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Background: Sarcoidosis and tuberculosis (TB) are the two most common causes of granulomatous mediastinal lymphadenopathy. These often exhibit overlapping clinical and radiological characteristics, rendering accurate diagnosis difficult. MicroRNA (miRNA) analysis is increasingly utilised as a potential biomarker for various diseases. Exhaled breath condensate (EBC) is a noninvasive technique for biomarker evaluation in different respiratory conditions. We attempted to identify differentially expressed miRNAs in the EBC of sarcoidosis and mediastinal TB patients., Methods: EBC was obtained from subjects with a definitive diagnosis of sarcoidosis and mediastinal TB. EBC was also obtained from age- and sex-matched control subjects. From EBC, miRNA isolation, cDNA preparation and qPCR array were performed. Differentially expressed miRNAs were shortlisted. Further validation was conducted in the EBC of a new subset., Results: Subjects with a definitive diagnosis of sarcoidosis (50) and TB (50), and control subjects (50) were included. qPCR array from EBC (20 subjects from each group) shortlisted eight differentially expressed miRNAs (miR-126, miR-132, miR-139-3p, miR-139-5p, miR-181c, miR-454, miR-512-3p and miR-362-5p). In the validation set (EBC of 30 subjects from each group), miR-126 and miR-132 were differentially expressed significantly. The miR-126 and miR-132 expression ratio could differentiate sarcoidosis from mediastinal TB with an AUC of 0.618 (82% specificity and 41% sensitivity)., Conclusion: While EBC miRNA expression is significantly and differently altered in sarcoidosis and mediastinal TB, a simple ratiometric approach failed to provide clinically useful signatures for differentiating between the two in patients with mediastinal lymphadenopathy., Competing Interests: Conflict of interest: The authors have no conflicts of interest., (Copyright ©The authors 2024.)

Budd Chiari syndrome is a potentially treatable disease, and imaging is the key to its diagnosis. Clinical presentations may vary, ranging from asymptomatic to fulminant disease. Subacute BCS is the most common type encountered in clinical practice, characterized by ascites, hepatosplenomegaly, dilated abdominal wall veins, and varicosities in the lower limb and scrotum. While hepatic vein thrombosis is the leading cause in the West, membranous and short segmental occlusion are predominant in the Asian populations. These geographical variations have an impact on the treatment algorithm in managing BCS. Anticoagulation alone often fails to prevent disease progression, demanding further interventional therapy. Interventional therapy carries a lower morbidity and mortality than surgery. Anatomical recanalization and portosystemic shunting form the basis of endovascular management. Membranous or short-segment occlusion are best treated by angioplasty, which restores the physiological venous outflow and possibly disease reversal. Suboptimal results with angioplasty require stenting. Transjugular intrahepatic shunt (TIPS) or direct IVC to portal vein shunt (DIPS) decompresses the portal pressure and reduces the sinusoidal congestion, which in turn diminishes hepatocellular damage and hepatic fibrosis. Despite its ability to modify the disease course, TIPS carries several procedure and shunt-related complications, mainly hepatic encephalopathy. Thus, anatomical recanalization precedes TIPS in the traditional step-up approach in managing BCS. However, this concept is challenged by some authors, necessitating future reseach. TIPS is a valid bridge therapy in BCS with acute live failure awaiting liver transplantation. Despite all, interventional therapies fail in a subset of BCS patients, leaving them with only option of liver transplantation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endoscopic ultrasound guided fine-needle aspiration (EUS FNA) is the first-line modality to diagnose suspected solid pancreatic malignant lesions. Elastography-guided FNA has been shown to improve the diagnostic yield of EUS FNA but prospective studies are limited. The aim of the study was to compare diagnostic accuracy, sensitivity and specificity of conventional and elastography-guided EUS FNA in patients with suspected malignant pancreatic solid masses., Methods: Patients with suspected malignant solid pancreatic lesions presenting to our institute from July 2021 to January 2023 were recruited and randomized to conventional and elastography-guided EUS FNA using a 22-G EUS FNA needle. Diagnostic accuracy, sensitivity, specificity and positive and negative predictive values were calculated., Results: Total 48 patients were initially screened for inclusion in the study, of which six were excluded and 42 patients underwent randomization. Finally, 20 patients in each group underwent the assigned intervention and were analyzed further. Baseline patient characteristics were similar in conventional FNA and elastography-guided FNA group with median age 52 (range 29-74) years and 51.8 (range 31-72) years, respectively, males being 70% and 75%, respectively. Median size of the lesion was 34 mm (range 14-48 mm) and 37 (range 18 to 50 mm), respectively, for both conventional and elastography arm. The average size of the lesion was 35.7 mm. Overall, the diagnosis of adenocarcinoma was made in 65% of cases. In the remaining cases, diagnoses were inflammatory mass, Castleman's disease, solid pseudopapillary epithelial neoplasm (SPEN), diffuse large B-cell lymphoma (DLBCL), pancreatic gastrointestinal stromal tumor (GIST) and metastasis. Conventional EUS FNA had diagnostic accuracy, sensitivity, specificity and positive and negative predictive values of 90%, 87.5%, 100%, 100% and 62.92%, respectively, and elastography-guided EUS FNA had diagnostic accuracy, sensitivity, specificity and positive and negative predictive values of 85%, 100%, 100% and 54.59%, respectively. No severe adverse events were noted., Conclusion: There is no significant difference between conventional and elastography-guided EUS FNA in terms of diagnostic accuracy, sensitivity, specificity and positive and negative predictive values. Both techniques appear safe and effective for characterizing solid pancreatic masses and elastography did not score numerically over the conventional arm., (© 2024. Indian Society of Gastroenterology.)

