Cone Beam Computed Tomography-Based Online Adaptive Radiation Therapy of Esophageal Cancer: First Clinical Experience and Dosimetric Benefits.

Purpose: Radiation therapy (RT) plays a key role in the management of esophageal cancer (EC). However, toxicities caused by proximity of organs at risk (OAR) and daily target coverage caused by interfractional anatomic changes are of concern. Daily online adaptive RT (oART) addresses these concerns and has the potential to increase OAR sparing and improve target coverage.

Achieving a Pathologic Complete Response for Locally Advanced Esophageal Adenocarcinoma Using Cone-Beam Computed Tomography-Based Online Adaptive Radiotherapy.

Neo-adjuvant chemoradiotherapy (CRT) and perioperative chemotherapy are different strategies for treating non-metastatic esophageal cancer (EC). The advantages of neo-adjuvant therapies are primarily seen in patients who achieve a pathologic complete response (pCR) and therefore show higher survival rates and better prognosis. In general, less than one-third of patients with EC experience pCR after neo-adjuvant therapies; however, patients with esophageal adenocarcinoma (AC) demonstrate lower rates of pCR compared to those with esophageal squamous cell carcinoma (SCC), respectively.

3D genomic mapping reveals multifocality of human pancreatic precancers.

Pancreatic intraepithelial neoplasias (PanINs) are the most common precursors of pancreatic cancer, but their small size and inaccessibility in humans make them challenging to study. Critically, the number, dimensions and connectivity of human PanINs remain largely unknown, precluding important insights into early cancer development. Here, we provide a microanatomical survey of human PanINs by analysing 46 large samples of grossly normal human pancreas with a machine-learning pipeline for quantitative 3D histological reconstruction at single-cell resolution.

Congenital Hyperinsulinism in Humans and Insulin Secretory Dysfunction in Mice Caused by Biallelic Variants.

The BiP co-chaperone DNAJC3 protects cells during ER stress. In mice, the deficiency of DNAJC3 leads to beta-cell apoptosis and the gradual onset of hyperglycemia. In humans, biallelic variants cause a multisystem disease, including early-onset diabetes mellitus.

Structural Insights into Antibacterial Payload Release from Gold Nanoparticles Bound to E. coli Peptide Deformylase.

The lack of new antibiotics and the rapidly rising number of pathogens resistant to antibiotics pose a serious problem to mankind. In bacteria, the cell membrane provides the first line of defence to antibiotics by preventing them from reaching their molecular target. To overcome this entrance barrier, it has been suggested that small Gold-Nanoparticles (AuNP) could possibly function as drug delivery systems for antibiotic ligands.

A Novel Marine Mammal -Genome Sequencing Identifies a New Genotype with Potential Virulence.

The obligate intracellular bacterial pathogen has been identified in a few species of marine mammals, some of which are showing population declines. It has been hypothesized that in marine mammals is a distinct genotype that varies significantly from the typical terrestrial genotypes. It appears to lack an IS1111.

Clinical outcome after pencil beam scanning proton therapy and dysphagia/xerostomia NTCP calculations of proton and photon radiotherapy delivered to patients with cancer of the major salivary glands.

Objectives: The purpose of this study is to report the oncological outcome, observed toxicities and normal tissue complication probability (NTCP) calculation for pencil beam scanning (PBS) PT delivered to salivary gland tumour (SGT) patients.

Methods: We retrospectively reviewed 26 SGT patients treated with PBSPT (median dose, 67.5 Gy(RBE)) between 2005 and 2020 at our institute.

A Reinvestigation of the Role of the Sorbic Acid Tail on the Antibacterial and Anti-Tuberculosis Properties of Moiramide B.

Due to worldwide increasing resistances, there is a considerable need for antibacterial compounds with modes of action not yet realized in commercial antibiotics. One such promising structure is the acetyl-CoA carboxylase (ACC) inhibitor moiramide B which shows strong antibacterial activity against gram-positive bacteria such as Bacillus subtilis and weaker activities against gram-negative bacteria. However, the narrow structure-activity relationship of the pseudopeptide unit of moiramide B represents a formidable challenge for any optimization strategy.

Three-dimensional genomic mapping of human pancreatic tissue reveals striking multifocality and genetic heterogeneity in precancerous lesions.

Pancreatic intraepithelial neoplasia (PanIN) is a precursor to pancreatic cancer and represents a critical opportunity for cancer interception. However, the number, size, shape, and connectivity of PanINs in human pancreatic tissue samples are largely unknown. In this study, we quantitatively assessed human PanINs using CODA, a novel machine-learning pipeline for 3D image analysis that generates quantifiable models of large pieces of human pancreas with single-cell resolution.

Early outcome after craniospinal irradiation with pencil beam scanning proton therapy for children, adolescents and young adults with brain tumors.

