VISH-Pred: an ensemble of fine-tuned ESM models for protein toxicity prediction.

Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle for protein-based therapies. Thus, there is an urgent need for accurate in silico methods for determining toxic proteins to filter the pool of potential candidates. At the same time, it is imperative to precisely identify non-toxic proteins to expand the possibilities for protein-based biologics. To address this challenge, we proposed an ensemble framework, called VISH-Pred, comprising models built by fine-tuning ESM2 transformer models on a large, experimentally validated, curated dataset of protein and peptide toxicities. The primary steps in the VISH-Pred framework are to efficiently estimate protein toxicities taking just the protein sequence as input, employing an under sampling technique to handle the humongous class-imbalance in the data and learning representations from fine-tuned ESM2 protein language models which are then fed to machine learning techniques such as Lightgbm and XGBoost. The VISH-Pred framework is able to correctly identify both peptides/proteins with potential toxicity and non-toxic proteins, achieving a Matthews correlation coefficient of 0.737, 0.716 and 0.322 and F1-score of 0.759, 0.696 and 0.713 on three non-redundant blind tests, respectively, outperforming other methods by over $10\%$ on these quality metrics. Moreover, VISH-Pred achieved the best accuracy and area under receiver operating curve scores on these independent test sets, highlighting the robustness and generalization capability of the framework. By making VISH-Pred available as an easy-to-use web server, we expect it to serve as a valuable asset for future endeavors aimed at discerning the toxicity of peptides and enabling efficient protein-based therapeutics.

Partial Splenic Artery Embolization for the Management of Symptomatic Hypersplenism in Portal Hypertension: Clinical Insights from a Case Series.

Background and aims: Partial splenic artery embolization (PSAE) is an alternative treatment modality for managing hypersplenism secondary to portal hypertension. We are presenting a case series of patients with portal hypertension who underwent PSAE for symptomatic hypersplenism. Methods: We included patients with portal hypertension who underwent PSAE from January 2022 to December 2022. Patients' characteristics and procedure related complications were noted. Data were analyzed for improvement in the hematological parameters. Results: A total of 11 (7 women, median age 34 [18-56] years) patients were included. Three patients were cirrhotic (hepatitis B-2, metabolic dysfunction-associated steatotic liver disease -1) and 8 were non-cirrhotic (extra-hepatic portal vein obstruction-5, Non cirrhotic portal fibrosis-3). Splenic artery aneurysm was concomitantly present in 5 cases. Technical success was achieved in all cases. Post embolization, hemoglobin, white blood cells and platelet counts improved at 4 weeks, 12 weeks and 24 weeks along with symptomatic improvement. All patients had post-embolization syndrome. One patient developed transient ascites and secondary bacterial peritonitis which was managed conservatively. One patient died due to splenic abscess and septicemia. Conclusion: Although, hematological parameters and symptoms improve post procedure, PSAE is associated with major complications and should be performed judiciously in selected cases only. Graphical abstract is presented in Figure 1.

IL-22 promotes mucin-type O-glycosylation and MATH1+ cell-mediated amelioration of intestinal inflammation.

The interleukin (IL)-22 cytokine can be protective or inflammatory in the intestine. It is unclear if IL-22 receptor (IL-22Ra1)-mediated protection involves a specific type of intestinal epithelial cell (IEC). By using a range of IEC type-specific Il22Ra1 conditional knockout mice and a dextran sulfate sodium (DSS) colitis model, we demonstrate that IL-22Ra1 signaling in MATH1+ cells (goblet and progenitor cells) is essential for maintaining the mucosal barrier and intestinal tissue regeneration. The IL-22Ra1 signaling in IECs promotes mucin core-2 O-glycan extension and induces beta-1,3-galactosyltransferase 5 (B3GALT5) expression in the colon. Adenovirus-mediated expression of B3galt5 is sufficient to rescue Il22Ra1IEC mice from DSS colitis. Additionally, we observe a reduction in the expression of B3GALT5 and the Tn antigen, which indicates defective mucin O-glycan, in the colon tissue of patients with ulcerative colitis. Lastly, IL-22Ra1 signaling in MATH1+ progenitor cells promotes organoid regeneration after DSS injury. Our findings suggest that IL-22-dependent protective responses involve O-glycan modification, proliferation, and differentiation in MATH1+ progenitor cells.

