Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Circulating tumour DNA analysis for early detection of lung cancer: a systematic review.

Background: Circulating tumor DNA (ctDNA) analysis has been applied in cancer diagnostics including lung cancer. Specifically for the early detection purpose, various modalities of ctDNA analysis have demonstrated their potentials. Such analyses have showed diverse performance across different studies.

Differential detection of megakaryocytic and erythroid DNA in plasma in hematological disorders.

The tissues of origin of plasma DNA can be revealed by methylation patterns. However, the relative DNA contributions from megakaryocytes and erythroblasts into plasma appeared inconsistent among studies. To shed light into this phenomenon, we developed droplet digital PCR (ddPCR) assays for the differential detection of contributions from these cell types in plasma based on megakaryocyte-specific and erythroblast-specific methylation markers.

Evaluation of the Efficacy of a Novel Dermatotomy Device for Central Venous Cannulation.

Objective: To test the effectiveness of a novel wire-guided scalpel (Guideblade) to create a precise dermatotomy incision for central venous catheter (CVC) insertion.

Design: Prospective, nonrandomized interventional study.

Setting: Stanford University, single-center teaching hospital.

Endocuff With or Without Artificial Intelligence-Assisted Colonoscopy in Detection of Colorectal Adenoma: A Randomized Colonoscopy Trial.

Introduction: Both artificial intelligence (AI) and distal attachment devices have been shown to improve adenoma detection rate and reduce miss rate during colonoscopy. We studied the combined effect of Endocuff and AI on enhancing detection rates of various colonic lesions.

Methods: This was a 3-arm prospective randomized colonoscopy study involving patients aged 40 years or older.

Fragmentation landscape of cell-free DNA revealed by deconvolutional analysis of end motifs.

Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles).

Sex Differences in Association Between Gut Microbiome and Essential Hypertension Based on Ambulatory Blood Pressure Monitoring.

Background: Sex differences in the pathogenesis of hypertension exist. While gut microbiota (GM) has been associated with hypertension, it is unclear whether there are sex-linked differences in the association between GM and hypertension.

Methods: We conducted a cross-sectional study to investigate the sex differences in associations between GM characterized by shotgun sequencing, GM-derived short-chain fatty acids, and 24-hour ambulatory blood pressure in 241 Hong Kong Chinese (113 men and 128 women; mean age, 54±6 years).

Hypothalamic Oxytocin Neuron Activation Attenuates Intermittent Hypoxia-Induced Hypertension and Cardiac Dysfunction in an Animal Model of Sleep Apnea.

Background: Obstructive sleep apnea is a prevalent and poorly treated cardiovascular disease that leads to hypertension and autonomic imbalance. Recent studies that restore cardiac parasympathetic tone using selective activation of hypothalamic oxytocin neurons have shown beneficial cardiovascular outcomes in animal models of cardiovascular disease. This study aimed to determine if chemogenetic activation of hypothalamic oxytocin neurons in animals with existing obstructive sleep apnea-induced hypertension would reverse or blunt the progression of autonomic and cardiovascular dysfunction.

Long-term Hepatitis B Surface Antigen Profile and Seroclearance after Severe Acute Flares of Chronic Hepatitis B.

Background/aims: Hepatitis B surface antigen (HBsAg) seroclearance remains uncommon in chronic hepatitis B (CHB) infection. During acute flares of CHB (AFOCHB), alanine aminotransferase elevation reflects a mounting immune response toward viral clearance. We hypothesized that severe AFOCHB is associated with a greater quantitative HBsAg (qHBsAg) decline and HBsAg seroclearance rate.

Fragmentomics of urinary cell-free DNA in nuclease knockout mouse models.

Urinary cell-free DNA (ucfDNA) is a potential biomarker for bladder cancer detection. However, the biological characteristics of ucfDNA are not well understood. We explored the roles of deoxyribonuclease 1 (DNASE1) and deoxyribonuclease 1-like 3 (DNASE1L3) in the fragmentation of ucfDNA using mouse models.

Assessment of cytochrome P450 3A4-mediated drug-drug interactions for ipatasertib using a fit-for-purpose physiologically based pharmacokinetic model.

Purpose: Ipatasertib, a potent and highly selective small-molecule inhibitor of AKT, is currently under investigation for treatment of cancer. Ipatasertib is a substrate and a time-dependent inhibitor of CYP3A4. It exhibits non-linear pharmacokinetics at subclinical doses in the clinical dose escalation study.

