Limited Proportion Research Articles

MGA loss-of-function variants cause premature ovarian insufficiency.

Although premature ovarian insufficiency (POI), a common cause of female infertility and subfertility, has a well-established hereditary component, the genetic factors currently implicated in POI account for only a limited proportion of cases. Here, using an exome-wide, gene-based case-control analysis in a discovery cohort comprising 1,027 POI cases and 2,733 ethnically matched women controls from China, we found that heterozygous loss-of-function (LoF) variants of MAX dimerization protein (MGA) were significantly enriched in the discovery cohort, accounting for 2.6% of POI cases, while no MGA LoF variants were found in the matched control females. Further exome screening was conducted in 4 additional POI cohorts (2 from China and 2 from the United States) for replication studies, and we identified heterozygous MGA LoF variants in 1.0%, 1.4%, 1.0%, and 1.0% of POI cases, respectively. Overall, a total of 37 distinct heterozygous MGA LoF variants were discovered in 38 POI cases, accounting for approximately 2.0% of the total 1,910 POI cases analyzed in this study. Accordingly, Mga+/- female mice were subfertile, exhibiting shorter reproductive lifespan and decreased follicle number compared with WT, mimicking the observed phenotype in humans. Our findings highlight the essential role of MGA deficiency for impaired female reproductive ability.

Diabetes, chronic respiratory and cardiovascular diseases in Germany and Europe (EHIS-3 Survey)

Abstract Background We examined the prevalence of major NCD groups (diabetes, chronic respiratory diseases (CRD) and cardiovascular diseases (CVD)) as well as self-rated health (SRH) and health-related limitation in everyday activities among those with one of these NCD in Germany and Europe (average of 28 European countries (EU-28)). Methods Data was derived from the European Health Interview Survey (EHIS-3, 2019/20). Health indicators were: self-reported diabetes, CRD and CVD in the past 12 months; SRH (very good/good vs. fair, bad, very bad) and health-related limitations in usual everyday activities for at least 6 months (severe/moderate vs. no limitation). Educational level was operationalized via ISCED-11. Analyses are age-standardized to the European Standard Population 2013. Results Prevalence of major NCD in Germany were statistically significantly higher than in the EU-28: diabetes 8.1% vs. 7.1%, CRD 11.2% vs. 7.9% and CVD 6.6% vs. 5.4%. Highest prevalence was observed in the lowest educational group and lowest prevalence in the highest educational group for all of these NCD in Germany as well as in the EU-28. The proportion of a very good/good SRH among people having one of these NCD was higher in Germany compared to the EU-28: for people with diabetes 35.8% vs. 31.0%, with CRD 45.6% vs. 42.9% and with CVD 25.3% vs.19.1%. The proportion of health-related limitations among those having at least one of these NCD varied according to educational level in Germany as well as in the EU-28 with a higher prevalence among people with low educational level compared to high. Conclusions Even though prevalence of these NCD were higher in Germany, a higher proportion of very good/good SRH for people with one of these NCD was observed compared to the EU-28. Many factors such as severity of disease, disease management and care could explain this difference. Social inequalities were present not only in the prevalence of NCD but also in health-related limitations in Germany and Europe. Key messages • Prevalence of self-reported major NCD were higher in Germany while self-rated health among people having NCD was better than in Europe. • Health equity interventions in Germany and Europe are necessary.

Body composition derangements in lung cancer patients treated with first-line pembrolizumab: A multicentre observational study.

While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC. A retrospective review of consecutive patients with treatment-naïve NSCLC and PD-L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre-treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre-established cut-offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival and overall survival (PFS and OS), compared through the log-rank test and the Cox proportional hazards model. Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69years (range 36-85), with a median follow-up of 12months (range 1-131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m2. Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co-morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46-12.6, P<0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22-2.83, P=0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P<0.0001 and 30.7% vs. 73.2%, P<0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co-morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60-4.66, P<0.0001; sarcopenia: aHR 2.24, 95% CI 1.37-3.67, P=0.001; IMAT depot: aHR 2.26, 95% 1.40-3.63, P=0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96-6.01, P<0.0001; sarcopenia: aHR 4.68, 95% CI 2.44-8.99, P<0.0001; IMAT depot: aHR 3.18, 95% 1.72-5.88, P<0.0001). Skeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers.

