A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

Life Cycle Greenhouse Gas Impacts of Coal and Imported Gas-Based Power Generation in the Indian Context.

Few studies have evaluated the life cycle greenhouse gas (GHG) impacts associated with India's power sector, despite the expectation that it will dominate new thermal generation capacity additions over the coming decades. Here, we utilize India-specific supply chain data to estimate life cycle GHG emissions associated with power generated by combustion of Indian coal and liquefied natural gas (LNG) imported from the United States. Life cycle impacts of domestic coal power vary widely (80% confidence interval (CI): 951-1231 kg CO2eq/MWh) because of heterogeneity in existing power plant characteristics such as efficiency, age, and capacity. Less variability is observed for LNG sourced from northeast United States and used in the existing Indian combined cycle gas turbine (CCGT) fleet (80% CI: 523-648 kg CO2eq/MWh). On average, life cycle GHG emissions from LNG imported into India are ∼54% lower than those associated with Indian coal. However, the GHG intensity of the Indian coal-power sector may be reduced by 13% by retiring plants with the lowest efficiencies and replacing them with higher-efficiency supercritical plants. Improvement of the CCGT fleet efficiency from its current level (41%) to that of a new plant with an F-class turbine (50%) could reduce life cycle GHG emissions for LNG-sourced power by 19%.

Activation of ganglion cells and axon bundles using epiretinal electrical stimulation.

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-µm diameter, 60-µm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses.NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

QVZ: lossy compression of quality values.

MOTIVATION: Recent advancements in sequencing technology have led to a drastic reduction in the cost of sequencing a genome. This has generated an unprecedented amount of genomic data that must be stored, processed and transmitted. To facilitate this effort, we propose a new lossy compressor for the quality values presented in genomic data files (e.g. FASTQ and SAM files), which comprise roughly half of the storage space (in the uncompressed domain). Lossy compression allows for compression of data beyond its lossless limit. RESULTS: The proposed algorithm QVZ exhibits better rate-distortion performance than the previously proposed algorithms, for several distortion metrics and for the lossless case. Moreover, it allows the user to define any quasi-convex distortion function to be minimized, a feature not supported by the previous algorithms. Finally, we show that QVZ-compressed data exhibit better performance in the genotyping than data compressed with previously proposed algorithms, in the sense that for a similar rate, a genotyping closer to that achieved with the original quality values is obtained. AVAILABILITY AND IMPLEMENTATION: QVZ is written in C and can be downloaded from https://github.com/mikelhernaez/qvz. CONTACT: mhernaez@stanford.edu or gmalysa@stanford.edu or iochoa@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

True scale-invariant random spatial networks.

Some aspects of real-world road networks seem to have an approximate scale invariance property, motivating study of mathematical models of random networks whose distributions are exactly invariant under Euclidean scaling. This requires working in the continuum plane, so making a precise definition is not trivial. We introduce an axiomatization of a class of processes we call scale-invariant random spatial networks, whose primitives are routes between each pair of points in the plane. One concrete model, based on minimum-time routes in a binary hierarchy of roads with different speed limits, has been shown to satisfy the axioms, and two other constructions (based on Poisson line processes and on dynamic proximity graphs) are expected also to do so. We initiate study of structure theory and summary statistics for general processes in the class. Many questions arise in this setting via analogies with diverse existing topics, from geodesics in first-passage percolation to transit node-based route-finding algorithms.

Decarbonization of the Indian electricity sector: Technology choices and policy trade-offs.

India is the third largest CO2 emitter worldwide, and its electricity demand, which is primarily supplied by coal-fired generation, is expected to increase almost threefold over the next twenty years. Here, we simulate 40 scenarios for the 2040 Indian electricity sector, considering uncertainty in future natural gas prices and costs for batteries and variable renewable energy (VRE) technologies, under different CO2 emissions limits and renewable portfolio standard (RPS) targets. We find a large-scale expansion of VRE, particularly, solar PV, in most scenarios. Furthermore, energy storage competes with natural gas and coal to provide flexibility to integrate VRE. Given a set of technology assumptions, policies that explicitly limit CO2 emissions are more cost-effective at reducing emissions than RPS policies. The former are also more effective at reducing air pollution than RPS policies by explicitly penalizing CO2 emissions, thereby reducing coal generation more substantially than RPS policies.