Exceptional behavior of a high-temperature superconductor in proximity to a ferromagnet in a bilayer film, La0.67Sr0.33MnO3/YBa2Cu3O7.

We studied the electronic properties of a high-temperature superconductor in proximity to a ferromagnetic material in a bilayer film of La0.67Sr0.33MnO3 (LSMO)/YBa2Cu3O7 (YBCO). High-quality single-crystalline films of YBCO and LSMO/YBCO were grown epitaxially on an SrTiO3 (001) surface. Magnetization data of the LSMO/YBCO bilayer exhibit ferromagnetic transition at about 255 K, which is much smaller than the Curie temperature of bulk LSMO. Experimental data show the emergence of magnetic anisotropy with cooling, which becomes significantly stronger in the superconducting phase. The onset temperature of diamagnetism is observed at 86 K in the YBCO sample for the out-of-plane magnetization and at 89 K in the in-plane data. Interestingly, the diamagnetism sets in at about 86 K for both magnetization directions in the LSMO/YBCO film despite the presence of the ferromagnetic LSMO layer underneath. Ba 4d and Y 3d core-level spectra show different surface and bulk electronic structures. Surface contribution is reduced significantly in the LSMO/YBCO sample, suggesting enhanced bulk-like behavior due to an enhancement of electron density near the surface arising from charge transfer across the interface. These results reveal an outstanding platform for on-demand tuning of properties without affecting the superconductivity of the system for the exploration of fundamental science and applications in advanced technology.

A murine model of post-acute neurological sequelae following SARS-CoV-2 variant infection.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.

Perturbed Lipid Metabolism Transduction Pathways in SARS-CoV-2 Infection and Their Possible Treating Nutraceuticals.

The coronavirus disease 2019 (COVID-19) epidemic has evolved into an international public health concern. Its causing agent was SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), a lipid bilayer encapsulated virus. Lipids have relevance in the host's viral cycle; additionally; viruses have been speculated to manipulate lipid signaling and production to influence the lipidome of host cells. SARS-CoV-2 engages the host lipid pathways for replication, like fatty acid synthesis activation via upregulation of AKT and SREBP pathway and inhibiting lipid catabolism by AMPK and PPAR deactivation. Consequently, lipoprotein levels are altered in most cases, i.e., raised LDL, TG, VLDL levels and reduced HDL levels like a hyperlipidemic state. Apo lipoproteins, a subsiding structural part of lipoproteins, may also impact viral spike protein binding to host cell receptors. In a few studies conducted on COVID-19 patients, maintaining Apo lipoprotein levels has also shown antiviral activity against SARS-CoV-2 infection. It was speculated that several potent hypolipidemic drugs, such as statins, hydroxychloroquine, and metformin, could be used as add-on treatment in COVID-19 management. Nutraceuticals like Garlic, Fenugreek, and vinegar have the potency to lower the lipid capability acting via these pathways. A link between COVID-19 and post-COVID alteration in lipoprotein levels has not yet been fully understood. In this review, we try to look over the possible modifications in lipid metabolism due to SARS-CoV-2 viral exposure, besides the prospect of focusing on the potential of lipid metabolic processes to interrupt the viral cycle.

Viral infection mainly alters the lipid profile similar to the hyperlipidemia state.SARS-CoV infection affects cell lipidome by promoting lipid anabolism through AKT and SREBP pathways.Viral infection also inhibits lipid metabolism via AMPK and PPAR signaling pathways.Nutraceuticals could be a potent antiviral agent by targeting the lipid transduction mechanisms and maintaining cell lipidome.

Formulation and Characterization of Soybean Oil-in-Water Emulsions Stabilized Using Gelatinized Starch Dispersions from Plant Sources.

