PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Structural remodeling of the brain cortex and functional recovery following hypoglossal-facial neurorrhaphy in patients with facial paralysis.

Objective: Peripheral nerve injury results in functional alterations of the corresponding active brain areas, which are closely related to functional recovery. Whether such functional plasticity induces relative anatomical structural changes remains to be investigated.

Methods: In this study, we investigated the changes in brain cortical thickness in patients with facial paralysis following neurorrhaphy treatment at different follow-up times.

Optimising Venturi flume oxygen transfer efficiency using uncertainty-aware decision trees.

This study optimizes standard oxygen transfer efficiency (SOTE) in Venturi flumes investigating the impact of key parameters such as discharge per unit width (), throat width (), throat length (), upstream entrance width (), and gauge readings ( and ). To achieve this, a comprehensive experimental dataset was analyzed using multiple linear regression (MLR), multiple nonlinear regression (MNLR), gradient boosting machine (GBM), extreme gradient boosting (XRT), random forest (RF), M5 (pruned and unpruned), random tree (RT), and reduced error pruning (REP). Model performance was evaluated based on key metrics: correlation coefficient (CC), root mean square error (RMSE), and mean absolute error (MAE).

Structural and functional determination of peptide versus small molecule ligand binding at the apelin receptor.

We describe a structural and functional study of the G protein-coupled apelin receptor, which binds two endogenous peptide ligands, apelin and Elabela/Toddler (ELA), to regulate cardiovascular development and function. Characterisation of naturally occurring apelin receptor variants from the UK Genomics England 100,000 Genomes Project, and AlphaFold2 modelling, identifies T89 as important in the ELA binding site, and R168 as forming extensive interactions with the C-termini of both peptides. Base editing to introduce an R/H168 variant into human stem cell-derived cardiomyocytes demonstrates that this residue is critical for receptor binding and function.

Sperm Functional Status: A Multiparametric Assessment of the Fertilizing Potential of Bovine Sperm.

Sperm viability is routinely assessed for the quality control of cryopreserved bovine sperm batches but is not usually conclusive regarding their fertilizing potential. In this study, we investigated the fertility predictive value of bull sperm viability in combination with DNA integrity or the functional status of viable sperm. In addition to sperm viability, we flow cytometrically assessed the percentage of sperm with high DNA fragmentation index (%DFI) and the fraction of viable sperm with low intracellular Ca content and functional mitochondria using the Sperm Chromatin Structure Assay and a five-color staining panel in 791 and 733 cryopreserved batches with non-return rate (NRR) records after ≥100 first services, respectively.

Determination of Intrinsic Clearance and Fraction Unbound in Human Liver Microsomes and In Vitro-In Vivo Extrapolation of Human Hepatic Clearance for Marketed Central Nervous System Drugs.

Objective: The objective of this study was to determine the apparent intrinsic clearance (Cl) and fraction unbound in human liver microsomes (f) of 86 marketed central nervous system (CNS) drugs and to predict the in vivo hepatic blood clearance (CL).

Methods: Cl in human liver microsomes (HLM) was determined by substrate depletion, and f was determined by equilibrium dialysis. The relationship between lipophilicity (logP) and unbound intrinsic clearance (Cl) was explored using the Biopharmaceutical Drug Disposition Classification System (BDDCS) and Extended Clearance Classification System (ECCS).

Clinical Impact and Significant Technical Points of Transarterial Chemoembolization (TACE) Using the Smaller Drug-Eluting Bead M1 (DC Bead M1™) for Hepatocellular Carcinoma: A Case Series.

Background: This case series evaluated the clinical impact and significant technical points of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) using the smaller drug-eluting bead (DEB) M1 (DC Bead M1; 70-150 µm).

Methods: We evaluated 12 patients and 14 HCC nodules treated with DEB-TACE using the DC Bead M1 (named DEM1-TACE). In addition to evaluating the early treatment efficacy for each treated node after DEM1-TACE, the study also used interventional radiology (IVR)- computed tomography (CT) to focus on the presence or absence of retention of the homogeneous contrast medium in target nodules after DEM1-TACE as a predictor of a good treatment response.

[Effect of retrograde dissection of the facial nerve along the mandibular margin on postoperative quality of life in patients with benign superficial parotid tumors].

Purpose: To assess the impact of retrograde dissection of the facial nerve along the mandibular margin on the postoperative quality of life in patients with benign superficial parotid tumors.

Methods: One hundred and sixteen patients who underwent surgical treatment for benign superficial parotid tumors at Qingdao Central Hospital from January 2020 to January 2023 were involved. The patients were randomly allocated into two groups, with 58 patients in each group using the touch ball method.

