Progressive Form Research Articles

Exact planetary waves and jet streams

We investigate exact nonlinear waves on surfaces locally approximating the rotating sphere for two-dimensional inviscid incompressible flow. Our first system corresponds to a $\beta$ -plane approximation at the equator, and the second to a $\gamma$ approximation, with the latter describing flow near the poles. We find exact wave solutions in the Lagrangian reference frame that cannot be written down in closed form in the Eulerian reference frame. The wave particle trajectories, contours of potential vorticity and Lagrangian mean velocity take relatively simple forms. The waves possess a non-trivial Lagrangian mean flow that depends on the amplitude of the waves and on a particle label that characterizes values of constant potential vorticity. The mean flow arises due to potential vorticity conservation on fluid particles. Solutions over the entire space are generated by assuming that the flow far from the origin is zonal and there is a region of uniform potential vorticity between this zonal flow and the waves. In the $\gamma$ approximation, a class of waves is found that, based on analogous solutions on the plane, we call Ptolemaic vortex waves. The mean flow of some of these waves, which we can describe in highly nonlinear scenarios due to the exact nature of the solutions, resembles polar jet streams. Several illustrative solutions are used as initial conditions in the fully spherical rotating Navier–Stokes equations, where integration is performed via the numerical scheme presented in Salmon & Pizzo (Atmosphere, vol. 14, issue 4, 2023, 747). The potential vorticity contours found from these numerical experiments vary between stable permanent progressive form and fully turbulent flows generated by wave breaking.

Imaging of Ischemic Cholangiopathy Following Donation after Circulatory Death Liver Transplant.

Ischemic cholangiopathy (IC) is the leading cause of inferior long-term outcomes following donation after circulatory death (DCD) liver transplant. Biliary strictures related to IC are nonanastomotic strictures (NASs) by definition and involve the donor hepatic ducts proximal to the anastomosis, compared with postsurgical anastomotic strictures that form due to fibrotic healing. IC-related NASs can be microangiopathic with patent hepatic artery or macroangiopathic with occluded or stenotic hepatic artery. Recently, IC with NASs have been described to have four distinct patterns at imaging: diffuse necrosis, multifocal progressive, confluence dominant, and minor form, which correlate clinically with graft prognosis. Severe IC can lead to ductal wall breakdown with subsequent bile leaks that can cause significant patient morbidity, with imaging playing a vital role in diagnosis and guiding intervention. IC also predisposes the transplanted liver to biliary stasis and subsequent formation of stones, casts, and sludge. Some cases of posttransplant biliary stricturing are not IC but are a sequela of reflux cholangitis seen with choledochojejunal anastomosis. Other biliary findings in the posttransplant liver can be explained by sphincter of Oddi dysfunction that results from denervation. The authors describe and comprehensively categorize the various IC types and their imaging patterns at MRI and MR cholangiopancreatography, review the prognostic significance of these imaging patterns, and discuss imaging features of additional biliary complications associated with IC after DCD liver transplant. ©RSNA, 2024 Supplemental material is available for this article.

Association of Gougerot-Sjögren syndrome and pulmonary adenocarcinoma: A case report

Interstitial lung disease represents the primary pulmonary involvement in Sjögren's syndrome. A number of patients with Sjögren's syndrome develop a progressive fibrosing form of interstitial lung disease, but there is no data on the prevalence of such presentations. The incidental association of malignant tumors has been described independent of any therapy. We report a case of a patient with chronic interstitial lung disease at the fibrosis stage secondary to Sjögren's syndrome, in whom bronchoscopy incidentally revealed metastatic pulmonary adenocarcinoma.

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma.

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.