Consumers are concerned about employing green processing technologies and natural ingredients in different manufacturing sectors to achieve a "clean label" standard for products and minimize the hazardous impact of chemical ingredients on human health and the environment. In this study, we investigated the effects of gelatinized starch dispersions (GSDs) prepared from six plant sources (indica and japonica rice, wheat, corn, potatoes, and sweet potatoes) on the formulation and stability of oil-in-water (O/W) emulsions. The effect of gelatinization temperature and time conditions of 85-90 °C for 20 min on the interfacial tension of the two phases was observed. Emulsification was performed using a primary homogenization condition of 10,000 rpm for 5 min, followed by high-pressure homogenization at 100 MPa for five cycles. The effects of higher oil weight fractions (15-25% w/w) and storage stability at different temperatures for four weeks were also evaluated. The interfacial tension of all starch GSDs with soybean oil decreased compared with the interfacial tension between soybean oil and water as a control. The largest interfacial tension reduction was observed for the GSD from indica rice. Microstructural analysis indicated that the GSDs stabilized the O/W emulsion by coating oil droplets. Emulsions formulated using a GSD from indica rice were stable during four weeks of storage with a volume mean diameter (d4,3) of ~1 µm, minimal viscosity change, and a negative ζ-potential.

Changing Etiological Spectrum of Hepatocellular Carcinoma in India-A Systematic Review and Meta-analysis.

Background: Recent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. Methods: Electronic databases of PubMed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. Results: A total of 60 studies (n = 12,327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5-62.6) and 43.1% (36.5-49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8-46.1), while those with positive markers for hepatitis C virus were 20.3 (17.0-23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6-22.4), and those related to nonalcoholic fatty liver disease (NAFLD) were 16.9% (12.1-21.7). Around 7.9% (5.8-10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with hepatitis C virus and alcohol did not change significantly. Conclusion: Viral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.

Clinical evaluation of ophthalmic findings in active, amateur, adult, competitive male boxers in India.

Background: In the popular fighting sport of boxing, opponents strike each other above the belt line in the face, chest, and belly. The physical parts most exposed are therefore the nose and eyes. In amateur boxing, fights go only three rounds - three minutes for men and one minute for women - with a one-minute break in between. They wear gloves, but the head protection used in the men's game has been removed by AIBA due to the high likelihood of concussion when using head protection. Because chronic ocular changes may take longer than the expected short-term effects, this study included at least 3 years of competitive sports participation. Study design and setting: Institutional-based cross-sectional study. Materials and methods: To evaluate ophthalmic outcomes, 200 eyes of 100 active amateur, adult, and competitive male boxers were studied. Results: Of the 100 boxers, 51 had ophthalmic changes in at least one eye, and 49 had normal eyes. The average age of boxers was 24.98 years. The average duration of boxing training was 7.04 years. Healed eyelid scars, subconjunctival hemorrhages, conjunctival papillae, traumatic mydriasis, posterior synechiae, angulation abnormalities, traumatic cataracts, lens subluxation, increased intraocular pressure, and peripapillary atrophy were observed on the ocular side. None of these could be attributed to boxing. Conclusion: Boxing-related eye injuries are common in India and the most common vision-threatening eye abnormalities include traumatic cataracts, lens subluxation, and angle abnormalities. Surprisingly, no macular lesions were found on physical examination and OCT. Additional studies with a larger number of boxers will be needed to evaluate and prevent clinical symptoms. All boxers should have a complete eye exam regularly. Abbreviations: AIBA = Association Internationale de Boxe Amateur, OCT = Optical Coherence Tomography.

Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. AIM: To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. METHODS: We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. RESULTS: Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. CONCLUSION: This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.

Furanocoumarins promote proteasomal degradation of viral HBx protein and down-regulate cccDNA transcription and replication of hepatitis B virus.