Percutaneous transhepatic biliary drainage (PTBD) is a routinely performed interventional radiological procedure. A myriad of complications can occur after PTBD, the most important being hemorrhagic complications that require immediate attention. Hemorrhage following PTBD may result from arterial, portal, or hepatic venous injury. A catheter or pull-back cholangiogram often demonstrates the venous injury. A computed tomogram angiogram aids in identifying bleeding sources and procedural planning. Catheter repositioning, upsizing, or clamping often suffice for minor venous bleeding. However, major venous injury necessitates tract embolization, portal vein embolization, or stent grafting. Arterial injury may lead to significant blood loss unless treated expeditiously. Transarterial embolization is the treatment of choice in such cases. Adequate knowledge about the hemorrhagic complications of PTBD will allow an interventional radiologist to take necessary precautionary measures to reduce their incidence and take appropriate steps in their management. This article entails four different hemorrhagic complications of PTBD and their interventional management. It also discusses the various treatment options to manage different kinds of post-PTBD hemorrhagic complications., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Vascular plug-assisted retrograde transvenous obliteration (PARTO) obliterates the gastric varices and portosystemic shunt, thus resulting in a lower rebleeding rate than endoscopic glue/sclerotherapy., Aims: To evaluate the safety and efficacy of PARTO as salvage therapy in liver cirrhosis with gastric variceal bleed (GVB) after failed endotherapy. We assessed the clinical success rate and changes in liver function at 6- months., Materials and Methods: Patients who underwent salvage PARTO after failed endotherapy for GVB (between December 2021 and November 2022) were searched and analyzed from the hospital database. Clinical success rate and rebleed rate were obtained at six months. Child-Pugh score (CTP) and Model for end-stage liver disease (MELD) score were calculated and compared between baseline and 6-month follow-up., Results: Fourteen patients (n = 14, Child-Pugh class A/B) underwent salvage PARTO. Nine had GOV-2, and five had IGV-1 varices. The mean shunt diameter was 11.6 ± 1.6 mm. The clinical success rate of PARTO was 100% (no recurrent gastric variceal hemorrhage within six months). No significant deterioration in CTP (6.79 ± 0.98 vs. 6.21 ± 1.52; p = 0.12) and MELD scores (11.5 ± 4.05 vs. 10.21 ± 3.19; p = 0.36) was noted at 6 months. All patients were alive at 6 months. One patient (n = 1, 7.1%) bled from esophageal varices after three days of PARTO and was managed with variceal banding. 21.4% (3/14) patients had progression of esophageal varices at 6 months requiring prophylactic band ligation. Three patients (21.4%) had new onset or worsening ascites and responded to low-dose diuretics therapy., Conclusions: PARTO is a safe and effective procedure for bleeding gastric varices without any deterioration in liver function even after six months. Patient selection is critical to prevent complications. Further prospective studies with larger sample size are required to validate our findings., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

