Enhancing Liver Transplant Outcomes through Liver Precooling to Mitigate Inflammatory Response and Protect Mitochondrial Function.

Transplanted organs experience several episodes of ischemia and ischemia-reperfusion. The graft injury resulting from ischemia-reperfusion (IRI) remains a significant obstacle to the successful survival of transplanted grafts. Temperature significantly influences cellular metabolic rates because biochemical reactions are highly sensitive to temperature changes. Consequently, lowering the temperature could reduce the degradative reactions triggered by ischemia. In mitigating IRI in liver grafts, the potential protective effect of localized hypothermia on the liver prior to blood flow obstruction has yet to be explored. In this study, we applied local hypothermia to mouse donor livers for a specific duration before stopping blood flow to liver lobes, a procedure called "liver precooling". Mouse donor liver temperature in control groups was controlled at 37 °C. Subsequently, the liver donors were preserved in cold University of Wisconsin solution for various durations followed by orthotopic liver transplantation. Liver graft injury, function and inflammation were assessed at 1 and 2 days post-transplantation. Liver precooling exhibited a significant improvement in graft function, revealing more than a 47% decrease in plasma aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, coupled with a remarkable reduction of approximately 50% in liver graft histological damage compared to the control group. The protective effects of liver precooling were associated with the preservation of mitochondrial function, a substantial reduction in hepatocyte cell death, and a significantly attenuated inflammatory response. Taken together, reducing the cellular metabolism and enzymatic activity to a minimum level before ischemia protects against IRI during transplantation.

Optimizing the Tensile Strength of Weld Lines in Glass Fiber Composite Injection Molding.

Weld line defects, commonly occurring during the plastic product manufacturing process, are caused by the merging of two opposing streams of molten plastic. The presence of weld lines harms the product's aesthetic appeal and durability. This study uses artificial neural networks to forecast the ultimate tensile strength of a PA6 composite incorporating 30% glass fibers (GFs). Data were collected from tensile strength tests and the technical parameters of injection molding. The packing pressure factor is the one that significantly affects the tensile strength value. The melt temperature has a significant impact on the product's strength as well. In contrast, the filling time factor has less impact than other factors. According to the scanning electron microscope result, the smooth fracture surface indicates the weld line area's high brittleness. Fiber bridging across the weld line area is evident in numerous fractured GF pieces on the fracture surface, which enhances this area. Tensile strength values vary based on the injection parameters, from 65.51 MPa to 73.19 MPa. In addition, the experimental data comprise the outcomes of the artificial neural networks (ANNs), with the maximum relative variation being only 4.63%. The results could improve the PA6 reinforced with 30% GF injection molding procedure with weld lines. In further research, mold temperature improvement should be considered an exemplary method for enhancing the weld line strength.

Evaluation of Selective Culling as a Containment Strategy for African Swine Fever at a Vietnamese Sow Farm.

Selective culling, also known as the "tooth extraction approach", is a strategy for controlling African swine fever (ASF) by removing only sick and suspect animals instead of the entire herd in Vietnam. This method prioritizes preserving healthy animals, particularly valuable breeding pigs. Despite its implementation in various forms, no standardized protocol based on scientific principles has been established. Farms typically adapt this strategy based on their understanding, which can vary significantly. In implementing of selective culling that is not based on scientific principles, there is a significant risk of spreading the disease. The aim of this study is to evaluate the consequences of selective culling as currently implemented in Vietnam. Our analysis on a large sow farm revealed that current practices rely heavily on clinical observations without laboratory confirmations. This approach allows ASF-infected animals to remain on the farm longer, potentially exacerbating the spread of the virus. Thus, selective culling poses a substantial risk by potentially exacerbating the spread of disease. Our findings emphasize that early diagnosis of ASF and systematic removal of infected pigs are critical components for the effective implementation of selective culling strategies and that a high level of fragmentation to minimize contact between animals plays a key role. The optimal approach is to test conspicuous animals and separate them. Under no circumstances should suspect animals be left in the herd for several days before they become severely ill and succumb to the disease.

Experiences of patient organizations' involvement in medicine appraisal and reimbursement processes in Finland - a qualitative study.

