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Purpose: The IMbrave150 Phase III trial demonstrated the superiority of atezolizumab and bevacizumab (Atezo/Bev) over sorafenib for unresectable hepatocellular carcinoma (HCC). The present study aims to evaluate the feasibility of TARE in combination with Atezo/Bev for the treatment of intermediate and advanced staged HCC. Methods: A retrospective review at a single institution was performed between May 2021 and December 2022. Patients who received TARE using yttrium-90 (Y90) with concomitant or sequential Atezo/Bev systemic treatment were included. The following outcomes were retrieved: overall survival (OS), radiologic tumor response, progression-free survival, technical adverse events related to TARE, and toxicity based on the National Cancer Institute–Common Terminology Criteria for Adverse Events version 5.0. Results: Ten consecutive patients with intermediate (n ​= ​4) and advanced stage HCC (n ​= ​6) were treated with TARE and sequential/concomitant Atezo/Bev. Tumor control was achieved in all TARE-treated target lesions (100%). Overall disease progression occurred in 4 patients with PFS of 78.8% and 66.7% at 6- and 12- months, respectively. Two patients died at follow-up, with 6-month and 12-month OS rates of 90.0% and 77.1%, respectively. Three (75%) patients with intermediate stage disease were downstaged into Milan criteria. One patient developed grade 3 transaminitis and hypoglobulinemia, while Atezo/Bev was switched to Lenvatinib in another patient due to immunotherapy related myositis. Conclusion: This study demonstrates the initial safety and feasibility of combined TARE with Atezo/Bev for intermediate/advanced stage HCC. Further prospective studies with larger sample sizes are warranted.

Inferior pancreaticoduodenal artery (IPDA) aneurysms have been associated with celiac axis stenosis and occlusion. Retrograde flow through the IPDA arcade has been hypothesized to cause enlargement of these vessels and lead to aneurysm formation. However, objective proof of this hypothesis is lacking, given the fact that celiac stenosis or occlusion and IPDA aneurysms are typically diagnosed concurrently and recurrent aneurysms have not been described. This report presents a patient with celiac axis stenosis and an IPDA aneurysm treated with median arcuate ligament lysis, celiac stenting, and aneurysmectomy. Seventeen years later, he developed a second IPDA aneurysm treated with a flow diverting stent.

Leptadenia pyrotechnica Forssk. Decne (LP) is a medicinal herb from the Asclepiadaceae family with many advantageous properties. The goal of this research is to identify, quantify, and evaluate the antioxidant potential of LP to validate its remarkable therapeutic advantages. The hot soxhlet extraction method was employed to prepare different extracts of LP (stem and root). These extracts were evaluated physiochemically to check their impurity, purity, and quality; qualitatively to detect different phytochemicals; and quantitatively for phenol, saponin, tannin, flavonoid, and alkaloid contents. Then, the in vitro antioxidant potential was estimated by DPPH, NO, H2O2 scavenging assays, and MC and FRAP assays. The most prevalent phytochemicals of LP were then analysed by AAS, FT-IR, UV–visible, and GC-MS techniques. A higher extractive yield was shown by LPSE and LPRE (7.37 ± 0.11 and 5.70 ± 0.02). The LP stem showed better physicochemical and qualitative results than the root. The quantitative and in vitro antioxidant results indicated maximal phenols, tannins, and alkaloid contents in LPSE, which was further confirmed by UV–visible, FT-IR, and GC-MS results. The extraction methods (soxhlation or ultrasonication) were optimized by utilizing RSM to determine the impacts of multiple parameters. The study concluded that the plant has remarkable therapeutic advantages to promote additional clinical investigations and the mechanisms of its action.