The role of gut microbiota in clinical complications, disease severity, and treatment response in severe alcoholic hepatitis.

BACKGROUND: Dysbiotic gut bacteria engage in the development and progression of severe alcoholic hepatitis (SAH). We aimed to characterize bacterial communities associated with clinical events (CE), identify significant bacteria linked to CE, and define bacterial relationships associated with specific CE and outcomes at baseline and after treatment in SAH. METHODS: We performed 16-s rRNA sequencing on stool samples (n=38) collected at admission and the last follow-up within 90 days in SAH patients (n=26; 12 corticosteroids; 14 granulocyte colony-stimulating factor, [G-CSF]). Validated pipelines were used to plot bacterial communities, profile functional metabolism, and identify significant taxa and functional metabolites. Conet/NetworkX® was utilized to identify significant non-random patterns of bacterial co-presence and mutual exclusion for clinical events. RESULTS: All the patients were males with median discriminant function (DF) 64, Child-Turcotte-Pugh (CTP) 12, and model for end-stage liver disease (MELD) score 25.5. At admission, 27%, 42%, and 58% had acute kidney injury (AKI), hepatic encephalopathy (HE), and infections respectively; 38.5% died at end of follow-up. Specific bacterial families were associated with HE, sepsis, disease severity, and death. Lachnobacterium and Catenibacterium were associated with HE, and Pediococcus with death after steroid treatment. Change from Enterococcus (promotes AH) to Barnesiella (inhibits E. faecium) was significant after G-CSF. Phenylpropanoid-biosynthesis (innate-immunity) and glycerophospholipid-metabolism (cellular-integrity) pathways in those without infections and the death, respectively, were upregulated. Mutual interactions between Enterococcus cecorum, Acinetobacter schindleri, and Mitsuokella correlated with admission AKI. CONCLUSIONS: Specific gut microbiota, their interactions, and metabolites are associated with complications of SAH and treatment outcomes. Microbiota-based precision medicine as adjuvant treatment may be a new therapeutic area.

Amphicrine carcinoma of the liver.

Amphicrine tumors are defined by evidence of both glandular and neuroendocrine differentiation in the same cell. These are extremely rare tumors, with only scattered case reports in the pancreas and stomach. We here report a case of amphicrine carcinoma occurring in apparent isolation in the liver. The tumor was characterized by signet ring cell morphology, mucicarmine, and periodic acid Schiff with diastase (PASD) positivity, and expression of chromogranin, synaptophysin, villin, and CDX2. No other tumor was identified by radiological or endoscopic examination of the gastrointestinal tract. The patient is disease-free 22 months after the resection. We speculate that this represents the first reported occurrence of primary amphicrine carcinoma of the liver.

Novel Mutations in the DGKE Gene in Two Indian Patients with Early-onset Atypical Haemolytic Uraemic Syndrome.

Atypical haemolytic uremic syndrome (aHUS) is a clinically and genetically heterogeneous condition caused by a complex interplay between genomic susceptibility factors and environmental influences. Pathogenic variants in the DGKE gene are recently identified in cases with infantile-onset autosomal recessive aHUS. The presence of low serum C3 levels, however, has rarely been described in cases of DGKE-associated aHUS. Molecular genetic testing was performed by a commercial next-generation sequencing (NGS) panel as well and by an in-house developed targeted NGS for DGKE gene. Copy number variations (CNVs) were computed from NGS data by calculating a normalised copy number ratio of aligned number of reads at targeted genomic regions against multiple reference regions of the same sample and multiple controls. We report here two such novel clinically relevant variants (c.727_730delTTGT and c.251_259delGCGCCTTC) in the DGKE gene, in two families of infantile aHUS with low serum C3 levels.

Clinical application of a novel next generation sequencing assay for CYP21A2 gene in 310 cases of 21- hydroxylase congenital adrenal hyperplasia from India.

