Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

Background: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS.

Methods: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m) and cisplatin (75 mg/m).

Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking.

SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.

CT-Based Radiomics Predicts the Malignancy of Pulmonary Nodules: A Systematic Review and Meta-Analysis.

Rationale And Objectives: More pulmonary nodules (PNs) have been detected with the wide application of computed tomography (CT) in lung cancer screening. Radiomics is a noninvasive approach to predict the malignancy of PNs. We aimed to systematically evaluate the methodological quality of the eligible studies regarding CT-based radiomics models in predicting the malignancy of PNs and evaluate the model performance of the available studies.

Evaluation on leachability of heavy metals from tailings: risk factor identification and cumulative influence.

The leachability of heavy metals (HMs) in tailings is significantly affected by multivariate factors associated with environmental conditions. However, the leaching patterns of HMs in molybdenum (Mo) tailings due to environmental change and cumulative influences of multi-leaching factors remain unclear. The leaching behaviors of HMs in Mo tailings were studied through static leaching tests.

Facile high-quantum-yield sulfur-quantum-dot-based photoluminescent probe for nifedipine detection.

Monitoring of dihydropyridine drugs, such as nifedipine (NIF), has attracted considerable attention owing to the side effects arising from the consumption of such drugs. Herein, a highly sensitive and facile fluorescence-sensing platform based on a high-quantum-yield sulfur quantum dot (SQDs) probe for NIF detection is proposed. Based on the principle of the inner filter effect, the rapid detection of NIF with high sensitivity is successfully realized on the basis of the change in the fluorescence signal due to the quenching effect of NIF on SQDs.

A Prospective Phase II Study of Automated Non-Coplanar VMAT for Recurrent Head and Neck Cancer: Initial Report of Feasibility, Safety, and Patient-Reported Outcomes.

This study reports the initial results for the first 15 patients on a prospective phase II clinical trial exploring the safety, feasibility, and efficacy of the HyperArc technique for recurrent head and neck cancer treatment. Eligible patients were simulated and planned with both conventional VMAT and HyperArc techniques and the plan with superior dosimetry was selected for treatment. Dosimetry, delivery feasibility and safety, treatment-related toxicity, and patient-reported quality of life (QOL) were all evaluated.

Genetic discovery and risk characterization in type 2 diabetes across diverse populations.

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the gene (rs11466334, risk allele frequency (RAF) = 6.

Interfractional Geometric Variations and Dosimetric Benefits of Stereotactic MRI Guided Online Adaptive Radiotherapy (SMART) of Prostate Bed after Radical Prostatectomy: Post-Hoc Analysis of a Phase II Trial.

Purpose: To evaluate geometric variations of patients receiving stereotactic body radiotherapy (SBRT) after radical prostatectomy and the dosimetric benefits of stereotactic MRI guided adaptive radiotherapy (SMART) to compensate for these variations.

Materials/methods: The CTV and OAR were contoured on 55 MRI setup scans of 11 patients treated with an MR-LINAC and enrolled in a phase II trial of post-prostatectomy SBRT. All patients followed institutional bladder and rectum preparation protocols and received five fractions of 6-6.

Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular Vesicles.

Objective: To develop a reliable and fast assay to quantify the α-synuclein (α-syn)-containing extracellular vesicles (EVs) in CSF and to assess their diagnostic potential for Parkinson disease (PD).

Methods: A cross-sectional, multicenter study was designed, including 170 patients with PD and 131 healthy controls (HCs) with a similar distribution of age and sex recruited from existing center studies at the University of Washington and Oregon Health and Science University. CSF EVs carrying α-syn or aggregated α-syn were quantified using antibodies against total or aggregated α-syn, respectively, and highly specific, sensitive, and rapid assays based on the novel Apogee nanoscale flow cytometry technology.

Palbociclib in advanced acral melanoma with genetic aberrations in the cyclin-dependent kinase 4 pathway.

Background: Genetic aberrations in the cyclin-dependent kinase (CDK)4 pathway occur in 82% of patients with acral melanoma (AM), which is the predominant subtype of melanoma in China. We aimed to evaluate the anti-tumour activity of palbociclib, a selective CDK4/6 inhibitor, in patients with advanced AM with CDK4 pathway gene aberrations.

Methods: In this phase II trial, patients with advanced AM with CDK4 or/and CCND1 gain or/and CDKN2A loss were treated with oral palbociclib (125 mg) on days 1-21 of a 28-day cycle.

Treatment of Masked Hypertension with a Chinese Herbal Formula: A Randomized, Placebo-Controlled Trial.

Background: Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)-lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension.

Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy in Chinese Ischemic Stroke Patients: The ASIAN Score.

Background And Purpose: Symptomatic intracranial hemorrhage (sICH), potentially associated with poor prognosis, is a major complication of endovascular thrombectomy (EVT) for ischemic stroke patients. We aimed to develop and validate a risk model for predicting sICH after EVT in Chinese patients due to large-artery occlusions in the anterior circulation.

Methods: The derivation cohort recruited patients with EVT from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China.

Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B-Reactive CD4 T-Regulatory Cells.

Background: Throughout the inflammatory response that accompanies atherosclerosis, autoreactive CD4 T-helper cells accumulate in the atherosclerotic plaque. Apolipoprotein B (apoB), the core protein of low-density lipoprotein, is an autoantigen that drives the generation of pathogenic T-helper type 1 (T1) cells with proinflammatory cytokine secretion. Clinical data suggest the existence of apoB-specific CD4 T cells with an atheroprotective, regulatory T cell (T) phenotype in healthy individuals.

Cardiovascular End Points and Mortality Are Not Closer Associated With Central Than Peripheral Pulsatile Blood Pressure Components.

Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.

Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs.

Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology.

Background: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients.

Use, Temporal Trends, and Outcomes of Endovascular Therapy After Interhospital Transfer in the United States.

Background: The use of endovascular therapy (EVT) in patients with acute ischemic stroke who have large vessel occlusion has rapidly increased in the United States following pivotal trials demonstrating its benefit. Information about the contribution of interhospital transfer in improving access to EVT will help organize regional systems of stroke care.

Methods: We analyzed trends of transfer-in EVT from a cohort of 1 863 693 patients with ischemic stroke admitted to 2143 Get With The Guidelines-Stroke participating hospitals between January 2012 and December 2017.

Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and metastasis-inhibiting effects on breast cancer cells.

Drug resistance and cancer cells metastasis have been the leading causes of chemotherapy failure and cancer-associated death in breast cancer patients. In present, various active molecules either exhibiting novel mechanism of action such as inducing autophagy or inhibiting metastasis have been developed to address these problems. However, the compounds exhibiting such dual functions have rarely been described.

Delays in Door-to-Needle Times and Their Impact on Treatment Time and Outcomes in Get With The Guidelines-Stroke.

Background And Purpose: Despite quality improvement programs such as the American Heart Association/American Stroke Association Target Stroke initiative, a substantial portion of acute ischemic stroke patients are still treated with tissue-type plasminogen activator (alteplase) later than 60 minutes from arrival. This study aims to describe the documented reasons for delays and the associations between reasons for delays and patient outcomes.

Methods: We analyzed the characteristics of 55 296 patients who received intravenous alteplase in 1422 hospitals participating in Get With The Guidelines-Stroke from October 2012 to April 2015, excluding transferred patients and inpatient strokes.