DELTO Study: Delphi Consensus on Long-Term Textbook Outcome After Metabolic Bariatric Surgery.

Background: This study aimed to create a comprehensive Core Outcome Set (COS) for assessing the long-term outcome (≥ 5 years) after Metabolic Bariatric Surgery (MBS), through the use of the Delphi method.

Methods: The study utilized a three-phase approach. In Phase 1, a long list of items was identified through a literature review and expert input, forming the basis for an online Delphi survey.

Stereoselective Synthesis of -2,4-Disubstituted Tetrahydrofurans via a Pd-Catalyzed Hayashi-Heck Arylation and Rh-Catalyzed Hydroformylation Sequence.

A catalytic, two-step protocol for the expedient synthesis of -2,4-disubstituted tetrahydrofurans is described. In the first step, an enantioselective and regioselective Pd-catalyzed Hayashi-Heck arylation was developed using ()-hexaMeOBiphep to generate 5-aryl-2,3-dihydrofurans. A subsequent Rh-catalyzed hydroformylation step proceeds at low Rh loading with high regio- and diastereoselectivity for the -2,4-disubstituted tetrahydrofuran isomer.

Human post-mortem organotypic brain slice cultures: a tool to study pathomechanisms and test therapies.

Human brain experimental models recapitulating age- and disease-related characteristics are lacking. There is urgent need for human-specific tools that model the complex molecular and cellular interplay between different cell types to assess underlying disease mechanisms and test therapies. Here we present an adapted ex vivo organotypic slice culture method using human post-mortem brain tissue cultured at an air-liquid interface to also study brain white matter.

Case of pediatric cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome in a 2-year-old girl.

Cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome is a recently described entity that refers to a specific pattern of cerebellar edema with restricted diffusion and crowding of the fourth ventricle among other findings. The syndrome is commonly associated with toxic opioid exposure. While most commonly seen in adults, we present a case of a 2-year-old girl who survived characteristic history and imaging findings of CHANTER syndrome.

Long-term outcomes of patients with large B-cell lymphoma treated with axicabtagene ciloleucel and prophylactic corticosteroids.

ZUMA-1 safety management cohort 6 investigated the impact of prophylactic corticosteroids and earlier corticosteroids and/or tocilizumab on the incidence and severity of cytokine release syndrome (CRS) and neurologic events (NEs) following axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). Prior analyses of cohort 6 with limited follow-up demonstrated no Grade ≥3 CRS, a low rate of NEs, and high response rates, without negatively impacting axi-cel pharmacokinetics. Herein, long-term outcomes of cohort 6 (N = 40) are reported (median follow-up, 26.

Axicabtagene Ciloleucel in Combination with the 4-1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11.

Purpose: Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4-1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy.

Patients And Methods: In phase 1 of the single-arm ZUMA-11 trial, patients with R/R LBCL received a single axi-cel infusion (target dose, 2 × 106 cells/kg) plus utomilumab 10 to 200 mg intravenously every 4 weeks for up to 6 months in a dose-escalation design.

Second-Generation Atroposelective Synthesis of KRAS G12C Covalent Inhibitor GDC-6036.

A chromatography-free asymmetric synthesis of GDC-6036 () was achieved via a highly atroposelective Negishi coupling of aminopyridine and quinazoline catalyzed by 0.5 mol % [Pd(cin)Cl] and 1 mol % (,)-Chiraphite to afford the key intermediate ()-. An alkoxylation of ()- with ()--methylprolinol () and a global deprotection generates the penultimate heterobiaryl intermediate .

Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma.

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg).

Data-Driven Multi-Objective Optimization Tactics for Catalytic Asymmetric Reactions Using Bisphosphine Ligands.

Optimization of the catalyst structure to simultaneously improve multiple reaction objectives (e.g., yield, enantioselectivity, and regioselectivity) remains a formidable challenge.

The hibernation-derived compound SUL-138 shifts the mitochondrial proteome towards fatty acid metabolism and prevents cognitive decline and amyloid plaque formation in an Alzheimer's disease mouse model.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide and remains without effective cure. Increasing evidence is supporting the mitochondrial cascade hypothesis, proposing that loss of mitochondrial fitness and subsequent ROS and ATP imbalance are important contributors to AD pathophysiology.

Methods: Here, we tested the effects of SUL-138, a small hibernation-derived molecule that supports mitochondrial bioenergetics via complex I/IV activation, on molecular, physiological, behavioral, and pathological outcomes in APP/PS1 and wildtype mice.

High-Level Data Fusion Enables the Chemoinformatically Guided Discovery of Chiral Disulfonimide Catalysts for Atropselective Iodination of 2-Amino-6-arylpyridines.

The atropselective iodination of 2-amino-6-arylpyridines catalyzed by chiral disulfonimides (DSIs) is described. Key to the development of this transformation was the use of a chemoinformatically guided workflow for the curation of a structurally diverse training set of DSI catalysts. Utilization of this catalyst training set in the atropselective iodination across a variety 2-aminopyridine substrates allowed for the recommendation of statistically higher-performing DSIs for this reaction.

CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma.

Unlabelled: To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome.

Atroposelective Negishi Coupling Optimization Guided by Multivariate Linear Regression Analysis: Asymmetric Synthesis of KRAS G12C Covalent Inhibitor GDC-6036.

