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ABSTRACTForensic anthropology must embrace standards and credentialing that align with other medicolegal disciplines, such as forensic pathology and forensic odontology. This involves establishing itself more firmly as an essential specialty in the medicolegal system and limiting practice to qualified professionals. Without educational or professional requirements to practice forensic anthropology, the competencies of those involved in medicolegal cases vary, despite the potentially serious legal impact of errors. Negligent work can impede decedent identification or wrongly convict or free a suspect. Erroneous and unprofessional work also misrepresents the field and may deter agencies from utilizing forensic anthropologists. This commentary aims to convey the need to further professionalize forensic anthropology through the standardization of education, qualifications, and practice. Differences between certification and licensure and their implications are discussed. Recent and upcoming developments in the field highlight progress, including the development of a multi‐level certification system and list of core competencies by the American Board of Forensic Anthropology (ABFA). Additionally, the Anthropology subcommittee of the Organization of Scientific Area Committees for forensic science (OSAC) is developing a standard for qualifications in forensic anthropology. These developments emphasize the importance of certification and standardization in education and training for the advancement of forensic anthropology. Standardization efforts such as these will foster a cohesive, respected practice to serve the evolving needs of the medicolegal system.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

Importance Alzheimer disease (AD) predominates in females at almost twice the rate relative to males. Mounting evidence in adults without AD indicates that females exhibit higher tau deposition than age-matched males, particularly in the setting of elevated β-amyloid (Aβ), but the evidence for sex differences in tau accumulation rates is inconclusive. Objective To examine whether female sex is associated with faster tau accumulation in the setting of high Aβ (as measured with positron emission tomography [PET]) and the moderating influence of sex on the association between APOE ε4 carrier status and tau accumulation. Data Sources This meta-analysis used data from 6 longitudinal aging and AD studies, including the Alzheimer’s Disease Neuroimaging Initiative, Berkeley Aging Cohort Study, BioFINDER 1, Harvard Aging Brain Study, Mayo Clinic Study of Aging, and Wisconsin Registry for Alzheimer Prevention. Longitudinal data were collected between November 2004 and May 2022. Study Selection Included studies required available longitudinal [ 18 F]flortaucipir or [ 18 F]-MK-6240 tau-PET scans, as well as baseline [ 11 C] Pittsburgh Compound B, [ 18 F]flutemetamol or [ 18 F]florbetapir Aβ-PET scans. Recruitment criteria varied across studies. Analyses began on August 7, 2023, and were completed on February 5, 2024. Data Extraction and Synthesis In each study, primary analyses extracted estimates for the sex (female or male) and the sex by baseline Aβ-PET status (high or low) association with longitudinal tau-PET using a series of mixed-effects models. Secondary mixed-effects models extracted the interaction estimate for the association of sex by APOE ε4 carrier status with longitudinal tau-PET. Study-specific estimates for each mixed-effects model were then pooled in a meta-analysis, and the global fixed effect (β) and total heterogeneity ( I 2 ) across studies were estimated. This study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures Seven tau-PET outcomes that showed cross-sectional sex differences were examined across temporal, parietal, and occipital lobes. Results Among 6 studies assessed, there were 1376 participants (761 [55%] female; mean [range] age at first tau scan, 71.9 [46-93] years; 401 participants [29%] with high baseline Aβ; 412 APOE ε4 carriers [30%]). Among individuals with high baseline Aβ, female sex was associated with faster tau accumulation localized to inferior temporal (β = −0.14; 95% CI, −0.22 to −0.06; P = .009) temporal fusiform (β = −0.13; 95% CI, −0.23 to −0.04; P = .02), and lateral occipital regions (β = −0.15; 95% CI, −0.24 to −0.06; P = .009) compared with male sex. Among APOE ε4 carriers, female sex was associated with faster inferior-temporal tau accumulation (β = −0.10; 95% CI, −0.16 to −0.03; P = .01). Conclusions and Relevance These findings suggest that sex differences in the pathological progression of AD call for sex-specific timing considerations when administrating anti-Aβ and anti-tau treatments.

Abstract The growing prevalence of obesity, a risk factor for disorders such as Alzheimer’s Disease (AD), raises concerns about the effects on cognitive health. AD currently impacts 6.9 million Americans aged 65 and older and is characterized by the presence of amyloid beta (Aβ) plaques, neurofibrillary tau tangles, and neuroinflammation, all of which contribute to cognitive impairment. Insulin resistance, common in both obesity and AD, disrupts brain glucose metabolism and accelerates neurodegeneration. Understanding the factors that link these conditions could lead to new strategies for combating disease. Notably, the B-like vitamin choline is necessary for fat metabolism and has been shown to help reduce obesity incidence. However, ∼90% of Americans are deficient, and decreases in this nutrient have been associated with cognitive decline. Here, we examined circulating choline levels, inflammation, and metabolic dysfunction in human participants with obesity (BMI > 30) compared to normal BMIs (18.5–24.9), as well as in 3xTg-AD mice, an AD model, fed a choline-deficient diet throughout adulthood. Our results revealed that obese participants exhibited significantly lower circulating choline levels compared to those with a healthy BMI. Lower choline levels correlated with higher %Body fat and increased markers of insulin resistance. Elevated inflammatory cytokines in obese participants were also seen in 3xTg-AD mice on a choline-deficient diet, which exhibited significant weight gain and metabolic dysfunction. AD-like pathology was also exacerbated in choline deficient 3xTg-AD mice. These findings underscore the relationship between low choline levels, obesity, insulin resistance, and cognitive decline risk. Adequate choline intake may mitigate the risk of obesity, potentially preventing cognitive decline and associated diseases. Highlights Obesity is linked to increased insulin resistance (IR) and systemic inflammation, both of which are recognized risk factors for Alzheimer’s disease (AD). Women exhibit lower circulating choline levels compared to men, and obese individuals display significantly lower choline levels than those with a healthy BMI. Lower circulating choline levels are linked to a higher body fat percentage, increased markers of IR and liver dysfunction, as well as heightened systemic inflammation. 3xTg-AD mice on a choline-deficient diet experience considerable weight gain, metabolic dysfunction, heightened systemic inflammation, and AD-like pathology, resembling the conditions observed in obese human participants.