The Effect of Medicaid Expansion on Access to Anti-incontinence Surgery

Importance Medicaid expansion broadened access to care; however, limited data about the effect on access to anti-incontinence surgical procedures exist. Objective Since the Affordable Care Act (ACA) Medicaid expansion in 2014, some regions have had more states adopt expansion (NE—Northeast, W—West) than other regions (S—South, MW—Midwest). We aimed to determine if the proportion of Medicaid funded anti-incontinence procedures increased after Medicaid expansion and whether increases were different by U.S. region. Study Design This was a retrospective cohort study. Results The 2012–2018 Healthcare Cost and Utilization Project National Inpatient Sample was reviewed for anti-incontinence surgical procedures. Medicaid supported surgical procedures were compared by region and year, and among marginalized populations. During the study period 66,510 surgical procedures were performed. Medicaid as a primary payer for anti-incontinence procedures increased from 10% to 12% (P = &lt;0.001) between 2012 and 2018. The percentage of Medicaid supported procedures performed in the NE (13%) and W (17%) were greater than MW (9%) and S (8%). Procedures among Black, Hispanic or lowest income quartile patients were lowest in the S and did not increase after expansion during the study period (2012 vs 2018, all P = NS). When controlling for confounders, the MW (odds ratio [OR] 0.58; 95% CI 0.46–0.74) and S (OR 0.33; 95% CI 0.26–0.42) were less likely to have Medicaid covered surgical procedures compared to the NE and W (OR 1.04; 95% CI 0.84–1.29). Conclusions Nationally, the percentage of Medicaid-supported anti-incontinence procedures increased after expansion. Northeast and W access to procedures increased, and access by marginalized populations broadened, while the S and MW had the most limited proportion of anti-incontinence surgical procedures covered by Medicaid.

Identifying groundwater characteristics and controlling factors in Jiaozhou Bay’s northern coastal region, China: a combined approach of multivariate statistics, isotope analysis, and field empirical investigations

Explicit identification of hydrochemical processes and their controlling factors within groundwater systems is critical for the sustainable utilization of water resources in coastal urban areas. This study was undertaken in the North Coastal Region of Jiaozhou Bay (NCRJB), located in the eastern part of Shandong Province, China, an area grappling with significant issues of groundwater quality degradation and water scarcity. A total of 105 groundwater samples and 34 surface water samples, collected from 2020 to 2024, were analyzed and studied using various hydrogeological tools, multivariate statistical analyses, and water quality assessment methods. These include the Piper diagram, hydrochemical facies evolution diagram (HFE-D), Principal Components Analysis (PCA), correlation analysis, stable isotope analysis, Water Quality Index (WQI), and USSL diagrams. The results indicated that all surface water and pore groundwater samples were categorized as Na-Cl type, exhibiting high Total Dissolved Solids (TDS) and Electrical Conductivity (EC) values, characteristics that render them poor to unsuitable for drinking and irrigation purposes. The fracture groundwater is predominantly of the Ca-Na-Cl mixed type, with average suitability for irrigation and a limited proportion (22.5%) deemed suitable for drinking. Seawater intrusion, primarily through the surface water system, and the impact of human activities were identified as the predominant controlling factors con-tributing to the degradation of the local groundwater environment. Field empirical investigations further validated the results derived from hydrogeological assessments, multivariate statistical analyses, and isotopic approaches. The long-term shifts in hydrochemical properties, along with the latent threat of seawater intrusion, exhibit an upward trend during the dry season and show a certain degree of mitigation during the wet season. This study highlights that field investigations, in conjunction with hydrochemical tools, multivariate statistical analyses, and stable isotope analysis, can successfully furnish reliable insights into the predominant mechanisms governing regional groundwater evolution within the context of long-term and intricate envi-ronmental settings.

