Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Composition and in situ structure of the cell envelope and surface layer.

Archaea share genomic similarities with Eukarya and cellular architectural similarities with Bacteria, though archaeal and bacterial surface layers (S-layers) differ. Using cellular cryo-electron tomography, we visualized the S-layer lattice surrounding , a methanogenic archaeon. Though more compact than known structures, 's S-layer is a flexible hexagonal lattice of dome-shaped tiles, uniformly spaced from both the overlying cell sheath and the underlying cell membrane.

Autofluorescence Virtual Staining System for H&E Histology and Multiplex Immunofluorescence Applied to Immuno-Oncology Biomarkers in Lung Cancer.

We extend the capabilities of virtual staining from AF to a different disease and stain modality. Our work includes newly developed virtual stains for H&E and a multiplex immunofluorescence panel (DAPI, PanCK, PD-L1, CD3, and CD8) for non-small cell lung cancer, which reproduce the key features of real stains.

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Royal Australian and New Zealand College of Psychiatrists professional practice guidelines for the administration of repetitive transcranial magnetic stimulation.

Objectives: To provide guidance for the optimal administration of repetitive transcranial magnetic stimulation, based on scientific evidence and supplemented by expert clinical consensus.

Methods: Articles and information were sourced from existing guidelines and published literature. The findings were then formulated into consensus-based recommendations and guidance by the authors.

An evening of alcohol consumption negatively impacts next-day immune fitness in both hangover-sensitive drinkers and hangover-resistant drinkers.

Background: Survey research found poorer baseline immune fitness for self-reported hangover-sensitive drinkers compared to hangover-resistant drinkers. However, up to now a limited number of clinical studies revealed mixed results regarding the relationship between the concentrations of biomarkers of systemic inflammation in blood or saliva with hangover severity, and could not differentiate between hangover-sensitive drinkers and hangover-resistant drinkers. The aim of this study was to assess immune fitness and saliva biomarkers of systemic inflammation at multiple timepoints following an alcohol day and alcohol-free control day.

Evolutionary characterization of lung adenocarcinoma morphology in TRACERx.

Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis.

PD-L1 blockade in combination with carboplatin as immune induction in metastatic lobular breast cancer: the GELATO trial.

Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype, but ILC-specific trials are lacking. Translational research revealed an immune-related ILC subset, and in mouse ILC models, synergy between immune checkpoint blockade and platinum was observed. In the phase II GELATO trial ( NCT03147040 ), patients with metastatic ILC were treated with weekly carboplatin (area under the curve 1.

Acute-onset polyradiculoneuropathy after SARS-CoV2 vaccine in the West and North Midlands, United Kingdom.

Introduction/aims: We aimed to determine whether specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines may be associated with acute-onset polyradiculoneuropathy and if they may result in particular clinical presentations.

Methods: We retrospectively reviewed records of all persons presenting with acute-onset polyradiculoneuropathy from January 1, 2021, to June 30, 2021, admitted to two Neuroscience centers, of the West and North Midlands, United Kingdom. We compared subjects with previous SARS-CoV2 vaccine exposure with a local cohort of persons with acute-onset polyradiculoneuropathy admitted between 2005 and 2019 and compared admission numbers for the studied time frame with that of the previous 3 years.

A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade.

Immune checkpoint inhibitors demonstrate clinical activity in many tumor types, however, only a fraction of patients benefit. Combining CD137 agonists with these inhibitors increases anti-tumor activity preclinically, but attempts to translate these observations to the clinic have been hampered by systemic toxicity. Here we describe a human CD137xPD-L1 bispecific antibody, MCLA-145, identified through functional screening of agonist- and immune checkpoint inhibitor arm combinations.

Accuracy of a Deep Learning System for Classification of Papilledema Severity on Ocular Fundus Photographs.

Objective: To evaluate the performance of a deep learning system (DLS) in classifying the severity of papilledema associated with increased intracranial pressure on standard retinal fundus photographs.

Methods: A DLS was trained to automatically classify papilledema severity in 965 patients (2,103 mydriatic fundus photographs), representing a multiethnic cohort of patients with confirmed elevated intracranial pressure. Training was performed on 1,052 photographs with mild/moderate papilledema (MP) and 1,051 photographs with severe papilledema (SP) classified by a panel of experts.

Intraoperative Retinal Changes May Predict Surgical Outcomes After Epiretinal Membrane Peeling.

Purpose: To investigate whether intraoperative retinal changes during epiretinal membrane (ERM) peeling affect anatomic or functional outcomes after surgery.

Methods: We measured retinal thickness using an intraoperative optical coherence tomography (iOCT) device in patients undergoing pars plana vitrectomy with membrane peeling for idiopathic ERM. Changes in intraoperative central macular thickness (iCMT) were compared with postoperative improvements in CMT and best-corrected visual acuity (VA).

Genetic Studies of Hypertrophic Cardiomyopathy in Singaporeans Identify Variants in and That Are Common in Chinese Patients.

Background: To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry.

Methods: We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3634), compared findings with additional populations and White HCM cohorts (n=6179), and performed in vitro functional studies.

Results: Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (pathogenic/likely pathogenic: 18%, <0.

Potently neutralizing human antibodies that block SARS-CoV-2 receptor binding and protect animals.

The COVID-19 pandemic is a major threat to global health for which there are only limited medical countermeasures, and we lack a thorough understanding of mechanisms of humoral immunity . From a panel of monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein isolated from the B cells of infected subjects, we identified several mAbs that exhibited potent neutralizing activity with IC values as low as 0.9 or 15 ng/mL in pseudovirus or wild-type ( ) SARS-CoV-2 neutralization tests, respectively.

Tracking the Evolution of Non-Small-Cell Lung Cancer.

Background: Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.

Methods: In this prospective cohort study, we performed multiregion whole-exome sequencing on 100 early-stage NSCLC tumors that had been resected before systemic therapy.

Electrophysiological biomarkers of diagnosis and outcome in neurodevelopmental disorders.

Purpose Of Review: The heterogeneity in clinical presentation and outcome in neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD) autism spectrum disorder (ASD) necessitates the identification and validation of biomarkers that can guide diagnosis, predict developmental outcomes, and monitor treatment response. Electrophysiology holds both practical and theoretical advantages as a clinical biomarker in neurodevelopmental disorders, and considerable effort has been invested in the search for electroencephalography (EEG) biomarkers in ADHD and ASD.

Recent Findings: Here, we discuss the major themes in the evaluation of biomarkers and then review studies that have applied EEG to better inform diagnosis, focusing on the controversy surrounding the theta:beta ratio in ADHD; prediction of risk, highlighting recent studies of infants at high risk for ASD; and treatment monitoring, presenting new efforts in the redefinition of outcome measures in clinical trials of ASD treatment.

Pseudorapidity density of charged particles in p+Pb collisions at √(s(NN))=5.02 TeV.

The charged-particle pseudorapidity density measured over four units of pseudorapidity in nonsingle-diffractive p+Pb collisions at a center-of-mass energy per nucleon pair √(s(NN))=5.02 TeV is presented. The average value at midrapidity is measured to be 16.

Diversity and biocatalytic potential of epoxide hydrolases identified by genome analysis.

Epoxide hydrolases play an important role in the biodegradation of organic compounds and are potentially useful in enantioselective biocatalysis. An analysis of various genomic databases revealed that about 20% of sequenced organisms contain one or more putative epoxide hydrolase genes. They were found in all domains of life, and many fungi and actinobacteria contain several putative epoxide hydrolase-encoding genes.