FDG-PET/CT is a powerful tool to predict and evaluate response to chimeric antigen receptor (CAR) T-cell therapy in Non-Hodgkin-Lymphoma (NHL).

Chimeric antigen receptor (CAR) T-cell therapy has dramatically shifted the landscape of treatment especially for Non-Hodgkin-Lymphoma (NHL). This study evaluates the role of fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) in NHL treated with CAR T-cell therapy concerning response assessment and prognosis.We evaluated 34 patients with NHL who received a CAR T-cell therapy between August 2019 and July 2022.

Evolutionary trajectories of small cell lung cancer under therapy.

The evolutionary processes that underlie the marked sensitivity of small cell lung cancer (SCLC) to chemotherapy and rapid relapse are unknown. Here we determined tumour phylogenies at diagnosis and throughout chemotherapy and immunotherapy by multiregion sequencing of 160 tumours from 65 patients. Treatment-naive SCLC exhibited clonal homogeneity at distinct tumour sites, whereas first-line platinum-based chemotherapy led to a burst in genomic intratumour heterogeneity and spatial clonal diversity.

Small intestinal volvulus in 47 cows.

Objective: To describe the findings, treatment, and outcome of small intestinal volvulus (SIV) in 47 cows.

Animals And Procedure: Retrospective analysis of medical records. Comparison of the findings for 18 surviving and 29 non-surviving cows.

Baseline characteristics and progression of neovascular age-related macular degeneration in patients receiving over 60 intravitreal injections of anti-vascular endothelial growth factor.

Age-related macular degeneration (AMD) is the leading cause of vision loss in older populations of industrialized countries. Antibody-based therapy inhibiting the vascular endothelial growth factor (VEGF) has been very successful in the treatment of the neovascular form of AMD. This retrospective clinical study investigates the baseline characteristics and progression of neovascular age-related macular degeneration (nAMD) in patients who received over 60 anti-VEGF intravitreal injections.

Continuous therapy response references for BCR::ABL1 monitoring in pediatric chronic myeloid leukemia.

Response to tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML) is monitored by quantification of BCR::ABL1 transcript levels. Milestones for assessing optimal treatment response have been defined in adult CML patients and are applied to children and adolescents although it is questionable whether transferability to pediatric patients is appropriate regarding genetic and clinical differences. Therefore, we analyzed the molecular response kinetics to TKI therapy in 129 pediatric CML patients and investigated whether response assessment based on continuous references can support an early individual therapy adjustment.

Dilated small and large intestines combined with a severely abnormal demeanor are characteristic of mesenteric torsion in cattle.

Objective: To describe the clinical, laboratory, and ultrasonographic findings; treatment; and outcome of cattle with mesenteric torsion (MT).

Animals: 61 cattle with MT between November 1, 1986, and December 31, 2019.

Methods: Medical records were retrospectively reviewed.

A retrospective review of small intestinal intussusception in 126 cattle in Switzerland.

Background: Intussusception is a form of ileus of the intestines in which an oral intestinal segment slides into the adjacent aboral intestinal segment, causing obstruction of the bowel.

Methods: We analysed the medical records of 126 cattle with intussusception of the small intestine.

Results: Demeanour and appetite were abnormal in 123 cattle.

Unusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesis.

Ribosomally synthesized and post-translationally modified peptide natural products have provided many highly unusual scaffolds. This includes the intriguing alkaloids crocagins, which possess a tetracyclic core structure and whose biosynthesis has remained enigmatic. Here we use in vitro experiments to demonstrate that three proteins, CgnB, CgnC and CgnE, are sufficient for the production of the hallmark tetracyclic crocagin core from the precursor peptide CgnA.

Multifamily therapy for young people with OCD: An acceptability and satisfaction study.

Individual cognitive-behavioral therapy (CBT) is the recommended first-line psychological treatment for young people with obsessive-compulsive disorder (OCD), with good outcomes. However, because some young people only partially respond to CBT, it is necessary to improve treatment outcomes. This is the first study to explore the acceptability and satisfaction of a new multifamily therapy (MFT).

