Combining dense elements with attention mechanisms for 3D radiotherapy dose prediction on head and neck cancers.

Purpose: External radiation therapy planning is a highly complex and tedious process as it involves treating large target volumes, prescribing several levels of doses, as well as avoiding irradiating critical structures such as organs at risk close to the tumor target. This requires highly trained dosimetrists and physicists to generate a personalized plan and adapt it as treatment evolves, thus affecting the overall tumor control and patient outcomes. Our aim is to achieve accurate dose predictions for head and neck (H&N) cancer patients on a challenging in-house dataset that reflects realistic variability and to further compare and validate the method on a public dataset.

Temsavir Treatment of HIV-1-Infected Cells Decreases Envelope Glycoprotein Recognition by Broadly Neutralizing Antibodies.

The heavily glycosylated HIV-1 envelope glycoprotein (Env) is the sole viral antigen present at the surface of virions and infected cells, representing the main target for antibody responses. The FDA-approved small molecule temsavir acts as an HIV-1 attachment inhibitor by preventing Env-CD4 interaction. This molecule also stabilizes Env in a prefusion "closed" conformation that is preferentially targeted by several broadly neutralizing antibodies (bNAbs).

Non-contrast CT markers of intracerebral hematoma expansion: a reliability study.

Objectives: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion.

Methods: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions.

SARS-CoV-2 Variants Increase Kinetic Stability of Open Spike Conformations as an Evolutionary Strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) harbor mutations in the spike (S) glycoprotein that confer more efficient transmission and dampen the efficacy of COVID-19 vaccines and antibody therapies. S mediates virus entry and is the primary target for antibody responses, with structural studies of soluble S variants revealing an increased propensity toward conformations accessible to the human angiotensin-converting enzyme 2 (hACE2) receptor. However, real-time observations of conformational dynamics that govern the structural equilibriums of the S variants have been lacking.

Operationalising the 20-minute neighbourhood.

Background: Recent rapid growth in urban areas and the desire to create liveable neighbourhoods has brought about a renewed interest in planning for compact cities, with concepts like the 20-minute neighbourhood (20MN) becoming more popular. A 20MN broadly reflects a neighbourhood that allows residents to meet their daily (non-work) needs within a short, non-motorised, trip from home. The 20MN concept underpins the key planning strategy of Australia's second largest city, Melbourne, however the 20MN definition has not been operationalised.

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer.

Aside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk.

Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis.

Background: Resolution of inflammation is an active and regulated process that leads to the clearance of cell debris and immune cells from the challenged tissue, facilitating the recovery of homeostasis. This physiological response is coordinated by endogenous bioactive lipids known as specialized pro-resolving mediators (SPMs). When resolution fails, inflammation becomes uncontrolled leading chronic inflammation and tissue damage, as occurs in multiple sclerosis (MS).

SARS-CoV-2 Spike Expression at the Surface of Infected Primary Human Airway Epithelial Cells.

Different serological assays were rapidly generated to study humoral responses against the SARS-CoV-2 Spike glycoprotein. Due to the intrinsic difficulty of working with SARS-CoV-2 authentic virus, most serological assays use recombinant forms of the Spike glycoprotein or its receptor binding domain (RBD). Cell-based assays expressing different forms of the Spike, as well as pseudoviral assays, are also widely used.

Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern.

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here, we elucidate the structural basis and mode of action for two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 and CV3-25, which remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggers potent shedding of the S1 subunit.

Stress Signal ULBP4, an NKG2D Ligand, Is Upregulated in Multiple Sclerosis and Shapes CD8 T-Cell Behaviors.

Background And Objectives: We posit the involvement of the natural killer group 2D (NKG2D) pathway in multiple sclerosis (MS) pathology via the presence of specific NKG2D ligands (NKG2DLs). We aim to evaluate the expression of NKG2DLs in the CNS and CSF of patients with MS and to identify cellular stressors inducing the expression of UL16-binding protein 4 (ULBP4), the only detectable NKG2DL. Finally, we evaluate the impact of ULBP4 on functions such as cytokine production and motility by CD8 T lymphocytes, a subset largely expressing NKG2D, the cognate receptor.

Repetitive transcranial magnetic stimulation for major depressive disorder: basic principles and future directions.

Repetitive transcranial magnetic stimulation (rTMS) is a safe and well-tolerated intervention for major depressive disorder (MDD). Over 150 randomized controlled trials (RCTs) have been carried out, and its efficacy has been confirmed in dozens of meta-analyses. Real world data has also confirmed the effectiveness of rTMS for MDD in clinical practice, with the most recent literature indicating response rates of 40-50% and remission rates of 25-30%.

Structural Connectivity Alterations in Operculo-Insular Epilepsy.

Operculo-insular epilepsy (OIE) is an under-recognized condition that can mimic temporal and extratemporal epilepsies. Previous studies have revealed structural connectivity changes in the epileptic network of focal epilepsy. However, most reports use the debated streamline-count to quantify 'connectivity strength' and rely on standard tracking algorithms.

Impact of STEMI Diagnosis and Catheterization Laboratory Activation Systems on Sex- and Age-Based Differences in Treatment Delay.