Use of Antibiotics during Immune Checkpoint Inhibitor Treatment Is Associated with Lower Survival in Hepatocellular Carcinoma.

Background: Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC).

Methods: This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019.

The Association of Choroidal Thickening by Atropine With Treatment Effects for Myopia: Two-Year Clinical Trial of the Low-concentration Atropine for Myopia Progression (LAMP) Study.

Purpose: To evaluate longitudinal changes in subfoveal choroidal thickness (SFChT) among children receiving atropine 0.05%, 0.025%, or 0.

Quantitative single-cell analysis of immunofluorescence protein multiplex images illustrates biomarker spatial heterogeneity within breast cancer subtypes.

Background: The extent of cellular heterogeneity in breast cancer could have potential impact on diagnosis and long-term outcome. However, pathology evaluation is limited to biomarker immunohistochemical staining and morphology of the bulk cancer. Inter-cellular heterogeneity of biomarkers is not usually assessed.

Single-molecule sequencing reveals a large population of long cell-free DNA molecules in maternal plasma.

In the field of circulating cell-free DNA, most of the studies have focused on short DNA molecules (e.g., <500 bp).

Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers.

PD-1 blockade unleashes CD8 T cells, including those specific for mutation-associated neoantigens (MANA), but factors in the tumour microenvironment can inhibit these T cell responses. Single-cell transcriptomics have revealed global T cell dysfunction programs in tumour-infiltrating lymphocytes (TIL). However, the majority of TIL do not recognize tumour antigens, and little is known about transcriptional programs of MANA-specific TIL.

Final Report of a Trial of Intensive versus Standard Blood-Pressure Control.

Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.

Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes.

The Use of Cabozantinib in Advanced Hepatocellular Carcinoma in Hong Kong-A Territory-Wide Cohort Study.

(1) Background: Cabozantinib is approved in sorafenib-exposed advanced hepatocellular carcinoma (aHCC). We evaluated the real-life pattern of use, efficacy, and tolerability of cabozantinib in aHCC. (2) Methods: This territory-wide study included consecutive aHCC patients who received cabozantinib between February 2018 and September 2020 in Hong Kong.

A potent and selective PARP14 inhibitor decreases protumor macrophage gene expression and elicits inflammatory responses in tumor explants.

PARP14 has been implicated by genetic knockout studies to promote protumor macrophage polarization and suppress the antitumor inflammatory response due to its role in modulating interleukin-4 (IL-4) and interferon-γ signaling pathways. Here, we describe structure-based design efforts leading to the discovery of a potent and highly selective PARP14 chemical probe. RBN012759 inhibits PARP14 with a biochemical half-maximal inhibitory concentration of 0.

Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis.

Advanced marginal zone lymphoma (MZL) is an incurable B-cell malignancy dependent on B-cell receptor signaling. The phase 2 PCYC-1121 study demonstrated the safety and efficacy of single-agent ibrutinib 560 mg/d in 63 patients with relapsed/refractory MZL treated with prior rituximab (RTX) or rituximab-based chemoimmunotherapy (RTX-CIT). We report the final analysis of PCYC-1121 with median follow-up of 33.

Calibrating the In Vitro-In Vivo Correlation for OATP-Mediated Drug-Drug Interactions with Rosuvastatin Using Static and PBPK Models.

Organic anion-transporting polypeptide (OATP) 1B1/3-mediated drug-drug interaction (DDI) potential is evaluated in vivo with rosuvastatin (RST) as a probe substrate in clinical studies. We calibrated our assay with RST and estradiol 17--D-glucuronide (E17G)/cholecystokinin-8 (CCK8) as in vitro probes for qualitative and quantitative prediction of OATP1B-mediated DDI potential for RST. In vitro OATP1B1/1B3 inhibition using E17G and CCK8 yielded higher area under the curve (AUC) ratio (AUCR) values numerically with the static model, but all probes performed similarly from a qualitative cutoff-based prediction, as described in regulatory guidances.

Entecavir vs Tenofovir in Hepatocellular Carcinoma Prevention in Chronic Hepatitis B Infection: A Systematic Review and Meta-Analysis.

Introduction: Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line therapies for chronic hepatitis B (CHB) infection. Although both drugs reduce hepatocellular carcinoma (HCC) risk, their comparative effectiveness remains controversial. We aimed to determine whether TDF is superior to ETV in preventing HCC.