Understanding the impact of radiation-induced lymphopenia: Preclinical and clinical research perspectives.

Immunotherapy has revolutionized the field of cancer treatment, changing the standard of care to the use of immune checkpoint inhibitors. Radiotherapy can boost anti-tumour immune responses by changing the tumour microenvironment, but it also can cause radiotherapy-induced lymphopenia (RIL), a decrease in circulating lymphocyte counts. RIL has been associated with lower survival in patients undergoing radiotherapy, and new studies have suggested that it can also affect immunotherapy outcome.

GAL3ST1 Deficiency Reduces Epithelial-Mesenchymal Transition and Tumorigenic Capacity in a Cholangiocarcinoma Cell Line.

Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer.

Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination.

Background: Clostridium spp. has demonstrated therapeutic potential in cancer treatment through intravenous or intratumoral administration. This approach has expanded to include non-pathogenic clostridia for the treatment of various diseases, underscoring the innovative concept of oral-spore vaccination using clostridia.

Investigating reliable amyloid accumulation in Centiloids: Results from the AMYPAD Prognostic and Natural History Study.

Introduction: To support clinical trial designs focused on early interventions, our study determined reliable early amyloid-β (Aβ) accumulation based on Centiloids (CL) in pre-dementia populations.

Methods: A total of 1032 participants from the Amyloid Imaging to Prevent Alzheimer's Disease-Prognostic and Natural History Study (AMYPAD-PNHS) and Insight46 who underwent [F]flutemetamol, [F]florbetaben or [F]florbetapir amyloid-PET were included. A normative strategy was used to define reliable accumulation by estimating the 95 percentile of longitudinal measurements in sub-populations (N = 101/750, N = 35/382) expected to remain stable over time.

Caffeic Acid Phenethyl Ester (CAPE), a natural polyphenol to increase the therapeutic window for lung adenocarcinomas.

Background And Purpose: Lung cancers are highly resistant to radiotherapy, necessitating the use of high doses, which leads to radiation toxicities such as radiation pneumonitis and fibrosis. Caffeic Acid Phenethyl Ester (CAPE) has been suggested to have anti-proliferative and pro-apoptotic effects in tumour cells, while radioprotective anti-inflammatory and anti-oxidant effects in the normal tissue. We investigated the radiosensitizing and radioprotective effects of CAPE in lung cancer cell lines and normal tissue in vitro and ex vivo, respectively.

Tight Blood-Glucose Control without Early Parenteral Nutrition in the ICU.

Background: Randomized, controlled trials have shown both benefit and harm from tight blood-glucose control in patients in the intensive care unit (ICU). Variation in the use of early parenteral nutrition and in insulin-induced severe hypoglycemia might explain this inconsistency.

Methods: We randomly assigned patients, on ICU admission, to liberal glucose control (insulin initiated only when the blood-glucose level was >215 mg per deciliter [>11.

Overcoming radioresistance with the hypoxia-activated prodrug CP-506: A pre-clinical study of local tumour control probability.

Background And Purpose: Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause anti-tumour activity. The current study investigates whether CP-506 improves outcome of radiotherapy in vivo.

Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study.

Background: Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat.

Objectives: To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis.

A Blue-Enriched Light Intervention Counteracts the Alertness Decrement Among Mine Workers on Extended 12-Hour Night Shift Periods.

Objective: The aim of the study is to assess whether a blue-enriched light intervention improves nocturnal alertness and daytime sleep of night workers.

Methods: Thirteen miners performing 12-hour night shifts for 12 consecutive nights were exposed to a baseline and a blue-enriched light condition. All subjects wore an actigraph and completed a Psychomotor Vigilance Task at the beginning and at the end of each shift.

Use of 3D Spheroid Models for the Assessment of RT Response in Head and Neck Cancer.

Radiotherapy (RT) is a key player in the treatment of head and neck cancer (HNC). The RT response, however, is variable and influenced by multiple tumoral and tumor microenvironmental factors, such as human papillomavirus (HPV) infections and hypoxia. To investigate the biological mechanisms behind these variable responses, preclinical models are crucial.

Homologous Recombination Deficiency Scar: Mutations and Beyond-Implications for Precision Oncology.

Homologous recombination deficiency (HRD) is a prevalent in approximately 17% of tumors and is associated with enhanced sensitivity to anticancer therapies inducing double-strand DNA breaks. Accurate detection of HRD would therefore allow improved patient selection and outcome of conventional and targeted anticancer therapies. However, current clinical assessment of HRD mainly relies on determining germline mutational status and is insufficient for adequate patient stratification as mechanisms of HRD occurrence extend beyond functional BRCA1/2 loss.

GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice.

