Safety and Efficacy of Toripalimab in Patients with Cholangiocarcinoma: An Open-Label, Phase 1 Study.

Introduction: This was the first phase 1 study conducted in the United States. It consisted of dose-escalation (part A) and multiple indication-specific cohort expansion (part B), investigating the safety and preliminary efficacy of toripalimab (anti-programmed cell death-1 inhibitor) in patients with advanced malignancies.

Methods: Patients with advanced malignancies that progressed after treatment with at least one prior line of standard systemic therapy, including the patients with advanced/recurrent cholangiocarcinoma (CCA), received toripalimab 240 mg every 3 weeks in part B.

CRISPR/Cas9 screens identify LIG1 as a sensitizer of PARP inhibitors in castration-resistant prostate cancer.

PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment.

High-Throughput Drug Screening in Chondrosarcoma Cells Identifies Effective Antineoplastic Agents Independent of IDH Mutation.

The term chondrosarcoma refers to a rare and heterogeneous group of malignant cartilaginous tumors that are typically resistant to chemotherapy and radiotherapy. Metastatic chondrosarcoma has a poor prognosis, and effective systemic therapies are lacking. Isocitrate dehydrogenase (IDH) mutations represent a potential therapeutic target, but IDH inhibitors alone have shown limited clinical efficacy to date.

"OMICS" in Human Milk: Focus on Biological Effects on Bone Homeostasis.

Human milk (HM) is a complex biofluid rich in nutrients and bioactive compounds essential for infant health. Recent advances in omics technologies-such as proteomics, metabolomics, and transcriptomics-have shed light on the influence of HM on bone development and health. This review discusses the impact of various HM components, including proteins, lipids, carbohydrates, and hormones, on bone metabolism and skeletal growth.

Global change, climate change, and asthma in children: Direct and indirect effects - A WAO Pediatric Asthma Committee Report.

The twenty-first century has seen a fundamental shift in disease epidemiology with anthropogenic environmental change emerging as the likely dominant factor affecting the distribution and severity of current and future human disease. This is especially true of allergic diseases and asthma with their intimate relationship with the natural environment. Climate change-related variables including increased ambient temperature, heat waves, extreme weather events, air pollution, and rainfall distribution, all can affect asthma in children, but each of these variables also affects asthma via alterations in pollen production and release, outdoor allergen exposure or the microbiome.

Sorafenib or anthracycline-based chemotherapy for progressive desmoid tumors.

Background: Desmoid tumors can cause morbidity due to local invasion, potentially being fatal when fast growth compromises vital structures. In this context, a timely treatment response is required. This study aims to compare the activity of sorafenib and anthracycline-containing regimens during the first year of treatment.

Aesthetic Approaches to Zygomatic Fracture Management: Achieving Optimal Outcomes With Minimal Scarring.

The zygomaticomaxillary complex is integral to facial aesthetics and is frequently involved in facial fractures. These injuries often necessitate surgical intervention, with open reduction and internal fixation being the standard treatment. This article presents a novel philosophy for managing zygomatic fractures, emphasizing the "Scarless Surgery" technique.

Cardiac Phenotype and Gene Mutations in RASopathies.

Cardiac involvement is a major feature of RASopathies, a group of phenotypically overlapping syndromes caused by germline mutations in genes encoding components of the RAS/MAPK (mitogen-activated protein kinase) signaling pathway. In particular, Noonan syndrome (NS) is associated with a wide spectrum of cardiac pathologies ranging from congenital heart disease (CHD), present in approximately 80% of patients, to hypertrophic cardiomyopathy (HCM), observed in approximately 20% of patients. Genotype-cardiac phenotype correlations are frequently described, and they are useful indicators in predicting the prognosis concerning cardiac disease over the lifetime.

Clinical Outcomes of CAD-CAM Subperiosteal Implants for the Rehabilitation of Atrophic Jaws.

Thanks to the use of new digital technologies and innovations in materials, there has been an increasing interest in subperiosteal implants. These implants are considered to be helpful for the rehabilitation of severe jaw atrophies, as they overcome some disadvantages of endosseous implantology. In the present clinical retrospective study, 18 patients were treated and the clinical outcomes of the treatment were recorded after 12 months of follow-up.

Molecular Basis of Cardiomyopathies in Type 2 Diabetes.