BACKGROUND: This study investigated how patient representatives have experienced their involvement in medicines appraisal and reimbursement processes with the Council for Choices in Health Care in Finland (COHERE) and the Pharmaceuticals Pricing Board (PPB) and how authorities perceive the role of patient organizations' input. METHODS: Semi-structured thematic individual and pair interviews were conducted in 2021 with representatives (n = 14) of patient organizations and government officials (n = 7) of the Ministry of Social Affairs and Health. The interview data were analyzed using qualitative content analysis. RESULTS: Patient representatives expressed their appreciation for the PPB and the COHERE in creating consultation processes and systematic models that support involvement. However, there were many challenges: patient representatives were uncertain about how their submissions were utilized in official processes and whether their opinions had any significance in decision-making. Patients or patient organizations lack representation in appraisal and decision-making bodies, and patient representatives felt that decision-making lacked transparency. The importance of patient involvement was highlighted by the authorities, but they also emphasized that the patient organizations' contributions were complementary to the other materials. Submissions regarding the medications used to treat rare diseases and those with limited research evidence were considered particularly valuable. However, the submissions may not necessarily have a direct impact on decisions. CONCLUSIONS: The interviews provided relevant input for the development of involvement processes at the PPB and COHERE. The interviews confirmed the need for increased transparency in the medicines assessment, appraisal, and decision-making procedures in Finland.

The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1-linked chromatin opening.

A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.

Comparison of the outcomes of first metatarsophalangeal joint arthrodesis by locking plate and compression screw in patients with severe hallux valgus or hallux valgus revision.

INTRODUCTION: Arthrodesis of the first metatarsophalangeal joint (MTP1) is indicated for hallux rigidus, septic arthritis, severe hallux valgus (HV) or HV revision. Few studies have compared the functional and radiographic outcomes between indications. The goal of this study was to compare the results of MTP1 arthrodesis in patients with severe HV or HV revision at 6 months postoperative. The hypothesis was that there are no differences in the fusion rate, functional scores and radiological correction between the two groups. MATERIALS AND METHODS: This was a retrospective, observational, single-center study conducted between January 1, 2018 and July 31, 2021. The inclusion criteria were patients treated for severe HV or HV revision by MTP1 arthrodesis with a compression screw and locking plate who were at least 18 years of age. The exclusion criteria were a history of septic arthritis of MTP1 without prior HV surgery, primary hallux rigidus, rheumatoid arthritis, incomplete medical record. The functional outcomes consisted of the Foot Function Index (FFi-f) and the European Foot and Ankle Society (EFAS) score. Radiographs were made to evaluate preoperative and postoperative deformity, the correction and the fusion rate. These outcomes were compared between two groups: severe HV and HV revision. RESULTS: An analysis was done of 58 cases of MTP1 arthrodesis: 45 severe HV and 13 HV revisions. The mean patient age was 66 years, and the mean follow-up was 15.7 months. There were no significant differences between the two groups in the postoperative functional scores: EFAS (p = 0.85) and FFI-f (p = 0.14). At the final review, there were no significant differences between the two groups in the foot angle measurements (hallux valgus angle, p = 0.08 and intermetatarsal angle, p = 0.15) and fusion rate (p = 0.89) with a 93% fusion rate in patients with severe HV and 92% in patients with HV revision. CONCLUSION: Given the good radiographic and functional outcomes, MTP1 arthrodesis by locking plate and compression screw is indicated as a first line surgical treatment for patients with severe HV or for patients undergoing HV revision. There is no evidence of a significant difference in the functional scores, fusion rate and radiographic correction between these two indications. LEVEL OF PROOF: IV; retrospective case series.

Doxycycline pharmacokinetics and tissue depletion in striped catfish (Pagasianodon hypophthalmus) after oral administration.