PURPOSE: Accurate diagnosis is required for management of Congenital adrenal hyperplasia (CAH). The conventional method for detection of mutations in the CYP21A2 gene is targeted capillary sequencing which is labor intensive and has limited multiplexing capability. Next generation sequencing (NGS) provides data with high sequence coverage and depth. Our objective was to develop an accurate NGS-based assay to characterize the mutation spectrum in CYP21A2 gene in Indian patients suspected to have 21-OH CAH. METHODS: Cases with 21-OH CAH from 12 endocrine units across India were studied. DNA was extracted from proband's and parent's(subset) blood. Locus-specific long-range PCR and gel electrophoresis of amplicons was followed by NGS where no visible 30 kb homozygous/whole gene deletion was observed. Orthogonal confirmation was performed by capillary sequencing (ABI 3500) and Multiplex Ligation-dependent Probe Amplification (MLPA, MRC-Holland). PCR products were purified and individual libraries were pooled and sequenced (Illumina). RESULTS: Of the 310 CAH cases, biallelic mutations (pathogenic/ likely pathogenic variants involving both CYP21A2 gene copies) were detected in 256 (82.6%), heterozygous mutations in 13 (4.2 %), and none in 41 (13.2%). Most common mutation was c.293-13A/C>G (29.03%), followed by 30 kb deletion (18.24%). Thirty samples tested orthogonally (by capillary sequencing or MLPA) showed 100% concordance with NGS assay. Nine novel variants were identified. CONCLUSIONS: We have developed and validated a comprehensive NGS-based assay for detection of variants in CYP21A2 gene in patients with 21-OH CAH. We describe CYP21A2 mutation spectrum and novel variants in a large cohort of Indian patients with CAH.

Detection of a novel mutation in the rpoB gene in a multidrug resistant Mycobacterium tuberculosis isolate using whole genome next generation sequencing.

BACKGROUND: Mycobacterium tuberculosis (Mtb) drug resistance is a global concern. Moreover, multiple drug resistant (MDR), extensively drug resistant (XDR), and totally drug resistant (TDR) Mtb cases are on the rise in developing countries like India. Most of these cases are identified only 3-6 months after initiation of treatment owing to incomplete/failed clinical response and incomplete information from phenotypic drug resistance assays and/or targeted Mtb mutation analysis. Here, we report the development of an in-house whole genome sequencing (WGS) assay and bioinformatics pipeline that helped resolve the phenotype-genotype discrepancy in a clinical isolate. METHODOLOGY AND RESULTS: A sample from a suspected drug resistant Mtb case tested by line probe assay (LPA) showed the absence of both the mutant and wild type alleles for an rpoB gene mutation site. An in-house next generation sequencing (NGS) assay was used for WGS of this isolate. Bioinformatics analysis revealed that the isolate harboured a novel insertional mutation in the 81-bp hotspot region of the rpoB gene and a S315T mutation in the katG gene, which could explain resistance to rifampicin and isoniazid, respectively. These results correlated with the clinical diagnosis, LPA, solid culture drug susceptibility testing, and pyrosequencing carried out on the sample. The WGS data also provided information regarding the isolate's lineage and indicated an absence of known mutations conferring resistance to other antitubercular drugs. CONCLUSION: WGS is a highly sensitive, specific, and unbiased approach for identification of all possible drug resistance-conferring mutations, which can help clinicians make more informed treatment-related decisions.

MR imaging of liver fibrosis: current state of the art.

Chronic liver disease is a major public health problem worldwide. Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves the accumulation of collagen, proteoglycans, and other macromolecules within the extracellular matrix. Fibrosis tends to progress, leading to hepatic dysfunction, portal hypertension, and ultimately cirrhosis. Liver biopsy, the standard of reference for diagnosing liver fibrosis, is invasive, costly, and subject to complications and sampling variability. These limitations make it unsuitable for diagnosis and longitudinal monitoring in the general population. Thus, development of a noninvasive, accurate, and reproducible test for diagnosis and monitoring of liver fibrosis would be of great value. Conventional cross-sectional imaging techniques have limited capability to demonstrate liver fibrosis. In clinical practice, imaging studies are usually reserved for evaluation of the presence of portal hypertension or hepatocellular carcinoma in cases that have progressed to cirrhosis. In response to the rising prevalence of chronic liver diseases in Western nations, a number of imaging-based methods including ultrasonography-based transient elastography, computed tomography-based texture analysis, and diverse magnetic resonance (MR) imaging-based techniques have been proposed for noninvasive diagnosis and grading of hepatic fibrosis across its entire spectrum of severity. State-of-the-art MR imaging-based techniques in current practice and in development for noninvasive assessment of liver fibrosis include conventional contrast material-enhanced MR imaging, double contrast-enhanced MR imaging, MR elastography, diffusion-weighted imaging, and MR perfusion imaging.

