Citations

AbstractINTRODUCTIONAlzheimer's disease (AD) pathology causes corticobasal syndrome (CBS) in 21%–50% of patients. Studies have assessed hypometabolism in CBS according to β‐amyloid (A) positron emission tomography (PET), but the understanding of the association of both AD‐tau (T) and A with hypometabolism is incomplete.METHODSThirty‐three CBS patients and 45 controls underwent fluorodeoxyglucose (FDG), flortaucipir, and Pittsburgh compound‐B PET and were classified as A± and T±. FDG‐PET uptake was extracted for 12 regions‐of‐interest in dominant (most affected) and non‐dominant hemispheres and compared across A/T groups.RESULTSA+T+ patients had greater hypometabolism in temporo‐parieto‐occipital cortices than A+T‐ and A‐T‐ groups, with no differences observed between the A+T‐ and A‐T‐ groups. FDG asymmetry was more accentuated in A+T+ patients. Medial temporal and basal ganglia metabolism were similar across AT groups.DISCUSSIONAmyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in temporo‐parieto‐occipital cortices in CBS, with AD‐like patterns of hypometabolism observed only in A+T+ patients.Highlights Amyloid (A) and tau PET (T) status can be used to stratify CBS patients. A+T+ CBS patients show more hypometabolism in temporo‐parieto‐occipital cortices. Medial temporal metabolism (typical AD pattern) is similar across AT groups. Parieto‐occipital cortices should be assessed when investigating AT pathology in CBS. Amyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in CBS.

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.

Abstract Introduction While certainty of evidence assessment is key to a rigorous and transparent systematic review, it is unknown how – and how frequently – it is assessed in systematic reviews. The objective of this study was to examine the prevalence and approaches used for certainty of evidence assessment in systematic reviews published in high‐impact medicine journals over the past 11 years. Methods A PubMed search and hand‐searching of relevant journal websites identified systematic reviews published between 24 January 2013 and 23 January 2024 in any of the ten highest‐impact journals in the General and Internal Medicine category of the Journal Citation Report. Two reviewers independently selected any systematic review related to health outcomes assessing certainty of evidence using any method. We extracted data related to review characteristics, certainty of evidence and risk of bias/methodological quality assessment frameworks, and reported consideration of certainty of evidence domains. Logistic regression examined year of publication to determine whether the prevalence of certainty of evidence assessment changed over time. Results Of 1,023 included reviews, 346 (33.8%) assessed certainty of evidence. Prevalence of certainty of evidence assessment increased over time (0.16 ± 0.2; p < .001). Most (89.3%) of reviews used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess certainty of evidence. Conclusion Only one in three systematic reviews published in the highest‐impact medical journals over the past 11 years assessed certainty of evidence, though prevalence increased over time. The use of specific domains within each certainty of evidence framework was not clearly described in all reviews.

AbstractAlthough electricity has been used in medicine for thousands of years, bioelectronic medicine for treating epilepsy has become increasingly common in recent years. Invasive neurostimulation centers primarily around three approaches: vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS). These approaches differ by target (e.g., cranial nerve, cortex, or thalamus) and stimulation parameters (e.g., triggered stimulation or continuous stimulation). Although typically noncurative, these approaches can dramatically reduce the seizure burden and offer patients new treatment options. There remains much to be understood about optimal targets and individualized stimulation protocols. Objective markers of seizure burden and biomarkers that quickly quantify neural excitability are still needed. In the future, bioelectronic medicine could become a curative approach that remodels neural networks to reduce pathological activity.