INPP4A has been shown to be involved in the regulation of cell proliferation and apoptosis of multiple cell types including fibroblasts. Previous reports from our group have demonstrated the role of inositol polyphosphate 4-phosphatase Type I A (INPP4A) in these functions. Though existing evidences suggest a critical role for INPP4A in the maintenance of lung homeostasis, its role in chronic lung diseases is relatively under explored. In the current study, we made an attempt to understand the regulation of INPP4A in idiopathic pulmonary fibrosis (IPF). Through integration of relevant INPP4A gene expression data from public repositories with our results from in vitro experiments and mouse models, we show that INPP4A is altered in IPF. Interestingly, the direction of the change is dependent both on the disease stage and the region of the lung used. INPP4A was found to be upregulated when analyzed in lung sample representative of the whole lung, but was downregulated in the fibrotic regions of the lung. Similarly, INPP4A was found to be high, compared to controls, only in the early stage of the disease. Though the observed increase in INPP4A was found to be negatively correlated to physiological indices, FVC, and DL CO , of lung function, treatment with anti-INPP4A antibody worsened the condition in bleomycin treated mice. These contrasting results taken together are suggestive of a nuanced regulation of INPP4A in IPF which is dependent on the disease stage, cellular state and extent of fibrosis in the lung region being analyzed., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Idiopathic pulmonary fibrosis (IPF) is a rare and devastating fibrotic lung disorder with unknown etiology. Although it is believed that genetic component is an important risk factor for IPF, a comprehensive understanding of its genetic landscape is lacking. Hence, we aimed to highlight the susceptibility genes and pathways implicated in IPF pathogenesis through a two-staged systematic literature search of genetic association studies on IPF, followed by meta-analysis and pathway enrichment analysis., Methods: This study was performed based on PRISMA guidelines (PROSPERO, registration number: CRD42022297970). The first search was performed (using PubMed and Web of Science) retrieving a total of 5642 articles, of which 52 were eligible for inclusion in the first stage. The second search was performed (using PubMed, Web of Science and Scopus) for ten polymorphisms, identified from the first search, with 2 or more studies. Finally, seven polymorphisms, [rs35705950/MUC5B, rs2736100/TERT, rs2609255/FAM13A, rs2076295/DSP, rs12610495/DPP9, rs111521887/TOLLIP and rs1800470/TGF-β1] qualified for meta-analyses. The epidemiological credibility was evaluated using Venice criteria., Results: From the systematic review, 222 polymorphisms in 118 genes showed a significant association with IPF susceptibility. Meta-analyses findings revealed significant association of rs35705950/T [OR = 3.92(3.26-4.57)], rs2609255/G [OR = 1.50(1.18-1.82)], rs2076295/G [OR = 1.19(0.82-1.756)], rs12610495/G [OR = 1.28(1.12-1.44)], rs2736100/C [OR = 0.68(0.54-0.82), rs111521887/G [OR = 1.34(1.06-1.61)] and suggestive evidence for rs1800470/T [OR = 1.08(0.82-1.34)] with IPF susceptibility. Four polymorphisms- rs35705950/MUC5B, rs2736100/TERT, rs2076295/DSP and rs111521887/TOLLIP, exhibited substantial epidemiological evidence supporting their association with IPF risk. Gene ontology and pathway enrichment analysis performed on IPF risk-associated genes identified a critical role of genes in mucin production, immune response and inflammation, host defence, cell-cell adhesion and telomere maintenance., Conclusions: Our findings present the most prominent IPF-associated genetic risk variants involved in alveolar epithelial injuries (MUC5B, TERT, FAM13A, DSP, DPP9) and epithelial-mesenchymal transition (TOLLIP, TGF-β1), providing genetic and biological insights into IPF pathogenesis. However, further experimental research and human studies with larger sample sizes, diverse ethnic representation, and rigorous design are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gastrointestinal hemorrhage remains one of the most common causes of morbidity and mortality among patients with liver cirrhosis. Mostly, these patients bleed from the gastroesophageal varices. However, nonvariceal bleeding is also more likely to occur in these patients. Because of frequent co-existing coagulopathy, cirrhotics are more prone to bleed from a minor vascular injury while performing percutaneous interventions. Ultrasound-guided bedside vascular access is an essential procedure in liver critical care units. Transjugular portosystemic shunts (TIPS) with/without variceal embolization is a life-saving measure in patients with refractory variceal bleeding. Whenever feasible, balloon-assisted retrograde transvenous obliteration (BRTO) is an alternative to TIPS in managing gastric variceal bleeding, but without a risk of hepatic encephalopathy. In cases of failed or unfeasible endotherapy, transarterial embolization using various embolic agents remains the cornerstone therapy in patients with nonvariceal bleeding such as ruptured hepatocellular carcinoma, gastroduodenal ulcer bleeding, and procedure-related hemorrhagic complications. Among various embolic agents, N-butyl cyanoacrylate (NBCA) enables better vascular occlusion in cirrhotics, even in coagulopathy, making it a more suitable embolic agent in an expert hand. This article briefly entails the different interventional radiological procedures in vascular emergencies among patients with liver cirrhosis., (© 2023. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Background: Ameloblastoma is one of the major odontogenic neoplasms with an invasive and recurrence potential. Its tumourigenesis and proliferative capacity can be attributed to the activation or inactivation of certain molecular signalling pathways. Hippo signalling pathway is known to regulate diverse physiological processes related to mitosis and organ growth and is an emerging tumour suppressor pathway, the dysfunction of which is implicated in various diseases including cancers. Yes-associated protein1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the downstream effectors in the Hippo cascade, which on nuclear activation leads to cellular proliferation in various tumours., Aim: The current study was undertaken to evaluate the expression of YAP in various histopathological variants of ameloblastoma and unicystic ameloblastoma., Materials and Methods: Fifty formalin-fixed paraffin-embedded tissue samples of histopathologically diagnosed cases of ameloblastoma, and 10 histopathologically diagnosed cases of unicystic ameloblastoma were obtained from the departmental archives to evaluate the immunohistochemical expression of YAP both manually and by software analysis., Results: More than 90% of cases of conventional ameloblastoma and unicystic ameloblastoma elicited positive expression of YAP. No statistical difference was found among different histopathological variants of conventional ameloblastoma. Significant difference between the means of all four quantitative score groups was observed., Conclusion: In view of the modulating effect of YAP in tumourigenesis and its higher expression in ameloblastoma, further exploration of this molecule appears to be a promising area of research., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Oral and Maxillofacial Pathology.)

Lung cancer is one of the common cancers globally with high mortality and poor prognosis. Most cases of lung cancer are diagnosed at an advanced stage due to limited diagnostic resources. Screening modalities, such as sputum cytology and annual chest radiographs, have not proved sensitive enough to impact mortality. In recent years, annual low-dose computed tomography has emerged as a potential screening tool for early lung cancer detection, but it may not be a feasible option for developing countries. In this context, exhaled breath condensate (EBC) analysis has been evaluated recently as a noninvasive tool for lung cancer diagnosis. The breath biomarkers also have the advantage of differentiating various types and stages of lung cancer. Recent studies have focused more on microRNAs (miRNAs) as they play a key role in tumourigenesis by regulating the cell cycle, metastasis and angiogenesis. In this review, we have consolidated the current published literature suggesting the utility of miRNAs in EBC for the detection of lung cancer., Competing Interests: Conflict of interest: The authors have no conflicts of interest or disclosures., (Copyright ©ERS 2024.)