Stand age-related effects of mangrove on archaeal methanogenesis in sediments: Community assembly and co-occurrence patterns

Mangrove sediment is a key source of methane emissions; however, archaea community structure dynamics and methanogenesis activities during long-term mangrove restoration remain unclear. In this study, microcosm incubations revealed a substantial reduction in microbial-mediated methane production potential from mangrove sediments with increasing stand age; methane production rates decreased from 0.42 ng g−1 d−1 in 6-year-old stands to 0.23 ng g−1 d−1 in 64-year-old stands. High-throughput sequencing revealed a reduction in community diversity because of specific microorganism colonization and species loss, notably a decline in the relative abundance of Bathyarchaeia in sediments of 64-year-old stands. In addition, mangrove sediments, especially those in older stands (20- and 64-year-old), had more complex and stable co-occurrence microbial networks than mudflats. Furthermore, archaea community assembly in older stands was dominated by stochastic processes wherein dispersal limitation was prominent, and that in younger stands (6- and 12-year-old) was driven by deterministic processes. The proportion of dispersal limitation of Bathyarchaeia and traditional methanogens in sediment decreased with an increase in stand age. Quantitative polymerase chain reaction analysis confirmed a decrease in Bathyarchaeia (from 3.50 to 0.54 copies g−1) and mcrA gene (from 3.83 to 0.25 copies g−1) abundance in mangrove sediments with an increase in stand age. These findings demonstrate the critical role of Bathyarchaeia in methanogenesis; the decline in microbial interactions and abundance, and the reduced proportion of dispersal limitation of Bathyarchaeia and traditional methanogens collectively contributed to the mitigation of microbial-mediated methane production potential in older mangrove stands.

Trends in the development of micro and small enterprises and the challenges of TVET programs in Ethiopia: Implication for curriculum development

This study aimed to examine the development trends of micro and small enterprises and the challenges of Technical and Vocational Education and Training (TVET) interventions in Ethiopia, focusing on Bahir Dar City. For this purpose, a mixed methods research approach involving both quantitative and qualitative data from archives and interviews with officers, trainers, and enterprise owners was employed. The results of the study revealed an increase in enterprise enrollment from 2008 to 2021. However, the overall development progress remained notably low, as indicated by the limited proportions of enterprises reaching maturity stages. Moreover, the planning and implementation of TVET programs were found to be misaligned with the needs of various employment sectors, primarily due to lack of occupational standards, inadequacies in trainer availability, and deficiencies in skills and resources. This study proposed strategies to improve current performance and to address systemic challenges sustainably, including training on curriculum development.

Allogeneic hematopoietic cell transplantation from alternative donors in acute myeloid leukemia.

Allogeneic hematopoietic cell transplantation (HCT) potentially provides a cure for patients with acute myeloid leukemia (AML) who are unlikely to be cured with chemotherapy alone. Previously, human leukocyte antigen (HLA)-matched related donors were used exclusively, which made the procedure available for a limited proportion of patients. The introduction of high-resolution HLA-typing technology, innovations in immunosuppressive therapy, and improved supportive care measures have significantly changed the situation. Now, patients without a matched related donor have an ample opportunity to receive allogeneic HCT with the use of matched or mismatched unrelated donors, umbilical cord blood grafts, or haploidentical related donors. The outcomes of alternative donor transplantations have improved over the past decades, and the growth of unrelated donor registries as well as the donor diversification have enhanced the chance of finding a suitable donor. With multiple alternative donor choices available for most patients, the donor selection is becoming increasingly important. To discuss the optimal donor choice in case of unavailability of an HLA-matched related donor, this article reviews the existing literature of retrospective and prospective comparisons of different alternative donor transplantations in AML and discusses the current state-of-art modalities in allogeneic HCT using alternative donors.