Central nervous system (CNS) tumors are the most common solid malignancies in children and adolescents and young adults (C-AYAs). Craniospinal irradiation (CSI) is an essential treatment component for some malignancies, but it can also lead to important toxicity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of dose delivered to organs at risk and, thus, potentially reduced acute and late toxicity.

Nanoparticle-based modulation of CD4 T cell effector and helper functions enhances adoptive immunotherapy.

Helper (CD4) T cells perform direct therapeutic functions and augment responses of cells such as cytotoxic (CD8) T cells against a wide variety of diseases and pathogens. Nevertheless, inefficient synthetic technologies for expansion of antigen-specific CD4 T cells hinders consistency and scalability of CD4 T cell-based therapies, and complicates mechanistic studies. Here we describe a nanoparticle platform for ex vivo CD4 T cell culture that mimics antigen presenting cells (APC) through display of major histocompatibility class II (MHC II) molecules.

Social disparities in unplanned 30-day readmission rates after hospital discharge in patients with chronic health conditions: A retrospective cohort study using patient level hospital administrative data linked to the population census in Switzerland.

Unplanned readmissions shortly after discharge from hospital are common in chronic diseases. The risk of readmission has been shown to be related both to hospital care, e.g.

Measuring the latent reservoir for HIV-1: Quantification bias in near full-length genome sequencing methods.

Antiretroviral therapy (ART) effectively inhibits HIV-1 replication but is not curative due to the persistence of a latent viral reservoir in resting CD4+ T cells. This reservoir is a major barrier to cure. Sequencing studies have revealed that the population of proviruses persisting in ART-treated individuals is dominated by defective proviruses that cannot give rise to viral rebound due to fatal defects including large deletions and APOBEC3-mediated hypermutation.

Social inequalities, length of hospital stay for chronic conditions and the mediating role of comorbidity and discharge destination: A multilevel analysis of hospital administrative data linked to the population census in Switzerland.

Social factors are recognized determinants of morbidity and mortality and also have an impact on use of medical services. The objective of this study was to assess the associations of educational attainment, social and financial resources, and migration factors with length of hospital stays for chronic conditions. In addition, the study investigated the role of comorbidity and discharge destination in mediating these associations.

Phenotype of Idiopathic Epilepsy in Great Swiss Mountain Dogs in Germany-A Retrospective Study.

Genetic predisposition of idiopathic epilepsy (IE) has been demonstrated in individual breeds. According to the responsible breeding association in Germany, the average incidence of registered Great Swiss Mountain Dogs (GSMDs) with seizures between the years 1999 and 2019 is 2.56%, a genetic predisposition in this breed is suspected.

Hyperinsulinemic Hypoglycemia Associated with a Ca1.2 Variant with Mixed Gain- and Loss-of-Function Effects.

The voltage-dependent L-type calcium channel isoform Ca1.2 is critically involved in many physiological processes, e.g.

Clinical Outcome After Pencil Beam Scanning Proton Therapy of Patients With Non-Metastatic Malignant and Benign Peripheral Nerve Sheath Tumors.

Objective: Peripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment.

Characterization of three novel DyP-type peroxidases from Streptomyces chartreusis NRRL 3882.

Aims: Actinobacteria are known to produce extracellular enzymes including DyPs. We set out to identify and characterize novel peroxidases from Streptomyces chartreusis NRRL 3882, because S. chartreusis belongs to the small group of actinobacteria with three different DyPs.

Social and Regional Factors Predict the Likelihood of Admission to a Nursing Home After Acute Hospital Stay in Older People With Chronic Health Conditions: A Multilevel Analysis Using Routinely Collected Hospital and Census Data in Switzerland.

If hospitalization becomes inevitable in the course of a chronic disease, discharge from acute hospital care in older persons is often associated with temporary or persistent frailty, functional limitations and the need for help with daily activities. Thus, acute hospitalization represents a particularly vulnerable phase of transient dependency on social support and health care. This study examines how social and regional inequality affect the decision for an institutionalization after acute hospital discharge in Switzerland.

Progressive liver, kidney, and heart degeneration in children and adults affected by TULP3 mutations.

Organ fibrosis is a shared endpoint of many diseases, yet underlying mechanisms are not well understood. Several pathways governed by the primary cilium, a sensory antenna present on most vertebrate cells, have been linked with fibrosis. Ciliopathies usually start early in life and represent a considerable disease burden.

Crystal structure of 1,1',2,2',4,4'-hexa-iso-propyl-magnesocene.

The title compound, CpMg or [Mg(CH)], was synthesized from the cor-res-ponding triiso-propyl-cyclo-penta-diene by treatment with -butyl--butyl-magnesium. The structural characterization by single-crystal X-ray diffraction revealed that the compound crystallizes in the triclinic space group with half a mol-ecule per asymmetric unit and a staggered arrangement of the cyclo-penta-dienide ligands.