Idiopathic Pulmonary Fibrosis (IPF) is a progressively fatal and incurable disease characterized by the loss of alveolar structures, increased epithelial-mesenchymal transition (EMT), and aberrant tissue repair. In this study, we investigated the role of Nuclear Factor I-B (NFIB), a transcription factor critical for lung development and maturation, in IPF. Using both human lung tissue samples from patients with IPF, and a mouse model of lung fibrosis induced by bleomycin, we showed that there was a significant reduction of NFIB both in the lungs of patients and mice with IPF. Furthermore, our in vitro experiments using cultured human lung cells demonstrated that the loss of NFIB was associated with the induction of EMT by transforming growth factor beta (TGF-β). Knockdown of NFIB promoted EMT, while overexpression of NFIB suppressed EMT and attenuated the severity of bleomycin-induced lung fibrosis in mice. Mechanistically, we identified post-translational regulation of NFIB by miR-326, a miRNA with anti-fibrotic effects that is diminished in IPF. Specifically, we showed that miR-326 stabilized and increased the expression of NFIB through its 3'UTR target sites for Human antigen R (HuR). Moreover, treatment of mice with either NFIB plasmid or miR-326 reversed airway collagen deposition and fibrosis. In conclusion, our study emphasizes the critical role of NFIB in lung development and maturation, and its reduction in IPF leading to EMT and loss of alveolar structures. Our study highlights the potential of miR-326 as a therapeutic intervention for IPF. The schema shows the role of NFIB in maintaining the normal epithelial cell characteristics in the lungs and how its reduction leads to a shift towards mesenchymal cell-like features and pulmonary fibrosis. A In normal lungs, NFIB is expressed abundantly in the epithelial cells, which helps in maintaining their shape, cell polarity and adhesion molecules. However, when the lungs are exposed to factors that induce pulmonary fibrosis, such as bleomycin, or TGF-β, the epithelial cells undergo epithelial to mesenchymal transition (EMT), which leads to a decrease in NFIB. B The mesenchymal cells that arise from EMT appear as spindle-shaped with loss of cell junctions, increased cell migration, loss of polarity and expression of markers associated with mesenchymal cells/fibroblasts. C We designed a therapeutic approach that involves exogenous administration of NFIB in the form of overexpression plasmid or microRNA-326. This therapeutic approach decreases the mesenchymal cell phenotype and restores the epithelial cell phenotype, thus preventing the development or progression of pulmonary fibrosis., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: This study aimed to analyze risk factors and develop a predictive model for early allograft loss due to early graft dysfunction (EGD) in adult live-donor liver transplantation (LDLT)., Methods: Data of patients who underwent LDLT from 2011 to 2019 were reviewed for EGD, associated factors, and outcomes. A homogeneous group of 387 patients was analyzed: random cohort A (n = 274) for primary analysis and random cohort B (n = 113) for validation., Results: Of 274 recipients, 92 (33.6%) developed EGD. The risk of graft loss within 90 days was 29.3% and 7.1% in those with and without EGD, respectively ( P < 0.001). Multivariate logistic regression analysis determined donor age ( P = 0.045), estimated (e) graft weight ( P = 0.001), and the model for end-stage liver disease (MELD) score (0.001) as independent predictors of early graft loss due to EGD. Regression coefficients of these factors were employed to formulate the risk model: Predicted (P) early graft loss risk (e-GLR) score = 10 × [(donor age × 0.052) + (e-Graft weight × 1.681) + (MELD × 0.145)] - 8.606 (e-Graft weight = 0, if e-Graft weight ≥640 g and e-Graft weight = 1, and if e-Graft weight < 640 g). Internal cross-validation revealed a high predictive value (C-statistic = 0.858)., Conclusions: Our novel risk score can efficiently predict early allograft loss following graft dysfunction, which enables donor-recipient matching, evaluation, and prognostication simply and reliably in adult LDLT., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hepatoid adenocarcinoma of the stomach is a rare histologic subtype of gastric carcinoma. Morphologically, it shows hepatocyte-like features and the tumor cells can show the expression of alpha-fetoprotein (AFP) in the tumor cells as well as in serum. There are a few AFP-negative hepatoid adenocarcinoma tumors that have been reported in the literature. A 45-year-old male patient presented with abdominal pain. Endoscopy and radiological studies showed an ulceronodular thickening in the antropyloric thickening with lymphadenopathy. He underwent radical subtotal gastrectomy with lymph node dissection. Microscopic examination showed adenocarcinoma with hepatocytic morphology, the presence of lymphovascular and perineural invasion, prominent peritumoral lymphocytic infiltration, multiple metastatic tumor deposit involving regional lymoh nodes and omentum. Adjacent gastric mucosa showed Helicobacter pylori -associated chronic atrophic gastritis with intestinal metaplasia. On immunohistochemistry (IHC), tumor cells were immunopositive for keratin 7, CDX2, and HepPar-1, p53 (focal), and MUC5AC (focal) while immunonegative for AFP, SALL4, MUC2, CD10, and HER2 (ERBB2) was negative. We report this AFP-negative hepatoid adenocarcinoma with its associated uncommon features and discussed the literature review and diagnostic approach.

