Miracle-dz/UniFAR-FTUs huggingface dataset:
Gossypin mitigates oxidative damage by downregulating the molecular signaling pathway in oleic acid‐induced acute lung injury

One of the leading causes of acute lung injury, which is linked to a high death rate, is pulmonary fat embolism. Increases in proinflammatory cytokines and the production of free radicals are related to the pathophysiology of acute lung injury. Antioxidants that scavenge free radicals play a protective role against acute lung injury. Gossypin has been proven to have antioxidant, antimicrobial, and anti‐inflammatory properties. In this study, we compared the role of Gossypin with the therapeutically used drug Dexamethasone in the acute lung injury model caused by oleic acid in rats. Thirty rats were divided into five groups; Sham, Oleic acid model, Oleic acid+Dexamethasone (0.1 mg/kg), Oleic acid+Gossypin (10 and 20 mg/kg). Two hours after pretreatment with Dexamethasone or Gossypin, the acute lung injury model was created by injecting 1 g/kg oleic acid into the femoral vein. Three hours following the oleic acid injection, rats were decapitated. Lung tissues were extracted for histological, immunohistochemical, biochemical, PCR, and SEM imaging assessment. The oleic acid injection caused an increase in lipid peroxidation and catalase activity, pathological changes in lung tissue, decreased superoxide dismutase activity, and glutathione level, and increased TNF‐α, IL‐1β, IL‐6, and IL‐8 expression. However, these changes were attenuated after treatment with Gossypin and Dexamethasone. By reducing the expression of proinflammatory cytokines and attenuating oxidative stress, Gossypin pretreatment provides a new target that is equally effective as dexamethasone in the treatment of oleic acid‐induced acute lung injury.
An analysis of a new rapid difficult airway response team in a vertically built children's hospital

Intrahospital transport is associated with adverse events. This challenge is amplified during airway management. Although difficult airway response teams have been described, little attention has been paid to patient transport during difficult airway management versus the alternative of managing patient airways without moving the patient. This is especially needed in a 22‐floor vertical hospital.
Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation

Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs’ intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (ΔΨm), differentially modulates ETC complex activities and consequently results in leak of electrons from ETC complex III and superoxide formation. The ODN-induced mitochondrial ROS yield protective antibacterial effects. Together, these studies identify a therapeutic metabolic manipulation strategy to broadly protect against pneumonia without reliance on antibiotics.
Two-dimensionalization of a three-dimensional bluff body wake

The three-dimensional flow characteristics of a circular cylinder with synthetic jet control are numerically studied using large eddy simulation. The Reynolds number based on the diameter of the cylinder is Re = 500. The control effects and underlying mechanism are revealed to show how the synthetic jet changes the three-dimensional wake pattern. Analysis of the dynamic control process indicates that the blowing stroke helps the shear layer to assemble vorticity, and then, the suction stroke accelerates the detachment of the concentrated vorticity. The vortex shedding process will be gradually dominated by symmetric actuation of the synthetic jets. Thus, the asymmetric vortex shedding mode could be changed into a symmetric mode several periods after actuation at certain excitation frequencies, leading to significant suppression of lift fluctuations. A periodic pressure variation at the leeward surface of the circular cylinder caused by the changes of the separation point for the flow over a circular cylinder and recirculation region results in a large drag fluctuation. The excitation phase influences only the control process, but not the final state, while the excitation frequency plays an important role in the formation of different wake patterns. It is also found that the synthetic jet can completely suppress the formation of streamwise vortices due to the three-dimensional instability suppression and reduce the deformation of spanwise vortices, resulting in a conversion of the original three-dimensional flow into a two-dimensional one. Such two-dimensionalization can be achieved for both asymmetric and symmetric wake patterns, indicating that it is not influenced by the excitation phase and frequency as long as the actuation is two-dimensional.The three-dimensional flow characteristics of a circular cylinder with synthetic jet control are numerically studied using large eddy simulation. The Reynolds number based on the diameter of the cylinder is Re = 500. The control effects and underlying mechanism are revealed to show how the synthetic jet changes the three-dimensional wake pattern. Analysis of the dynamic control process indicates that the blowing stroke helps the shear layer to assemble vorticity, and then, the suction stroke accelerates the detachment of the concentrated vorticity. The vortex shedding process will be gradually dominated by symmetric actuation of the synthetic jets. Thus, the asymmetric vortex shedding mode could be changed into a symmetric mode several periods after actuation at certain excitation frequencies, leading to significant suppression of lift fluctuations. A periodic pressure variation at the leeward surface of the circular cylinder caused by the changes of the separation point for the flow over a circular cylin.
Interleukin-34 is more suitable than macrophage colony-stimulating factor for predicting liver significant fibrosis in patients with chronic hepatitis B

