CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities.

The advent of chimeric antigen receptor (CAR)-T cells has recently changed the prognosis of relapsing/refractory diffuse large B-cell lymphomas, showing response rates as high as 60 to 80%. Common toxicities reported in the pivotal clinical trials include the cytokine release syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), a stereotyped encephalopathy related to myeloid cell activation and blood-brain barrier dysfunction, presenting with a distinctive cascade of dysgraphia, aphasia, disorientation, attention deficits, vigilance impairment, motor symptoms, seizures, and diffuse brain oedema. The tremendous oncological efficacy of CAR-T cells observed in systemic B-cell malignancies is leading to their growing use in patients with primary or secondary central nervous system (CNS) lymphomas and in patients with solid tumours, including several CNS cancers.

Formative evaluation of the implementation of digital therapeutics for opioids and other substance use disorders in primary care (DIGITS trial).

Background: Substance use disorders (SUDs) result in individual and societal burden. However, most individuals with SUD receive no treatment. Implementing SUD interventions in primary care could address this population's treatment needs.

Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents.

The ADP-ribosyl hydrolases PARG and ARH3 counteract PARP enzymatic activity by removing ADP-ribosylation. PARG and ARH3 activities have a synthetic lethal effect; however, the specific molecular mechanisms underlying this response remain unknown. Here, we show that the PARG and ARH3 synthetic lethality is enhanced further in the presence of DNA alkylating agents, suggesting that the inability to revert ADP-ribosylation primarily affects the repair of alkylated DNA bases.

Prescription Digital Therapeutics for Substance Use Disorder in Primary Care: Mixed Methods Evaluation of a Pilot Implementation Study.

Background: Delivering prescription digital therapeutics (ie, evidence-based interventions designed to treat, manage, or prevent disorders via websites or smartphone apps) in primary care could increase patient access to substance use disorder (SUD) treatments. However, the optimal approach to implementing prescription digital therapeutics in primary care remains unknown.

Objective: This pilot study is a precursor to a larger trial designed to test whether implementation strategies (practice facilitation [PF] and health coaching [HC]) improve the delivery of prescription digital therapeutics for SUDs in primary care.

Liquid biopsy in brain tumors: moving on, slowly.

Purpose Of Review: Due to limited access to the tumor, there is an obvious clinical potential for liquid biopsy in patients with primary brain tumors. Here, we review current approaches, present limitations to be dealt with, and new promising data that may impact the field.

Recent Findings: The value of circulating tumor cell-free DNA (ctDNA) in the cerebrospinal fluid (CSF) for the noninvasive diagnosis of primary brain tumors has been confirmed in several reports.

Getting cozy with causality: Advances to the causal pathway diagramming method to enhance implementation precision.

Background: Implementation strategies are theorized to work well when carefully matched to implementation determinants and when factors-preconditions, moderators, etc.-that influence strategy effectiveness are prospectively identified and addressed. Existing methods for strategy selection are either imprecise or require significant technical expertise and resources, undermining their utility.

A Novel Framework Based on Deep Learning Architecture for Continuous Human Activity Recognition with Inertial Sensors.

Frameworks for human activity recognition (HAR) can be applied in the clinical environment for monitoring patients' motor and functional abilities either remotely or within a rehabilitation program. Deep Learning (DL) models can be exploited to perform HAR by means of raw data, thus avoiding time-demanding feature engineering operations. Most works targeting HAR with DL-based architectures have tested the workflow performance on data related to a separate execution of the tasks.

Patients with NPSLE experience poorer HRQoL and more fatigue than SLE patients with no neuropsychiatric involvement, irrespective of neuropsychiatric activity.

Objectives: Substantial proportions of patients with SLE report poor health-related quality of life (HRQoL). Our objective was to investigate the impact of neuropsychiatric involvement (NP) in SLE on patient-reported outcomes.

Methods: We analysed data from four phase III trials (BLISS-52, BLISS-76, BLISS-SC, EMBRACE; N = 2968).

A pragmatic randomized clinical trial of multilevel interventions to improve adherence to lung cancer screening (The Larch Study): Study protocol.

Background: In real-world settings, low adherence to lung cancer screening (LCS) diminishes population-level benefits of reducing lung cancer mortality. We describe the Larch Study protocol, which tests the effectiveness of two patient-centered interventions (Patient Voices Video and Stepped Reminders) designed to address barriers and improve annual LCS adherence.

Methods: The Larch Study is a pragmatic randomized clinical trial conducted within Kaiser Permanente Washington.

Young Women's Perspectives on Being Screened for Hereditary Breast and Ovarian Cancer Risk During Routine Primary Care.

Purpose: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.

Study protocol: Novel Methods for Implementing Measurement-Based Care with youth in Low-Resource Environments (NIMBLE).

Background: For youth receiving care in community mental health centers, comorbidities are the rule rather than the exception. Using measurement-based care (MBC), or the routine evaluation of symptoms to inform care decisions, as the foundation of treatment for youth with comorbid problems significantly improves the impact of psychotherapy by focusing care and building engagement and alliance. MBC increases the rate of symptom improvement, detects clients who would otherwise deteriorate, and alerts clinicians to non-responders.