Background: Alcohol relapse after liver transplantation has a negative impact on outcomes. There is limited data on its burden, the predictors, and impact following live donor liver transplantation (LDLT)., Methods: A single-center observational study was carried out between July 2011 and March 2021 for patients undergoing LDLT for alcohol associated liver disease (ALD). The incidence, predictors of alcohol relapse, and post-transplant outcomes were assessed., Results: Altogether 720 LDLT were performed during the study period, 203 (28.19%) for ALD. The overall relapse rate was 9.85% (n = 20) with a median follow-up of 52 months (range, 12-140 months). Sustained harmful alcohol use was seen in 4 (1.97%). On multivariate analysis, pre-LT relapse (P = .001), duration of abstinence period (P = .007), daily intake of alcohol (P = .001), absence of life partner (P = .021), concurrent tobacco abuse before transplant (P = .001), the donation from second-degree relative (P = .003) and poor compliance with medications (P = .001) were identified as predictors for relapse. Alcohol relapse was associated with the risk of graft rejection (HR 4.54, 95% CI: 1.751-11.80, P = .002)., Conclusion: Our results show that the overall incidence of relapse and rate of harmful drinking following LDLT is low. Donation from spouse and first degree relative was protective. History of daily intake, prior relapse, shorter pretransplant abstinence duration and lack of family support significantly predicted relapse., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Propolis is a promising natural product that has been extensively researched and studied for its potential health and medical benefits. The lack of requisite high oil-containing propolis and existing variation in the quality and quantity of essential oil within agro-climatic regions pose a problem in the commercialization of essential oil. As a result, the current study was carried out to optimize and estimate the essential oil yield of propolis. The essential oil data of 62 propolis samples from ten agro-climatic areas of Odisha, as well as an investigation of their soil and environmental parameters, were used to construct an artificial neural network (ANN) based prediction model. The influential predictors were determined using Garson's algorithm. To understand how the variables interact and to determine the optimum value of each variable for the greatest response, the response surface curves were plotted. The results revealed that the most suited model was multilayer-feed-forward neural networks with an R2 value of 0.93. According to the model, altitude was found to have a very strong influence on response, followed by phosphorous & maximum average temperature. This research shows that using an ANN-based prediction model with a response surface methodology technique to estimate oil yield at a new site and maximize propolis oil yield at a specific site by adjusting variable parameters is a viable commercial option. To our knowledge, this is the first report on the development of a model to optimize and estimate the essential oil yield of propolis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nayak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lung cancer is one of the common malignancies with high mortality rate and a poor prognosis. Most lung cancer cases are diagnosed at an advanced stage either due to limited resources of infrastructure, trained human resources, or delay in clinical suspicion. Low-dose computed tomography has emerged as a screening tool for lung cancer detection but this may not be a feasible option for most developing countries. Electronic nose is a unique non-invasive device that has been developed for lung cancer diagnosis and monitoring response by exhaled breath analysis of volatile organic compounds. The breath-print have been shown to differ not only among lung cancer and other respiratory diseases, but also between various types of lung cancer. Hence, we postulate that the breath-print analysis by electronic nose could be a potential biomarker for the early detection of lung cancer along with monitoring treatment response in a resource-limited setting. In this review, we have consolidated the current published literature suggesting the use of an electronic nose in the diagnosis and monitoring treatment response of lung cancer., (Creative Commons Attribution license.)

The major global concern on energy is focused on conventional fossil resources. The burning of fossil fuels is an origin of greenhouse gas emissions resulting in the utmost threat to the environment and subsequently which leads to global climate changes. As far as sustainability is concerned, fuels and materials derived from organic or plant wastes overcome this downside establishing the solution to the fossil resource crisis. In this context, exploration of agricultural residue appears to be a suitable alternative of non-renewable resources to support the environmental feasibility and meet the high energy crisis. The use of agricultural waste as a feedstock for the biorefinery approach emerges to be an eco-friendly process for the production of biofuel and value-added chemicals, intensifying energy security. Therefore, a prospective choice of this renewable biomass for the synthesis of green fuel and other green biochemicals comes up with a favorable outcome in terms of cost-effectiveness and sustainability. Exploiting different agricultural biomass and exploring various biomass conversion techniques, biorefinery generates bioenergy in a strategic way which eventually fits in a circular bioeconomy. Sources and production of agricultural waste are critically explained in this paper, which provides a path for further value addition by various technologies. Biorefinery solutions, along with a life cycle assessment of agricultural waste biomass toward a wide array of value-added products aiding the bioeconomy, are summarized in this paper., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Quantitation of microRNAs secreted by lung cells can provide valuable information regarding lung health. Exhaled breath condensate (EBC) offers a non-invasive way to sample the secreted microRNAs, and could be used as diagnostic tools for lung cancer., Materials & Methods: EBC samples from twenty treatment-naïve patients with pathologically confirmed lung cancer and twenty healthy subjects were profiled for miRNAs expression. Selected microRNAs were further validated, using quantitative-PCR, in an independent set of 10 subjects from both groups., Results: A total of 78 miRNAs were found to be significantly upregulated in the EBC of lung cancer patients compared to the control group. Six of these 78 miRNAs were shortlisted for validation. Of these, miR-31-3p, let7i, and miR-449c were significantly upregulated, exhibited good discriminatory power., Discussion: Differential expression of miRNAs secreted by lung cells could be quantitated in EBC samples, and could be used as a potential non-invasive tool for early diagnosis of lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The structurally and genetically distinct sigma-1 receptor (S1R) and sigma-2 receptor (S2R) comprise a unique class of drug binding sites. Their alleles are associated with human diseases involving neuronal systems, such as age-related macular degeneration (AMD) characterized by photoreceptor and retinal pigment epithelium (RPE) atrophy. Previous studies have suggested neuroprotective benefits for the brain and retina from pharmacological modulation of S1R and/or S2R. However, the effect of such modulation on AMD pathology remains underexplored. Here, we evaluated S1R- or S2R-selective modulation in an AMD-related model of Abca4 -/- Rdh8 -/- mice with a disrupted visual cycle that predisposes RPE and photoreceptors to illumination-induced damage. For S1R modulation, we used (+)-pentazocine, which is a high-affinity S1R-selective drug. For S2R modulation, we chose CM398, a high-affinity and highly S2R-selective ligand with drug-like properties. Abca4 -/- Rdh8 -/- mice received a single i.p. injection of (+)-pentazocine or CM398 or vehicle 30 min before illumination. Pretreatment with (+)-pentazocine improved electroretinogram a- and b-waves compared to that with vehicle. Consistently, in another AMD-related mouse model induced by tail-vein injected NaIO 3 , S1R genetic ablation aggravated photoreceptor loss. In Abca4 -/- Rdh8 -/- mice, pretreatment with CM398 appeared to partially avert illumination-induced photoreceptor loss and autofluorescent granule formation that signals RPE damage, as revealed by optical coherence tomography. Thus, this study using AMD-related models provides evidence of photoreceptor protection afforded by selective modulation of S1R or S2R., Competing Interests: The authors declare no conflict of interest.