Spatial transcriptomics of meningeal inflammation reveals inflammatory gene signatures in adjacent brain parenchyma

While modern high efficacy disease modifying therapies have revolutionized the treatment of relapsing-remitting multiple sclerosis, they are less effective at controlling progressive forms of the disease. Meningeal inflammation is a recognized risk factor for cortical gray matter pathology which can result in disabling symptoms such as cognitive impairment and depression, but the mechanisms linking meningeal inflammation and gray matter pathology remain unclear. Here, we performed magnetic resonance imaging (MRI)-guided spatial transcriptomics in a mouse model of autoimmune meningeal inflammation to characterize the transcriptional signature in areas of meningeal inflammation and the underlying brain parenchyma. We found broadly increased activity of inflammatory signaling pathways at sites of meningeal inflammation, but only a subset of these pathways active in the adjacent brain parenchyma. Subclustering of regions adjacent to meningeal inflammation revealed the subset of immune programs induced in brain parenchyma, notably complement signaling and antigen processing/presentation. Trajectory gene and gene set modeling analysis confirmed variable penetration of immune signatures originating from meningeal inflammation into the adjacent brain tissue. This work contributes a valuable data resource to the field, provides the first detailed spatial transcriptomic characterization in a model of meningeal inflammation, and highlights several candidate pathways in the pathogenesis of gray matter pathology.

Prevalence and prognostic significance of restriction versus systolic dysfunction in patients with transthyretin and light chain cardiac amyloidosis

Abstract The tenet of cardiac amyloidosis (CA) as a paradigm of heart failure with restrictive ventricular physiology and preserved systolic function has come under scrutiny. Thus, we aimed to evaluate the prevalence and clinical significance of left ventricular (LV) systolic dysfunction versus restriction in a large real-world cohort with CA, assessed at the time of diagnosis. Methods This is a multicenter retrospective analysis including 540 transthyretin (ATTR)-CA and 280 light chain (AL)-CA. Patients were divided into 3 phenotypes: 1) preserved LV function: LV ejection fraction (EF) ≥50% associated with grade 0/I diastolic dysfunction; 2) restriction: LV-EF≥50% associated with grade II/III diastolic dysfunction; 3) systolic dysfunction: LV-EF<50% irrespective of diastolic function. We analysed progression from preserved LV function towards the other two phenotypes and their survival. Results In ATTR-CA, prevalence of preserved LV function was 27%, restriction was 44% and systolic dysfunction was 28%. Among patients with preserved LV function, annual conversion rate to restriction was 24% and to systolic dysfunction was 17%. At 3 years, survival free from all-cause mortality was 88%, 76% and 63% respectively (figure A). In AL-CA, prevalence of preserved LV function was 30%, restriction was 49% and systolic dysfunction was 20%. Among patients with preserved LV function, annual conversion rate to restriction was 28% and to systolic dysfunction was 8%. At 3 years, survival free from all-cause mortality was 56%, 39% and 29% respectively (figure B). Conclusions Restriction was the presenting phenotype in less than half of patients, while systolic dysfunction in approximately one quarter. The annual rate of progression form preserved LV function towards restriction or systolic dysfunction was high. In ATTR systolic dysfunction was associated with worse outcome, compared to restriction; in AL both restriction and systolic dysfunction were associated with equally ominous outcome.

Trends and patterns in pulmonary arterial hypertension-associated hospital admissions among methamphetamine users: a decade-long study