Dual agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPARɑ/ɣ) have beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to potential adverse effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPARɑ/ɣ dual-agonist tesaglitazar to a GLP-1 receptor agonist (GLP-1RA) to allow for GLP-1R-dependent cellular delivery of tesaglitazar. GLP-1RA/tesaglitazar does not differ from the pharmacokinetically matched GLP-1RA in GLP-1R signalling, but shows GLP-1R-dependent PPARɣ-retinoic acid receptor heterodimerization and enhanced improvements of body weight, food intake and glucose metabolism relative to the GLP-1RA or tesaglitazar alone in obese male mice.

Deep Learning-based Automatic Lung Segmentation on Multiresolution CT Scans from Healthy and Fibrotic Lungs in Mice.

Purpose: To develop a model to accurately segment mouse lungs with varying levels of fibrosis and investigate its applicability to mouse images with different resolutions.

Materials And Methods: In this experimental retrospective study, a U-Net was trained to automatically segment lungs on mouse CT images. The model was trained ( = 1200), validated ( = 300), and tested ( = 154) on longitudinally acquired and semiautomatically segmented CT images, which included both healthy and irradiated mice (group A).

A machine learning approach to screen for preclinical Alzheimer's disease.

Combining multimodal biomarkers could help in the early diagnosis of Alzheimer's disease (AD). We included 304 cognitively normal individuals from the INSIGHT-preAD cohort. Amyloid and neurodegeneration were assessed on F-florbetapir and F-fluorodeoxyglucose PET, respectively.

Efficacy of MAVIG X-Ray Protective Drapes in Reducing Operator Radiation Dose in the Cardiac Catheterization Laboratory: A Randomized Controlled Trial.

Background: Interventional cardiologists are occupationally exposed to high doses of ionizing radiation. The MAVIG X-ray protective drape (MXPD) is a commercially available light weight, lead-free shield placed over the pelvic area of patients to minimize operator radiation dose. The aim of this study was to examine the efficacy of the MXPD during routine cardiac catheterization, including percutaneous coronary interventions.

Long-Lasting Ventricular Fibrillation in Humans ECG Characteristics and Effect of Radiofrequency Ablation.

Background: Studies of ventricular fibrillation (VF) in humans are limited because of the short available duration. We sought to study surface ECG waveforms and effect of ablation in long-lasting VF in patients with left assist devices.

Methods: Continuous 12-lead ECG of 5 episodes of long-lasting VF occurring in 3 patients with left ventricular assist device were analyzed.

Effect of Activation Wavefront on Electrogram Characteristics During Ventricular Tachycardia Ablation.

Background Catheter ablation of ventricular tachycardia (VT) in structural heart disease is challenging because of noninducibility or hemodynamic compromise. Ablation often depends on elimination of local abnormal ventricular activities (LAVAs) but which may be hidden in far-field signal. We investigated whether altering activation wavefront affects activation timing and LAVA characterization and allows a better understanding of isthmus anatomy.

The Critical Portions of Carpal Tunnel Release, Ulnar Nerve Transposition, and Open Reduction and Internal Fixation of the Distal Part of the Radius.

Background: Overlapping surgery is attracting increased scrutiny. The American College of Surgeons states that the attending surgeon must be present for all critical portions of a surgical procedure; however, critical portions of surgical procedures are not defined. We hypothesized that a Delphi panel process would measure consensus on critical portions of 3 common hand surgical procedures.

Characteristics of Scar-Related Ventricular Tachycardia Circuits Using Ultra-High-Density Mapping: A Multi-Center Study.

Background: Ventricular tachycardia (VT) with structural heart disease is dependent on reentry within scar regions. We set out to assess the VT circuit in greater detail than has hitherto been possible, using ultra-high-density mapping.

Methods: All ultra-high-density mapping guided VT ablation cases from 6 high-volume European centers were assessed.

Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death.

Background: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported.

Methods: We evaluated 24 patients (29±13 years) who survived idiopathic VF.

Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children.

Background: Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions.

Methods: We enrolled patients with consecutively and prospectively identified TRK fusion-positive cancers, detected by molecular profiling as routinely performed at each site, into one of three protocols: a phase 1 study involving adults, a phase 1-2 study involving children, or a phase 2 study involving adolescents and adults.

Lomustine and Bevacizumab in Progressive Glioblastoma.

Background: Bevacizumab is approved for the treatment of patients with progressive glioblastoma on the basis of uncontrolled data. Data from a phase 2 trial suggested that the addition of bevacizumab to lomustine might improve overall survival as compared with monotherapies. We sought to determine whether the combination would result in longer overall survival than lomustine alone among patients at first progression of glioblastoma.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified mutations in 50% of patients with CM-AVM.