Abstract Aims Interleukin-34 (IL-34) and macrophage colony-stimulating factor (CSF-1) have similar functions, such as promoting the formation of liver fibrosis. This study aimed to evaluate and compare the diagnostic value of serum IL-34 and CSF-1 for significant liver fibrosis in patients with chronic hepatitis B (CHB). Methods A total of 369 CHB patients, consisting of 208 HBeAg-negative patients and 161 HBeAg-positive patients, were enrolled in this study. Additionally, 72 healthy individuals served as healthy controls (HCs). Serum levels of IL-34 and CSF-1 were measured using the enzyme-linked immunosorbent assay method. Liver fibrosis grades were assessed using the modified Scheuer scoring system. Results Serum IL-34 and CSF-1 levels exhibited significant elevation in both HBeAg-negative and HBeAg-positive patients in comparison to HCs (p < 0.001). IL-34 emerged as an independent factor linked to significant liver fibrosis, whereas CSF-1 did not exhibit such an association. Receiver operating characteristic (ROC) analysis indicated higher areas under the curves (AUCs) for IL-34 (0.814, p < 0.001 and 0.673, p < 0.001) when diagnosing significant liver fibrosis in HBeAg-negative and HBeAg-positive patients, respectively, as opposed to CSF-1 (0.602, p < 0.001; 0.619, p = 0.385). Within the HBeAg-negative patient subgroup, the AUC for IL-34 surpassed that of FIB-4 (p = 0.009) and APRI (p = 0.045). Conclusion Serum IL-34 has the potential to be a straightforward and practical biomarker that demonstrates superior performance to serum CSF-1 in the diagnosis of significant liver fibrosis in CHB patients, especially within the HBeAg-negative patients.
Beyond Babylon: Art, Trade, and Diplomacy in the Second Millennium B.C.

This important volume describes the extraordinary art created in the second millennium B.C. for royal palaces, temples, and tombs from Mesopotamia, Syria, and Anatolia to Cyprus, Egypt, and the Aegean. Objects of the highest artistry reflect the development of a sophisticated trade network throughout the eastern Mediterranean region and the resulting fusion of Near Eastern, Aegean, and Egyptian cultural styles.The impact of these far-flung connections is documented in the precious materials sent to royal and temple treasuries and, most dramatically, in objects discovered on merchant shipwrecks off the shores of southern Anatolia. The history of the period and the artistic creativity fostered by interaction among the powers of the ancient Near East, both great and small, are discussed by an international group of scholars in essays and entries on the more than 350 objects included in the exhibition, continuing the fascinating story begun in the landmark catalogue "Art of the First Cities" (2003).
Mixed, nonclassical behavior in a classic allosteric protein

Significance A major unresolved problem in structural biology today is how proteins achieve allostery, where ligand binding of a protein at one site alters activity at a distant site. Allosteric regulation is widespread in cells and is of great interest for protein and drug design. Classic models of allostery employ switching between two conformations, but in classical allosteric systems (e.g., with subunit symmetry), the allosteric conformational dynamics have not been observed in detail. Here, using NMR spectroscopy in the enzyme chorismate mutase, we observe coordinated switching of residues throughout much, but not all, of the protein. The observed dynamics share some features of the classic models, yet show that the allosteric mechanisms are likely to be more complex in many systems.
Metabolic dysfunction‐associated steatotic liver disease in older adults is associated with frailty and social disadvantage

The burden of metabolic dysfunction‐associated steatotic liver disease (MASLD) is growing rapidly, as is the number of older adults globally. However, relatively few studies have been performed evaluating the prevalence and risk factors for MASLD in older adults. As such, we aimed to identify the prevalence of MASLD in older adults, as well as sociodemographic, clinical, functional and biochemical associations.
Life years lost for users of specialized mental healthcare

Mental disorders are burdensome and are associated with increased mortality. Mortality has been researched for various mental disorders, especially in countries with national registries, including the Nordic countries. Yet, knowledge gaps exist around national differences, while also relatively less studies compare mortality of those seeking help for mental disorders in specialized mental healthcare (SMH) by diagnosis. Additional insight into such mortality distributions for SMH users would be beneficial for both policy and research purposes. We aim to describe and compare the mortality in a population of SMH users with the mortality of the general population. Additionally, we aim to investigate mortality differences between sexes and major diagnosis categories: anxiety, depression, schizophrenia spectrum and other psychotic disorders, and bipolar disorder.
Current status and issues with the dosimetric assay of iodine-125 seed sources at medical facilities in Japan: a questionnaire-based survey