The pharmacokinetics and residue depletion of doxycycline (DOX) in striped catfish (Pagasianodon hypophthalmus) after oral dosage were investigated. The pharmacokinetic experiment was conducted in an aquarium, while the experiment of residue depletion was performed in both an aquarium and earth ponds. Medicated feed was administered orally using the gavage method at a dosage of 20 mg/kg body weight. Blood, liver, and kidney from medicated fish samples were collected. In the depletion experiments, fish were fed medicated feed for five consecutive days at a dosage of 20 mg/kg body weight, with samples collected during and after medication. The concentrations of DOX were quantified using an LC-MS/MS system. The pharmacokinetics parameters of DOX in striped catfish included the absorption rate constant (ka), absorption half-life (T1/2abs), maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), and area under the plasma concentration-time curve from time 0 to 96 h (AUC0-96 h) which were 0.12 h-1, 5.68 h, 1123.45 ng/mL, 8.19 h, and 25,018 ng/mL/h, respectively. Residue depletion results indicated that the withdrawal times of DOX in muscle (with skin) from fish kept in the aquarium were slightly longer than that in fish raised in earth ponds, corresponding to 194 degree-days compared with 150 degree-days. In conclusion, administration of DOX at the dosage of 20 mg/kg body weight can be used for treatment of bacterial infections in striped catfish, and a withdrawal time of 5 days at 29.4°C will ensure consumer food safety due to the rapid depletion of DOX from muscle and skin.

Aquaporin-0-protein interactions elucidated by crosslinking mass spectrometry.

Aquaporin-0 (AQP0) constitutes 50 % of the lens membrane proteome and plays important roles in lens fiber cell adhesion, water permeability, and lens transparency. Previous work has shown that specific proteins, such as calmodulin (CaM), interact with AQP0 to modulate its water permeability; however, these studies often used AQP0 peptides, rather than full-length protein, to probe these interactions. Furthermore, the specific regions of interaction of several known AQP0 interacting partners, i.e. αA and αB-crystallins, and phakinin (CP49) remain unknown. The purpose of this study was to use crosslinking mass spectrometry (XL-MS) to identify interacting proteins with full-length AQP0 in crude lens cortical membrane fractions and to determine the specific protein regions of interaction. Our results demonstrate, for the first time, that the AQP0 N-terminus can engage in protein interactions. Specific regions of interaction are elucidated for several AQP0 interacting partners including phakinin, α-crystallin, connexin-46, and connexin-50. In addition, two new interacting partners, vimentin and connexin-46, were identified.

Detection and margin assessment of thyroid carcinoma with microscopic hyperspectral imaging using transformer networks.

Significance: Hyperspectral imaging (HSI) is an emerging imaging modality for oncological applications and can improve cancer detection with digital pathology. Aim: The study aims to highlight the increased accuracy and sensitivity of detecting the margin of thyroid carcinoma in hematoxylin and eosin (H&E)-stained histological slides using HSI and data augmentation methods. Approach: Using an automated microscopic imaging system, we captured 2599 hyperspectral images from 65 H&E-stained human thyroid slides. Images were then preprocessed into 153,906 image patches of dimension 250 × 250 × 84 pixels . We modified the TimeSformer network architecture, which used alternating spectral attention and spatial attention layers. We implemented several data augmentation methods for HSI based on the RandAugment algorithm. We compared the performances of TimeSformer on HSI against the performances of pretrained ConvNext and pretrained vision transformers (ViT) networks on red, green, and blue (RGB) images. Finally, we applied attention unrolling techniques on the trained TimeSformer network to identify the biological features to which the network paid attention. Results: In the testing dataset, TimeSformer achieved an accuracy of 90.87%, a weighted F 1 score of 89.79%, a sensitivity of 91.50%, and an area under the receiving operator characteristic curve (AU-ROC) score of 97.04%. Additionally, TimeSformer produced thyroid carcinoma tumor margins with an average Jaccard score of 0.76 mm. Without data augmentation, TimeSformer achieved an accuracy of 88.23%, a weighted F 1 score of 86.46%, a sensitivity of 85.53%, and an AU-ROC score of 94.94%. In comparison, the ViT network achieved an 89.98% accuracy, an 88.14% weighted F 1 score, an 84.77% sensitivity, and a 96.17% AU-ROC. Our visualization results showed that the network paid attention to biological features. Conclusions: The TimeSformer model trained with hyperspectral histological data consistently outperformed conventional RGB-based models, highlighting the superiority of HSI in this context. Our proposed augmentation methods improved the accuracy, the F 1 score, and the sensitivity score.