Abstract “Nonclassical” myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) represent a heterogeneous group of malignancies characterized by a wide range of clinical manifestations. Unlike classical MPNs, there is no standardized management approach for these conditions, particularly concerning the indications for and management of allogeneic hematopoietic cell transplantation. To address this gap, the European Society for Blood and Marrow Transplantation (EBMT) Practice Harmonization and Guidelines (PH&G) Committee and the Chronic Malignancies Working Party (CMWP) have collaborated to develop shared guidelines aimed at optimizing the selection and management of patients with these rare forms of neoplasms. A comprehensive review of the literature from the publication of the revised fourth edition of the (2016) World Health Organization classification onward was conducted. A multidisciplinary group of experts in the field convened to produce this document, which was developed through multiple rounds of draft circulation. Key recommendations include the early identification of potential transplant candidates, particularly in cases of chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL)/CEL, not otherwise specified (CEL-NOS), myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions with FGFR1, JAK2, ABL1, and FLT3 rearrangements, MDS/MPN with neutrophilia/atypical chronic myeloid leukemia, and MDS/MPN, NOS. For patients with MPN, NOS/MPN unclassifiable, standard recommendations for myelofibrosis should be applied. Similarly, in MDS/MPN with thrombocytosis, transplantation is recommended on the basis of established MDS guidelines. Given the current lack of robust evidence, this document will serve as a valuable resource to guide future research activities, providing a framework for addressing critical unanswered questions and advancing the field.

ABSTRACT Cellular senescence is an irreversible form of cell-cycle arrest caused by excessive stress or damage. While various biomarkers of cellular senescence have been proposed, there are currently no universal, stand-alone indicators of this condition. The field largely relies on the combined detection of multiple biomarkers to differentiate senescent cells from non-senescent cells. Here we introduce a new approach: unbiased cell culture selections to identify senescent cell-specific folded DNA aptamers from vast libraries of trillions of random 80-mer DNAs. Senescent mouse adult fibroblasts and their non-senescent counterparts were employed for selection. We demonstrate aptamer specificity for senescent mouse cells in culture, identify a form of fibronectin as the molecular target of two selected aptamers, show increased aptamer staining in naturally aged mouse tissues, and demonstrate decreased aptamer staining when p16 expressing cells are removed in a transgenic INK-ATTAC mouse model. This work demonstrates the value of unbiased cell-based selections to identify new senescence-specific DNA reagents.

Abstract Key unanswered questions in biology center on the causes, consequences, and maintenance of sexual reproduction (“sex”). Genome-driven processes are central to the evolutionary and genetic mechanisms inherent to sex, making genomic resources a fundamental part of answering these questions. We present the first genome assembly for a species that is uniquely well-suited for the study of (a)sex in nature, Potamopyrgus antipodarum . This New Zealand snail is unusual in featuring multiple separate transitions from obligately sexual to obligately asexual reproduction, leading to the coexistence of phenotypically similar sexual and asexual forms, a feature that is required to directly study the maintenance of sex. These separately derived asexual lineages constitute separate evolutionary experiments, providing a powerful means of characterizing how the absence of sex affects genome evolution. Our genome assembly provides critical steps towards understanding causes and consequences of sex in this system and important resources for the rapidly growing P. antipodarum and molluscan genomics research community. In characterizing this genome, we uncovered unexpected evidence for a recent whole-genome duplication (WGD) in P. antipodarum . This discovery sets the stage for using P . antipodarum to evaluate processes of rediploidization following WGD and assess whether WGD might drive transitions to asexuality.

ABSTRACT Recent development of single-cell technology across multiple omics platforms has provided new ways to obtain holistic views of cells to study disease pathobiology. Alzheimer’s disease (AD) is the most common form of dementia worldwide, yet the detailed understanding of its cellular and molecular mechanisms remains limited. In this study, we analyzed paired single-cell transcriptomic (scRNA-seq) and chromatin accessibility (scATAC-seq) data from the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) Consortium to investigate the molecular mechanisms of AD at a cell-subpopulation-specific resolution focusing on glial cells. We benchmarked various multi-omics integration methods using diverse metrics and built an analytic workflow that enabled effective batch correction and cross-modality alignment, creating a unified cell state space. Through integrative analysis of 26 human brain samples, we uncovered AD-associated gene expression and pathway changes in glial subpopulations and highlighted important transcriptomic and epigenomic signatures via functional inference and interpretable machine learning paradigms, discovering the profound involvement of the Solute Carrier proteins (SLC) family genes in multiple glial cell types. We also identified glial cell-specific regulatory programs mediated by key transcription factors such as JUN and FOSL2 in astrocytes, the Zinc Finger (ZNF) family genes in microglia, and the SOX family of transcription factors in oligodendrocytes. Our study provides a comprehensive workflow and a high-resolution view of how glial regulatory programs are disrupted in AD. Our findings offer novel insights into disease-related changes in gene regulation and suggest potential targets for further research and therapy.