Intellectual disability (ID) is seen in around 2.5% of global population and can vary from mild to severe and profound ID. There can be multiple affected family members if it is inherited, though many autosomal dominant ID cases would be due to de novo mutations are very less likely to recur in families. A confirmatory diagnosis is facilitated by genetic testing like chromosomal microarray and next generation sequencing. We describe here our cohort of 15 patients: children and adolescents with ID diagnosed by using sequencing technologies and parental segregation studies. Most of the variants identified were de novo variants and consistent with sporadic occurrence, and blended phenotypes were identified. Appropriate genetic counseling was performed and options for prenatal diagnosis were discussed. Thus, advanced sequencing technologies enable identification of likely causative de novo variants associated with intellectual disability and dysmorphism.

Non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS), without previous bariatric surgery, is a rare form of hypoglycemia in adult patients and is associated with nesidioblastosis. Adult-onset nesidioblastosis in diabetic patients is rare and histologically identical to "non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS)". Nesidioblastosis is rare in adults and clinically and biochemically mimics Insulinoma. In the literature, there have only been four cases of adult nesidioblastosis that followed diabetes mellitus. We report a case of nesidioblastosis in a 36-year-old diabetic female presenting with dizziness, sweating, and palpitations for three years. Selective non-invasive techniques failed to detect a tumor. Based on the pursuit of an insulinoma, a distal pancreatectomy specimen was received at our laboratory, and a diagnosis of nesidioblastosis was made. She is currently on follow-up with a favorable outcome. The definitive diagnosis of nesidioblastosis is made on a histological basis. The preferred form of treatment is pancreatic surgical resection. Nesidioblastosis should be taken into consideration in cases where diabetes transforms into hyperinsulinemic hypoglycemia.

Virulence gene expression in the human pathogen, S. aureus is regulated by the agr (accessory gene regulator) quorum sensing (QS) system which is conserved in diverse Gram-positive bacteria. The agr QS signal molecule is an autoinducing peptide (AIP) generated via the initial processing of the AgrD pro-peptide by the transmembrane peptidase AgrB. Since structural information for AgrB and AgrBD interactions are lacking, we used homology modelling and molecular dynamics (MD) annealing to characterise the conformations of AgrB and AgrD in model membranes and in solution. These revealed a six helical transmembrane domain (6TMD) topology for AgrB. In solution, AgrD behaves as a disordered peptide, which binds N-terminally to membranes in the absence and in the presence of AgrB. In silico, membrane complexes of AgrD and dimeric AgrB show non-equivalent AgrB monomers responsible for initial binding and for processing, respectively. By exploiting split luciferase assays in Staphylococcus aureus, we provide experimental evidence that AgrB interacts directly with itself and with AgrD. We confirmed the in vitro formation of an AgrBD complex and AIP production after Western blotting using either membranes from Escherichia coli expressing AgrB or with purified AgrB and T7-tagged AgrD. AgrB and AgrD formed stable complexes in detergent micelles revealed using synchrotron radiation CD (SRCD) and Landau analysis consistent with the enhanced thermal stability of AgrB in the presence of AgrD. Conformational alteration of AgrB following provision of AgrD was observed by small angle X-ray scattering from proteodetergent micelles. An atomistic description of AgrB and AgrD has been obtained together with confirmation of the AgrB 6TMD membrane topology and existence of AgrBD molecular complexes in vitro and in vivo.

Recently, there has been significant research on the environmental, social, and governance (ESG) aspects of wealth generation. Managers have tried to attract investors for sustainable growth by pushing for ESG investments. This study attempts to determine the relationship between ESG scores on shareholders' wealth and define possible selection criteria for future investments. Notably, there are funds and investment avenues that are specifically designed for ESG themes, urging toward sustainable wealth creation. However, investors' focus remains on their returns and wealth creation. In recent years, reporting ESG scores has become standard practice for most rating agencies to report the financial health of companies. Thus, this study employs a linear regression model to analyze the impact of ESG scores on the equity returns of 225 Indian companies. The results show empirical evidence of the positive impact of the governance (G) factor on equity returns, while it reports the negative impact of the environmental (E) factor on equity returns. Moreover, the impact of the social (S) factor is found to be insignificant. Therefore, we conclude that financial motivations may be needed to trigger E− and S- factor practices by companies. It is important for companies to be very conscious of their governance practices to improve their shareholders’ wealth.