Towards Equitable Representations of Ageing: Evaluation of Gender, Territories, Aids and Artificial Intelligence

There are few studies on the representation of older people regarding aids and assistive devices and even fewer that incorporate more inclusive views (gender, emotions, anti-ageist, territorial or land approach) as well as virtual or land ethnography or artificial intelligence. The general objective was to evaluate digital images of aids and assistive aids in the older population, from the perspectives mentioned above. Method. A descriptive and cross-sectional study that searched, observed and analyzed images. An evaluation of intentionally selected images from Freepik, Pixabay, Storyblocks, Splitshire, Gratisography and ArtGPT, included in an original database constructured by several authors of this article, was carried out in the context of the ENCAGEn-CM project (2020–2023, financed by the CAM and FSE). This base was updated and expanded in October and November 2023. In addition, an image generation process was carried out using artificial intelligence, and this was also part of the analysis (ArtGPT). Finally, algorithms were used to solve and retrain with the images. Results. Of the total final images included in the expanded database until November 2023 (n = 427), only a third (28.3%, 121/427) included the aids and assistive aids label. Representations of mixed groups predominated (38.8%) and, to a lesser extent, those of women. A large proportion of the devices were ‘glasses’ (74.6%) and the ‘use of a cane’ (14.9%). To a lesser extent, ‘wheelchairs’ (4.4%) or ‘hearing aids’ (0.9%) and the presence of more than one device (simultaneously) (5.3%) were noted. The main emotions represented were ‘joy’ (45.6%) and ‘emotion not recognized’ (45.6%), with, to a lesser extent, ‘sadness’ (3.5%), ‘surprise’ (4.4%) and ‘anger’ (0.9%). Differences by sex were found in the represented emotions linked to aids and assistive aids. The representation of images of the built environment predominated significantly (70.2%), and it was observed that older women were less represented in natural environments than men. Based on the previous findings, a method is proposed to address stereotypes in images of older individuals. It involves identifying common stereotypical features, like glasses and hospital settings, using deep learning and quantum computing techniques. A convolutional neural network identifies and suppresses these elements, followed by the use of quantum algorithms to manipulate features. This systematic approach aims to mitigate biases and enhance the accuracy in representing older people in digital imagery. Conclusion. A limited proportion of images of assistive devices and older people were observed. Furthermore, among them, the lower representation of images of women in a built environment was confirmed, and the expressions of emotions were limited to only three basic ones (joy, sadness and surprise). In these evaluated digital images, the collective imagination of older people continues to be limited to a few spaces/contexts and emotions and is stereotyped regarding the same variables (sex, age, environment). Technology often overlooks innovative support tools for older adults, and AI struggles in accurately depicting emotions and environments in digital images. There is a pressing need for thorough pretraining analysis and ethical considerations to address these challenges and ensure more accurate and inclusive representations of older persons in digital media.

A scoping review of the graduate outcome literature

Higher education (HE) policymaking is increasingly concerned with graduate outcomes. Policies often use narrow economic metrics, such as employment rates and salaries, to set strategic goals for HE and assess `value for money´. Despite this policy relevance, little attempt has been made to assess the academic literature in this area. The field’s strengths and weaknesses, areas of focus and level of criticality are unknown, leaving us unable to judge its ability to inform policy. This paper addresses this gap using a novel two-phase scoping review method. Phase 1 assesses literature that explicitly uses the term `graduate outcome´, finding a field that is largely fragmented into subfields. Phase 2 then performs a series of `top-level´ scoping reviews on each sub-field and combines them to assess the `overall´ literature. This `overall´ literature is found to share HE policy’s focus on economic graduate outcomes. While several well-developed non-economic subfields exist, such as critical thinking and lifelong learning, these are comparatively small. A limited proportion of the literature considers issues of inequality and other `critical´ topics. If research is to better inform policy in this area, it would be beneficial to develop a broader and more critical research programme.