Foot-and-mouth disease (FMD) is a significant threat to animal health globally. Prophylactic vaccination using inactivated FMD virus (FMDV) antigen is being practised for the control in endemic countries. A major limitation of the current vaccine is its susceptibility to high environmental temperature causing loss of immunogenicity, thus necessitating the cold chain for maintenance of its efficacy. Hence, the FMD vaccine with thermostable virus particles will be highly useful in sustaining the integrity of whole virus particle (146S) during storage at 4°C. In this study, 12 recombinant mutants of Indian vaccine strain of FMDV serotype O (O/IND/R2/1975) were generated through reverse genetics approach and evaluated for thermostability. One of the mutant viruses, VP2&#95;Y98F was more thermostable than other mutants and the parent FMDV. The oil-adjuvanted vaccine formulated with the inactivated VP2&#95;Y98F mutant FMDV was stable up to 8 months when stored at 4°C and induced protective antibody response till dpv 180 after primary vaccination. It is concluded that the VP2&#95;Y98F mutant FMDV was thermostable and has the potential to replace the parent vaccine strain., (© 2022 Wiley-VCH GmbH.)

Antigenic profiling of recent field outbreak strains of foot-and-mouth disease virus (FMDV) serotype A in India has revealed considerable antigenic drift from the vaccine strain, A IND 40/2000, necessitating the selection of a new strain. The complete genome sequence of A IND 27/2011 was analysed. Vaccine quality attributes of the new candidate strain including potency as an inactivated vaccine in cattle were evaluated. The capsid coding region of A IND 27/2011 showed variation at eight antigenically critical amino acid positions from that of A IND 40/2000. The strain suited well with traits required by a vaccine in terms of its adaptability to adherent and suspension cell line, its immunogenicity, and potency as an inactivated vaccine formulation in cattle. Complete protection was observed upon homologous virus challenge at 4 weeks post-vaccination. Taken together, these data demonstrate the suitability of A IND 27/2011 as an effective vaccine strain of FMDV serotype A., (© 2021 Wiley-VCH GmbH.)

Foot-and-mouth disease (FMD) is endemic in India, where circulation of serotypes O, A and Asia1 is frequent. Here, we provide an epidemiological assessment of the ongoing mass vaccination programs in regard to post-vaccination monitoring and outbreak occurrence. The objective of this study was assessing the contribution of mass vaccination campaigns in reducing the risk of FMD in India from 2008 to 2016 by evaluating sero-monitoring data and modelling the spatiotemporal dynamics of reported outbreaks. Through analyzing antibody titre data from >1 million animals sampled as part of pre- and post-vaccination monitoring, we show that the percent of animals with inferred immunological protection (based on ELISA) was highly variable across states but generally increased through time. In addition, the number of outbreaks in a state was negatively correlated with the percent of animals with inferred protection. We then analyzed the distribution of reported FMD outbreaks across states using a Bayesian space-time model. This approach provides better acuity to disentangle the effect of mass vaccination programs on outbreak occurrence, while accounting for other factors that contribute to spatiotemporal variability in outbreak counts, notably proximity to international borders and inherent spatiotemporal correlations in incidence. This model demonstrated a ∼50% reduction in the risk of outbreaks in states that were part of the vaccination program. In addition, after controlling for spatial autocorrelation in the data, states that had international borders experienced heightened risk of FMD outbreaks. These findings help inform risk-based control strategies for India as the country progresses towards reducing reported clinical disease., (© 2022 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

Pneumonia, an acute respiratory tract infection, is one of the major causes of mortality worldwide. Depending on the site of acquisition, pneumonia can be community acquired pneumonia (CAP) or nosocomial pneumonia (NP). The risk of pneumonia, is partially driven by host genetics. CYP1A1 is a widely studied pulmonary CYP family gene primarily expressed in peripheral airway epithelium. The CYP1A1 genetic variants, included in this study, alter the gene activity and are known to contribute in lung inflammation, which may cause pneumonia pathogenesis. In this study, we performed a meta-analysis to establish the possible contribution of CYP1A1 gene, and its three variants (rs2606345, rs1048943 and rs4646903) towards the genetic etiology of pneumonia risk. Using PRISMA guidelines, we systematically reviewed and meta-analysed case-control studies, evaluating risk of pneumonia in patients carrying the risk alleles of CYP1A1 variants. Heterogeneity across the studies was evaluated using I2 statistics. Based on heterogeneity, a random-effect (using maximum likelihood) or fixed-effect (using inverse variance) model was applied to estimate the effect size. Pooled odds ratio (OR) was calculated to estimate the overall effect of the risk allele association with pneumonia susceptibility. Egger's regression test and funnel plot were used to assess publication bias. Subgroup analysis was performed based on pneumonia type (CAP and NP), population, as well as age group. A total of ten articles were identified as eligible studies, which included 3049 cases and 2249 healthy controls. The meta-analysis findings revealed CYP1A1 variants, rs2606345 [T vs G; OR = 1.12 (0.75-1.50); p = 0.02; I2 = 84.89%], and rs1048943 [G vs T; OR = 1.19 (0.76-1.61); p = 0.02; I2 = 0.00%] as risk markers whereas rs4646903 showed no statistical significance for susceptibility to pneumonia. On subgroup analysis, both the genetic variants showed significant association with CAP but not with NP. We additionally performed a spatial analysis to identify the key factors possibly explaining the variability across countries in the prevalence of the coronavirus disease 2019 (COVID-19), a viral pneumonia. We observed a significant association between the risk allele of rs2606345 and rs1048943, with a higher COVID-19 prevalence worldwide, providing us important links in understanding the variability in COVID-19 prevalence., (Copyright © 2022. Published by Elsevier B.V.)