Diabetic cardiomyopathy (DbCM) is a common complication in individuals with type 2 diabetes mellitus (T2DM), and its exact pathogenesis is still debated. It was hypothesized that chronic hyperglycemia and insulin resistance activate critical cellular pathways that are responsible for numerous functional and anatomical perturbations in the heart. Interstitial inflammation, oxidative stress, myocardial apoptosis, mitochondria dysfunction, defective cardiac metabolism, cardiac remodeling, hypertrophy and fibrosis with consequent impaired contractility are the most common mechanisms implicated.

Imaging-Based Disease Assessment and Management Recommendations: Impact of Multidisciplinary Sarcoma Tumor Board.

Multidisciplinary tumor boards (MTBs) facilitate decision-making among subspecialists in the care of oncology patients, but the mechanisms by which they enhance outcomes remain incompletely understood. Our aim was to measure the agreement between sarcoma MTBs and radiology reports' disease assessment and management recommendations. This single-center IRB-approved retrospective study evaluated cases presented at a weekly sarcoma MTB from 1 August 2020 to 31 July 2021.

The Incidence of Obstructive Sleep Apnea in Patients with Dento-Skeletal Malformation.

The aim of this article is to analyze the incidence of undiagnosed obstructive sleep apnea (OSA) in patients affected by dento-skeletal malformation. We also evaluated the patterns most affected by the condition and calculated the post surgical changes. We conducted a retrospective cohort study on 71 patients including 35 men and 36 women.

Molecular Regulation of Cardiac Conduction System Development.

Purpose Of Review: The cardiac conduction system, composed of pacemaker cells and conducting cardiomyocytes, orchestrates the propagation of electrical activity to synchronize heartbeats. The conduction system plays a crucial role in the development of cardiac arrhythmias. In the embryo, the cells of the conduction system derive from the same cardiac progenitors as the contractile cardiomyocytes and and the key question is how this choice is made during development.

Biomarkers and Biochemical Indicators to Evaluate Bone Metabolism in Preterm Neonates.

The purpose of the present study was to evaluate the concentrations of some bone turnover markers in preterm neonates with uncomplicated clinical course in the first month of life. Samples from 13 preterm neonates were collected at three different times: at birth (T0) from umbilical cord blood (UCB); and at 15 (T1) and 30 (T2) days of life from peripheral blood (PB). The concentrations of calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), Collagen Type 1 Amino-terminal Propeptide (PINP), osteocalcin (OC), Collagen Type 1 Carboxyl-Terminal Telopeptide (CTX) and Leptin were assessed.

Air pollution and rhinitis.

Rhinitis arises from either allergic or non-allergic inflammation of the nasal mucosa, characterized by the infiltration of inflammatory cells into the tissue and nasal secretions, along with structural alterations in the nasal mucosa. The pathways through which air pollution affects rhinitis may diverge from those affecting asthma. This article aims to review the effects of diverse air pollutants on the nose, the correlation of climate change and pollution, and how they aggravate the symptoms of patients with rhinitis.

Relationship between Skeletal Malocclusion and Radiomorphometric Indices of the Mandible in Long Face Patients.

This study aimed to assess the relationship between skeletal malocclusion and radiomorphometric indices of the mandible in long face patients. This cross-sectional study evaluated 174 lateral cephalograms and panoramic radiographs of long face patients between the ages of 17 and 30 presenting at the Orthodontics Department of Qazvin Dental School. The gonial angle, antegonial angle, type of antegonial notch, and depth of antegonial notch were measured bilaterally on panoramic radiographs.

The impact of indoor pollution on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Systematic review using GRADE of the impact of exposure to volatile organic compounds (VOCs), cleaning agents, mould/damp, pesticides on the risk of (i) new-onset asthma (incidence) and (ii) adverse asthma-related outcomes (impact). MEDLINE, EMBASE and Web of Science were searched for indoor pollutant exposure studies reporting on new-onset asthma and critical and important asthma-related outcomes. Ninety four studies were included: 11 for VOCs (7 for incidenceand 4 for impact), 25 for cleaning agents (7 for incidenceand 8 for impact), 48 for damp/mould (26 for incidence and 22 for impact) and 10 for pesticides (8 for incidence and 2 for impact).

The impact of outdoor pollution and extreme temperatures on asthma-related outcomes: A systematic review for the EAACI guidelines on environmental science for allergic diseases and asthma.

Air pollution is one of the biggest environmental threats for asthma. Its impact is augmented by climate change. To inform the recommendations of the EAACI Guidelines on the environmental science for allergic diseases and asthma, a systematic review (SR) evaluated the impact on asthma-related outcomes of short-term exposure to outdoor air pollutants (PM2.