Development of an automated liquid biopsy assay for methylated markers in advanced breast cancer.

Current molecular liquid biopsy assays to detect recurrence or monitor response to treatment require sophisticated technology, highly trained personnel, and a turnaround time of weeks. We describe the development and technical validation of an automated Liquid Biopsy for Breast Cancer Methylation (LBx-BCM) prototype, a DNA methylation detection cartridge assay that is simple to perform and quantitatively detects nine methylated markers within 4.5 h.

Nivolumab drug holiday in patients treated for metastatic renal cell carcinoma: A real-world, single-centre experience.

Introduction: Immunotherapy with nivolumab (a monoclonal antibody that targets the programmed cell death protein 1, PD1) has become the standard treatment for patients with metastatic renal cell carcinoma (mRCC) after progression to single-agent tyrosine kinase inhibitors. However, the optimal duration of immunotherapy in this setting has not yet been established.

Patients And Methods: We retrospectively reviewed all patients treated with nivolumab at our institution from January 2014 to December 2021 and identified those who discontinued treatment for reasons other than disease progression (PD).

Robotic Versus Laparoscopic Left and Extended Left Hepatectomy: An International Multicenter Study Propensity Score-Matched Analysis.

Background: Controversies exist among liver surgeons regarding clinical outcomes of the laparoscopic versus the robotic approach for major complex hepatectomies. The authors therefore designed a study to examine and compare the perioperative outcomes of laparoscopic left hepatectomy or extended left hepatectomy (L-LH/L-ELH) versus robotic left hepatectomy or extended left hepatectomy (R-LH/R-ELH) using a large international multicenter collaborative database.

Methods: An international multicenter retrospective analysis of 580 patients undergoing L-LH/L-ELH or R-LH/R-ELH at 25 specialized hepatobiliary centers worldwide was undertaken.

Tegaserod maleate exhibits antileukemic activity by targeting TRPM8.

To identify therapeutic targets in acute myeloid leukemia (AML), we conducted growth inhibition screens of 2040 small molecules from a library of FDA-approved drugs using a panel of 12 AML cell lines. Tegaserod maleate, a 5-hydroxytryptamine 4 receptor partial agonist, elicits strong anti-AML effects in vitro and in vivo by targeting transient receptor potential melastatin subtype 8 (TRPM8), which plays critical roles in several important processes. However, the role of TRPM8 remains incompletely described in AML, whose treatment is based mostly on antimitotic chemotherapy.

LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization.

Renal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in human renal tubular cells by regulating the suppressor of cytokine signal 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway.

Intrinsic capacity and 10-year mortality: Findings from a cohort of older people.

Background And Objectives: Longitudinal data with regard to the association between intrinsic capacity (IC) and mortality is required for prevention efforts. We examined the association between IC and 10-year mortality among older people.

Research Design And Methods: We recruited a cohort of 2032 Chinese people aged 70 years and older, 1371 of them could be traced over follow-up, of which 1096 died within 10 years.

Validation of the easy-to-use lenvatinib prognostic index to predict prognosis in advanced hepatocellular carcinoma patients treated with lenvatinib.

Aim: The identification of new prognostic factors able to stratify hepatocellular carcinoma patients candidate to first-line therapy is urgent. In the present work we validated the prognostic value of the lenvatinib prognostic index.

Methods: Data of Eastern and Western patients treated with lenvatinib as first-line for Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma were recollected.

Actinide Decorporation: A Review on Chelation Chemistry and Nanocarriers for Pulmonary Administration.

Chelation is considered the best method for detoxification by promoting excretion of actinides (Am, Np, Pu, Th, U) from the human body after internal contamination. Chemical agents that possess carboxylic acid or hydroxypyridinonate groups play a vital role in actinide decorporation. In this review article, we provide considerable background details on the chelation chemistry of actinides with an aim to formulate better decorporation agents.

Tacrolimus Causes Hypertension by Increasing Vascular Contractility via RhoA (Ras Homolog Family Member A)/ROCK (Rho-Associated Protein Kinase) Pathway in Mice.

Background: To provide tacrolimus is first-line treatment after liver and kidney transplantation. However, hypertension and nephrotoxicity are common tacrolimus side effects that limit its use. Although tacrolimus-related hypertension is well known, the underlying mechanisms are not.

Oral anticoagulant decreases stroke recurrence in patients with atrial fibrillation detected after stroke.

Background: Atrial fibrillation detected after stroke (AFDAS) has a lower risk of ischemic stroke recurrence than known atrial fibrillation (KAF). While the benefit of oral anticoagulants (OAC) for preventing ischemic stroke recurrence in KAF is well established, their role in patients with AFDAS is more controversial. This study aimed to evaluate the association between OAC use and the risk of recurrent ischemic stroke in patients with AFDAS in a real-world setting.

Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with Mutations.

Background: Both Lowe syndrome and Dent-2 disease are caused by variants in the gene. However, the reason why patients with similar gene mutations presented with different phenotypes remains uncertain.

Methods: Children with hemizygous pathogenic or likely pathogenic variants in were compiled from published and unpublished consecutive cases from China.

Molecular Analysis of pSK1 par: A Novel Plasmid Partitioning System Encoded by Staphylococcal Multiresistance Plasmids.