BackgroundPulmonary arterial hypertension (PAH) is a rare, chronic, progressive form of pulmonary hypertension in which increased arterial pressure causes remodeling of the arterial system and is associated with heart failure. Methamphetamine is a stimulant that has recently become a focus in PAH research, but the recent trends and demographics of this cohort of patients are not known. The study aimed to analyze the overall trends and demographics of PAH patients with and without concurrent methamphetamine usage.MethodsThe study used the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality (AHRQ) from 2008 to 2020 to calculate nationally weighted estimates for both conditions by ICD-9 and ICD-10 diagnosis codes. We used several statistical measures, including descriptive statistics with design-based chi-square and t-tests, trend analysis with Cochran-Armitage test, generalized linear models, and other data preprocessing measures.ResultsA significant increase was evident in patients with pulmonary arterial hypertension (PAH) and concurrent methamphetamine use (9.2-fold). Most of the hospitalized patients were males (59.16%), aged 41–64 (45.77%), White (68.64%), from the West (53.09%), with Medicaid (50.48%), and with median income <$25,000. The rate of increase over the period was higher for males (11.8-fold), race (not sure which race; please check and modify), aged 41–64 (11.3-fold), and in the South (15.1-fold). An overall adjusted prevalence ratio (PR) for PAH hospitalizations among concurrent methamphetamine users was 32.19 (CI = 31.19–33.22) compared to non-users. With respective reference categories, the significantly higher PR was evident for males, patients aged 41–64, White, with Medicare, median income <$25,000, all regions compared to Northeast, length of hospital stays, and conditions, including chronic pulmonary disease, diabetes, hypertension, obesity, and peripheral vascular disorders.ConclusionThis study reveals a national overall and demographic-specific trend of increasing PAH with concurrent methamphetamine usage and associated factors. The findings may help to understand the current patterns and identify the vulnerable sociodemographic cohorts for further research and to take appropriate policy measures.

Effectiveness of Implant Therapy in Patients With and Without a History of Periodontitis: A Systematic Review With Meta-Analysis of Prospective Cohort Studies.

This systematic review investigates the effectiveness of implant therapy in patients with and without a history of periodontitis in terms of implant loss, peri-implant marginal bone loss (MBL), and occurrence of peri-implant diseases. The protocol of the present meta-analysis was registered on PROSPERO (CRD42021264980). An electronic search was conducted up to April 2024. All prospective cohort studies reporting implant loss, MBL, and occurrence of peri-implant diseases in both patients with a history of periodontitis (HP) and patients with no history of periodontitis (NHP) after at least 36-month follow-up were included. The risk of bias was evaluated using the Newcastle-Ottawa Scale and the quality of the evidence was also assessed. A meta-analysis was performed on the selected outcomes at the available follow-up time points. Subgroup analyses were conducted based on follow-up time, rate of progression and severity of periodontitis, and implant surface characteristics. Publication bias was evaluated using the Funnel plot and Egger's test. From 13 761 initial records, 14 studies (17 articles) were finally included. Eight studies had a low risk of bias level, and six had a medium risk of bias level. Meta-analysis showed that HP patients had a significantly greater risk for implant loss (HR: 1.75; 95% CI: 1.28-2.40; p = 0.0005; I2 = 0%), MBL (MD: 0.41 mm; 95% CI 0.19, 0.63; p = 0.0002; I2 = 54%), and peri-implantitis (3.24; 95% CI: 1.58-6.64; p = 0.001; I2 = 57%) compared to NHP, whereas no significant intergroup difference for peri-implant mucositis was found. Subgroup analyses revealed a particularly greater risk for implant loss for HP patients over a ≥ 10-year follow-up (HR: 2.02; 95% CI: 1.06-3.85; p = 0.03; I2 = 0%) and for patients with a history of grade C (formerly aggressive) periodontitis (HR: 6.16; 95% CI: 2.53-15.01; p < 0.0001; I2 = 0%). A greater risk for implant loss for stages III-IV (severe) periodontitis, and implants with rough surfaces was also found. Within the limits of heterogeneous case definitions and methods of assessment, a history of periodontitis has been proved to significantly increase the risk for implant loss, particularly at long follow-up (≥ 10 years) and in case of rapidly progressive forms (grade C), and for MBL and peri-implantitis.