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

BACKGROUND: Patients with arrhythmogenic mitral valve prolapse syndrome are at increased risk for life-threatening ventricular arrhythmias, but studies have been limited by small sample sizes. We sought to assemble an international arrhythmogenic mitral valve prolapse syndrome registry to delineate the clinical, imaging, and treatment characteristics of patients with arrhythmogenic mitral valve prolapse syndrome who survived sudden cardiac arrest (SCA) or had sustained ventricular tachycardia (VT) or ventricular fibrillation. METHODS: In this descriptive registry, we characterized patients with arrhythmogenic mitral valve prolapse syndrome who survived SCA, sustained VT, or ventricular fibrillation. Deidentified data were abstracted locally and combined centrally. RESULTS: We included 148 patients who had SCA or VT/ventricular fibrillation. Patients had a mean age of 43.7±15.4 years; 68% were women, 73% had bileaflet prolapse, 65% had mitral annular disjunction, 67% had nonsustained VT, and 59% had inferolateral T-wave inversions. Syncope (n=54, 48%) and anterolateral T-wave inversion (n=26, 22%) were relatively common. Catheter ablation was performed in 50 (35%) patients for premature ventricular complexes and in 18 (17.7%) patients for VT. Sites of origin for arrhythmias were commonly in the papillary muscles, fascicles, mitral annulus, and inferior/inferolateral left ventricle. CONCLUSIONS: In this international descriptive registry of patients with arrhythmogenic mitral valve prolapse syndrome and SCA, patients were young, women, and had bileaflet mitral valve prolapse, mitral annular disjunction, inferolateral T-wave inversions, and nonsustained VT. A history of syncope and anterolateral T-wave inversions was relatively common in patients who survived SCA or sustained VT/ventricular fibrillation.

Host antibody responses are key components in the protection of animals against pathogens, yet the defining properties of viral antigens and induction of B cell responses that result in varied protection are still poorly understood. Parvoviruses are simple molecular structures that display 60 repeated motifs on their capsid surface, and rapidly induce strong antibody responses that protect animals from infection. We recently showed that following canine parvovirus infection of its natural host, the polyclonal response in the sera contained only two or three dominant antibodies that bound two epitopes on the capsid. Here, we characterize key antibodies present in that immune response, identifying their sequences, defining their binding properties on the capsid by cryoelectron microscopic (cryoEM) analysis, and testing their effects on viral infectivity. Two antibodies sharing the same heavy chain bound to the side of the capsid threefold spike (B-site), while another distinct antibody bound close to the threefold axis (A-site). The epitopes of these antibodies overlapped the binding site of the host receptor, the transferrin receptor type-1, but to varying degrees. The antibodies varied widely in their neutralization efficiencies as either immunoglobulins (IgGs) or monomeric antigen-binding fragments (Fabs), which was consistent with their ability to compete for the receptor. The monoclonal antibodies characterized here matched the structures from the cryoEM analysis of polyclonal sera, including those present in a different dog than the monoclonal source. This shows that after infection, a focused response to the viral antigen is produced that protects against infection.

AbstractBackgroundAcute lymphoblastic leukemia (ALL) in adults is aggressive, with long‐term outcomes impacted by treatment resistance and toxicity. CD52 is expressed in most cases of B‐ and T‐lineage ALL. Alemtuzumab, a humanized immunoglobulin G1 monoclonal antibody that targets CD52, was identified as a potential agent to improve treatment efficacy without increasing toxicity.MethodsIn this phase 1/2 study (Cancer and Leukemia Group B [CALGB] 10102, NCT00061945), a course of single‐agent alemtuzumab was intercalated into CALGB 19802 backbone chemotherapy after the third course of intensive chemotherapy in those who were CD52+ at diagnosis. Phase 1 tested three dose levels of subcutaneous alemtuzumab (10, 20, and 30 mg 3 times weekly for 4 weeks/12 doses) and demonstrated that 30 mg was tolerable. Phase 2 established feasibility.ResultsThe study enrolled 295 evaluable patients (115 in phase 1, 180 in phase 2); 206 (69.8%) were CD52+. Among evaluable CD52+ patients, 43.7% (90/206) completed the first three treatment modules; 97.8% (88 of 90) were treated with alemtuzumab. Alemtuzumab was associated with cytomegalovirus viremia, which occurred in 23.3% (14 of 60) of patients during and 29.2% (19 of 65) after alemtuzumab treatment. With a median follow‐up of 101.2 months, median overall survival (OS) was 26.3 months (3‐year rate, 44%; 5‐year rate, 36%; 10‐year rate, 31%). Landmark analysis at the start of the fourth course of treatment demonstrated no difference in OS or disease‐free survival between patients who did and who did not receive alemtuzumab.ConclusionAlemtuzumab was feasible to administer in adults with ALL receiving intensive chemotherapy, but was without evidence of benefit.

ImportanceThe advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood.ObservationsIn December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies.Conclusions and RelevanceTen key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.