An efficient asymmetric synthesis of a potent KRAS G12C covalent inhibitor, GDC-6036 (), is reported. The synthesis features a highly atroposelective Negishi coupling to construct the key C-C bond between two highly functionalized pyridine and quinazoline moieties by employing a Pd/Walphos catalytic system. Statistical modeling by comparing computational descriptors of a range of Walphos chiral bisphosphine ligands to a training set of experimental results was used to inform the selection of the best ligand, , which afforded the desired Negishi coupling product in excellent selectivity.

Hypophosphatemia Due to Increased Effector Cell Metabolic Activity Is Associated with Neurotoxicity Symptoms in CD19-Targeted CAR T-cell Therapy.

A major complication of chimeric antigen receptor (CAR) T-cell therapy is immune effector cell-associated neurotoxicity syndrome (ICANS), which presents as aphasia, confusion, weakness, somnolence, seizures, and coma. This is similar to the neurologic manifestations of hypophosphatemia, which can result from sudden increases in metabolic demand for phosphorylated intermediates (e.g.

Epistemic community in transboundary river regime: a case study in the Mekong River Commission regarding mainstream hydropower development.

Despite the importance of transboundary water management, cooperation mechanisms are limited, especially in the case of Mekong River basin where environmental and social aspects are threatened by recent anthropogenic pressures like hydropower development. Existing transboundary mechanism such as the Mekong River Commission (MRC) is challenged to facilitate the cooperation between riparian states. An epistemic community (EC) is considered to effectively influence international governance and is studied as part of transboundary river regimes.

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results.

Introduction: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates.

Methods: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers.

The Need for Objective Physical Activity Measurements in Routine Bariatric Care.

Purpose: This study aims to (1) quantify physical behavior through self-reports and sensor-based measures, (2) examine the correlation between self-reported and sensor-based physical activity (PA) and (3) assess whether bariatric patients adhere to PA guidelines.

Methods: A Fitbit accelerometer was used to collect minute-to-minute step count and heart rate data for 14 consecutive days. Total physical activity levels (PAL), moderate-to-vigorous intensity physical activity (MVPA) and sedentary behavior (SB) were used to quantify physical behavior.

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study.

Purpose: Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in the pivotal ZUMA-2 study of KTE-X19 in relapsed/refractory MCL are reported, including for subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics.

Methods: Patients with relapsed/refractory MCL (one to five prior therapies, including prior BTKi exposure) received a single infusion of KTE-X19 (2 × 10 CAR T cells/kg).

A Residency Program Curriculum to Improve Health Care Transitions for Autistic Individuals.

Objectives: Physical and mental health outcomes of autistic individuals deteriorate during transition to adulthood. The study aims to identify opportunities to improve physician knowledge in health-care transitions (HCT) for autistic individuals by understanding perceived versus experienced facilitators and barriers in overall HCT curriculum implementation in graduate medical education.

Methods: Medicine-Pediatrics program directors participated in a Health Care Transition Residency Curriculum Collaborative Improvement Network and used an iterative process to develop and improve HCT curricula.

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results.

Introduction: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates.

Methods: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers.

89Zr-ImmunoPET Shows Therapeutic Efficacy of Anti-CD20-IFNα Fusion Protein in a Murine B-cell Lymphoma Model.

Antibody-mediated tumor delivery of cytokines can overcome limitations of systemic administration (toxicity, short half-lives). Previous work showed improved antitumor potency of anti-CD20-IFNα fusion proteins in preclinical mouse models of B-cell lymphoma. Although tumor targeting is mediated by the antibody part of the fusion protein, the cytokine component might strongly influence biodistribution and pharmacokinetics, as a result of its affinity, size, valency, and receptor distribution.

A Multi-Institutional Collaborative To Assess the Knowledge and Skills of Medicine-Pediatrics Residents in Health Care Transition.

Background Pediatric to adult health care transition (HCT) is an essential process in the care of youth with special health care needs (YSHCN). Many internal medicine-pediatrics (med-peds) residency programs have developed curricula to teach transition knowledge and skills for the care of YSHCN. Objective Using a national med-peds program director quality improvement collaborative to improve transition curriculum, we aim to identify curricular content areas of improvement by describing baseline trainee knowledge and skills taught through existing transition curricula in med-peds programs.

Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience.

Background: CD19-directed chimeric antigen T-cell receptor (CAR-T) therapies have revolutionized the treatment of patients with relapsed/refractory (R/R) aggressive B-cell lymphomas (aBCL). The results of the landmark ZUMA-1 and JULIET trials have been reproducible in real-world settings across multiple institutions, and patients with double (DHL) or triple (THL) hit lymphomas have demonstrated non-inferior outcomes compared to non-DHL/THL counterparts.

Materials And Methods: This retrospective cohort study included 53 patients with R/R aBCL who received CAR-T from October 2017 to June 2020 at the University of California, Los Angeles.

Pediatric Household Transmission of Severe Acute Respiratory Coronavirus-2 Infection-Los Angeles County, December 2020 to February 2021.

This brief report presents transmission rates from a prospective study of 15 households with pediatric index cases of severe acute respiratory coronavirus-2 in Los Angeles County from December 2020 to February 2021. Our findings support ongoing evidence that transmission from pediatric index cases to household contacts is frequent but can be mitigated with practicing well-documented control measures at home, including isolation, masking and good hand hygiene.