Evidence of Circulation and Phylogenetic Analysis of Hepatitis E Virus (HEV) in Wild Boar in South-East Italy.

Hepatitis E virus (HEV) is an important cause of acute viral hepatitis in humans worldwide. The food-borne transmission of HEV appears to be a major route in Europe through the consumption of pork and wild boar meat. HEV epidemiology in wild boars has been investigated mainly in Northern and Central Italian regions, whilst information from Southern Italy is limited.

Amyotrophic Lateral Sclerosis and Its Management during the COVID-19 Pandemic: A Qualitative Study with Thematic Analysis of Patients and Caregivers Who Participated in Self-Help Groups.

This study employs a qualitative methodology to explore the effects of the pandemic on the lives of ALS patients and their caregivers. It aims to understand whether and how online self-help groups have assisted families dealing with amyotrophic lateral sclerosis (ALS) patients. ALS is a neurodegenerative disease with both physical and psychosocial implications.

Exploring Emotions Related to the COVID-19 Pandemic through Death Education: A Qualitative Study at Italian Primary Schools.

Background: The COVID-19 pandemic has impacted the lives of individuals, families, and children worldwide. In Italy, the implementation of measures such as lockdowns and distance learning in schools affected the mental health of children and families.

Methods: This article employs a qualitative method to explore the efficacy of a death education project that aimed to help primary school children process the emotions and losses that they experienced during the COVID-19 pandemic.

Effect of Belimumab on Preventing Renal Lupus Flares.

Introduction: Belimumab was recently approved for treating lupus nephritis (LN), yet LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative.

Methods: We evaluated belimumab efficacy in preventing renal flares and factors associated with renal flare occurrence in nephritis-naïve patients with systemic lupus erythematosus (SLE) who are receiving add-on belimumab or placebo in 5 phase 3 clinical trials using Cox regression analysis.

Determinants of neuropsychiatric flares in patients with systemic lupus erythematosus: results from five phase III trials of belimumab.

Objective: To identify determinants of neuropsychiatric (NP) flares in patients with SLE treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo.

Methods: We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; n = 3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression.

Endoscopic Ultrasound-guided Radiofrequency Ablation Versus Surgical Resection for Treatment of Pancreatic Insulinoma.

Background & Aims: Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is emerging as a safe and effective treatment for pancreatic neuroendocrine tumors. We aimed to compare EUS-RFA and surgical resection for the treatment of pancreatic insulinoma (PI).

Methods: Patients with sporadic PI who underwent EUS-RFA at 23 centers or surgical resection at 8 high-volume pancreatic surgery institutions between 2014 and 2022 were retrospectively identified and outcomes compared using a propensity-matching analysis.

The DarT/DarG Toxin-Antitoxin ADP-Ribosylation System as a Novel Target for a Rational Design of Innovative Antimicrobial Strategies.

The chemical modification of cellular macromolecules by the transfer of ADP-ribose unit(s), known as ADP-ribosylation, is an ancient homeostatic and stress response control system. Highly conserved across the evolution, ADP-ribosyltransferases and ADP-ribosylhydrolases control ADP-ribosylation signalling and cellular responses. In addition to proteins, both prokaryotic and eukaryotic transferases can covalently link ADP-ribosylation to different conformations of nucleic acids, thus highlighting the evolutionary conservation of archaic stress response mechanisms.

Study protocol for a factorial-randomized controlled trial evaluating the implementation, costs, effectiveness, and sustainment of digital therapeutics for substance use disorder in primary care (DIGITS Trial).

Background: Experts recommend that treatment for substance use disorder (SUD) be integrated into primary care. The Digital Therapeutics for Opioids and Other SUD (DIGITS) Trial tests strategies for implementing reSET® and reSET-O®, which are prescription digital therapeutics for SUD and opioid use disorder, respectively, that include the community reinforcement approach, contingency management, and fluency training to reinforce concept mastery. This purpose of this trial is to test whether two implementation strategies improve implementation success (Aim 1) and achieve better population-level cost effectiveness (Aim 2) over a standard implementation approach.

Strengths and Weaknesses of Children Witnessing Relatives with Amyotrophic Lateral Sclerosis.

Research on minors who have a close family member with amyotrophic lateral sclerosis (ALS) is scarce. This study aims to analyze the relationships between reflective function and wellbeing among such children, considering their reflective function, representations of death, and behavioral problems with the following instruments: Reflective Functioning Questionnaire, Testoni Death Representation Scale for Children, Positive and Negative Affect Schedule for Children, and Strengths and Difficulties Questionnaire. Participants were 248 minors divided into the target group (38 children-16 females, 22 males-7-18 years old (M = 11.

in wild boar meat from Italy, 2015-2021: A citizen science approach to surveillance.

As a result of the increase of game meat intended for human consumption through Europe, a plethora of food-borne diseases, including trichinellosis, may occur in consumers, posing a relevant public health threat. Thus, this study aims to a citizen science approach to monitor the occurrence of spp. in wild boar meat intended for human consumption, evaluating the risk of infection for consumers.