CT- and MRI-based Factors Associated with Rapid Growth in Early-Stage Hepatocellular Carcinoma.

Background Prediction of the tumor growth rates is clinically important in patients with hepatocellular carcinoma (HCC), but previous studies have presented conflicting results and generally lacked radiologic evaluations. Purpose To evaluate the percentage of rapidly growing early-stage HCCs in each Liver Imaging Reporting and Data System (LI-RADS) category and to identify prognostic factors associated with rapid growth. Materials and Methods Retrospective study of patients with risk factors for HCC and those with surgically proven early-stage HCC who underwent two or more preoperative multiphasic CT or MRI examinations between January 2016 and December 2020.

Impaired Wnt/Planar Cell Polarity Signaling in Yellow Nail Syndrome.

Background: Yellow nail syndrome (YNS) is a rare disorder characterized by a triad of yellow dystrophic nails, lymphedema, and chronic lung disease. Most patients present in adulthood, with only a few congenital or familial cases described. The cause of YNS remains largely unknown, although defects in lymphatic vessel development are suggested to play a significant role.

Multifaceted Hidden Catalysis Revealed by Mechanistic Analysis of FeBr3-Catalysed Arene Borylation.

Arene borylation reactions provide direct access to aryl organoboranes, including aryl boronic esters. Precious metals, namely Ir, Rh, Pt, remain the go-to for metal-catalysed borylation reactions, however, significant efforts have been expended in developing Earth-abundant metal alternatives. The iron-catalysed borylation of 2-aryl pyridine derivatives with 9-borabicyclo[3.

Patterns and predictors of multiple sclerosis phenotype transition.

Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes.

Arthroscopic-Assisted Lateral Ulnar Collateral Ligament Reconstruction for Posterolateral Rotatory Instability of the Elbow: A Technical Note.

The lateral collateral ligament complex of the elbow is pivotal for maintaining the stability of the elbow joint. The open technique for reconstructing the lateral ulnar collateral ligament (LUCL) is a standard procedure to treat elbow instability caused by LUCL deficiency. Nevertheless, as arthroscopy procedures in the elbow have advanced, we describe an arthroscopic technique to reconstruct the LUCL with suture anchors and bone tunnel techniques.

Epstein-Barr virus hijacks B cell metabolism to establish persistent infection and drive pathogenesis.

When B cells engage in an immune response, metabolic reprogramming is key to meeting cellular energetic and biosynthetic demands. Epstein-Barr virus (EBV) is a highly prevalent gamma-herpesvirus, latently infecting B cells for the human host's lifetime. By hijacking signaling pathways of T cell-dependent humoral immunity, EBV activates B cells in a T cell-independent manner, forcing lymphoblastoid transformation.

Endosomal pH is an evolutionarily conserved driver of phenotypic plasticity in colorectal cancer.

Dysregulated pH is now recognised as a hallmark of cancer. Recent evidence has revealed that the endosomal pH regulator Na/H exchanger NHE9 is upregulated in colorectal cancer to impose a pseudo-starvation state associated with invasion, highlighting an underexplored mechanistic link between adaptive endosomal reprogramming and malignant transformation. In this study, we use a model that quantitatively captures the dynamics of the core regulatory network governing epithelial mesenchymal plasticity.

Muscle atrophy and organ enlargement associated with quality of life during systemic therapy for melanoma: findings from an AI-based body composition analysis.

Introduction: Health-related quality of life (HRQoL) is emerging as an endpoint, adjunct to survival, in cancer treatment. For this reason, the European Organization for Research and Treatment of Cancer (EORTC) has developed standardized quality-of-life questionnaires to collect patient-reported outcome measurement (PROM), which so far have been widely used in clinical trials to evaluate the impact of new drugs on cancer patients. However, while these questionnaires comprehensively describe patient functions, little is known about their association with patient characteristics.

A prospective comparison of two computer aided detection systems with different false positive rates in colonoscopy.

This study evaluated the impact of differing false positive (FP) rates in two computer-aided detection (CADe) systems on the clinical effectiveness of artificial intelligence (AI)-assisted colonoscopy. The primary outcomes were adenoma detection rate (ADR) and adenomas per colonoscopy (APC). The ADR in the control, system A (3.

Exome and Genome Sequencing to Diagnose the Genetic Basis of Neonatal Hypotonia: An International Consortium Study.