MEDIA FRAMING OF TECHNOLOGICAL ADVANCEMENT AND HUMAN RIGHTS TO SAUDI ARABIA'S NEOM PROJECT

This research examines how Asharq al-Awsat and ALQST media framed the NEOM infrastructure project in Saudi Arabia. NEOM is a futuristic city project that is part of Saudi Arabia's Vision 2030. The project is designed to be the center of technological innovation, environmental sustainability, and economic development in the northwestern region of Saudi Arabia. It also explores the framing tools used and their impact on public perception and global outlook. This research uses a qualitative approach with Gamson and Modigliani’s framing analysis. The results show that Asharq al-Awsat tends to frames the NEOM project as a form of technological progress and innovation that provides economic benefits. Meanwhile, ALQST highlights the negative impacts such as human rights violations and environmental damage. These framing differences affected public perception and political discourse regarding the project. This research expands the understanding of how the media frames large infrastructure projects in the Middle East region. In addition, it reveals the implications of framing for public perception and international policy regarding infrastructure projects and human rights.

Experimental and statistical methods for microrheological characterization of heterogeneity in human respiratory mucus mimics of health and disease progression

Human respiratory mucus (HRM) is extremely soft, compelling passive microrheology for linear viscoelastic characterization. We focus this study on the use of passive microrheology to characterize HRM heterogeneity, a phenomenon in normal HRM that becomes extreme during cystic fibrosis (CF) disease. Specifically, a fraction of the mucin polymers comprising HRM phase-separate into insoluble structures, called flakes, dispersed in mucin-depleted solution. We first reconstitute HRM samples to the MUC5B:MUC5AC mucin ratios consistent with normal and CF clinical samples, which we show recapitulate progressive flake formation and heterogeneity. We then employ passive particle tracking with 200 nm and 1 μm diameter beads in each reconstituted sample. To robustly analyze the tracking data, we introduce statistical denoising methods for low signal-to-noise tracking data within flakes, tested and verified using model-generated synthetic data. These statistical methods provide a fractional Brownian motion classifier of all successfully denoised, tracked beads in flakes and the dilute solution. From the ensemble of classifier data, per bead diameter and mucus sample, we then employ clustering methods to learn and infer multiple levels of heterogeneity: (i) tracked bead data within vs. outside flakes and (ii) within-flake data buried within or distinguishable from the experimental noise floor. Simulated data consistent with experimental data (within and outside flakes) are used to explore form(s) of the generalized Stokes–Einstein relation (GSER) that recover the dynamic moduli of homogeneous and heterogeneous truth sets of purely flakelike, dilute solution, and mixture samples. The appropriate form of GSER is applied to experimental data to show (i) flakes are heterogeneous with gel and sol domains; (ii) dilute solutions are heterogeneous with only sol domains; and (iii) flake and dilute solution properties vary with probe diameter.

GIANT CELL MYOCARDITIS: AUTOPSY CONFIRMATION OF A DIAGNOSTIC DILEMMA - A RARE CASE REPORT

Abstract Introduction/Objective Giant cell myocarditis (GCM) is a rare and rapidly progressive form of myocarditis, commonly leading to fulminant heart failure (HF), refractory ventricular arrhythmias or conduction system abnormalities and carrying a high mortality rate without prompt treatment. Due to its rarity, there is limited data on its prevalence, although studies show an incidence of 0.007–0.053% among autopsied cases. This entity primarily affects the heart, exhibiting a rapid clinical course and a poor prognosis necessitating immunosuppressive therapy and, in most instances, heart transplantation to improve survival rates. Methods/Case Report We present a case of a 62-year-old male with a prior history of complete heart block status post permanent pacemaker placement, presenting with acute decompensated heart failure. Laboratory investigations revealed elevated cardiac troponin levels (&amp;gt;35000) with echocardiography showing a reduced ejection fraction of 25% and an initial diagnosis of non-ST elevation myocardial infarction (NSTEMI) was made. Endomyocardial biopsy revealed GCM. Despite aggressive management, including immunosuppressive therapy and mechanical circulatory support, his condition deteriorated rapidly, leading to multiorgan failure and eventual death. The diagnosis was confirmed on autopsy. The diagnostic challenge of GCM lies in its clinical or pathologic overlap with other myocardial disorders such as cardiac sarcoidosis, viral myocarditis, and cardiac amyloidosis. Endomyocardial biopsy (EMB) remains the gold standard for diagnosing this entity which is characterized by a widespread inflammatory cell infiltrate with multinucleated giant cells in association with myocyte damage. The etiology of GCM remains unclear, but it is believed to be immune-mediated, possibly triggered by an autoimmune response. Results (if a Case Study enter NA) NA Conclusion Pathologists should give importance to consider GCM in the differential diagnosis of patients presenting with acute heart failure refractory to standard therapy. Early recognition and prompt initiation of immunosuppressive therapy are crucial for improving outcomes in patients with GCM. Awareness of this entity is crucial to make a timely diagnosis.

