Long-Term Cognitive Outcomes in Adult Patients Receiving Chimeric Antigen Receptor T-Cell Therapies.

Background: CAR T-cell therapy (CAR-T) is leading to durable responses in patients with cancer but there is concern that cytokine release syndrome (CRS) and neurotoxicity may impact survivors' cognitive function. We assessed long-term cognitive function in CAR-T recipients and examine factors associated with change in cognition over time.

Methods: We assessed perceived cognition (Functional Assessment of Cancer Therapy - Cognition) and neurocognitive performance (standardized neuropsychological battery) in adult patients prior to receiving CAR-T and at 6 month follow-up.

Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial.

Importance: In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.

Objective: To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.

Ciliary Body Medulloepithelioma: Clinical and Pathologic Challenges with a Focus on Molecular Genetics.

Objective: Ciliary body medulloepithelioma (CBME), a pediatric intraocular tumor with potential for locally aggressive behavior and metastasis, may present with a diverse spectrum of clinical and histopathologic features leading to diagnostic and management challenges. Examination of unusual CBME cases highlights challenges and modern diagnostic techniques which facilitate accurate diagnosis and guide management.

Methods: A retrospective clinicopathologic analysis of 6 patients with unusual clinical or pathologic features of CBME was performed.

Genetic Services in Appalachia Conference Series.

This study examined the data generated as part of a seven-session webinar series that focused on genetics care provision in the medically underserved, rural Appalachian region and examined how these services have adapted to challenging practice environments. Barriers and facilitators to care in our region were considered. Data included a baseline survey of registrants, transcripts of sessions, and feedback about sessions.

Insulin Therapy for Acute Pancreatitis in a Patient With Lipase Maturation Factor 1 Mutation: A Case Report.

Acute pancreatitis is a frequent cause of hospital admission, managed with intravenous (IV) fluids, analgesia, and oral feeding when tolerated. In patients with hypertriglyceridemia-induced pancreatitis, insulin and other therapies may be necessary for disease resolution. We present a case of a patient with severe acute pancreatitis and euglycemic diabetic ketoacidosis (DKA) with known lipase maturation factor 1 (LMF1) gene mutations, which can impact insulin efficacy on triglyceride metabolism through altered lipoprotein lipase activity, successfully treated with intravenous insulin.

Kinematic Alignment Compared with Mechanical Alignment Techniques Results in Greater Peak Three-Dimensional Knee Joint Moments During Stair Negotiation.

Background: This study investigated the influence of surgical alignment techniques on knee joint biomechanics during stair negotiation tasks. Our hypothesis was that a more personalized joint alignment would result in reduced medial knee loading biomechanics to negotiate the stairs.

Methods: There were 28 adults (14 mechanical alignments [MA], 14 kinematic alignment [KA]) who underwent total knee arthroplasty (TKA) at least one year post-operatively and performed five stair ascent and descent trials at their preferred velocities.

Setting standards for brain collection procedures in metabolomic studies.

Current metabolomics technologies can measure hundreds of chemical entities in tissue extracts with good reliability. However, long-recognized requirements to halt enzyme activities during the initial moments of sample preparation are usually overlooked, allowing marked postmortem shifts in levels of labile metabolites representing diverse pathways. In brain many such changes occur in a matter of seconds.

Assembly and Annotation of the Tetraploid Salsola tragus (Russian thistle) Genome.

This report presents two phased chromosome-scale genome assemblies of allotetraploid Salsola tragus (2n=4x=36) and fills the current genomics resource gap for this species. Flow cytometry estimated 1C genome size was 1.319 Gbp.

Emerging Roles of TRIM56 in Antiviral Innate Immunity.

The tripartite-motif protein 56 (TRIM56) is a RING-type E3 ubiquitin ligase whose functions were recently beginning to be unveiled. While the physiological role(s) of TRIM56 remains unclear, emerging evidence suggests this protein participates in host innate defense mechanisms that guard against viral infections. Interestingly, TRIM56 has been shown to pose a barrier to viruses of distinct families by utilizing its different domains.

Structure-Based Discovery of MolPort-137: A Novel Autotaxin Inhibitor That Improves Paclitaxel Efficacy.

The autotaxin-lysophosphatidic acid receptor (ATX-LPAR) signaling axis is pivotal in various clinical conditions, including cancer and autoimmune disorders. This axis promotes tumorigenicity by interacting with the tumor microenvironment, facilitating metastasis, and conceding antitumor immunity, thereby fostering resistance to conventional cancer therapies. Recent studies highlight the promise of ATX/LPAR inhibitors in combination with conventional chemotherapeutic drugs to overcome some forms of this resistance, representing a novel therapeutic strategy.

Microlipophagy from Simple to Complex Eukaryotes.

Lipophagy is a selective degradation of lipid droplets in lysosomes or vacuoles. Apart from its role in generating energy and free fatty acids for membrane repair, growth, and the formation of new membranes, lipophagy emerges as a key player in other cellular processes and disease pathogenesis. While fungal, plant, and algal cells use microlipophagy, the most prominent form of lipophagy in animal cells is macrolipophagy.

Constraint of Different Knee Implant Designs Under Anterior-Posterior Shear Forces and Internal-External Rotation Moments in Human Cadaveric Knees.

Instability remains one of the most common indications for revision after total knee arthroplasty. To gain a better understanding of how an implant will perform in vivo and support surgeons in selecting the most appropriate implant design for an individual patient, it is crucial to evaluate the implant constraint within clinically relevant ligament and boundary conditions. Therefore, this study investigated the constraint of three different implant designs (symmetrical implants with and without a post-cam mechanism and an asymmetrical medial-stabilized implant) under anterior-posterior shear forces and internal-external rotation moments at different flexion angles in human cadaveric knees using a six-degrees-of-freedom joint motion simulator.

Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms.

Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders.

Management of children with food allergies by allergists in the United States.

Background: Management of patients with food allergies is complex, especially in cases of patients with multiple and potentially severe food allergies. Although international guidelines exist for food allergy management, the role of the allergist in the decision-making process is key.

Objective: Our aim was to investigate the management patterns and educational needs of practicing allergists treating patients with food allergies.

Leveraging a phased pangenome for haplotype design of hybrid potato.

The tetraploid genome and clonal propagation of the cultivated potato (Solanum tuberosum L.) dictate a slow, non-accumulative breeding mode of the most important tuber crop. Transitioning potato breeding to a seed-propagated hybrid system based on diploid inbred lines has the potential to greatly accelerate its improvement.

Comparison of Lean, Obese, and Weight Loss Models Reveals TREM2 Deficiency Attenuates Breast Cancer Growth Uniquely in Lean Mice and Alters Clonal T Cell Populations.

Obesity is an established risk factor for breast cancer development and poor prognosis. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression, and TREM2, a transmembrane receptor expressed on macrophages in adipose tissue and tumors, is an emerging therapeutic target for cancer. A better understanding of the mechanisms for the obesity-breast cancer association and the potential benefits of weight loss could help inform treatment strategies.

A computational tool to infer enzyme activity using post-translational modification profiling data.

Enzymes play a pivotal role in orchestrating complex cellular responses to external stimuli and environmental changes through signal transduction pathways. Despite their crucial roles, measuring enzyme activities is typically indirect and performed on a smaller scale, unlike protein abundance measured by high-throughput proteomics. Moreover, it is challenging to derive the activity of enzymes from proteome-wide post-translational modification (PTM) profiling data.

Sleeve gastrectomy reveals the plasticity of the human gastric epithelium.

Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs).

Single PEdicle Embolization of Distal Middle Meningeal Artery using n-BCA (SPEED-n technique).

The Single Pedicle Embolization of the Distal Middle Meningeal Artery using n-butyl cyanoacrylate (n-BCA) (SPEED-n technique) offers an innovative approach to treating chronic subdural hematomas by targeting the pathological subdural membranes with precise and efficient embolization.1 2 3 This technical video demonstrates the SPEED-n technique, which employs a single catheter and dilute n-BCA (15-20%) to achieve distal penetration of the middle meningeal artery (MMA) network while minimizing procedure time and risks (video 1).neurintsurg;jnis-2024-022751v1/V1F1V1Video 1-Key features include a stepwise embolization strategy, leveraging inherent MMA anastomoses to ensure comprehensive vascular coverage and reduced non-target embolization.

The Novel Role of GDI2: A Mini-Review.

GDP Dissociation Inhibitor 2 (GDI2) plays a crucial role in maintaining cellular homeostasis by regulating Rab GTPases involved in vesicular transport. This review highlights the importance of GDI2 in various biological processes, particularly embryonic development, apoptosis regulation, cancer, and immune responses. GDI2's essential function in embryonic development is evidenced by the embryonic lethality observed in GDI2 knockout mice.

Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial.

Background: Support for the treatment of uncomplicated appendicitis with non-operative management rather than surgery has been increasing in the literature. We aimed to investigate whether treatment of uncomplicated appendicitis with antibiotics in children is inferior to appendicectomy by comparing failure rates for the two treatments.

Methods: In this pragmatic, multicentre, parallel-group, unmasked, randomised, non-inferiority trial, children aged 5-16 years with suspected non-perforated appendicitis (based on clinical diagnosis with or without radiological diagnosis) were recruited from 11 children's hospitals in Canada, the USA, Finland, Sweden, and Singapore.

Integrated Phase I Pharmacokinetics and Pharmacodynamics of Epinephrine Administered via Sublingual Film, Autoinjector, or Manual Injection.

Background: Epinephrine is the first-line treatment for anaphylaxis and is administered via intramuscular (IM) or subcutaneous (SC) injection. AQST-109, a sublingual film containing a prodrug of epinephrine, is in development as an alternative delivery method for the treatment of severe allergic reactions including anaphylaxis.

Objective: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of epinephrine following administration of AQST-109 to epinephrine delivered by manual IM injection and epinephrine autoinjectors (EAIs).

DNA methylation at birth and IgE trajectories from birth to adolescence, different patterns between White and Asian.

Aim: We aim to assess association of DNA methylation (DNAm) at birth with total immunoglobulin E (IgE) trajectories from birth to late adolescence and whether such association is ethnicity-specific.

Methods: We examined the association of total IgE trajectories from birth to late adolescence with DNAm at birth in two independent birth cohorts, the Isle of wight birth cohort (IOWBC) in UK ( = 796; White) and the maternal and infant cohort study (MICS) in Taiwan ( = 60; Asian). Biological pathways and methylation quantitative trait loci (methQTL) for associated Cytosine-phosphate-Guanine sites were studied.

Impacts of Ethical Dilemmas and Moral Distress in Pediatric Hematology Oncology Nurses.

Purpose: To assess the level of moral distress (MD) and perceptions of ethical climate among pediatric hematology/oncology (PHO) nurses and to identify bioethics topics where increased education was desired.

Methods: In this cross-sectional study, we administered the 26-item Swedish Moral Distress Scale-Revised (sMDS-R), specifically revised and validated for pediatric oncology, in conjunction with the Clinical Ethics Needs Assessment Survey (CENAS). Electronic surveys were sent to inpatient and outpatient PHO nurses.