Nucleot(s)ide analogues, the current antiviral treatments against chronic hepatitis B (CHB) infection, are non-curative due to their inability to eliminate covalently closed circular DNA (cccDNA) from the infected hepatocytes. Preclinical studies have shown that coumarin derivatives can effectively reduce the HBV DNA replication. We evaluated the antiviral efficacy of thirty new coumarin derivatives in cell culture models for studying HBV. Furanocoumarins Fc-20 and Fc-31 suppressed the levels of pre-genomic RNA as well as cccDNA, and reduced the secretion of virions, HBsAg and HBeAg. The antiviral efficacies of Fc-20 and Fc31 improved further when used in combination with the hepatitis B antiviral drug Entecavir. There was a marked reduction in the intracellular HBx level in the presence of these furanocoumarins due to proteasomal degradation resulting in the down-regulation of HBx-dependent viral genes. Importantly, both Fc-20 and Fc-31 were non-cytotoxic to cells even at high concentrations. Further, our molecular docking studies confirmed a moderate to high affinity interaction between furanocoumarins and viral HBx via residues Ala3, Arg26 and Lys140. These data suggest that furanocoumarins could be developed as a new therapeutic for CHB infection.

Regulation of Notch signaling by non-muscle myosin II Zipper in Drosophila.

The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.

Accelerated hypofractionated chemoradiation for locally advanced head and neck cancer during COVID 19 pandemic: A tertiary care experience.

PURPOSE: To assess the role of Accelerated Hypofractionated Chemoradiation for Locally Advanced Head & Neck squamous cell cancer (HNSCC) during COVID 19 pandemic. MATERIALS AND METHODS: Previously untreated 20 patients with locally advanced HNSCC (Oral cavity/oropharynx/larynx/hypopharynx) were treated with definitive hypofractionated radiotherapy of 60Gy in 25 fractions with concurrent cisplatin @35 mg/m2 once weekly for 5 weeks from March 2020 to November 2021. The patients were treated on 6MV LINAC with Volumetric modulated arc therapy (VMAT) by the Sequential boost technique and concurrent chemotherapy @35 mg/m2. All the patients received 48Gy in 20 fractions to low-risk volume (CTV LR) in Phase I followed by 12Gy in 5 fractions boost to High-risk volume (CTV HR) in Phase II. The organs at risk (OARs) were contoured and appropriate constraints were given considering the hypofractionated regimen. RESULTS: Out of 20 patients, most of the patients were Stage IV (15;75%) & stage III 20%, out of which (55%) 11 were of the oral cavity, (40%) 8 were of the oropharynx, and (5%) 1 of larynx. All patients were treated with 60Gy/25#/5 weeks with the majority of the patients (17;85%) completing their treatment in less than 45 days. The Median follow-up was of 214 days. The locoregional control at 6 Months was 55%. Maximum acute toxicity was grade 3 mucositis which was observed in 18 (90%) patients. Ryle's tube feeding was needed in 11 (55%) patient. Out of 20 patients, 5 patients did not receive concurrent chemotherapy, and 8 (40%) patients received all 5 cycles of chemotherapy. 7, 35% of the patients could not complete all 5 cycles of concurrent chemotherapy due to grade 3 mucositis. CONCLUSION: During a pandemic crisis with limited manpower & technical resources accelerated hypofractionated radiotherapy with concurrent chemotherapy can be considered a feasible therapeutic option for HNSCC which can significantly reduce the overall Treatment Time (OTT) with comparable local control and manageable toxicities.

Assessment of Nursing Staff's Knowledge, Attitude and Practice Regarding Oral Hygiene Care in Intensive Care Unit Patients: A Multicenter Cross-sectional Study.