Rescue extracranial vertebral stenting in tandem occlusions: A preliminary Vietnamese study.

BACKGROUND AND PURPOSE: The acute vertebrobasilar occlusion associated with the poor prognosis, particularly tandem occlusion. However, few data on the efficacy of the endovascular therapy was indicated in this occlusion. We investigated whether the additional rescue extracranial vertebral stenting improved clinical outcome by modified Rankin scale (mRS) score within 3 months after the procedure. METHODS: This was a retrospective analysis of patients with acute posterior tandem occlusion who were treated with rescue extracranial vertebral stenting between December 2020 and January 2024 at our hospital. Clinical, neuroimaging, procedural, and complication data were collected. Primary outcomes included the rate of good outcomes (mRS ≤ 2) at 3-month follow-up. RESULTS: Nine patients who underwent rescue extracranial vertebral stenting in posterior circulation tandem occlusions were enrolled in the study. All patients were achieved the successful recanalization (mTICI ≥ 2b). Of Dotter technique in the "distal-to-proximal" approach, Diagnostic-Dotter made up 66.7%. Five patients (55.6%) with good outcome (mRS ≤ 2) at 3 months, and 1 patient (11.1%) underwent suboccipital decompressive craniectomy due to the malignant cerebellar infarction. CONCLUSION: Our study suggests that despite the small series with posterior tandem occlusions, the rescue extracranial vertebral stenting could be an important alternative treatment followed by mechanical thrombectomy.

Urchin-like CoP3/Cu3P heterostructured nanorods supported on a 3D porous copper foam for high-performance non-enzymatic electrochemical dopamine sensors.

In this study, we developed a high-performance non-enzymatic electrochemical sensor based on urchin-like CoP3/Cu3P heterostructured nanorods supported on a three-dimensional porous copper foam, namely, CoP3/Cu3P NRs/CF, for the detection of dopamine. Benefiting from the promising intrinsic catalytic activities of CoP3 and Cu3P, urchin-like microsphere structures, and a large electrochemically active surface area for exposing numerous accessible catalytic active sites, the proposed CoP3/Cu3P NRs/CF shows extraordinary electrochemical response towards the electrocatalytic oxidation of dopamine. As a result, the CoP3/Cu3P NRs/CF sensing electrode has a broad detection window (from 0.2 to 2000 µM), low detection limit (0.51 µM), high electrochemical sensitivity (0.0105 mA µM-1 cm-2), excellent selectivity towards dopamine in the coexistence of some interfering species, and good stability for dopamine determination. More importantly, the CoP3/Cu3P NRs/CF catalyst also exhibits excellent catalytic activity, sensitivity, and selectivity for dopamine detection under simulated human body conditions at a physiological pH of 7.25 (0.1 M PBS) at 36.6 °C.

Using Virtual Reality to teach ultrasound-guided needling skills for regional anaesthesia: A randomised controlled trial.

STUDY OBJECTIVE: We previously designed and validated a virtual reality-based simulator to help train novices in ultrasound-guided needling skills necessary for safe and competent ultrasound-guided regional anaesthesia. This study was designed to compare the performance and error rates of novices trained by a human faculty aided with the assistance of this virtual reality simulator (virtual reality-assisted training), versus novices trained wholly by humans (conventional training). DESIGN, SETTING, AND PARTICIPANTS: In this single centre, randomised controlled study, we used a standardised teaching protocol, rigorous blinding, iterative training of assessors, and validated global rating scale and composite error score checklists to assess skills learning of novice participants. MAIN RESULTS: We recruited 45 novices and scored 270 assessments of performance and error rates. Inter-rater correlation coefficient of reliability of scoring between assessors for the global rating scale was 0.84 (95%CI 0.68-0.92) and for the composite error score checklist was 0.87 (95%CI 0.73-0.93). After adjustment for age, sex, Depression, Anxiety and Stress-21, and baseline score, there was no statistical difference for virtual reality-assisted training compared to conventional training in final global rating score (average treatment effect -3.30 (95%CI-13.07-6.48), p = 0.51) or in the final composite error score (average treatment effect 1.14 (95%CI -0.60-2.88), p = 0.20). Realism in the virtual reality simulator was similar to real-life when measured by the Presence Questionnaire, all components p > 0.79; and task workload assessed by the NASA-Task Load Index was not statistically different between groups, average treatment effect 5.02 (95%CI -3.51-13.54), p = 0.25. Results were achieved in the virtual reality-assisted group with half the human faculty involvement. CONCLUSION: Novices trained using a hybrid, virtual reality-assisted teaching program showed no superiority to novices trained using a conventional teaching program, but with less burden on teaching resources.