Purpose: To assess the efficacy and clinical outcome of Tenon's patch graft (TPG) in corneal perforation and descemetocele. Methods: In this retrospective study, medical records of 83 patients (85 eyes) who underwent TPG for corneal perforation (58, 68%) or descemetocele (27, 32%) between July 2018 and October 2021 were reviewed. Clinical examination and anterior segment optical coherence tomography (AS-OCT) were performed on every follow-up visit. Anatomical success was considered as the restoration of the structural integrity with the formation of scar and anterior chamber (AC). Results: The mean size of the corneal lesions (corneal perforation or descemetocele) was 4.20 ± 1.01 mm. The mean follow-up period was 9.2 ± 5.48 months. The common underlying etiologies were infectious keratitis in 48% and autoimmune disorders in 35% of cases. TPG successfully restored the globe integrity in 74 (87%) eyes (83% in perforation and 96% in descemetocele). Anatomical failure occurred in 11 eyes (13%). The failures were due to graft dehiscence (8 eyes), graft ectasia (1 eye), and scarring with flat AC (2 eyes). The median time to epithelialization and scar formation were 3 and 15 weeks, respectively. Logistic regression analysis showed few predictors for a successful outcome: descemetoceles, noninfective causes, viral keratitis in infectious etiology, and paracentral or peripheral lesions. Conclusion: TPG can be considered an effective and inexpensive treatment for restoring the structural integrity in the eyes with perforations and descemetoceles, particularly when the donor tissue is unavailable. AS-OCT is a valuable noninvasive tool for monitoring the graft status.

Turdoides affinis is a species of group dwelling old world passerine of family Leiothrichidae. Unavailability of genome-wide sequence and species-specific molecular markers have hindered comprehensive understanding of cooperative breeding behaviour in T. affinis. Therefore, we generated genome-wide microsatellite markers through whole genome short read sequencing of T. affinis. A total of 68.8 gigabytes of paired-end raw data were sequenced containing 195,067,054 reads. Total sequenced reads spanned a coverage of 17X with genome size of 1.18 Gb. A large number of microsatellite markers (265,297) were mined in the T. affinis genome using Krait, and 50 most informative markers were identified and validated further. In-silico PCR results validated 47 markers. Of these 47 markers, five were randomly selected and validated in-vitro in twelve individuals of T. affinis. Genotyping data on these five loci estimated observed heterozygosity (H0) and expected heterozygosity (He) ratios between 0.333 – 0.833 and 0.851–0.906, respectively. Effective allele size ranged from 6.698 to 10.667, inbreeding coefficient of the population ranged from 0.080 to 0.631 and null allele frequency was calculated at 0.055 to 0.303. Polymorphic information content of all the five loci varied between 0.850 and 0.906. Probabilities of exclusion and identity across 5 loci was estimated to be 0.95 and 0.0036, respectively. All the loci showed significant adherence to Hardy-Weinberg equilibrium. The microsatellite markers reported in this study will facilitate future population genetics studies on T. affinis and other congeneric species.

Thoracic duct embolization (TDE) is a minimally invasive alternative to surgery for the treatment of postoperative chylous leaks that fail conventional medical management. TDE can be a technically challenging procedure that requires real-time image guidance to visualize the thoracic duct. This case report describes using hybrid angiography/computed tomography technology to perform TDE through direct access of the cisterna chyli, potentially eliminating the need for intranodal lymphangiography, and reducing procedure length.