Background: Oral care is one of the fundamental nursing care procedures used to decrease oral colonization, dental plaque, respiratory infections, patient stay, and cost. The importance of good oral hygiene for patients in intensive care units (ICUs) is well recognized, however, the most effective way to achieve good oral care in the ICU is unclear. Therefore, the aim of this study was to assess the knowledge, attitude, and practice of nursing professionals regarding oral healthcare in ICUs among various medical institutes across India. Materials and methods: A questionnaire-based multicentric cross-sectional survey was conducted among registered nursing professionals employed at ICUs of three government tertiary healthcare centers (THC) of India: THC-I, THC-II, and THC-III located in the eastern and northern parts of India between February 2022 and July 2022. Results: A total of 150 nurses completed the questionnaire form (response rate: 62.5%) comprised of 49 (32.7%) males and 101 (67.3%) females with a mean age of 35.69 ± 7.7 years. Nursing officers' knowledge surpassed that of staff nurses regarding the duration of toothbrushing (p = 0.033). Among interinstitutional comparisons, THC-I nurses showed the greatest knowledge regarding the duration of toothbrushing and the mechanism of preventing saliva accumulation to reduce microbial growth (p = 0.013 and p = 0.003, respectively). Based on total work experience, participants were segregated into three groups: Group I (<7 years), group II (7.1-13.9 years), and group III (>14 years). Group II surpassed the knowledge of denture removal during sleep, cleaning after every meal, and storing in personalized air-tight containers (p = 0.001 and p = 0.036, respectively). The majority from group II recommended plain saline as the material for oral hygiene maintenance in ICU patients (p = 0.008). Group III predominantly practiced the ideal handwashing technique pre- and post-patient contact which was statistically significant (p = 0.001). Conclusion: This study observed that a knowledge gap exists among the nurses of the three institutes across India pertaining to the oral hygiene care of ICU patients. Nurse's education and implementation of the proper oral hygiene measures for intubated patients in ICU setup is an essential need. How to cite this article: Kumar S, Singh B, Mahuli AV, Kumar S, Singh A, Jha AK. Assessment of Nursing Staff's Knowledge, Attitude and Practice Regarding Oral Hygiene Care in Intensive Care Unit Patients: A Multicenter Cross-sectional Study. Indian J Crit Care Med 2024;28(1):48-57.

Role of contrast-enhanced ultrasound for differentiation of benign vs. malignant portal vein thrombosis in hepatocellular carcinoma - A systematic review a meta-analysis.

Introduction/Purpose: Patients with cirrhosis and hepatocellular carcinoma (HCC) can develop both benign and malignant portal vein thrombosis (PVT). Characterising the nature of PVT is important for planning an optimal therapeutic strategy. In the absence of typical findings or contraindications to computed tomography (CT) or magnetic resonance imaging (MRI), contrast-enhanced ultrasound (CEUS) could help in this differentiation. The present meta-analysis aimed to evaluate the performance of CEUS for characterising PVT in patients with HCC. Methods: Electronic databases of PubMed, Embase and Scopus were searched from inception to 31 December 2022 for studies analysing the role of CEUS in the differentiation of benign and malignant PVT in HCC. Using the bivariate random effect model, pooled sensitivity and specificity were calculated, and the summary receiver operating characteristic (sROC) curve was plotted. Results: A total of 12 studies with data from 712 patients were included in the meta-analysis. The pooled sensitivity and specificity of CEUS for the diagnosis of tumour in vein were 97.0% (95% CI: 93.0-98.7) and 96.8% (95% CI: 92.1-98.7), respectively, without significant heterogeneity. A sROC curve was plotted, and the area under the receiver operating characteristic was 0.99 (95% CI: 0.98-1.00). Despite the presence of publication bias, sensitivity analysis did not show any change in sensitivity and specificity. Discussion: Our meta-analysis summarises the accuracy data from 12 studies, including >700 subjects. Contrast-enhanced ultrasound had excellent diagnostic accuracy with pooled sensitivity and specificity of 97.5% (95% CI: 93.5-99.1) and 98.2% (95% CI: 91.5-99.6), respectively, without any significant heterogeneity. Additionally, the pooled positive LR, negative LR and DOR were 54.6 (95% CI: 11.1-25.6), 0.02 (0.01-0.07) and 2186.8 (318.3-15022.2), respectively. A positive result increases the pretest probability of malignant PVT from 50% to 98%, whereas a negative result decreases it from 50% to 2%. Most of the studies included in our meta-analysis used identical techniques and 6-12-month follow-up scans to check for thrombus progression or regression. Our analysis showed no significant heterogeneity in the studies, and area under receiver operating characteristic curve (AUROC) with 95% CI was 1.00 (95% CI: 0.99-1.00). This critical meta-analysis thus propels CEUS to the forefront for differentiating benign from tumoural PVT and suggests routinely using CEUS in patients presenting with HCC and evidence of thrombus on greyscale ultrasound. Conclusion: Contrast-enhanced ultrasound is an effective diagnostic modality differentiation of benign and malignant PVT in patients with HCC and can be an alternative modality to CT or MRI. Further studies are required to study the role of CEUS as initial diagnostic modality for the characterisation of PVT in HCC.