Eculizumab for Shiga-toxin-induced hemolytic uremic syndrome in adults with neurological involvement.

The role of eculizumab in treating Shiga-toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) patients with neurological involvement remains unclear. We describe two distinctly different STEC-HUS patients with neurologic involvement successfully managed with eculizumab, and perform a literature review of all published cases. Both patients had complete resolution of neurological symptoms after initiation of eculizumab. Eighty patients with STEC-HUS treated with eculizumab were identified in the literature, 68.7% had complete resolution of neurological symptoms. Based on our experience and literature review, three prevailing themes were noted: 1) Early eculizumab administration optimized neurological outcomes, 2) Symptom resolution may not be immediate, neurological symptoms may initially worsen before improvement, and 3) Plasma exchange yielded no benefit. Early administration of eculizumab may reverse neurotoxicity in patients with STEC-HUS.

Genomic Insights into Edwardsiella ictaluri: Molecular Epidemiology and Antimicrobial Resistance in Striped Catfish (Pangasianodon hypophthalmus) Aquaculture in Vietnam.

Edwardsiella ictaluri is responsible for causing bacillary necrosis (BNP) in striped catfish (Pangasianodon hypophthalmus) in Vietnam. This study offers a comprehensive genomic characterization of E. ictaluri to enhance understanding of the molecular epidemiology, virulence, and antimicrobial resistance. E. ictaluri isolates were collected from diseased striped catfish in the Mekong Delta. The species was confirmed through PCR. Antimicrobial susceptibility testing was conducted using minimum inhibitory concentrations for commonly used antimicrobials. Thirty representative isolates were selected for whole genome sequencing to delineate their genomic profiles and phylogeny. All strains belonged to ST-26 and exhibited genetic relatedness, differing by a maximum of 90 single nucleotide polymorphisms. Most isolates carried multiple antimicrobial resistance genes, with the tet(A) gene present in 63% and floR in 77% of the genomes. The ESBL gene, blaCTX-M-15, was identified in 30% of the genomes. Three plasmid replicon types were identified: IncA, p0111, and IncQ1. The genomes clustered into two clades based on their virulence gene profile, one group with the T3SS genes and one without. The genetic similarity among Vietnamese isolates suggests that disease spread occurs within the Mekong region, underscoring the importance of source tracking, reservoir identification, and implementation of necessary biosecurity measures to mitigate spread of BNP.

Antiepileptic and Neuroprotective Effects of Rheum tanguticum Root Extract on Trimethyltin-Induced Epilepsy and Neurodegeneration: In Vivo and in Silico Analyses.