Abstract In conducting dosimetric assays of seed sources containing iodine-125 (125I), several major guidelines require the medical physicist to verify the source strength before patient treatment. Japanese guidelines do not mandate dosimetric assays at medical facilities, but since 2017, three incidents have occurred in Japan wherein seeds with incorrect strengths were delivered to medical facilities. Therefore, this study aimed to survey the current situation and any barriers to conducting the dosimetric assay of iodine-125 seeds at medical facilities in Japan. We conducted a questionnaire-based survey from December 2020 to April 2021, to examine whether seed assay and verification of the number of seeds delivered were being performed. We found that only 9 facilities (16%) performed seed assay and 28 (52%) verified the number of seeds. None of the facilities used an assay method that ensured traceability. The reasons for not performing an assay were divided into two categories: lack of resources and legal issues. Lack of resources included lack of instruments, lack of knowledge of assay methods, shorthand, or all of the above, whereas legal issues included the inability to resterilize iodine-125 seeds distributed in Japan and/or purchase seeds dedicated to the assay. Dosimetric assays, including simple methods, are effective in detecting calibration date errors and non-radioactive seeds. The study findings suggest that familiarization of medical personnel with these assay methods and investigation of the associated costs of labor and equipment should be recommended, as these measures will lead to medical reimbursement for quality assurance.
Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension

BACKGROUND: Epigenetic regulation of vascular remodeling in pulmonary hypertension (PH) is poorly understood. Transcription regulating, histone acetylation code alters chromatin accessibility to promote transcriptional activation. Our goal was to identify upstream mechanisms that disrupt epigenetic equilibrium in PH. METHODS: Human pulmonary artery smooth muscle cells (PASMCs), human idiopathic pulmonary arterial hypertension (iPAH):human PASMCs, iPAH lung tissue, failed donor lung tissue, human pulmonary microvascular endothelial cells, iPAH:PASMC and non-iPAH:PASMC RNA-seq databases, NanoString nCounter, and cleavage under targets and release using nuclease were utilized to investigate histone acetylation, hyperacetylation targets, protein and gene expression, sphingolipid activation, cell proliferation, and gene target identification. SPHK2 (sphingosine kinase 2) knockout was compared with control C57BL/6NJ mice after 3 weeks of hypoxia and assessed for indices of PH. RESULTS: We identified that Human PASMCs are vulnerable to the transcription-promoting epigenetic mediator histone acetylation resulting in alterations in transcription machinery and confirmed its pathological existence in PH:PASMC cells. We report that SPHK2 is elevated as much as 20-fold in iPAH lung tissue and is elevated in iPAH:PASMC cells. During PH pathogenesis, nuclear SPHK2 activates nuclear bioactive lipid S1P (sphingosine 1-phosphate) catalyzing enzyme and mediates transcription regulating histone H3K9 acetylation (acetyl histone H3 lysine 9 [Ac-H3K9]) through EMAP (endothelial monocyte activating polypeptide) II. In iPAH lungs, we identified a 4-fold elevation of the reversible epigenetic transcription modulator Ac-H3K9:H3 ratio. Loss of SPHK2 inhibited hypoxic-induced PH and Ac-H3K9 in mice. We discovered that pulmonary vascular endothelial cells are a priming factor of the EMAP II/SPHK2/S1P axis that alters the acetylome with a specificity for PASMC, through hyperacetylation of histone H3K9. Using cleavage under targets and release using nuclease, we further show that EMAP II–mediated SPHK2 has the potential to modify the local transcription machinery of pluripotency factor KLF4 (Krüppel-like factor 4) by hyperacetylating KLF4 Cis-regulatory elements while deletion and targeted inhibition of SPHK2 rescues transcription altering Ac-H3K9. CONCLUSIONS: SPHK2 expression and its activation of the reversible histone H3K9 acetylation in human pulmonary artery smooth muscle cell represent new therapeutic targets that could mitigate PH vascular remodeling.
Sexual harassment, sexual assault and rape by colleagues in the surgical workforce, and how women and men are living different realities: observational study using NHS population-derived weights

