Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas.

Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer's disease and frontotemporal lobe degeneration from Latin America and the United States.

Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia.

Background: Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia.

Increased copeptin may reflect vasopressin-related metabolic changes after bariatric surgery.

Objective: Mechanisms underlying metabolic improvement following metabolic and bariatric surgery (MBS) may provide insight into novel therapies. Vasopressin improves body composition and protects against hypoglycemia. Associations of copeptin, a stable cleavage product of vasopressin, with BMI and insulin resistance suggest an adaptive increase in vasopressin to counteract metabolic disruption.

Causes of Death Following Coronary Revascularization in Patients with Diabetes.

Background: In patients with diabetes and multivessel coronary artery disease, percutaneous coronary intervention (PCI) has been associated with higher long-term cardiovascular mortality compared to coronary artery bypass grafting (CABG), but the specific causes of death are not well known. We aimed to determine the causes of death among patients with diabetes and multivessel disease undergoing coronary revascularization with PCI versus CABG.

Methods: We analyzed the centrally adjudicated causes of death of 1,900 participants in the FREEDOM trial.

Superimposed Wavefront Imaging of Diffraction-enhanced X-rays: sparsity-aware CT reconstruction from limited-view projections.

Purpose: In this paper, we describe an algebraic reconstruction algorithm with a total variation regularization (ART + TV) based on the Superimposed Wavefront Imaging of Diffraction-enhanced X-rays (SWIDeX) method to effectively reduce the number of projections required for differential phase-contrast CT reconstruction.

Methods: SWIDeX is a technique that uses a Laue-case Si analyzer with closely spaced scintillator to generate second derivative phase-contrast images with high contrast of a subject. When the projections obtained by this technique are reconstructed, a Laplacian phase-contrast tomographic image with higher sparsity than the original physical distribution of the subject can be obtained.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

Spotlight on YAP: Unlocking New Insights to Overcome the Barriers to Heart Regeneration.

This editorial refers to “Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration” by Liu . and “YAP Overcomes Mechanical Barriers to Induce Mitotic Rounding and Adult Cardiomyocyte Division” by Morikawa

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

Long-term Changes in Pain, Depression, Function and Informal Caregiving after Major Elective Surgeries Among Seriously Ill Older Adults.

Objective: To compare differences in pain, depression, function, and informal caregiving pre-and-post major elective surgery among older adults with and without serious illness; and determine if serious illness was independently associated with increasing pain, depression, assistance in activities of daily living (ADLs) and informal caregiving post-surgery.

Background: The American College of Surgeons has endorsed the integration of palliative care (PC) into surgical care in adults with serious illness but targets for PC during surgical episodes such as pain, depression, function, and informal caregiving are understudied.

Methods: We used Health and Retirement Study-linked Medicare data (2008-2018) to identify older (≥66 y) adults with and without serious illness who had major elective surgery.

FBG-driven simulation for virtual augmentation of fluoroscopic images during endovascular interventions.

Endovascular interventions are procedures designed to diagnose and treat vascular diseases, using catheters to navigate inside arteries and veins. Thanks to their minimal invasiveness, they offer many benefits, such as reduced pain and hospital stays, but also present many challenges for clinicians, as they require specialized training and heavy use of X-rays. This is particularly relevant when accessing (i.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction and With Reduced Ejection Fraction According to the Prognostic Nutritional Index: Findings From PARADIGM-HF and PARAGON-HF.

Background: The importance of nutritional status is underappreciated in patients with heart failure (HF). This study aimed to describe the range of the prognostic nutrition index (PNI), and the clinical characteristics and outcomes according to PNI, in patients with HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The primary outcome was the composite of HF hospitalization or cardiovascular death.

Essential role of sulfide oxidation in brain health and neurological disorders.

Hydrogen sulfide (HS) is an environmental hazard well known for its neurotoxicity. In mammalian cells, HS is predominantly generated by transsulfuration pathway enzymes. In addition, HS produced by gut microbiome significantly contributes to the total sulfide burden in the body.

Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab.

Background: Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown.

Methods: This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension.

Fine particulate matter and nonaccidental and cause-specific mortality: Do associations vary by exposure assessment method?

Background: There is considerable heterogeneity in fine particulate matter (PM)-mortality associations between studies, potentially due to differences in exposure assessment methods. Our aim was to evaluate associations of PM predicted from different models with nonaccidental and cause-specific mortality.

Methods: We followed 107,906 participants of the Nurses' Health Study cohort from 2001 to 2016.

Upper airway collapsibility during rapid eye movement sleep tracks the response to upper airway surgery for obstructive sleep apnea.

Objectives: Endotype-based intervention has shown promise in treatment for patients with obstructive sleep apnea, and upper airway surgery is an important therapeutic option. However, the response to surgery varies among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and their association with surgical outcome.

Impact of Anemia on Clinical Outcomes in Atrial Fibrillation Patients on Oral Anticoagulants: A Prognostic Meta-Analysis.

Background: Anemia is frequently observed as a comorbidity in atrial fibrillation (AF), especially in elderly patients and in those on anticoagulation. This has been associated with poor clinical outcomes. We aim to investigate the impact of anemia on clinical outcomes in patients with AF on oral anticoagulation.

The Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for specialty care.

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's disease (AD) or a related dementia (ADRD) are two decades old. This evidence-based guideline was developed to empower all clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. An expert workgroup conducted a review of 7374 publications (133 met inclusion criteria) and developed recommendations as steps in an evaluation process.

Alzheimer's Association clinical practice guideline for the Diagnostic Evaluation, Testing, Counseling, and Disclosure of Suspected Alzheimer's Disease and Related Disorders (DETeCD-ADRD): Executive summary of recommendations for primary care.

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's disease (AD) or AD and related dementias (ADRD) are decades old and aimed at specialists. This evidence-based guideline was developed to empower all-including primary care-clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. Through a modified-Delphi approach and guideline-development process (7374 publications were reviewed; 133 met inclusion criteria) an expert workgroup developed recommendations as steps in a patient-centered evaluation process.

The Alzheimer's Association clinical practice guideline for the diagnostic evaluation, testing, counseling, and disclosure of suspected Alzheimer's disease and related disorders (DETeCD-ADRD): Validated clinical assessment instruments.

US clinical practice guidelines for the diagnostic evaluation of cognitive impairment due to Alzheimer's Disease (AD) or AD and related dementias (ADRD) are decades old and aimed at specialists. This evidence-based guideline was developed to empower all-including primary care-clinicians to implement a structured approach for evaluating a patient with symptoms that may represent clinical AD/ADRD. As part of the modified Delphi approach and guideline development process (7374 publications were reviewed; 133 met inclusion criteria) an expert workgroup developed recommendations as steps in a patient-centered evaluation process.

Psychotropic medication usage in sporadic versus genetic behavioral-variant frontotemporal dementia.

Introduction: Psychotropic medication (PM) use in behavioral-variant frontotemporal dementia (bvFTD) is higher than in other dementias. However, no information exists on whether PM use differs between sporadic and genetic bvFTD.

Methods: We analyzed data from sporadic and genetic bvFTD participants with PM prescriptions in the Advancing Research and Treatment in Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects study.

Longitudinal cognitive performance of participants with sporadic early onset Alzheimer's disease from LEADS.

Introduction: Early-onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%-8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early-onset dementia.

Methods: Data from 307 cognitively normal (CN) volunteer participants and those with amyloid-positive EOAD or amyloid-negative cognitive impairment (EOnonAD) were compared.

MaAsLin 3: Refining and extending generalized multivariable linear models for meta-omic association discovery.

A key question in microbial community analysis is determining which microbial features are associated with community properties such as environmental or health phenotypes. This statistical task is impeded by characteristics of typical microbial community profiling technologies, including sparsity (which can be either technical or biological) and the compositionality imposed by most nucleotide sequencing approaches. Many models have been proposed that focus on how the relative abundance of a feature (e.