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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Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial

alexandrossfakianakis shared this article with you from Inoreader Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial via Clinical Infectious Diseases Advance Access Abstract BackgroundCervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells. Methods Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry. Results Unlike the LNG implant or copper-IUD, DMPA-IM was as sociated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4β7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non–Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post–DMPA-IM (P = .03), although this did not influence barrier function. Conclusions Our data suggest that D MPA-IM–driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity. View on Web

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Leucovorin (folinic acid) rescue for high‐dose methotrexate: A review

alexandrossfakianakis shared this article with you from Inoreader Leucovorin (folinic acid) rescue for high‐dose methotrexate: A review via Journal of Clinical Pharmacy and Therapeutics Leucovorin rescue is a cornerstone for toxicity prevention in high dose methotrexate treatment. Leucovorin rescue protocols differ greatly across tumor types and medical institutions. Leucovorin rescue protocols were reviewed for patients with ALL, lymphomas, and osteosarcoma. Abstract High-dose methotrexate (HDMTX) is active against various malignancies; it possesses serious toxicities and is associated with patient characteristics, dosage regimens, comedications, and physiological status. There are many strategies to overcome HDMTX-induced toxicities, such as hydration, alkalization, leucovorin rescue, and haemodialysis. Leucovorin rescue is a cornerstone for toxicity prevention in HDMTX treatment. However, the leucovorin dose adjustment and the existence of leucovorin overrescue are still controversial. At present, various methods for calculating leucovorin doses in different tumour types have been proposed, including empirical calculations based on MTX plasma concentration, the Bleyer nomogram, and other methods. Nonetheless, leucovorin rescue protocols differ greatly across tumour types and medical institutions. Further studies are needed to investigate the optimal dosage regimen for leucovorin rescue in various tumours using HDMTX. View on Web

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Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration

alexandrossfakianakis shared this article with you from Inoreader Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration via ScienceDirect Publication: Experimental Cell Research Publication date: Available online 5 August 2022 Source: Experimental Cell Research Author(s): Bing Zhou, Nan Wu, Yuan Yan, Lu-Lu Wu, Guo-Qing Zhu, Xiao-Qing Xiong View on Web

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Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma via Head & Neck Abstract Background To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC). Methods We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery. Results Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%–53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%–76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086). Conclusion In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival. View on Web

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