Background: Women and the elderly with ST-elevation myocardial infarction (STEMI) experience longer treatment delays despite prehospital STEMI diagnosis and catheterization laboratory activation systems. It is not known what role specific STEMI referral systems might play in mediating this gap in care. We therefore examined sex- and age-based differences in STEMI treatment delay (TD) in different STEMI activation systems.

The first 100 days: how has COVID-19 affected poor and vulnerable groups in India?

In India, strict public health measures to suppress COVID-19 transmission and reduce burden have been rapidly adopted. Pandemic containment and confinement measures impact societies and economies; their costs and benefits must be assessed holistically. This study provides an evolving portrait of the health, economic and social consequences of the COVID-19 pandemic on vulnerable populations in India.

Optimized repetitive transcranial magnetic stimulation techniques for the treatment of major depression: A proof of concept study.

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device.

Chitosan Microbeads Produced by One-Step Scalable Stirred Emulsification: A Promising Process for Cell Therapy Applications.

Cell microencapsulation is a promising approach to improve cell therapy outcomes by protecting injected cells from rapid dispersion and allowing bidirectional diffusion of nutrients, oxygen, and waste that promote cell survival in the target tissues. Here, we describe a simple and scalable emulsification method to encapsulate animal cells in chitosan microbeads using thermosensitive gel formulations without any chemical modification and cross-linker. The process consists of a water-in-oil emulsion where the aqueous phase droplets contain cells (L929 fibroblasts or human mesenchymal stromal cells), chitosan acidic solution and gelling agents (sodium hydrogen carbonate and phosphate buffer or beta-glycerophosphate).

Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) mediates viral entry into cells and is critical for vaccine development against coronavirus disease 2019 (COVID-19). Structural studies have revealed distinct conformations of S, but real-time information that connects these structures is lacking. Here we apply single-molecule fluorescence (Förster) resonance energy transfer (smFRET) imaging to observe conformational dynamics of S on virus particles.

Vagus Nerve Stimulation for Treatment-Resistant Depression: a Case Series of Clinical Symptoms Associated with the End of Service Period.

Background: This work describes the clinical symptoms associated with end of service (EOS) of the batteries of vagus nerve stimulation (VNS) generators in treatment-resistant depression (TRD). Because neurostimulator software may not provide reliable information on battery depletion, careful monitoring of clinical symptoms during the EOS period is an important concern in the follow-up of TRD patients treated with VNS therapy.

Methods: Twenty-six (26) patients were implanted and followed at the Centre Hospitalier de l'Université de Montréal.

Artificial Intelligence Applications for Workflow, Process Optimization and Predictive Analytics.

There is great potential for artificial intelligence (AI) applications, especially machine learning and natural language processing, in medical imaging. Much attention has been garnered by the image analysis tasks for diagnostic decision support and precision medicine, but there are many other potential applications of AI in radiology and have potential to enhance all levels of the radiology workflow and practice, including workflow optimization and support for interpretation tasks, quality and safety, and operational efficiency. This article reviews the important potential applications of informatics and AI related to process improvement and operations in the radiology department.

An approach to classifying occupational exposures to endocrine disrupting chemicals by sex hormone function using an expert judgment process.

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the endocrine system and cause adverse effects. We aimed to classify the effects of 24 known EDCs, prevalent in certain occupations, according to four modes of action (estrogenic, antiestrogenic, androgenic, and/or antiandrogenic). A literature search, stratified into four types of literature was conducted (namely: national and international agency reports; review articles; primary studies; ToxCast).

The pros and cons of interferons for oncolytic virotherapy.

Interferons (IFN) are potent immune stimulators that play key roles in both innate and adaptive immune responses. They are considered the first line of defense against viral pathogens and can even be used as treatments to boost the immune system. While viruses are usually seen as a threat to the host, an emerging class of cancer therapeutics exploits the natural capacity of some viruses to directly infect and kill cancer cells.

Adrenal vein sampling: External validation of multinomial regression modelling and left adrenal vein-to-peripheral vein ratio to predict lateralization index without right adrenal vein sampling.

Background: Adrenal vein sampling (AVS) failure is mainly due to right adrenal vein unavailability. Multinomial regression modelling (MRM) and left adrenal vein-to-peripheral vein ratio (LAV/PV) were proposed to predict the lateralization index without the right AVS.

Objective: To assess external validity of MRM and LAV/PV to predict lateralization index when right adrenal vein sampling is missing.

Acute carotid stenting in patients undergoing thrombectomy: a systematic review and meta-analysis.

Background: The benefit of acute carotid stenting compared with no acute stenting on clinical outcomes among patients with tandem lesions (TL) undergoing endovascular thrombectomy (EVT) remains unknown.

Methods: We conducted a a systematic review and meta-analysis of studies comparing acute carotid stenting versus no stenting among TL patients undergoing EVT with regards to 90 day modified Rankin Scale (mRS) score, symptomatic intracerebral hemorrhage (sICH), and mortality. Four reviewers screened citations for eligibility and two assessed retained studies for risk of bias and data extraction.