The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus

alexandrossfakianakis shared this article with you from Inoreader The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus via Journal of Medical Virology ABSTRACT Hepatitis B Virus (HBV) infections remain a major global health burden with an estimated 296 million people living with a chronic infection and 884,00 HBV-related deaths annually. Notably, patients with a chronic hepatitis B (CHB) infection are at a 30-fold greater risk of developing hepatocellular carcinoma (HCC), the 3rd deadliest cancer worldwide. Several groups have assessed HBV-related aberrant expression of host-cell long non-coding RNAs (lncRNAs) and how altered expression of specific lncRNAs affects HBV replication and progression to associated disease states. Given the challenges in establishing effective HBV models and analyzing transcriptomic data, this review focuses on lncRNA expression data primarily collected from clinical patient samples and primary human hepatocytes (PHHs), with subsequent mechanism of action analysis in cell lines or other model systems. Ultimately, understanding HBV-induced lncRNA-expression dysregulation could lead to new treatments and biomarkers for HBV infection and its associated diseases. This article is protected by copyright. All rights reserved. View on Web

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A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics

alexandrossfakianakis shared this article with you from Inoreader A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics via Neuro-Oncology Advance Access Abstract Background Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive LMD. Methods This multicenter study enrolled 34 LMD patients in a combined Phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the Phase I; the Phase II was limited to HER2-positive breast cancer. Results Intrathecal trastuzumab was well tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended Phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80mg w ere included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for Phase 2 dose treated patients was 8.3 months (95% CI 5.2 to 19.6). The Phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2 to 20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable CSF concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. Conclusion This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients. View on Web

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Could red cell distribution width be used for predicting cardiac injury in neonates with COVID‐19?

alexandrossfakianakis shared this article with you from Inoreader Could red cell distribution width be used for predicting cardiac injury in neonates with COVID‐19? via Journal of Medical Virology ABSTRACT Background Coronavirus disease 2019 (COVID-19) can affect people of all age groups and it can occasionally cause life-threatening clinical illness in immunologically immature population, especially in newborns. High red cell distribution width (RDW) values were used as early prognostic biomarker of some neonatal diseases. We aimed to determine the prognostic value of red cell distribution width in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infected neonates. Methods Newborns with positive SARS-CoV-2 polymerase chain reaction (PCR) test from a nasopharyngeal swab sample, who had refractory fever (>38°C and lasting more than 24 hours during hospitalization) screened for multisystem inflammatory syndrome in newborns (MIS-N), systemic inflammatory indexes calculated and cardiologic evaluation performed to these patients. Due to troponin levels (high: >45 ng/L and low: ≤45 ng/L) patients were grouped. Results Of the 68 SARS-CoV-2 PCR-positive newborns, 26 patients had refractory fever. Comparison of laboratory findings between the high and low troponin groups showed that RDW and neutrophil/lymphocyte ratio values were significantly higher in patients with high troponin levels (p = 0.022 and p = 0.030, respectively). The cut-off values with optimal sensitivity and specificity were determined as 1.00 for neutrophil/lymphocyte ratio (p = 0.205) and 16.6 for red cell distribution width (p = 0.014). None of the patients died. Conclusions Neonatal coronavirus disease 2019 generally has a benign prognosis, but can progress to severe disease and cases of MIS-N are rare. RDW could be prognostic in diagnosis and management of neonates with SARS-CoV-2 infection with high troponin levels. This article is protected by copyright. All rights reserved. View on Web

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Rapid quantitative monitoring of SARS‐CoV‐2 spike protein mediated syncytia formation using split NanoLuc

alexandrossfakianakis shared this article with you from Inoreader Rapid quantitative monitoring of SARS‐CoV‐2 spike protein mediated syncytia formation using split NanoLuc via Journal of Medical Virology Abstract SARS-CoV-2 infection causes syncytial pneumocyte in patients and this has been considered as a defining feature of severe COVID-19 cases. Traditional methods of syncytia quantification require the morphology characterization of fused cells either with light microscope or fluorescent microscope, which is time-consuming and not accurate. Here we developed a rapid and sensitive coculture system measuring spike-induced syncytia by using NanoLuc complementation system. We found the formation of syncytia occurred rapidly after ACE2-expressing cells exposure to spike protein. In addition, we found furin cleavage as well as the cell surface protease TMPRSS2 enhanced syncytia formation. Finally, we showed that this coculture system can be used to test the ability of different compound to inhibit syncytia formation, thus providing a useful tool to screen anti-syncytial drugs. This article is protected by copyright. All rights reserved. View on Web

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Humoral responses after inactivated COVID‐19 vaccination in individuals with and without prior SARS‐CoV‐2 infection: A prospective cohort study

alexandrossfakianakis shared this article with you from Inoreader Humoral responses after inactivated COVID‐19 vaccination in individuals with and without prior SARS‐CoV‐2 infection: A prospective cohort study via Journal of Medical Virology Abstract Background We evaluated and compared humoral immune responses after inactivated COVID-19 vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. Methods In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after two doses of inactivated COVID-19 vaccination. Results Among 392 SARS-CoV-2-naïve individuals, the seroconversion rate increased significantly from 51.8% (median anti-spike protein pan-immunoglobulins [S-Igs] titer:0.8 U/mL) after the first dose to 96% (median S-Igs titer:79.5 U/mL) after the second dose. 32% of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain, but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S-Igs titers of 757.8U/mL, 1247.0U/mL, 1280.0U/mL, and 2367.0U/mL for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Conclusions Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose. This article is protected by copyright. All rights reserved. View on Web

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A case of primary neuroendocrine carcinoma of the mandibular gingiva treated using multimodal therapy

alexandrossfakianakis shared this article with you from Inoreader A case of primary neuroendocrine carcinoma of the mandibular gingiva treated using multimodal therapy via ScienceDirect Publication: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Publication date: Available online 8 August 2022 Source: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Author(s): Tomoaki Hamana, Shigeru Sakurai, Atsuko Hamada, Shinnichi Sakamoto, Hisako Furusho, Shigeaki Toratani View on Web

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Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: a cross‐sectional study

alexandrossfakianakis shared this article with you from Inoreader Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: a cross‐sectional study via Journal of Medical Virology Abstract Multiple human papillomavirus (HPV) infections are common, but their impact on cervical lesions remains controversial. A total of 6225 female patients who underwent colposcopies/conization following abnormal cervical cancer screening results were included in the study. The final pathological diagnosis was determined by the most severe pathological grade among the cervical biopsy, ECC and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between multiple HPV infections and cervical lesions, adjusting for age, HPV genotype, gravidity and parity. In total, 33.3% (n=2076) of the study population was infected with multiple HPV genotypes. Multiple HPV infections were more prevalent in patients younger than 25 years and older than 55 years, with the rate of multiple HPV infections at 52.8% and 44.3%, respectively. HPV16\52\18\58 are the most common HPV genotypes and usually appear as a single infection. Co mpared to single HR-HPV infection, multiple HR-HPV infections do not increase the risk of HSIL+, while single HR-HPV coinfected with LR-HPV seems to reduce the risk of HSIL+ (OR=0.515, CI: 0.370-0.719, P＜0.001). Multiple HR-HPV infections cannot be risk-stratified for triage of HR-HPV-positive women. This article is protected by copyright. All rights reserved. View on Web

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