The octapeptide-repeat surface protein of Entamoeba nuttalli is a novel virulence factor that promotes adherence to host cells

Entamoeba nuttalli is genetically the closest to Entamoeba histolytica, the causative agent of human amebiasis, and its natural host is Macaca species. A unique E. nuttalli specific surface protein (PTORS) containing 42 repeats of octapeptide was identified by comparative genomic analysis of Entamoeba species. We aimed to elucidate the function of this protein. When trophozoites from various E. nuttalli strains were examined by immunofluorescence microscopy and flow cytometry using a PTORS-specific monoclonal antibody, only a limited proportion of trophozoites were stained, indicating that the protein was not commonly expressed in all E. nuttalli trophozoite. The proportion of trophozoites expressing PTORS increased after passage in hamster livers, suggesting that the protein functions in the virulence of trophozoites in the liver tissue. Single-cell analysis revealed that in the cluster including trophozoites with PTORS gene expression, genes of virulence-related proteins were also upregulated. Trophozoites of E. histolytica transfected with PTORS showed enhanced adherence and subsequent phagocytic activity towards human Jurkat cells, independent of the lectin. E. histolytica trophozoites expressing PTORS formed larger liver abscesses in hamsters. These results demonstrate that PTORS is a novel virulence factor in Entamoeba species.

Inhomogeneous deformation behavior and recrystallization mechanism of Mg-Gd-Y-Zn-Zr alloy containing only intragranular lamellar LPSO phase

Inhomogeneous plastic deformation and recrystallization behavior of Mg-Gd-Y-Zn-Zr alloy containing only intragranular lamellar long-period stacking ordered (LPSO) phase were investigated by isothermal compression experiments at the temperatures of 350–450 °C, and the strain rates of 0.001 ∼ 10 s−1. Results showed that Mg-Gd-Y-Zn-Zr alloys with varying degrees of bimodal structures were obtained after compression. The lamellar LPSO phase directions in residual coarse grains were aligned in the radial direction (RD). Dynamic recrystallization (DRX) grains induced at grain boundaries, kinked bands, and lamellar shearing regions during compression synergistically promoted coarse grain refinement. Moreover, the condition of high temperature and medium strain rate (450 °C-0.1 s−1) contributed to the uniform extension of "mantle layers" of fine DRX grains. In contrast, the condition of medium temperature and high strain rate (400 °C-10 s−1) could accelerate the deflection of CD-directed (compression direction) LPSO lamellae and the formation of local high-energy regions, facilitating the generation of recrystallization band. In addition, a high strain rate (400 °C-10 s−1) is more conducive to the formation of a heavily bimodal structure than a high temperature (450 °C-0.1 s−1). Only a larger spacing of LPSO lamellae (∼1.4 μm) could meet the spatial requirements of recrystallization. Further analysis revealed that the continuous dynamic recrystallization (CDRX) mechanism characterized by the expansion of "mantle layers" and nucleation along kinked boundaries and lamellar shearing regions was the primary grain refinement mechanism. The discontinuous dynamic recrystallization (DDRX) mechanism only exhibited a limited role due to the inhibition of the highly dense lamellar LPSO phase on grain boundaries bulging. After compression, the orientation of residual coarse grains gradually deviated toward the CD. While the recrystallization with limited proportion and random orientation cannot significantly weaken the basal texture.

The Influence of Diabetes on Thrombotic Profiles and Outcomes on Patients with Peripheral Artery Disease