Background And Objectives: Hypotonia is a relatively common finding among infants in the neonatal intensive care unit (NICU). Consideration of genetic testing is recommended early in the care of infants with unexplained hypotonia. We aimed to assess the diagnostic yield and overall impact of exome and genome sequencing (ES and GS).

Primary charge separation in Chloroflexus aurantiacus reaction centers at room temperature: ultrafast transient absorption measurements on Q-depleted preparations with native and chemically modified bacteriopheophytin composition.

The initial electron transfer (ET) processes in reaction centers (RCs) of Chloroflexus (Cfl.) aurantiacus were studied at 295 K using femtosecond transient absorption (TA) difference spectroscopy. Particular attention was paid to the decay kinetics of the primary electron donor excited state (P) and the formation/decay of the absorption band of the monomeric bacteriochlorophyll a anion (B) at ~ 1035 nm, which reflects the dynamics of the charge-separated state PB.

Heterogeneity in response to neoadjuvant radiotherapy between soft tissue sarcoma histotypes: associations between radiology and pathology findings.

Objective: To investigate imaging biomarkers of tumour response by describing changes in imaging and pathology findings after neoadjuvant radiotherapy (nRT) and exploring their correlations.

Materials And Methods: Tumour diameter, volume, and tumour-to-muscle signal intensity (SI) ratio were collected before and after radiotherapy in a cohort of 107 patients with intermediate/high-grade STS and were correlated with post-radiotherapy pathology findings (percentage of necrosis, viable cells, and fibrosis) using Spearman Rank test. Pathological complete response (pCR) was defined as no residual viable cells present, whereas the presence of < 10% viable cells was defined as near-complete pathologic response (near-pCR).

Covered Stent Correction for Sinus Venosus Atrial Septal Defects, an Emerging Alternative to Surgical Repair: Results of an International Registry.

Background: Covered stent correction for a sinus venosus atrial septal defect (SVASD) was first performed in 2009. This innovative approach was initially viewed as experimental and was reserved for highly selected patients with unusual anatomic variants. In 2016, increasing numbers of procedures began to be performed, and in several centers, it is now offered as a standard of care option alongside surgical repair.

Correlation between P2-PCA volume flow rate and BOLD cerebrovascular reactivity in patients with symptomatic carotid artery occlusion.

Background And Purpose: Identifying and assessing hemodynamic and flow status in patients with symptomatic internal carotid artery (ICA) occlusion is crucial for evaluating recurrent stroke risk. The aim of this study was to analyze the correlation between two quantitative imaging modalities: (1) blood oxygenation level-dependent (BOLD) cerebrovascular reactivity (CVR) and (2) quantitative magnetic resonance angiography (qMRA) with non-invasive optimal vessel analysis (NOVA), measuring volume flow rate (VFR). Comparing these modalities is relevant for assessing collateral circulation and hemodynamic impairment.

Ebola Outbreak Response in the DRC with rVSV-ZEBOV-GP Ring Vaccination.

Background: At the beginning of the 2018-2020 outbreak of Ebola virus disease (EVD) in eastern Democratic Republic of Congo (DRC), no vaccine had been licensed. However, cluster-randomized evidence from Guinea in 2015 had indicated that ring vaccination around new cases (targeting contacts and contacts-of-contacts) with the use of single-dose live-replicating rVSV-ZEBOV-GP vaccine reduced EVD rates starting 10 days after vaccination. Thus, ring vaccination was added to the standard control measures for that outbreak.

An additive opinion to the committee opinion of ASRM and SART on the use of preimplantation genetic testing for aneuploidy (PGT-A).

After over 20 years of progressively increasing clinical utilization of PGT-A (and its precursors), the American Society for Reproductive Medicine (ASRM) and its daughter society, the Society for Assisted Reproduction (SART), for the first time published a committee opinion clearly acknowledging that "the value of PGT-A as a routine screening test for patients undergoing in vitro fertilization (IVF) has not been demonstrated." This statement is timely and welcome but requires some additions and raises some new questions, among those why, if PGT-A in a general population does not improve IVF cycle outcomes, the routine clinical utilization of PGT-A should continue.

Discordance between MR enterography and endoscopic detection of Crohn's disease ileal strictures: evidence to inform recommendations.

Purpose: To evaluate correlation between terminal ileal (TI) stricture diagnosis at MR enterography (MRE) and ileocolonoscopy (IC) in patients with Crohn's disease (CD).

Methods: One hundred and four patients with CD (51% females; 41 ± 15 years) underwent IC and MRE within 3 months in this retrospective case-control study. Positive cases had TI strictures diagnosed by endoscopy (n = 35); or MRE (threshold small bowel dilation ≥ 3cm; n = 34).