Bereaved Family Quality of Life Varies With Comorbid Psychological Distress and ICU-Care Quality.

Context: Health-related quality of life (HRQOL) is highly endorsed, but HRQOL studies scarcely investigate the following: ICU family members; modifiable end-of-life (EOL) ICU-care factors; conjoint associations with prolonged grief disorder (PGD), post-traumatic stress disorder (PTSD), and depression; and long-term bereavement outcomes.

Objectives: Exploratorily investigate associations of PGD-PTSD-depressive-symptom states (resilient, subthreshold-depression dominant, PGD dominant, and PGD-PTSD-depression comorbid) and quality of EOL ICU care with families' HRQOL 6-24 months post loss.

Methods: This cohort study examined symptoms of PGD (11 items of the PG-13), PTSD (Impact of Event Scale-Revised), and depression (Hospital Anxiety and Depression Scale), and HRQOL (Medical Outcomes Study 36-Item Short-Form Health Survey) among 303 ICU family members.

Economic Evidence on Cost Sharing and Alternative Insurance Designs to Address Moral and Behavioral Hazards in High-Income Health Care Systems: A Systematic Review.

In health insurance, "moral hazard" describes the concept that coverage without an out-of-pocket cost to consumers could result in health care utilization beyond economically efficient levels. In response, payers in the United States (US) have designed pharmaceutical benefit plans with significant cost exposure (e.g.

Human tNeurons reveal aging-linked proteostasis deficits driving Alzheimer's phenotypes.

Aging is a prominent risk factor for Alzheimer's disease (AD), but the cellular mechanisms underlying neuronal phenotypes remain elusive. Both accumulation of amyloid plaques and neurofibrillary tangles in the brain and age-linked organelle deficits are proposed as causes of AD phenotypes but the relationship between these events is unclear. Here, we address this question using a transdifferentiated neuron (tNeuron) model directly from human dermal fibroblasts.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

Background: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.

Massively parallel profiling of RNA-targeting CRISPR-Cas13d.

CRISPR-Cas13d cleaves RNA and is used in vivo and for diagnostics. However, a systematic understanding of its RNA binding and cleavage specificity is lacking. Here, we describe an RNA Chip-Hybridized Association-Mapping Platform (RNA-CHAMP) for measuring the binding affinity for > 10,000 RNAs containing structural perturbations and other alterations relative to the CRISPR RNA (crRNA).

Factors Associated With Family Surrogate Decisional-Regret Trajectories.

Context/objectives: The scarce research on factors associated with surrogate decisional regret overlooks longitudinal, heterogenous decisional-regret experiences and fractionally examines factors from the three decision-process framework stages: decision antecedents, decision-making process, and decision outcomes. This study aimed to fill these knowledge gaps by focusing on factors modifiable by high-quality end-of-life (EOL) care.

Methods: This observational study used a prior cohort of 377 family surrogates of terminal-cancer patients to examine factors associated with their membership in the four preidentified distinct decisional-regret trajectories: resilient, delayed-recovery, late-emerging, and increasing-prolonged trajectories from EOL-care decision making through the first two bereavement years by multinomial logistic regression modeling using the resilient trajectory as reference.

Risk factors for thromboembolic events in patients with paroxysmal nocturnal hemoglobinuria (PNH): a nested case-control study in the International PNH Registry.

The objective of this analysis was to identify risk factors for thromboembolic events (TE) in patients with paroxysmal nocturnal hemoglobinuria (PNH) who were not treated with C5 inhibitors. Patients with PNH and a history of ≥ 1 TE at enrollment in the International PNH Registry (NCT01374360; registration date, January 2011) were each matched with up to 5 patients without TE. Multivariable analysis was performed with the following variables: percentage glycosylphosphatidylinositol (GPI)-negative cells, high disease activity (HDA), non-TE major adverse vascular event history, and recent anticoagulation.

Large language models encode clinical knowledge.

Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA.

LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts.

Background: As a part of natural disease progression, acute kidney injury (AKI) can develop into chronic kidney disease via renal fibrosis and inflammation. LTBP4 (latent transforming growth factor beta binding protein 4) regulates transforming growth factor beta, which plays a role in renal fibrosis pathogenesis. We previously investigated the role of LTBP4 in chronic kidney disease.

Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease.

Aging is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits AD-linked vulnerabilities.

Decisional-Regret Trajectories From End-of-Life Decision Making Through Bereavement.

Context: Regret plays a central role in surrogate decision making. Research on decisional regret in family surrogates is scarce and lacks longitudinal studies to illustrate the heterogenous, dynamic evolution of decisional regret.

Objectives: To identify distinct decisional-regret trajectories from end-of-life (EOL) decision making through the first two bereavement years among surrogates of cancer patients.

 (Gesneriaceae), a new species from eastern Guangxi, China.

C.Xiong, W.C.

Measurements of the associated production of a W boson and a charm quark in proton-proton collisions at .

Measurements of the associated production of a W boson and a charm ( ) quark in proton-proton collisions at a centre-of-mass energy of 8 are reported. The analysis uses a data sample corresponding to a total integrated luminosity of 19.7 collected by the CMS detector at the LHC.

