Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

Tumor-intrinsic kinome landscape of pancreatic cancer reveals new therapeutic approaches.

Effective therapies for pancreatic ductal adenocarcinoma (PDAC) have been largely elusive. Here, we perform Multiplexed kinase Inhibitor Bead Mass Spectrometry on 102 patient derived xenografts derived from 14 unique primary PDAC to define the tumor-intrinsic kinome landscape. Our findings uncover three kinome subgroups making up two tumor-intrinsic kinome subtypes that we call kinotypes.

A two-stage deep-learning model for determination of the contact of mandibular third molars with the mandibular canal on panoramic radiographs.

Objectives: This study aimed to assess the accuracy of a two-stage deep learning (DL) model for (1) detecting mandibular third molars (MTMs) and the mandibular canal (MC), and (2) classifying the anatomical relationship between these structures (contact/no contact) on panoramic radiographs.

Method: MTMs and MCs were labeled on panoramic radiographs by a calibrated examiner using bounding boxes. Each bounding box contained MTM and MC on one side.

Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group.

Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

Conversation-based AI for anxiety disorders might lower the threshold for traditional medical assistance: a case report.

Artificial intelligence (AI) offers a wealth of opportunities for medicine, if we also bear in mind the risks associated with this technology. In recent years the potential future integration of AI with medicine has been the subject of much debate, although practical clinical experience of relevant cases is still largely absent. This case study examines a particular patient's experience with different forms of care.

Quantitative MRI Measures and Cognitive Function in People With Drug-Resistant Juvenile Myoclonic Epilepsy.

Background And Objectives: Neuroimaging studies have so far identified structural changes in individuals with juvenile myoclonic epilepsy (JME) when compared with controls. However, the underlying mechanisms of drug-resistant JME remain unknown. In this study, we aimed at characterizing the structural underpinnings of drug-resistant JME using MRI-derived cortical morphologic markers.

Exploring Associations of Somatic Symptom Disorder with Personality Dysfunction and Specific Maladaptive Traits.

Introduction: According to ICD-11, personality disorders (PDs) are defined by the severity of self and interpersonal dysfunction in terms of personality functioning (PF) and an optional assessment of specific maladaptive personality trait expressions. Also, somatoform disorders are replaced by somatic symptom disorder (SSD). This study examines associations using the novel diagnostic criteria of SSD in an unselected primary care sample, PF, and maladaptive traits in patients with and without SSD.

The Infiltrative Margins in Glioblastoma: Important Is What Has Been Left behind.

Supramaximal resection beyond the contrast-enhancing tumor borders represents an emerging surgical strategy for patients with newly diagnosed glioblastoma. A recent study provides evidence detailing the interactive effects of more aggressive surgery on other clinical predictors of outcome, supporting guidance for surgical decision-making and informing clinical trialists about the need to stratify for extent of resection. See related article by Park et al.

Sodium valproate is associated with cortical thinning of disease-specific areas in juvenile myoclonic epilepsy.

Background: Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME.

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.

Lessons learned from applying established cut-off values of questionnaires to detect somatic symptom disorders in primary care: a cross-sectional study.

Introduction: Based on two diagnostic accuracy studies in high-prevalence settings, two distinctly different combinations of cut-off values have been recommended to identify persons at risk for somatic symptom disorder (SSD) with the combination of the Patient-Health Questionnaire-15 (PHQ-15) and the Somatic Symptom Disorder-B Criteria Scale (SSD-12). We investigated whether the reported sensitivity and specificity of both recommended cut-off combinations are transferable to primary care.

Methods: In a cross-sectional study, 420 unselected adult primary care patients completed PHQ-15 and SSD-12.

Minimal Residual Disease Status Predicts Outcome in Patients With Previously Untreated Follicular Lymphoma: A Prospective Analysis of the Phase III GALLIUM Study.

Purpose: We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial.

Patients And Methods: Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders.

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group.

Background: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement.

Peripheral cholinesterase activity is not correlated with postoperative delirium in urological surgery.

The value of biomarkers, such as acetylcholinesterase and butyrylcholinesterase, for guiding perioperative patients suffering from postoperative delirium and/or (possibly related) postoperative cognitive dysfunction is unclear. Only recently have different biomarkers are being explored to assess postoperative delirium's occurrence and/or course. The aim of this work is to investigate whether acetylcholinesterase and butyrylcholinesterase can help detect increased risks of the development and course of postoperative delirium in urological patients undergoing surgery.

Concomitant Drug Use among Opioid-Dependent Patients with and without Attention Deficit Hyperactivity Disorder: Does Methylphenidate Merit a Trial?

Introduction: Concomitant drug use is common among opioid-dependent patients in maintenance therapy. Attention deficit hyperactivity disorder (ADHD), a common comorbidity among opioid users, is associated with a higher risk of concomitant drug use. Earlier studies showed that methylphenidate (MPH) can reduce cocaine consumption among patients with ADHD.

Viral Etiology and Clinical Characteristics of Acute Respiratory Tract Infections in Hospitalized Children in Southern Germany (2014-2018).

Background: Viral acute respiratory tract infections (ARTIs) are a leading cause of hospitalization in infants and young children.

Methods: During the winter seasons of 2014-2018, hospitalized children (<18 years) with symptoms of ARTI were prospectively included at the University Hospital Heidelberg, Germany. Nasopharyngeal swabs were obtained for multiplex molecular analysis of 10 groups of respiratory viruses, and clinical data were obtained using a standardized questionnaire.

Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro.

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts.

Toll-like receptors 2 and 4 stress signaling and sodium-glucose cotransporter-2 in kidney disease.

Kidney disease is the 6th fastest-growing cause of death and a serious global health concern that urges effective therapeutic options. The inflammatory response is an initial reaction from immune and parenchymal cells in kidney diseases. Toll-like receptors (TLR) 2 and 4 are highly expressed by various kidney cells and respond to 'signaling danger' proteins, such as high mobility group box binding protein 1 (HMGB1) and prompt the progression of kidney disease by releasing inflammatory mediators.