Probing Surface-Mediated Electronic Coupling in Flat Hexagonal Phosphorus Nanostructures and Monolayer on Au(111).

Due to its diverse allotropes and intriguing properties, 2D phosphorus, also known as phosphorene, is a material of great interest. Here, the successful growth of flat hexagonal 2D phosphorus on Au(111) is reported. Starting from phosphorus linear chains at low coverage, a porous network and finally an extended 2D flat hexagonal (HexP) layer while increasing phosphorus deposition is formed. Using scanning tunneling microscopy/spectroscopy combined with ab initio calculations, the structure and electronic properties of the as-grown phosphorus structures are followed. The progressive formation of a phosphorus electronic band in the conduction band region is followed. More strikingly, a partial flatband that appears only on the HexP phase characterized by a sharp peak in the electronic spectrum is observed. These bands arise from the hybridization of phosphorus and gold atoms. This novel phosphorus-based structure exhibits remarkable electronic properties due to gold mediated phosphorus-phosphorus electronic coupling. This work paves the way for new interface material developments with attractive electronicproperties.

Investigating the Dynamics of a Soft Crystalline Covalent Organic Framework during Benzene and Cyclohexane Adsorption by in situ Powder X‐ray Diffraction

Due to their similar boiling points, separation of benzene and cyclohexane mixtures is among the current challenging processes faced by the petrochemical industry. As recently assessed, the soft imine‐based covalent organic framework [(TAM)(BDA)2] (COF‐300; TAM = tetrakis(4‐aminophenyl)methane, BDA = terephthaldehyde) possesses higher affinity for benzene than cyclohexane in both static conditions at 298 K and dynamic conditions in the range of 298–348 K. As shown in this contribution, in situ powder X‐ray diffraction while dosing benzene and cyclohexane vapors in the range of 0.01–4.74 bar on the narrow‐pore form of COF‐300 confirmed the coherent switchability of its framework, unveiling the progressive formation of different intermediate‐ and large‐pore forms. In addition, a basket of otherwise inaccessible key crystallochemical details—“on/off” structural‐feature changes cooperating to adsorption, primary adsorption sites, and host–guest and guest–guest interactions—was successfully retrieved. Overall, these findings allowed to shed light on the framework dynamics underneath the previously observed selectivity toward benzene over cyclohexane, completing this case of study and providing relevant information for the design of new‐generation adsorbents for this applicative context.

Identification of hsa_circ_0018905 as a New Potential Biomarker for Multiple Sclerosis.

Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by early onset, for which the interaction of genetic and environmental factors is crucial. Dysregulation of the immune system as well as myelinization-de-myelinization has been shown to correlate with changes in RNA, including non-coding RNAs. Recently, circular RNAs (circRNAs) have emerged as a key player in the complex network of gene dysregulation associated with MS. Despite several efforts, the mechanisms driving circRNA regulation and dysregulation in MS still need to be properly elucidated. Here, we explore the panorama of circRNA expression in PBMCs purified from five newly diagnosed MS patients and five healthy controls (HCs) using the Arraystar Human circRNAs microarray. Experimental validation was then carried out in a validation cohort, and a possible correlation with disease severity was tested. We identified 64 differentially expressed circRNAs, 53 of which were downregulated in PBMCs purified from MS compared to the HCs. The discovery dataset was subsequently validated using qRT-PCR with an independent cohort of 20 RRMS patients and 20 HCs. We validated seven circRNAs differentially expressed in the RRMS group versus the HC group. hsa_circ_0000518, hsa_circ_0000517, hsa_circ_0000514, and hsa_circ_0000511 were significantly upregulated in the MS group, while hsa_circ_0018905, hsa_circ_0048764, and hsa_circ_0003445 were significantly downregulated; Among them, the expression level of hsa_circ_0018905 was significantly decreased in patients showing a higher level of disability and in progressive forms of MS. We described the circRNAs expression profile of PBMCs in newly diagnosed MS patients and proposed hsa_circ_0018905 as potential MS biomarker.

Ultrafast transient absorption spectra and kinetics of human blue cone visual pigment at room temperature

The ultrafast photochemical reaction mechanism, transient spectra, and transition kinetics of the human blue cone visual pigment have been recorded at room temperature. Ultrafast time-resolved absorption spectroscopy revealed the progressive formation and decay of several metastable photo-intermediates, corresponding to the Batho to Meta-II photo-intermediates previously observed with bovine rhodopsin and human green cone opsin, on the picosecond to millisecond timescales following pulsed excitation. The experimental data reveal several interesting similarities and differences between the photobleaching sequences of bovine rhodopsin, human green cone opsin, and human blue cone opsin. While Meta-II formation kinetics are comparable between bovine rhodopsin and blue cone opsin, the transition kinetics of earlier photo-intermediates and qualitative characteristics of the Meta-I to Meta-II transition are more similar for blue cone opsin and green cone opsin. Additionally, the blue cone photo-intermediate spectra exhibit a high degree of overlap with uniquely small spectral shifts. The observed variation in Meta-II formation kinetics between rod and cone visual pigments is explained based on key structural differences.

E-Presence Application Increases the Level of Health Personnel Discipline to Improve the Quality of Health Services in Hospitals (Systematic Review Paper)

ABSTRACT In the era of increasingly advanced digital technology development, the government in Indonesia uses the E-presence digital attendance application to make attendance easier for its health workers. The use of e-presence is a form of progress in information technology in government. It is necessary to research changes in the level of discipline of health workers in implementing E-presence so that it can improve the quality of service or even reduce the quality of service. Find out how the use of E-presence among health workers can improve work discipline and improve service quality. The research design in this article uses descriptive qualitative research with data originating from the results of systematic reviews from various relevant national journal sources. Articles were obtained from Google Scholar and PubMed with identification in 2023 via Google Scholar n=205 and PubMed n=80. National and International Articles. With the keywords "Digital E-Presence", "Discipline Level", "Service Quality", "Attendance", "Android", "QR Code", and "Discipline". Penelusuran artikel penelitian di tahun 2023 menggunakan kata kunci pada database (n=285). Dilakukan skrining berdasarkan kriteria inklusi dan ekslusi, dan menghasilkan 9 artikel penelitian yang layak sesuai dengan kriteria. This research has changed the motivation of health workers where the level of discipline of health workers has increased and their orientation towards achievement has also improved. The use of e-presence has the impact of increasing the quality of service in hospitals because health workers are present to serve patients on time. Keywords: Health Personnel, The Quality Of Health, Services In Hospitals

Identification of necroptosis genes and characterization of immune infiltration in non-alcoholic steatohepatitis