N4-acetylcytidine (ac4C) promotes mRNA localization to stress granules.

Stress granules are an integral part of the stress response that are formed from non-translating mRNAs aggregated with proteins. While much is known about stress granules, the factors that drive their mRNA localization are incompletely described. Modification of mRNA can alter the properties of the nucleobases and affect processes such as translation, splicing and localization of individual transcripts. Here, we show that the RNA modification N4-acetylcytidine (ac4C) on mRNA associates with transcripts enriched in stress granules and that stress granule localized transcripts with ac4C are specifically translationally regulated. We also show that ac4C on mRNA can mediate localization of the protein NOP58 to stress granules. Our results suggest that acetylation of mRNA regulates localization of both stress-sensitive transcripts and RNA-binding proteins to stress granules and adds to our understanding of the molecular mechanisms responsible for stress granule formation.

Comparison of diagnostic capability of macular ganglion cell complex vs retinal fiber layer thickness in primary open angle glaucoma patients of Indian origin.

PURPOSE: Comparison of diagnostic capability of macular ganglion cell complex thickness vs. retinal nerve fiber layer (RNFL) thickness in patients of primary open-angle glaucoma (POAG). SETTINGS AND DESIGN: This cross-sectional observational study was carried out between June 2021 and October 2022 at a tertiary care hospital in North India. METHODS: A total of 118 eyes were included in the study with 30 control and the rest 88 eyes with POAG were divided into three groups based on visual field loss Group 1 (30 eyes): early field loss with mean deviation (MD) < -6 dB; Group 2 (30 eyes): moderate field loss with MD -6 to -12 dB; and Group 3 (28 eyes): severe field loss with MD > -12 dB. Optical coherence tomography (OCT) scans to measure RNFL loss and ganglion cell inferior plexiform layer (GCIPL) loss were taken for each patient. STATISTICAL ANALYSIS USED: Categorical variables were analyzed using either the Chi-square test or Fisher's exact test. A receiver operating characteristics analysis was calculated to determine optimal cut-off values of superior, inferior, and average GCIPL and RNFL for determining the severity of field loss as compared to controls (30 normal eyes). RESULTS: In the mild field loss group the sensitivity of superior, inferior, and average GCIPL was 86.7, 96.7, and 96.7%, respectively. Similarly, the specificity was 96.7, 93.3, and 100%, respectively. In the same group, the sensitivity of superior, inferior, and average RNFL was 70, 93, and 66%, respectively. Similarly, the specificity was 46.7, 83.3, and 70%, respectively. In the moderate and severe groups, the results were comparable. CONCLUSION: The sensitivity and specificity of GCIPL loss are significantly better than that of RNFL parameters in the mild field loss group.

Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders.

IL-22 is critical for ameliorating obesity-induced metabolic disorders. However, it is unknown where IL-22 acts to mediate these outcomes. Here we examine the importance of tissue-specific IL-22RA1 signaling in mediating long-term high fat diet (HFD) driven metabolic disorders. To do so, we generated intestinal epithelium-, liver-, and white adipose tissue (WAT)-specific Il22ra1 knockout and littermate control mice. Intestinal epithelium- and liver-specific IL-22RA1 signaling upregulated systemic glucose metabolism. Intestinal IL-22RA1 signaling also mediated liver and WAT metabolism in a microbiota-dependent manner. We identified an association between Oscillibacter and elevated WAT inflammation, likely induced by Mmp12 expressing macrophages. Mechanistically, transcription of intestinal lipid metabolism genes is regulated by IL-22 and potentially IL-22-induced IL-18. Lastly, we show that Paneth cell-specific IL-22RA1 signaling, in part, mediates systemic glucose metabolism after HFD. Overall, these results elucidate a key role of intestinal epithelium-specific IL-22RA1 signaling in regulating intestinal metabolism and alleviating systemic obesity-associated disorders.