BACKGROUND: Rheum tanguticum root, cataloged as "Daehwang" in the Korean Pharmacopeia, is rich in various anthraquinones known for their anti-inflammatory and antioxidant properties. Formulations containing Daehwang are traditionally employed for treating neurological conditions. This study aimed to substantiate the antiepileptic and neuroprotective efficacy of R. tanguticum root extract (RTE) against trimethyltin (TMT)-induced epileptic seizures and hippocampal neurodegeneration. METHODS: The constituents of RTE were identified by ultra-performance liquid chromatography (UPLC). Experimental animals were grouped into the following five categories: control, TMT, and three TMT+RTE groups with dosages of 10, 30, and 100 mg/kg. Seizure severity was assessed daily for comparison between the groups. Brain tissue samples were examined to determine the extent of neurodegeneration and neuroinflammation using histological and molecular biology techniques. Network pharmacology analysis involved extracting herbal targets for Daehwang and disease targets for epilepsy from multiple databases. A protein-protein interaction network was built using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and pivotal targets were determined by topological analysis. Enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool to elucidate the underlying mechanisms. RESULTS: The RTE formulation was found to contain sennoside A, sennoside B, chrysophanol, emodin, physcion, (+)-catechin, and quercetin-3-O-glucuronoid. RTE effectively inhibited TMT-induced seizures at 10, 30, and 100 mg/kg dosages and attenuated hippocampal neuronal decay and neuroinflammation at 30 and 100 mg/kg dosages. Furthermore, RTE significantly reduced mRNA levels of tumor necrosis factor (TNF-α), glial fibrillary acidic protein (GFAP), and c-fos in hippocampal tissues. Network analysis revealed TNF, Interleukin-1 beta (IL-1ß), Interleukin-6 (IL-6), Protein c-fos (FOS), RAC-alpha serine/threonine-protein kinase (AKT1), and Mammalian target of rapamycin (mTOR) as the core targets. Enrichment analysis demonstrated significant involvement of R. tanguticum components in neurodegeneration (p = 4.35 × 10-5) and TNF signaling pathway (p = 9.94 × 10-5). CONCLUSIONS: The in vivo and in silico analyses performed in this study suggests that RTE can potentially modulate TMT-induced epileptic seizures and neurodegeneration. Therefore, R. tanguticum root is a promising herbal treatment option for antiepileptic and neuroprotective applications.

Towards long-tailed, multi-label disease classification from chest X-ray: Overview of the CXR-LT challenge.

Many real-world image recognition problems, such as diagnostic medical imaging exams, are "long-tailed" - there are a few common findings followed by many more relatively rare conditions. In chest radiography, diagnosis is both a long-tailed and multi-label problem, as patients often present with multiple findings simultaneously. While researchers have begun to study the problem of long-tailed learning in medical image recognition, few have studied the interaction of label imbalance and label co-occurrence posed by long-tailed, multi-label disease classification. To engage with the research community on this emerging topic, we conducted an open challenge, CXR-LT, on long-tailed, multi-label thorax disease classification from chest X-rays (CXRs). We publicly release a large-scale benchmark dataset of over 350,000 CXRs, each labeled with at least one of 26 clinical findings following a long-tailed distribution. We synthesize common themes of top-performing solutions, providing practical recommendations for long-tailed, multi-label medical image classification. Finally, we use these insights to propose a path forward involving vision-language foundation models for few- and zero-shot disease classification.

Strategies to address inequity of uncorrected refractive error in the Western Pacific: A modified Delphi process.

PURPOSE: Uncorrected refractive error is the leading cause of vision impairment globally; however, little attention has been given to equity and access to services. This study aimed to identify and prioritise: (1) strategies to address inequity of access to refractive error services and (2) population groups to target with these strategies in five sub-regions within the Western Pacific. METHODS: We invited eye care professionals to complete a two-round online prioritisation process. In round 1, panellists nominated population groups least able to access refractive error services, and strategies to improve access. Responses were summarised and presented in round 2, where panellists ranked the groups (by extent of difficulty and size) and strategies (in terms of reach, acceptability, sustainability, feasibility and equity). Groups and strategies were scored according to their rank within each sub-region. RESULTS: Seventy five people from 17 countries completed both rounds (55% women). Regional differences were evident. Indigenous peoples were a priority group for improving access in Australasia and Southeast Asia, while East Asia identified refugees and Oceania identified rural/remote people. Across the five sub-regions, reducing out-of-pocket costs was a commonly prioritised strategy for refraction and spectacles. Australasia prioritised improving cultural safety, East Asia prioritised strengthening school eye health programmes and Oceania and Southeast Asia prioritised outreach to rural areas. CONCLUSION: These results provide policy-makers, researchers and funders with a starting point for context-specific actions to improve access to refractive error services, particularly among underserved population groups who may be left behind in existing private sector-dominated models of care.

A systematic review of machine learning models for management, prediction and classification of ARDS.