BackgroundElevated glycated hemoglobin (HbA1c) is associated with vascular complications, including arterial thrombosis post-revascularization. However, the objective relationship between levels of HbA1c and coagulation profiles has not been established. This study aims to determine the association between specific coagulation parameters and variations in HbA1c in patients undergoing lower extremity revascularization. MethodsPatients with Peripheral Artery Disease (PAD) undergoing revascularization were prospectively evaluated between December 2020 and July 2023. Patients were categorized based on their HbA1c levels, and their thromboelastography with platelet mapping (TEG-PM) results were compared at baseline, post-operatively day 1, 1 month, 3 months and 6 months. The parameters included Maximum Amplitude (MA) with both adenosine diphosphate (ADP) and arachidonic acid (AA), as well as ADP and AA percent aggregation indicating clot strength. The study further assessed the differences in these parameters between groups with varying HbA1c levels through the use of unpaired Student t test for pairwise analysis and Mann-Whitney U tests. ResultsAmong 830 samples, those with HbA1c above 6.5 demonstrated a significant increase in ADP MA (52.6 vs. 43.5, p<0.01), AA MA (36.6 vs. 29.65, p<0.05), clot strength without platelets ActF MA (activator F: 13.10 vs. 10.80, p<0.01), and heparin neutralized uninhibited clot strength from thrombin activation HKH MA (heparinized kaolin with heparinase: 61.10 vs. 57.70, p<0.01) values at baseline. Post-operatively, patients with HbA1c levels greater than 6.5 had higher median functional fibrinogen CFF FLEV levels (citrated functional fibrinogen: 40.95 vs. 371.35, p<0.05) and higher formation of fibrin in response to stimulation of thrombin by tissue factor CFF MA values (22.90 vs. 20.40, p<0.05) when measured within 36 hours of intervention, with these trends staying consistent during the 1-month follow-up visit. The trend analysis revealed a progressive increase in ADP MA values with rising HbA1c values, indicating a unit increase in the thrombotic risk relationship. Regression analysis showed a positive relationship between HbA1c and both ADP MA (a 2.261 unit increase for each unit increase in HbA1c) and AA MA. The R-square values indicate that HbA1c only explains a small percentage of the variance in these parameters, suggesting the confounding influence of other factors contributing to thrombosis. ConclusionElevated HbA1c levels appear to be associated with pro-thrombotic tendencies in clot dynamics as measured by TEG-PM, particularly in parameters related to platelet function. HbA1c explains a limited proportion of the variability in these measures, emphasizing the need for a comprehensive approach to evaluating clotting profiles in patients. This study lays the groundwork for further investigation into personalized antithrombotic strategies for patients with varying HbA1c levels.

Exploring Selenoprotein P in Liver Cancer: Advanced Statistical Analysis and Machine Learning Approaches.

Selenoprotein P (SELENOP) acts as a crucial mediator, distributing selenium from the liver to other tissues within the body. Despite its established role in selenium metabolism, the specific functions of SELENOP in the development of liver cancer remain enigmatic. This study aims to unravel SELENOP's associations in hepatocellular carcinoma (HCC) by scrutinizing its expression in correlation with disease characteristics and investigating links to hormonal and lipid/triglyceride metabolism biomarkers as well as its potential as a prognosticator for overall survival and predictor of hypoxia. SELENOP mRNA expression was analyzed in 372 HCC patients sourced from The Cancer Genome Atlas (TCGA), utilizing statistical methodologies in R programming and machine learning techniques in Python. SELENOP expression significantly varied across HCC grades (p < 0.000001) and among racial groups (p = 0.0246), with lower levels in higher grades and Asian individuals, respectively. Gender significantly influenced SELENOP expression (p < 0.000001), with females showing lower altered expression compared to males. Notably, the Spearman correlation revealed strong positive connections of SELENOP with hormonal markers (AR, ESR1, THRB) and key lipid/triglyceride metabolism markers (PPARA, APOC3, APOA5). Regarding prognosis, SELENOP showed a significant association with overall survival (p = 0.0142) but explained only a limited proportion of variability (~10%). Machine learning suggested its potential as a predictive biomarker for hypoxia, explaining approximately 18.89% of the variance in hypoxia scores. Future directions include validating SELENOP's prognostic and diagnostic value in serum for personalized HCC treatment. Large-scale prospective studies correlating serum SELENOP levels with patient outcomes are essential, along with integrating them with clinical parameters for enhanced prognostic accuracy and tailored therapeutic strategies.

Alcohol-associated liver disease: Emerging therapeutic strategies.