The segregation of prokaryotic plasmids typically requires a centromere-like site and two proteins, a centromere-binding protein (CBP) and an NTPase. By contrast, a single 245 residue Par protein mediates partition of the prototypical staphylococcal multiresistance plasmid pSK1 in the absence of an identifiable NTPase component. To gain insight into centromere binding by pSK1 Par and its segregation function we performed structural, biochemical and in vivo studies.

TOB is an effector of the hippocampus-mediated acute stress response.

Stress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood.

Synthesis of Prussian Blue Nanoparticles and Their Antibacterial, Antiinflammation and Antitumor Applications.

In recent years, Prussian blue nanoparticles (PBNPs), also named Prussian blue nano-enzymes, have been shown to demonstrate excellent multi-enzyme simulation activity and anti-inflammatory properties, and can be used as reactive oxygen scavengers. Their good biocompatibility and biodegradability mean that they are ideal candidates for in vivo use. PBNPs are highly efficient electron transporters with oxidation and reduction activities.

Defining Global Benchmarks for Laparoscopic Liver Resections: An International Multicenter Study.

Objective: To establish global benchmark outcomes indicators after laparoscopic liver resections (L-LR).

Background: There is limited published data to date on the best achievable outcomes after L-LR.

Methods: This is a post hoc analysis of a multicenter database of 11,983 patients undergoing L-LR in 45 international centers in 4 continents between 2015 and 2020.

Safety and immunogenicity of intramuscular, single-dose V590 (rVSV-SARS-CoV-2 Vaccine) in healthy adults: Results from a phase 1 randomised, double-blind, placebo-controlled, dose-ranging trial.

Background: Vaccines against COVID-19 are needed to overcome challenges associated with mitigating the global pandemic. We report the safety and immunogenicity of V590, a live recombinant vesicular stomatitis virus-based COVID-19 vaccine candidate.

Methods: In this placebo-controlled, double-blind, three-part phase 1 study, healthy adults were randomised to receive a single intramuscular dose of vaccine or placebo.

Nitric Oxide Signalling in Descending Vasa Recta after Hypoxia/Re-Oxygenation.

Reduced renal medullary oxygen supply is a key factor in the pathogenesis of acute kidney injury (AKI). As the medulla exclusively receives blood through descending vasa recta (DVR), dilating these microvessels after AKI may help in renoprotection by restoring renal medullary blood flow. We stimulated the NO-sGC-cGMP signalling pathway in DVR at three different levels before and after hypoxia/re-oxygenation (H/R).

Regulated dicing of pre-mir-144 via reshaping of its terminal loop.

Although the route to generate microRNAs (miRNAs) is often depicted as a linear series of sequential and constitutive cleavages, we now appreciate multiple alternative pathways as well as diverse strategies to modulate their processing and function. Here, we identify an unusually profound regulatory role of conserved loop sequences in vertebrate pre-mir-144, which are essential for its cleavage by the Dicer RNase III enzyme in human and zebrafish models. Our data indicate that pre-mir-144 dicing is positively regulated via its terminal loop, and involves the ILF3 complex (NF90 and its partner NF45/ILF2).

Associations of thiazide use with skin cancers: a systematic review and meta-analysis.

Background: Previous findings on the associations of thiazide use with skin cancers were conflicting. This study aimed to examine the associations of individual thiazide use with skin cancer risk, differentiated by subtypes of skin cancers, geographic regions, and cumulative doses of individual thiazides.

Methods: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for relevant studies on January 5, 2022, scanned the references of included studies, and consulted experts.

Monoclonal antibodies and Fc-fusion protein biologic medicines: A multinational cross-sectional investigation of accessibility and affordability in Asia Pacific regions between 2010 and 2020.

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US).

Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database.

A Method for Variant Agnostic Detection of SARS-CoV-2, Rapid Monitoring of Circulating Variants, and Early Detection of Emergent Variants Such as Omicron.

The rapid emergence of SARS-CoV-2 variants raised public health questions concerning the capability of diagnostic tests to detect new strains, the efficacy of vaccines, and how to map the geographical distribution of variants to understand transmission patterns and loads on healthcare resources. Next-generation sequencing (NGS) is the primary method for detecting and tracing new variants, but it is expensive, and it can take weeks before sequence data are available in public repositories. This article describes a customizable reverse transcription PCR (RT-PCR)-based genotyping approach which is significantly less expensive, accelerates reporting, and can be implemented in any lab that performs RT-PCR.

A Paradigm Shift: Outcomes of Early Autologous Breast Reconstruction after Radiation Therapy.

Background:  Radiation creates significant challenges for breast reconstruction. There is no consensus regarding optimal timing for autologous reconstruction following radiation. This study explores clearly defined, shorter time intervals between completion of radiation and reconstruction than previously reported.

Comparison between the difficulty of laparoscopic limited liver resections of tumors located in segment 7 versus segment 8: An international multicenter propensity-score matched study.

Background: Presently, according to different difficulty scoring systems, there is no difference in complexity estimation of laparoscopic liver resection (LLR) of segments 7 and 8. However, there is no published data supporting this assumption. To date, no studies have compared the outcomes of laparoscopic parenchyma-sparing resection of the liver segments 7 and 8.