Long noncoding RNAs constitute a major fraction of the eukaryotic transcriptome, and together with proteins, they intricately fine-tune various growth regulatory signals to control cellular homeostasis. Here, we describe the functional characterisation of a novel pair of long intergenic noncoding RNAs (lincRNAs) comprised of complementary, fully overlapping sense and antisense transcripts Genomic Instability Inducing RNA (Ginir) and antisense RNA of Ginir (Giniras), respectively, from mouse cells. This transcript pair is expressed in a spatiotemporal manner during embryonic development. The individual levels of the sense and antisense transcripts are finely balanced during embryonic growth and in adult tissues. Functional studies of the individual transcripts performed using overexpression and knock-down strategies in mouse cells has led to the discovery that Ginir RNA is a regulator of cellular proliferation and can act as an oncogene having a preeminent role in malignant transformation. Mechanistically, we demonstrate that the oncogenic function of Ginir is mediated by its interaction with centrosomal protein 112 (Cep112). Additionally, we establish here a specific interaction between Cep112 with breast cancer type 1 susceptibility protein (Brca1), another centrosome-associated protein. Next, we prove that the mutual interaction between Cep112 with Brca1 is significant for mitotic regulation and maintenance of genomic stability. Furthermore, we demonstrate that the Cep112 protein interaction with Brca1 protein is impaired when an elevated level of Ginir RNA is present in the cells, resulting in severe deregulation and abnormality in mitosis, leading to malignant transformation. Inhibiting the Ginir RNA function in transformed cells attenuates transformation and restores genomic stability. Together, these findings unravel, to our knowledge, a hitherto-unknown mechanism of oncogenesis mediated by a long noncoding RNA and establishes a unique role of Cep112-Brca1 interaction being modulated by Ginir RNA in maintaining mitotic fidelity.

Diffuse gliomas are lethal tumors of the central nervous system (CNS) characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs) to be causal in driving tumor growth in glioblastoma. The presence of a stem and progenitor population possibly makes glioblastoma highly heterogeneous. Significantly, tumor growth is driven by interaction of cells residing within the tumor with the surrounding milieu termed as the tumor microenvironment. It comprises of various cell types such as endothelial cells, secreted factors, and the surrounding extracellular matrix, which altogether help perpetuate the proliferation of GSCs. One of the important mediators critical to the cross talk is extracellular vesicles (EVs). These nano-sized vesicles play important roles in intercellular communication by transporting bioactive molecules into the surrounding milieu, thereby altering cellular functions and/or reprogramming recipient cells. With the growing information on the contribution of EVs in modulation of the tumor microenvironment, it is important to determine their role in both supporting as well as promoting tumor growth in glioma. In this review, we provide a comprehensive overview of the role of EVs in tumor progression and glioma pathogenesis.

Aim: To conduct detailed pathomicrobial studies on Salmonella Gallinarum infection in broiler chickens.Materials and Methods: Bacteriological and pathological studies were conducted on 134 dead poultry birds collected from 23 different farms suspected to be infected with S. Gallinarum.Results: Mortality pattern revealed that maximum mortality occurred in 1-2 week aged birds. Out of 23 Salmonella isolates, 19 samples were identified as S. Gallinarum (9, 12) and 4 samples as Salmonella Enteritidis (9, 12: gm). Isolates were found to be most sensitive to Polymyxin B (100%). The present study also showed re-emergence of chloramphenicol sensitivity (83.33%). Pathological lesions observed were bronze discolouration of liver, splenomegaly and necrotic foci on liver, spleen and heart. Microscopically, liver and spleen revealed aggregation of heterophils, lymphocytes and macrophages, non-suppurative myocarditis, fibrinous pericarditis, interstitial nephritis, necrotic enteritis and serofibrinous pneumonia.Conclusion: It was concluded that S. Gallinarum 9, 12 was the main serotype causing Salmonellosis in poultry birds. Polymyxin B was the most sensitive drug (100%) for Salmonella infection along with re-emergence of chloramphenicol sensitivity for Salmonella (83.33%) infection.

Background Nationwide trends in the utilization of catheter-directed therapies for deep vein thrombosis and pulmonary embolism in the Medicare population are essential as they represent a major health care challenge. The annual incidence and mortality with venous thromboembolism are around 900,000 and 60,000 to 100,000 patients, respectively, in the United States.