BackgroundThe most common progressive form of non-alcoholic fatty liver disease (NAFLD) is non-alcoholic steatohepatitis (NASH), which is characterized by the development of cirrhosis, and requires liver transplantation. We screened for the differentially expressed necroptosis-related genes in NASH in this study, and analyzed immune infiltration through microarray and bioinformatics analysis to identify potential biomarkers, and explore the molecular mechanisms involved in NASH.MethodsThe GSE24807 microarray dataset of NASH patients and healthy controls was downloaded, and we identified the differentially expressed genes (DEGs). Necroptosis-related differential genes (NRDEGs) were extracted from these DEGs, and functionally annotated by enrichment analyses. The core genes were obtained by constructing gene co-expression networks using weighted gene co-expression network analysis (WGCNA). Finally, the transcription factor (TF) regulatory network and the mRNA-miRNA network were constructed, and the infiltrating immune cell populations were analyzed with CIBERSORT.ResultsWe identified six necroptosis-related genes (CASP1, GLUL, PYCARD, IL33, SHARPIN, and IRF9), and they are potential diagnostic biomarkers for NASH. In particular, PYCARD is a potential biomarker for NAFLD progression. Analyses of immune infiltration showed that M2 macrophages, γδ T cells, and T follicular helper cells were associated with the immune microenvironment of NASH, which is possibly regulated by CASP1, IL33, and IRF9.ConclusionsWe identified six necroptosis-related genes in NASH, which are also potential diagnostic biomarkers. Our study provides new insights into the molecular mechanisms and immune microenvironment of NASH.

Effectiveness of Resmetirom in Reducing Cholesterol Levels in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) associated with metabolic syndrome and increased cardiovascular risk. Resmetirom, a novel liver-directed selective thyroid hormone receptor-β (THR-β) agonist, has shown promise in addressing both hepatic and systemic lipid metabolism. This systematic review and meta-analysis aimed to evaluate the efficacy of resmetirom in improving cholesterol levels in NASH patients. A systematic literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, andClinicalTrials.gov, identifying three randomized controlled trials for inclusion. The meta-analysis revealed that resmetirom significantly reduced low-density lipoprotein cholesterol (LDL-C) levels compared to placebo (MD: -23.62; 95% CI: -37.32 to -9.93; p < 0.001). Similarly, triglyceride (TG) levels showed a significant reduction in the resmetirom group (MD: -33.86; 95% CI: -47.79 to -19.92; p < 0.001). Importantly, there was no significant difference in the risk of serious adverse events between resmetirom and placebo groups (RR: 1.09; 95% CI: 0.73 to 1.63; p = 0.67). These findings suggest that resmetirom effectively improves lipid profiles in NASH patients without compromising safety. However, the analysis was limited by the small number of studies, all from the same research group, and high heterogeneity in results. Future research should include more diverse studies, longer follow-up periods, and cost-effectiveness evaluations. Despite these limitations, resmetirom shows promise as a potential treatment for managing dyslipidemia and cardiovascular risk in NASH patients, potentially influencing future treatment guidelines for both liver and cardiovascular health in this population.

Small-scale BLEVE: Near-field aerial shock overpressure and impulse

This paper presents an investigation into one of the most damaging hazards associated with Boiling Liquid Expanding Vapor Explosion (BLEVE), specifically focusing on the near-field overpressure and impulse effects. Experiments were conducted at a small-scale to study the overpressure and impulse using aluminum tubes with a diameter of 50 mm and a length of 300 mm. The tubes were filled with pure propane liquid and vapor. The controlled variables, in this work included the failure pressure, the liquid fill level, and the weakened length along the tube top. These variables control the strength of the overpressure characterized by the peak overpressure amplitude, duration of this overpressure event, and the resultant impulse. Notably, these experiments at a small scale included experiments with a 100 % liquid fill level. This further confirmed that the vapor space is the main driver of the lead overpressure hazard. High-speed cameras and blast gauges effectively illustrated the progressive formation of the shock wave in both temporal and spatial dimensions. Furthermore, various predictive models available in the literature are discussed in this paper and new correlations were developed to quantify the overpressure duration and impulse. The current analysis aims to predict the potential consequences of overpressure events during a BLEVE.

Picturing the Multiple Sclerosis Patient Journey: A Symptomatic Overview.

Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease's natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing-remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research.