the high temperature and salinity of the reservoir brine limited their applications. Herein, copolymers including HPAM, zwitterion-modified HPAM (z-HPAM), PEG-modified HPAM (p-HPAM), and zwitterion/PEG-modified HPAM (zp-HPAM) were prepared by free radical polymerization in an aqueous solution. The viscosity of these copolymers under different temperature and salinity was measured in aqueous solution. It is found that the viscosity of the HPAM under the harsh condition (90oC, 20 × 104 mg/L salinity) is only 9.6% of that value under the normal condition (25oC, pure water), while the z-HPAM can significantly improve salt resistance by the effects of salting-in effect and intermolecular electrostatic crosslinking, showing a viscosity retention of 22.9% under the harsh condition. The addition of PEG-containing monomer can strengthen hydrogen bonding between the polymer chains and form a sterically ordered structure with improved salinity and temperature resistance. The synergistic effect of zwitterion units and PEG units endows the zp-HPAM with good salinity and temperature resistance; thus, the sample viscosity under the harsh condition remains 170 mPa s, which retains 29% of the value under the normal condition. The enhanced rheology properties of the zp-HPAM under the harsh condition are significant for the enhanced oil recovery of water-soluble polymer flooding.
The Impact of Heterogeneous Environmental Regulations on Location Choices of Pollution-Intensive Firms in China

The spatial transfer pattern and dynamic mechanisms of pollution-intensive industries are key issues for national and regional sustainable development. Although previous studies have emphasized the impact of environmental regulations on the transfer of pollution industries, there is a lack of firm-level analysis of the combined effects of different types of environmental regulations and other factors on them, which has led to the pollution haven hypothesis remaining contested. In order to provide micro evidence to test the pollution haven hypothesis, this paper reveals the temporal and spatial evolution of pollution-intensive foreign firms’ distribution in China, and explores the impact of heterogeneous environmental regulations on the location choices by using spatial analysis and zero-inflated negative binomial regression. The empirical results were as follows: Firstly, pollution-intensive foreign firms were highly concentrated in the eastern developed region and have a strong path dependency in China. Secondly, environmental regulations, especially the market-based environmental regulation, had a significant negative impact on the location choices of pollution-intensive foreign firms. Thirdly, the spatial distribution of pollution-intensive foreign firms was strongly influenced by new economic and geographic factors. Fourthly, pollution-intensive foreign firms have a significant pollution border effects in developed regions but not in economically less-developed regions due to transportation costs. The governments are expected to adopt heterogeneous environmental regulations based on the level of regional economic development to avoid the pollution haven phenomenon, thus achieving a sustainable development.
Effect ofBacillus velezensis JC-K3 on Endophytic Bacterial and Fungal Diversity in Wheat Under Salt Stress

Plant growth-promoting bacteria (PGPB) can effectively reduce salt damage in plants. Currently, there are many studies on the effects of PGPB on the microbial community structure of rhizosphere soil under salt stress, but fewer studies on the community structure of endophytic bacteria and fungi. We propose that inoculation of endophytic bacteria into the rhizosphere of plants can significantly affect the microbial community structure of the plant’s above-ground and underground parts, which may be the cause of the plant’s “Induced Systemic Tolerance. ” The isolated endophytes were re-inoculated into the rhizosphere under salinity stress. We found that, compared with the control group, inoculation with endophytic Bacillus velezensis JC-K3 not only increased the accumulation of wheat biomass, but also increased the content of soluble sugar and chlorophyll in wheat, and reduced the absorption of Na in wheat shoots and leaves. The abundance of bacterial communities in shoots and leaves increased and the abundance of fungal communities decreased after inoculation with JC-K3. The fungal community richness of wheat rhizosphere soil was significantly increased. The diversity of bacterial communities in shoots and leaves increased, and the richness of fungal communities decreased. JC-K3 strain improved wheat’s biomass accumulation ability, osmotic adjustment ability, and ion selective absorption ability. In addition, JC-K3 significantly altered the diversity and abundance of endophytic and rhizosphere microorganisms in wheat. PGPB can effectively reduce plant salt damage. At present, there are many studies on the effect of PGPB on the microbial community structure in rhizosphere soil under salt stress, but there are few studies on the community structure changes of endophytic bacteria and fungi in plants.
Investing to Improve Product Quality

Quality problems have traditionally been measured in term of cost penalties, and therefore efforts to improve quality have been aimed at a reduction in such factors as scrap or rework. When quality is viewed as a potential company asset however, a fundamental change in attitude is needed, because an asset is an attribute that can systematically be increased in value. Techniques have been developed at the University of Manchester Institute of Science and Technology (UMIST) which enable the company‐wide benefits of improving product quality to be included in a financial evaluation of technology needed to bring about the improvement. Various examples are given relating to investments in advanced manufacturing technology, and these show how quality improvement affects the technical specification that is required for new plant.
Associations Between Healthy Lifestyle Trajectories and the Incidence of Cardiovascular Disease With All-Cause Mortality: A Large, Prospective, Chinese Cohort Study

Background: Lifestyles generally change across the life course yet no prospective study has examined direct associations between healthy lifestyle trajectories and subsequent cardiovascular disease (CVD) or all-cause mortality risk. Methods: Healthy lifestyle score trajectories during 2006–2007, 2008–2009, and 2010–2011 were collated through latent mixture modeling. An age-scale based Cox proportional hazard regression model was implemented to calculate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for developing CVD or all-cause mortality across healthy lifestyle trajectories. Results: 52,248 participants were included with four distinct trajectories identified according to healthy lifestyle scores over 6 years i.e., low-stable (n = 11,248), high-decreasing (n = 7,374), low-increasing (n = 7,828), and high-stable (n = 25,799). Compared with the low-stable trajectory, the high-stable trajectory negatively correlated with lower subsequent risk of developing CVD (HR, 0.73; 95% CI, 0.65–0.81), especially stroke (HR, 0.70; 95% CI, 0.62–0.79), and all-cause mortality (HR, 0.89; 95% CI, 0.80–0.99) under a multivariable-adjusted model. A protective effect for CVD events was observed only in men and in those without diabetes, while a reduced risk of all-cause mortality was observed only in those older than 60 years, though interactions were not statistically significant. Marginally significant interactions were observed between the changing body mass index (BMI) group, healthy lifestyle score trajectories and stratified analysis. This highlighted an inverse correlation between the high-stable trajectory and CVD in BMI decreased and stable participants as well as all-cause mortality in the stable BMI group. The low-increasing trajectory also had reduced risk of CVD only when BMI decreased and in all-cause mortality only when BMI was stable. Conclusions: Maintaining a healthy lifestyle over 6 years corresponds with a 27% lower risk of CVD and an 11% lower risk in all-cause mortality, compared with those engaging in a consistently unhealthy lifestyle. The benefit of improving lifestyle could be gained only after BMI change is considered further. This study provides further evidence from China around maintaining/improving healthy lifestyles to prevent CVD and early death.