AIM: Acute respiratory distress syndrome or ARDS is an acute, severe form of respiratory failure characterised by poor oxygenation and bilateral pulmonary infiltrates. Advancements in signal processing and machine learning have led to promising solutions for classification, event detection and predictive models in the management of ARDS. METHOD: In this review, we provide systematic description of different studies in the application of Machine Learning (ML) and artificial intelligence for management, prediction, and classification of ARDS. We searched the following databases: Google Scholar, PubMed, and EBSCO from 2009 to 2023. A total of 243 studies was screened, in which, 52 studies were included for review and analysis. We integrated knowledge of previous work providing the state of art and overview of explainable decision models in machine learning and have identified areas for future research. RESULTS: Gradient boosting is the most common and successful method utilised in 12 (23.1%) of the studies. Due to limitation of data size available, neural network and its variation is used by only 8 (15.4%) studies. Whilst all studies used cross validating technique or separated database for validation, only 1 study validated the model with clinician input. Explainability methods were presented in 15 (28.8%) of studies with the most common method is feature importance which used 14 times. CONCLUSION: For databases of 5000 or fewer samples, extreme gradient boosting has the highest probability of success. A large, multi-region, multi centre database is required to reduce bias and take advantage of neural network method. A framework for validating with and explaining ML model to clinicians involved in the management of ARDS would be very helpful for development and deployment of the ML model.

Biological network comparison identifies a novel synergistic mechanism of Ginseng Radix-Astragali Radix herb pair in cancer-related fatigue.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng Radix and Astragali Radix are commonly combined to tonify Qi and alleviate fatigue. Previous studies have employed biological networks to investigate the mechanisms of herb pairs in treating different diseases. However, these studies have only elucidated a single network for each herb pair, without emphasizing the superiority of the herb combination over individual herbs. AIM OF THE STUDY: This study proposes an approach of comparing biological networks to highlight the synergistic effect of the pair in treating cancer-related fatigue (CRF). METHODS: The compounds and targets of Ginseng Radix, Astragali Radix, and CRF diseases were collected and predicted using different databases. Subsequently, the overlapping targets between herbs and disease were imported into the STRING and DAVID tools to build protein-protein interaction (PPI) networks and analyze enriched KEGG pathways. The biological networks of Ginseng Radix and Astragali Radix were compared separately or together using the DyNet application. Molecular docking was used to verify the predicted results. Further, in vitro experiments were conducted to validate the synergistic pathways identified in in silico studies. RESULTS: In the PPI network comparison, the combination created 89 new interactions and an increased average degree (11.260) when compared to single herbs (10.296 and 9.394). The new interactions concentrated on HRAS, STAT3, JUN, and IL6. The topological analysis identified 20 core targets of the combination, including three Ginseng Radix-specific targets, three Astragali Radix-specific targets, and 14 shared targets. In KEGG enrichment analysis, the combination regulated additional signaling pathways (152) more than Ginseng Radix (146) and Astragali Radix (134) alone. The targets of the herb pair synergistically regulated cancer pathways, specifically hypoxia-inducible factor 1 (HIF-1) signaling pathway. In vitro experiments including enzyme-linked immunosorbent assay and Western blot demonstrated that two herbs combination could up-regulate HIF-1α signaling pathway at different combined concentrations compared to either single herb alone. CONCLUSION: The herb pair increased protein interactions and adjusted metabolic pathways more than single herbs. This study provides insights into the combination of Ginseng Radix and Astragali Radix in clinical practice.

Stability of Cs2NaBiBr6 and Cs2NaBiCl6.

Bismuth-based halide perovskites are nontoxic alternatives to widely studied lead-based perovskites for optoelectronic applications. Here, we synthesized Cs2NaBiCl6 thin films and attempted to synthesize Cs2NaBiBr6 using physical vapor deposition. While Cs2NaBiCl6 forms a stable cubic structure with a 3.4 eV band gap and could be synthesized successfully, Cs2NaBiBr6 does not form and is unstable with respect to dissociation into Cs3-xNaxBi2Br9 and Cs3-xNaxBiBr6. Furthermore, the close X-ray diffraction patterns of Cs3-xNaxBi2Br9 and Cs2NaBiBr6 raise doubts about the previous reports of the latter's formation based on X-ray diffraction alone.