Nucleic acids, both DNA and small RNAs, have emerged as potential therapeutics for the treatment of various lung disorders. However, delivery of nucleic acids to the lungs is challenging due to the barrier property imposed by mucus, which is further reinforced in disease conditions such as chronic obstructive pulmonary disease and asthma. The presence of negatively charged mucins imparts the electrostatic barrier property, and the mesh network structure of mucus provides steric hindrance to the delivery system. To overcome this, the delivery system either needs to be muco-inert with a low positive charge such that the interactions with mucus are minimized or should have the ability to transiently dismantle the mucus structure for effective penetration. We have developed a mucus penetrating system for the delivery of both small RNA and plasmid DNA independently. The nucleic acid core consists of a nucleic acid (pDNA/siRNA) and a cationic/amphipathic cell penetrating peptide. The mucus penetrating coating consists of the hydrophilic biopolymer chondroitin sulfate A (CS-A) conjugated with a mucolytic agent, mannitol. We hypothesize that the hydrophilic coating of CS-A would reduce the surface charge and decrease the interaction with negatively charged mucins, while the conjugated mannitol residues would disrupt the mucin-mucin interaction or decrease the viscosity of mucus by increasing the influx of water into the mucus. Our results indicate that CS-A-mannitol-coated nanocomplexes possess reduced surface charge, reduced viscosity of artificial mucus, and increased diffusion in mucin suspension as well as increased penetration through the artificial mucus layer as compared to the non-coated ones. Further, the coated nanocomplexes showed low cytotoxicity as well as higher transfection in A-549 and BEAS-2B cells as compared to the non-coated ones.

Competing Interests: The authors have none to declare.

Tuberculosis (TB) remains a major infectious disease across the globe. With increasing TB infections and a rise in multi-drug resistance, rapid diagnostic modalities are required to achieve TB control. Radiological investigations and microbiological tests (microscopic examination, cartridge-based nucleic acid amplification tests, and cultures) are most commonly used to diagnose TB. Histopathological/cytopathological examinations are also required for an accurate diagnosis in many patients. The causative agent, Mycobacterium tuberculosis (Mtb), is known to circumvent the host's immune system. Circulating microRNAs (miRNAs) play a crucial role in biological pathways and can be used as a potential biomarker to detect tuberculosis. miRNAs are small non-coding RNAs and negatively regulate gene expression during post-transcriptional regulation. The differential expression of miRNAs in multiple clinical samples in tuberculosis patients may be helpful as potential disease biomarkers. This review summarizes the literature on miRNAs in various clinical samples as biomarkers for TB diagnosis., Competing Interests: None., (© 2022 The Authors.)

Background: Cardiac sarcoidosis (CS) is an underdiagnosed and life-threatening condition. Histopathological diagnosis is difficult due to the risks and variable diagnostic yield of endomyocardial biopsy., Objectives: To study the clinical profile and compare the diagnostic criteria of CS in a cohort of sarcoidosis., Methods: A retrospective review of the Sarcoidosis database (375 patients) was performed to identify patients with CS. Demographic and clinical details were retrieved. We applied the available diagnostic criteria for the diagnosis of CS: The World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG), Heart Rhythm Society (HRS), and Japanese Ministry of Health and Welfare (JMHW) criteria., Results: Out of the 375 patients, 15 (4%) were identified with CS. The median age was 41 years, and 53% were female. The most common symptoms were breathlessness, palpitation, and fatigue in 80%, 53.3%, and 46.6% of patients, respectively. Tuberculin positivity (≥ 10mm induration) was seen in 26.6%. 80% and 53.3% of the patients had abnormal ECG and 2D echocardiography findings, respectively. Six patients had a history of Ventricular tachycardia (40%). LV Ejection fraction was reduced in 12 subjects (80%). Cardiac-MRI showed late gadolinium enhancement in 53.3%. A definitive histopathological diagnosis for sarcoidosis was established in 86.6% (13/15) patients. Of the 15, all satisfied JMHW criteria and WASOG criteria (12 (80%) at least probable category, 3 (20%) possible CS), and 13 (86.6%) met HRS criteria for a diagnosis of CS., Conclusion: In a cohort of 375 patients with sarcoidosis in a tuberculosis endemic setting, 4% were diagnosed with cardiac sarcoidosis. Histopathological diagnosis may be obtained by sampling from extracardiac sites. JMHW and WASOG criteria perform equally well in TB endemic settings., Competing Interests: Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright: © 2021 SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES.)

Introduction: Sarcoidosis is a multisystem granulomatous disease with a varied clinical presentation. We describe the clinical characteristics of patients with sarcoidosis from a tuberculosis (TB) endemic setting., Methods: We performed an analysis of the sarcoidosis database at a tertiary care facility in North India., Results: Of the 327 patients, 50.8% were male, with a mean age of 42.8 years (range: 16-70 years). Females were significantly older. 42.6% had comorbidities, of which diabetes (17.1%) was most common. More than half (57.1%) were obese. Serum angiotensin-converting enzyme levels were elevated in 186 (57.9%). Eleven (3.8%) had hypercalcemia, while hypercalciuria was present in 54 (31.7%). The majority (89.9%) were tuberculin skin test negative (<10 mm induration), while 71.9% were tuberculin anergic. 47.7% had normal spirometry, while a restrictive impairment was the most common abnormality (44.6%). Obstruction on spirometry was present in 8.3%. Nearly half (160, 49%) had involvement of an extrapulmonary site. Most patients were (96%) symptomatic. Cough, shortness of breath, fatigue, weight loss, and fever were the predominant symptoms. A majority had Stage 1 (47.7%) sarcoidosis. Two hundred and eighty-seven (87.8%) patients underwent bronchoscopy or endosonographic (endobronchial ultrasound-guided transbronchial needle aspiration [EBUS-TBNA] or transesophageal bronchoscopic ultrasound-guided fine-needle aspiration [EUS-B-FNA]) sampling. A histopathological diagnosis with the demonstration of granulomas was achieved in 90.8%. The diagnostic yield of EBUS-TBNA/EUS-B-FNA was 77.4%. In 13.5% of patients, necrotizing granulomas were present in tissue samples., Conclusion: The clinical profile of patients with sarcoidosis in TB endemic settings has certain differences from nonendemic populations. Bronchoscopy and endosonography allow a confident diagnosis in the majority of patients., Competing Interests: None