Abstract Background This observational study, paired with National Health Service (NHS) workforce population data, examined gender differences in surgical workforce members’ experiences with sexual misconduct (sexual harassment, sexual assault, rape) among colleagues in the past 5 years, and their views of the adequacy of accountable organizations in dealing with this issue. Methods This was a survey of UK surgical workforce members, recruited via surgical organizations. Results Some 1704 individuals participated, with 1434 (51.5 per cent women) eligible for primary unweighted analyses. Weighted analyses, grounded in NHS England surgical workforce population data, used 756 NHS England participants. Weighted and unweighted analyses showed that, compared with men, women were significantly more likely to report witnessing, and be a target of, sexual misconduct. Among women, 63.3 per cent reported being the target of sexual harassment versus 23.7 per cent of men (89.5 per cent witnessing versus 81.0 per cent of men). Additionally, 29.9 per cent of women had been sexually assaulted versus 6.9 per cent of men (35.9 per cent witnessing versus 17.1 per cent of men), with 10.9 per cent of women experiencing forced physical contact for career opportunities (a form of sexual assault) versus 0.7 per cent of men. Being raped by a colleague was reported by 0.8 per cent of women versus 0.1 per cent of men (1.9 per cent witnessing versus 0.6 per cent of men). Evaluations of organizations’ adequacy in handling sexual misconduct were significantly lower among women than men, ranging from a low of 15.1 per cent for the General Medical Council to a high of 31.1 per cent for the Royal Colleges (men’s evaluations: 48.6 and 60.2 per cent respectively). Conclusion Sexual misconduct in the past 5 years has been experienced widely, with women affected disproportionately. Accountable organizations are not regarded as dealing adequately with this issue.
Variable phenotype of a null PPP1R13L allele in children with dilated cardiomyopathy

Childhood‐onset cardiomyopathy is a genetically heterogeneous group of conditions with several genes implicated. Recently, biallelic loss‐of‐function variants in PPP1R13L have been reported in association with a syndromic form of dilated cardiomyopathy (DCM). In addition, affected children manifest skin and hair abnormalities, cleft lip and palate (CLP), and eye findings. Here, we delineate the condition further by describing the phenotype associated with a homozygous frameshift variant (p.Arg330 ProfsTer76) in PPP1R13L detected in two sibships in a consanguineous family with six affected children. The index case had DCM and wooly hair, two of his siblings had DCM and CLP while three cousins had, in addition, glaucoma. Global developmental delay was observed in one child. All the children, except one, died during early childhood. Whole exome sequencing and whole genome sequencing did not reveal any other plausible variant. We provide further evidence that implicates PPP1R13L in a variable syndromic form of severe childhood‐onset DCM and suggests expanding the spectrum of this condition to include glaucoma. Given the variability of the phenotype associated with PPP1R13‐related DCM, a thorough evaluation of each case is highly recommended even in the presence of an apparently isolated DCM.
Gut microbiota and hypertensive disorders in pregnancy: evidence from the Mendelian randomization study

Background: Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation. Methods: We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran’s Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy. Results: The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of LachnospiraceaeUCG010, Olsenella, RuminococcaceaeUCG009, Ruminococcus2, Anaerotruncus, Bifidobacterium, and Intestinibacter with GH, of Eubacterium (ruminantium group), Eubacterium (ventriosum group), Methanobrevibacter, RuminococcaceaeUCG002, and Tyzzerella3 with PE, and of Dorea and RuminococcaceaeUCG010 with eclampsia, respectively. Conclusions: This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.
Residual Dialkyl Phosphate Metabolite Concentrations of Organophosphate Pesticides Among Indian Farmworkers

Objective Biomonitoring of urinary dialkyl phosphate (DAP) metabolites, a sensitive biomarker to assess pesticides exposure and also to study the impact of the use of personal protective equipment (PPE). Methods A preintervention-postintervention study to biomonitor dimethylphosphate, diethylphosphate, diethylthiophosphate, and diethyl-dithiophosphate using liquid chromatography with tandem mass spectrometry among Indian farmworkers (n = 120). Results Dimethylphosphate was detected in all samples at a mean concentration of 74.91 μg · L−1 (17.616 μg · g−1 creatinine), whereas diethylthiophosphate and diethyl-dithiophosphate were detected in 88% and 82% of samples, respectively, among farmworkers who adopted unsafe pesticide-handling practices. Intervention studies showed a significant reduction in the urinary DAP metabolites detected among the farmworkers using PPE provided to them (P < 0.01). Conclusions Study confirms the exposure to pesticides among farmworkers and highlights the importance of the use of PPE to minimize exposure.