The large and growing burden of alcohol-associated liver disease-and the considerable burden of morbidity and mortality associated with it-has been a drive toward ongoing research into novel strategies for its treatment, with a particular focus upon alcohol-associated hepatitis (AH). Management of alcohol-use disorder forms the central pillar of alcohol-associated liver disease care, with evidence-based psychological and pharmacological approaches being well established, and certain models demonstrating improved clinical outcomes when hepatology and addiction services are co-located. Corticosteroids have previously been used somewhat indiscriminately in patients with severe AH, but effective tools now exist to assess early response (and limit futile ongoing exposure). Techniques to predict risk of corticosteroid-related infection are also available, although current clinical strategies to mitigate this risk are limited. A variety of novel therapeutic approaches to AH are at different phases of trials and evidence gathering, with some of the most promising signals related to cytokine manipulation, epigenetic modulation, and targeting of the gut microbiota (ie, by means of fecal microbiota transplant). While remaining an ongoing source of debate, early liver transplant in severe AH has grown in interest and acceptability over the past decade as evidence supporting its efficacy builds, in the process challenging paradigms about mandatory pretransplant sobriety periods. However, uncertainty remains regarding the optimal selection criteria, and whether liver transplant has a role for only a highly limited proportion of patients with AH or more widespread application. This review aims to provide an overview of this fast-moving field.

Exploring Multicomponent Phase Space to Discover New Materials

Multicomponent phase space has been shown to consist of an enormous number of materials with different compositions, the vast majority of which have never been made or investigated, with great potential, therefore, for the discovery of exciting new materials with valuable properties. At the same time, however, the enormous size of multicomponent phase space makes it far from straightforward to identify suitable strategies for exploring the plethora of potential material compositions and difficult, therefore, to be successful in discovering desirable new materials. Unfortunately, all our knowhow and understanding has been developed for materials with relatively few components in relatively limited proportions, with most of our scientific theories relying essentially on linear assumptions of component dilution and independence that no longer apply in concentrated multicomponent materials. Trial and error, controlled substitution, parameterisation, thermodynamic modelling, atomistic modelling and machine learning techniques have all been employed as methods of exploring multicomponent phase space, with varying levels of success, but ultimately none of these techniques has proved capable of delivering consistent or guaranteed results. This paper provides an overview of the different techniques that have been used to explore multicomponent phase space, indicates their main advantages and disadvantages, and describes some of their successes and failures.

The Fenice project to evaluate and improve the quality of healthcare in high-dependency care units: results after the first year.

High-Dependency care Units (HDUs) have been introduced worldwide as intermediate wards between Intensive Care Units (ICUs) and general wards. Performing a comparative assessment of the quality of care in HDU is challenging because there are no uniform standards and heterogeneity among centers is wide. The Fenice network promoted a prospective cohort study to assess the quality of care provided by HDUs in Italy. This work aims at describing the structural characteristics and admitted patients of Italian HDUs. All Italian HDUs affiliated to emergency departments were eligible to participate in the study. Participating centers reported detailed structural information and prospectively collected data on all admitted adult patients. Patients' data are presented overall and analyzed to evaluate the heterogeneity across the participating centers. A total of 12 HDUs participated in the study and enrolled 3670 patients. Patients were aged 68years on average, had multiple comorbidities and were on major chronic therapies. Several admitted patients had at least one organ failure (39%). Mortality in HDU was 8.4%, raising to 16.6% in hospital. While most patients were transferred to general wards, a small proportion required ICU transfer (3.9%) and a large group was discharged directly home from the HDU (31%). The expertise of HDUs in managing complex and fragile patients is supported by both the available equipment and the characteristics of admitted patients. The limited proportion of patients transferred to ICUs supports the hypothesis of preventing of ICU admissions. The heterogeneity of HDU admissions requires further research to define meaningful patients' outcomes to be used by quality-of-care assessment programs.