Gut Microbiota in Alcoholic Hepatitis is Disparate from Those in Acute Alcoholic Pancreatitis and Biliary Disease.

BACKGROUND: Alcoholic hepatitis (AH) is associated with gut dysbiosis. Comparative gut microbial profiles of acute alcoholic pancreatitis (AAP) and acute biliary disease (ABD) are not demonstrated. We aimed to compare gut microbiota of AH, AAP, and ABD patients with each other and with their respective healthy controls (HCs). METHODS: From December 2016 to September 2017, consecutive patients with AH, AAP, and ABD (acute cholecystitis, acute biliary pancreatitis, and choledocholithiasis with cholangitis) were included in the study. Qualitative and functional stool microbiota comparative analysis was performed between groups, with AH as the reference comparator. RESULTS: Of 3564, 882, and 224 patients with liver disease, pancreatic disease, and biliary disease, respectively, after exclusion, 29 patients with AH and 7 patients each with AAP and ABD and their corresponding HCs were included in the study analysis. The alpha diversity between patients with AH and AAP was found to be significantly different. Significant relative abundance (RA) of Acinetobacter and Moraxella was noted among patients with AAP. Enterobacter, Atopobium, Synergistia, and Devosia were significantly higher in patients with ABD compared to patients with AH, in whom Faecalibacterium and Megamonas were higher. Functional pathways associated with carbohydrate metabolism, phenylpropanoid biosynthesis, and ethylbenzene degradation were significantly higher in AAP when compared to AH. Fatty acid and inositol phosphate metabolism and dioxin degradation were significantly upregulated in patients with ABD while lipid and fatty acid biosynthetic pathways and pathways associated with immune processes were upregulated in patients with AH. CONCLUSIONS: Differential gut dysbiosis is evident in both patients with AH, AAP, and ABD and also in comparison to HCs. The differential microbiota among patients with AH and AAP maybe important in promotion and progression of liver or pancreatic disease among alcohol users and may be a potential therapeutic target, which needs to be confirmed in larger multicenter studies.

Indian guidelines on imaging of the small intestine in Crohn's disease: A joint Indian Society of Gastroenterology and Indian Radiology and Imaging Association consensus statement.

The Indian Society of Gastroenterology (ISG) Task Force on Inflammatory Bowel Disease and the Indian Radiological and Imaging Association (IRIA) developed combined ISG-IRIA evidence-based best-practice guidelines for imaging of the small intestine in patients suspected to have or having Crohn's disease. The 29 consensus statements, developed through a modified Delphi process, are intended to serve as reference for teaching, clinical practice, and research.

Ultrasound of adnexal masses.

Current advancements in imaging technology, especially three-dimensional/four-dimensional ultrasound and contrast-enhanced imaging, have increased the diagnostic yield of adnexal masses. The benefit of ultrasound is the characterization of an adnexal mass, suggesting the probable etiology of the mass. Masses may be divided as solid, cystic, or complex. It is predominantly the solid and complex masses that need a thorough evaluation. The role of color-flow imaging is now gaining importance and criteria for distinguishing between benign and malignant masses are often possible. Availability of a scoring system enables the differentiation of small adnexal masses. Several benign lesions may present as complex masses but can be distinguished and diagnosed on sonography. The availability of 3D ultrasound has been of great use to understand spatial relations and vascular morphology. Sonography allows a more detailed assessment of morphologic features of an adnexal mass. With a benign-appearing adnexal mass on sonography, the need for any further diagnostic tests is often obviated.

Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.

INTRODUCTION: Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT. METHODS: Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3 months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT. RESULTS: All the patients were male. The proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p = 0.179] and 38%, 29%, 30%, and 75% [p = 0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes. CONCLUSIONS: Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.