Antibody escape and cryptic cross-domain stabilization in the SARS-CoV-2 Omicron spike protein.

The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. For the Omicron variant, sub-lineages BA.1 and BA.

Small molecule C381 targets the lysosome to reduce inflammation and ameliorate disease in models of neurodegeneration.

SignificanceNeurodegenerative diseases are poorly understood and difficult to treat. One common hallmark is lysosomal dysfunction leading to the accumulation of aggregates and other undegradable materials, which cause damage to brain resident cells. Lysosomes are acidic organelles responsible for breaking down biomolecules and recycling their constitutive parts.

Heat-Killed Lactobacilli Preparations Promote Healing in the Experimental Cutaneous Wounds.

Probiotics are defined as microorganisms with beneficial health effects when consumed by humans, being applied mainly to improve allergic or intestinal diseases. Due to the increasing resistance of pathogens to antibiotics, the abuse of antibiotics becomes inefficient in the skin and in systemic infections, and probiotics may also provide the protective effect for repairing the healing of infected cutaneous wounds. Here we selected two Lactobacillus strains, GMNL-6 and GMNL-653, in heat-killed format to examine the beneficial effect in skin wound repair through the selection by promoting collagen synthesis in Hs68 fibroblast cells.

Expression and characterization of SARS-CoV-2 spike proteins.

The severe acute respiratory syndrome coronavirus 2 spike protein is a critical component of coronavirus disease 2019 vaccines and diagnostics and is also a therapeutic target. However, the spike protein is difficult to produce recombinantly because it is a large trimeric class I fusion membrane protein that is metastable and heavily glycosylated. We recently developed a prefusion-stabilized spike variant, termed HexaPro for six stabilizing proline substitutions, that can be expressed with a yield of >30 mg/L in ExpiCHO cells.

Caregivers' Death-Preparedness States Impact Caregiving Outcomes and Patients' End-of-Life Care.

Background/objective: Preparing family caregivers, cognitively, emotionally, and behaviorally, for their relative's death is an actionable component of high-quality end-of-life care. We aimed to examine the never-before-examined associations of conjoint cognitive prognostic awareness and emotional preparedness for death with caregiving outcomes and end-of-life care received by cancer patients.

Design/setting/participants/main Measures: For this longitudinal study, associations of death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) with subjective caregiving burden, depressive symptoms, and quality of life (QOL) and patients' end-of-life care (chemotherapy and/or immunotherapy, cardiopulmonary resuscitation, intensive care unit care, intubation, mechanical ventilation support, vasopressors, nasogastric tube feeding, and hospice care) were evaluated using multivariate hierarchical linear and logistic regression modeling, respectively, for 377 caregivers in cancer patients' last 6 months and 1 month, respectively.

Arteriovenous Fistula Flow Dysfunction Surveillance: Early Detection Using Pulse Radar Sensor and Machine Learning Classification.

Vascular Access (VA) is often referred to as the "Achilles heel" for a Hemodialysis (HD)-dependent patient. Both the patent and sufficient VA provide adequacy for performing dialysis and reducing dialysis-related complications, while on the contrary, insufficient VA is the main reason for recurrent hospitalizations, high morbidity, and high mortality in HD patients. A non-invasive Vascular Wall Motion (VWM) monitoring system, made up of a pulse radar sensor and Support Vector Machine (SVM) classification algorithm, has been developed to detect access flow dysfunction in Arteriovenous Fistula (AVF).

Single-Layer Inverted Internal Limiting Membrane Flap Versus Conventional Peel for Small- or Medium-Sized Full-Thickness Macular Holes.

Purpose: To analyze the outcomes of using an internal limiting membrane (ILM) flap and the conventional ILM peel technique for small- or medium-sized full-thickness macular hole (FTMH) repair.

Design: Retrospective, interventional case series.

Methods: Eyes with an FTMH ≤400 µm that underwent vitrectomy with a single-layer inverted ILM flap (flap group, 55 eyes) or an ILM peel (peel group, 62 eyes) were enrolled.

Linking Stage-Specific Plasma Biomarkers to Gray Matter Atrophy in Parkinson Disease.

Background And Purpose: The shortcomings of synucleinopathy-based Parkinson disease staging highlight the need for systematic clinicopathologic elucidation and biomarkers. In this study, we investigated associations of proteinopathy and inflammation markers with changes in gray matter volume that accompany Parkinson disease progression.

Materials And Methods: We prospectively enrolled 42 patients with idiopathic Parkinson disease, subdivided into early-/late-stage groups and 27 healthy controls.

(Gesneriaceae), a new species from limestone areas of Guangxi, China.

Z.B. Xin, W.

Clinical implications of sequential MRD monitoring by NGS at 2 time points after chemotherapy in patients with AML.

Next-generation sequencing (NGS) has been applied to measurable/minimal residual disease (MRD) monitoring after induction chemotherapy in patients with acute myeloid leukemia (AML), but the optimal time point for the test remains unclear. In this study, we aimed to investigate the clinical significance of NGS MRD at 2 different time points. We performed targeted NGS of 54 genes in bone marrow cells serially obtained at diagnosis, first complete remission (first time point), and after the first consolidation chemotherapy (second time point) from 335 de novo AML patients.