Giving loss a personal course: Universal loss reweighting to improve stereo matching via uncertainty guidance

Although learning-based stereo matching methods have achieved remarkable performance, accurately recovering disparity maps for boundary areas (e.g., thin structures) remains an intractable issue. Existing stereo pipelines usually employ the standard L1 loss function, averaging pixel-wise losses equally despite variable difficulty. This mechanism inevitably overwhelms thin structures due to their limited proportion. In this paper, we propose reweighting the L1 loss to focus on pixels of varying hardness. First, we explicitly model the uncertainty of each pixel to gauge the confidence in its prediction. By aggregating the volume, uncertainty is obtained effortlessly. Second, uncertainty is mapped to weights, which reweight the L1 loss accordingly. The core of our approach lies in leveraging uncertainty to personalize the loss map adjustment, progressively optimizing challenging regions during training. Notably, our method requires no extra parameters or inference computations. Finally, we introduce the Boundary Pixel Error (BPE), a novel metric targeting boundary quality. Extensive experiments with the SceneFlow, KITTI 2012, and KITTI 2015 datasets demonstrate the effectiveness and universality of our elegant framework, seamlessly integrating it into existing models as a plug-and-play component, leading to substantial performance improvements.

Enhancing Small Object Detection in Aerial Images: A Novel Approach with PCSG Model

Generalized target detection algorithms perform well for large- and medium-sized targets but struggle with small ones. However, with the growing importance of aerial images in urban transportation and environmental monitoring, detecting small targets in such imagery has been a promising research hotspot. The challenge in small object detection lies in the limited pixel proportion and the complexity of feature extraction. Moreover, current mainstream detection algorithms tend to be overly complex, leading to structural redundancy for small objects. To cope with these challenges, this paper recommends the PCSG model based on yolov5, which optimizes both the detection head and backbone networks. (1) An enhanced detection header is introduced, featuring a new structure that enhances the feature pyramid network and the path aggregation network. This enhancement bolsters the model’s shallow feature reuse capability and introduces a dedicated detection layer for smaller objects. Additionally, redundant structures in the network are pruned, and the lightweight and versatile upsampling operator CARAFE is used to optimize the upsampling algorithm. (2) The paper proposes the module named SPD-Conv to replace the strided convolution operation and pooling structures in yolov5, thereby enhancing the backbone’s feature extraction capability. Furthermore, Ghost convolution is utilized to optimize the parameter count, ensuring that the backbone meets the real-time needs of aerial image detection. The experimental results from the RSOD dataset show that the PCSG model exhibits superior detection performance. The value of mAP increases from 97.1% to 97.8%, while the number of model parameters decreases by 22.3%, from 1,761,871 to 1,368,823. These findings unequivocally highlight the effectiveness of this approach.

Fully exposed copper single-atom sites on mesoporous N/S-codoped graphene for efficient zinc-air battery

Transition metal single-atom catalysts are recently emerging as the most potential candidates for the oxygen reduction reaction due to their remarkable activity and durability, yet subjected to limited availability proportion of active sites to reactant in practice due to the lack of favorable morphology. Herein, the ultrathin mesoporous N/S-codoped graphene is fabricated by a potassium thiocyanate (KSCN) assisted pyrolysis of metal-organic framework (ZIF-8) as the robust substrate for anchoring copper single-atom sites. The KSCN-assisted pyrolysis can not only create N and S coordination atoms but also regulate the fully exposed morphology. The graphene-supported copper single-atom catalysts (g-Cu-SACs) show typical mesoporous structure with larger surface area of 1612 m2 g–1. Spectral and microscopy results reveal highly isolated Cu single-atom sites on mesoporous graphene with unsymmetrical Cu-S1N3 structure. Theoretical analysis demonstrated that the asymmetric coordination environment effectively enhanced O2 adsorption and facilitated the ORR performance. The g-Cu-SACs show excellent catalytic activity in alkaline oxygen reduction reaction with a half-wave potential of 0.920 VRHE and good cycling stability, which are superior to that of three-dimensional copper single-atom catalysts (Cu-SACs, supported by N/S-codoped carbon framework directly derived from ZIF-8). Furthermore, the zinc-air battery assembled with g-Cu-SACs also exhibits high specific capacity and remarkable cycling lifetime. This work provides a novel strategy to construct highly exposed single-atom catalysts for energy-related applications.