Expanding the Ajudazol Cytotoxin Scaffold: Insights from Genome Mining, Biosynthetic Investigations, and Novel Derivatives.

Myxobacteria have proven to be a rich source of natural products, but their biosynthetic potential seems to be underexplored given the high number of biosynthetic gene clusters present in their genomes. In this study, a truncated ajudazol biosynthetic gene cluster in sp. SBCb004 was identified using mutagenesis and metabolomics analyses and a set of novel ajudazols (named ajudazols C-J, -, respectively) were detected and subsequently isolated.

Activation of a Ductal-to-Endocrine Transdifferentiation Transcriptional Program in the Pancreatic Cancer Cell Line PANC-1 Is Controlled by RAC1 and RAC1b through Antagonistic Regulation of Stemness Factors.

Epithelial-mesenchymal transition (EMT) is a driving force for tumor growth, metastatic spread, therapy resistance, and the generation of cancer stem cells (CSCs). However, the regained stem cell character may also be exploited for therapeutic conversion of aggressive tumor cells to benign, highly differentiated cells. The PDAC-derived quasimesenchymal-type cell lines PANC-1 and MIA PaCa-2 have been successfully transdifferentiated to endocrine precursors or insulin-producing cells; however, the underlying mechanism of this increased plasticity remains elusive.

An Outer Membrane Vesicle-Based Permeation Assay (OMPA) for Assessing Bacterial Bioavailability.

When searching for new antibiotics against Gram-negative bacterial infections, a better understanding of the permeability across the cell envelope and tools to discriminate high from low bacterial bioavailability compounds are urgently needed. Inspired by the phospholipid vesicle-based permeation assay (PVPA), which is designed to predict non-facilitated permeation across phospholipid membranes, outer membrane vesicles (OMVs) of Escherichia coli either enriched or deficient of porins are employed to coat filter supports for predicting drug uptake across the complex cell envelope. OMVs and the obtained in vitro model are structurally and functionally characterized using cryo-TEM, SEM, CLSM, SAXS, and light scattering techniques.

A Comparative Endocrine Trans-Differentiation Approach to Pancreatic Ductal Adenocarcinoma Cells with Different EMT Phenotypes Identifies Quasi-Mesenchymal Tumor Cells as Those with Highest Plasticity.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and therapy-resistant cancer types which is largely due to tumor heterogeneity, cancer cell de-differentiation, and early metastatic spread. The major molecular subtypes of PDAC are designated classical/epithelial (E) and quasi-mesenchymal (QM) subtypes, with the latter having the worst prognosis. Epithelial-mesenchymal transition (EMT) and the reverse process, mesenchymal-epithelial transition (MET), are involved in regulating invasion/metastasis and stem cell generation in cancer cells but also early pancreatic endocrine differentiation or de-differentiation of adult pancreatic islet cells in vitro, suggesting that pancreatic ductal exocrine and endocrine cells share common EMT programs.

miRMaster 2.0: multi-species non-coding RNA sequencing analyses at scale.

Analyzing all features of small non-coding RNA sequencing data can be demanding and challenging. To facilitate this process, we developed miRMaster. After the analysis of over 125 000 human samples and 1.

An ambruticin-sensing complex modulates Myxococcus xanthus development and mediates myxobacterial interspecies communication.

Starvation induces cell aggregation in the soil bacterium Myxococcus xanthus, followed by formation of fruiting bodies packed with myxospores. Sporulation in the absence of fruiting bodies can be artificially induced by high concentrations of glycerol through unclear mechanisms. Here, we show that a compound (ambruticin VS-3) produced by a different myxobacterium, Sorangium cellulosum, affects the development of M.

Inhibition of Tumor VEGFR2 Induces Serine 897 EphA2-Dependent Tumor Cell Invasion and Metastasis in NSCLC.

Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF)-VEGFR2 signaling has shown limited efficacy in lung cancer patients. Here, we demonstrate that inhibition of VEGFR2 in tumor cells, expressed in ∼20% of non-squamous non-small cell lung cancer (NSCLC) patients, leads to a pro-invasive phenotype. Drug-induced inhibition of tumor VEGFR2 interferes with the formation of the EphA2/VEGFR2 heterocomplex, thereby allowing RSK to interact with Serine 897 of EphA2.

Prognostic relevance of programmed death-ligand 1 expression and microsatellite status in small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a dreadful disease. Patient prognosis is limited due to late presentation and ineffective chemotherapy. PD-1/PD-L1 checkpoint immunotherapy is regarded as a promising approach in several cancer entities.

The Work and Social Adjustment Scale, Youth and Parent Versions: Psychometric Evaluation of a Brief Measure of Functional Impairment in Young People.

The Work and Social Adjustment Scale (WSAS) is a brief global measure of functional impairment that is widely used in adult health. We have adapted the WSAS for its use in youth, the WSAS-Youth version (WSAS-Y) and WSAS-Parent version (WSAS-P). This study evaluated the psychometric properties of the scale.

ERG Alteration Due to the rd8 Mutation of the Crb1 Gene in Cln3 Mice.

Mattapallil et al. described that vendor lines for C57BL/6 N mice may carry the rd8 mutation that leads to an ocular phenotype, which could be mistaken for an induced retinal degeneration. This mouse strain is widely used in ophthalmic research as a background for modeling retinal degeneration.

Clinical Resistome Screening of 1,110 Isolates Efficiently Recovers Diagnostically Relevant Antibiotic Resistance Biomarkers and Potential Novel Resistance Mechanisms.

Multidrug-resistant pathogens represent one of the biggest global healthcare challenges. Molecular diagnostics can guide effective antibiotics therapy but relies on validated, predictive biomarkers. Here we present a novel, universally applicable workflow for rapid identification of antimicrobial resistance (AMR) biomarkers from clinical isolates and quantitatively evaluate the potential to recover causal biomarkers for observed resistance phenotypes.

High hepatic expression of PDK4 improves survival upon multimodal treatment of colorectal liver metastases.

Background: Patients with borderline resectable colorectal liver metastases (CRLM) frequently receive neoadjuvant chemotherapy (NC) to reduce tumour burden, thus making surgical resection feasible. Even though NC can induce severe liver injury, most studies investigating tissue-based prognostic markers focus on tumour tissue. Here, we assessed the prognostic significance of pyruvate-dehydrogenase-kinase isoenzyme 4 (PDK4) within liver tissue of patients undergoing surgical resection due to CRLM.

Various effects of AAV9-mediated βARKct gene therapy on the heart in dystrophin-deficient (mdx) mice and δ-sarcoglycan-deficient (Sgcd-/-) mice.

So far effective strategies to treat cardiomyopathy in patients with muscular dystrophies are still not clearly defined. Previously, treatment with β-blockers showed beneficial effects on the development of cardiomyopathy in dystrophin-deficient (mdx) mice, but not in δ-sarcoglycan-deficient (Sgcd-/-) mice. We therefore aimed to study a more specific approach to target maladaptive β-adrenergic signalling in these mice.

Salinomycin: Anti-tumor activity in a pre-clinical colorectal cancer model.

Objectives: Salinomycin is a polyether antibiotic with selective activity against human cancer stem cells. The impact of salinomycin on patient-derived primary human colorectal cancer cells has not been investigated so far. Thus, here we aimed to investigate the activity of salinomycin against tumor initiating cells isolated from patients with colorectal cancer.

Adaptation of a Bacterial Multidrug Resistance System Revealed by the Structure and Function of AlbA.

To combat the rise of antimicrobial resistance, the discovery of new antibiotics is paramount. Albicidin and cystobactamid are related natural product antibiotics with potent activity against Gram-positive and, crucially, Gram-negative pathogens. AlbA has been reported to neutralize albicidin by binding it with nanomolar affinity.