Background: An ideal definition of early allograft dysfunction (EAD) after live donor liver transplantation (LDLT) remains elusive. The aim of the present study was to compare the diagnostic accuracies of existing EAD definitions, identify the predictors of early graft loss due to EAD, and formulate a new definition, estimating EAD-related mortality in LDLT recipients., Methods: Consecutive adult patients undergoing elective LDLT were analyzed. Patients with technical (vascular, biliary) complications and biopsy-proven rejections were excluded., Results: There were 19 deaths due to EAD of a total of 304 patients. On applying the existing definitions of EAD, we revealed their limitations of being either too broad with low specificity or too restrictive with low sensitivity in patients with LDLT. A new definition of EAD-LDLT (total bilirubin >10 mg/dL, international normalized ratio [INR] > 1.6 and serum urea >100 mg/dL, for five consecutive days after day 7) was derived after doing a multivariate analysis. In receiver operator characteristics analysis, an AUC for EAD-LDLT was 0.86. The calibration and internal cross-validation of the new model confirmed its predictability., Conclusion: The new model of EAD-LDLT, based on total bilirubin >10 mg/dL, INR >1.6 and serum urea >100 mg/dL, for five consecutive days after day 7, has a better predictive value for mortality due to EAD in LDLT recipients., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The production of useful phenolic flavor compounds by utilizing Lactobacillus acidophilus MTCC 10307 was studied. Ferulic acid, vanillic acid and vanillin were obtained as the significant phenolic acids from the fermentation medium. The compounds were identified and quantified by high-performance thin-layer chromatography. The phenolic acids were detected for 15 days. A maximum quantity of ferulic acid was quantified on the 9th day of incubation and the quantity decreased on further incubation. While the utmost amounts of vanillic acid and vanillin were detected on the 12th day of incubation. The concentration of carbohydrates from the de-starched bagasse was also estimated and was contrasted with that of the original (control) bagasse. The growth pattern of the microorganism was also studied. The quantity of ferulic acid measured per kg of sugarcane bagasse on the 9th day of incubation was determined to be approximately 275 mg whereas 18 mg and 15 mg of vanillic acid and vanillin, respectively, were measured per kg of bagasse on the 12th day of incubation. Ferulic acid esterase was isolated and the fermentation conditions such as pH, temperature and incubation period were standardized for the maximum recovery of the enzyme. The results revealed that in optimized condition, ferulic acid esterase yield was found to be 2.2 U ml -1 at 35 °C, whereas ferulic acid esterase yield was 2.3 U ml -1 at 6.5 pH and 2.4 U ml -1 after 60 h of the incubation period., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The foot-and-mouth disease virus (FMDV) causes a highly infectious disease of all cloven-footed animals. The RNA genome of the virus continuously evolves, leading to the generation of new strains; this necessitates the selection of new vaccine strains to ensure complete protection. Infection with one FMDV serotype does not provide cross-protection against the other FMDV serotypes. Many of the recovered animals may become carriers of the FMDV, but they still remain susceptible to the other serotypes. Coinfection with multiple FMDV serotypes has been reported and studied to understand the virus evolution. Isolation and characterization of all the involved serotypes in the mixed infection case is essential to understand the molecular evolution of the virus. In this study, two cases of coinfection were studied by selective isolation of each of the FMDV serotypes under the cross-serotype-specific immune pressure. It was estimated that the virus present in a minimum of 10 -0.92 TCID 50 could be isolated from the mixed population containing other serotypes in infective doses of 10 0.25 TCID 50 or less. All involved serotypes present in the mixed infection cases were isolated, without any cross-contamination. Virus characterization revealed that genotype 2 was of serotype A virus from a sample collected in 1995, which was last reported in 1986, indicating a possible subdued prevalence of the genetic group even after vanishing from the field., (© 2021. Sociedade Brasileira de Microbiologia.)

Edema factor (EF) is one of the major secretory proteins of anthrax bacteria along with protective antigen (PA) and lethal factor (LF). Edema factor is a calmodulin-and calcium-dependent adenylate cyclase that increases intracellular levels of cAMP. Intracellular trafficking of EF occurs through PA by binding to ATR/CMG2 receptors, which are also involved in other physiological functions of cells. cAMP is a secondary messenger which activates multiple signaling cascades involved in the cytokinetics of actin molecules and cell junction formation. The present study evaluated the effect of EF on growth and angiogenesis patterns in chicken embryos in the in ovo model. Angiogenesis in the chorioallantoic membrane (CAM) of an embryonated chicken egg was decreased and embryo growth was delayed by EF despite the absence of trafficking moiety PA, which is required for transferring the EF molecule inside the cell. Angiogenesis inhibition and embryo growth retardation indicate the use of an alternative receptor by EF to modulate these cellular functions. Additionally, docking was performed between EF as a ligand and hepatocyte growth factor receptor (cMET) and vascular endothelial growth factor (VEGF) receptors, which are mainly involved in growth and angiogenesis. The analysis revealed a very strong binding of EF to cMET receptor (in terms of the number of hydrogen bonds and energy) compared to its ligand hepatocyte growth factor (HGF), which indicates the use of cMET receptor by EF and induction of angiogenesis and embryo growth retardation possibly by competitive inhibition of HGF ligand or receptor-mediated endocytosis.