Accurate and scalable quantification of amyloid-β (Aβ) pathology is crucial for deeper disease phenotyping and furthering research in Alzheimer Disease (AD). This multidisciplinary study addresses the current limitations on neuropathology by leveraging a machine learning (ML) pipeline to perform a granular quantification of Aβ deposits and assess their distribution in the temporal lobe. Utilizing 131 whole-slide-images from consecutive autopsied cases at the University of California Davis Alzheimer Disease Research Center, our objectives were threefold: (1) Validate an automatic workflow for Aβ deposit quantification in white matter (WM) and gray matter (GM); (2) define the distributions of different Aβ deposit types in GM and WM, and (3) investigate correlates of Aβ deposits with dementia status and the presence of mixed pathology. Our methodology highlights the robustness and efficacy of the ML pipeline, demonstrating proficiency akin to experts\' evaluations. We provide comprehensive insights into the quantification and distribution of Aβ deposits in the temporal GM and WM revealing a progressive increase in tandem with the severity of established diagnostic criteria (NIA-AA). We also present correlations of Aβ load with clinical diagnosis as well as presence/absence of mixed pathology. This study introduces a reproducible workflow, showcasing the practical use of ML approaches in the field of neuropathology, and use of the output data for correlative analyses. Acknowledging limitations, such as potential biases in the ML model and current ML classifications, we propose avenues for future research to refine and expand the methodology. We hope to contribute to the broader landscape of neuropathology advancements, ML applications, and precision medicine, paving the way for deep phenotyping of AD brain cases and establishing a foundation for further advancements in neuropathological research.

BACKGROUND: The Surveillance, Epidemiology, and End Results (SEER) Program with the National Cancer Institute tested whether population-based cancer registries can serve as honest brokers to acquire tissue and data in the SEER-Linked Virtual Tissue Repository (VTR) Pilot.
METHODS: We collected formalin-fixed, paraffin-embedded tissue and clinical data from patients with pancreatic ductal adenocarcinoma (PDAC) and breast cancer (BC) for two studies comparing cancer cases with highly unusual survival (≥5 years for PDAC and ≤30 months for BC) to pair-matched controls with usual survival (≤2 years for PDAC and ≥5 years for BC). Success was defined as the ability for registries to acquire tissue and data on cancer cases with highly unusual outcomes.
RESULTS: Of 98 PDAC and 103 BC matched cases eligible for tissue collection, sources of attrition for tissue collection were tissue being unavailable, control paired with failed case, second control that was not requested, tumor necrosis ≥20%, and low tumor cellularity. In total, tissue meeting the study criteria was obtained for 70 (71%) PDAC and 74 (72%) BC matched cases. For patients with tissue received, clinical data completeness ranged from 59% for CA-19-9 after treatment to >95% for margin status, whether radiation therapy and chemotherapy were administered, and comorbidities.
CONCLUSIONS: The VTR Pilot demonstrated the feasibility of using SEER cancer registries as honest brokers to provide tissue and clinical data for secondary use in research. Studies using this program should oversample by 45% to 50% to obtain sufficient sample size and targeted population representation and involve subspecialty matter expert pathologists for tissue selection.

Odense University Hospital is a major tertiary vascular hospital in Scandinavia, performing approx. 200 aortic repairs annually. This article presents the rationale behind this endeavor and the early outcomes of the initial implantation of locally processed homografts. All patients receiving a homograft were identified from the established homograft biobank database and their medical records were reviewed after obtaining consent. All surgeons in charge of homograft implantations were semi structured interviewed regarding the harvesting procedure, the tools for detecting available homografts, their quality and delivery. The National board of Health approved the biobank fulling the EU Directive of Tissues and Cells after 18 months of preparation. From May 6, 2021, to March 1, 2023, 26 patients had a homograft implantation, with 7 for mycotic aneurysms, 10 for aorto-iliac graft infection, 6 for infra-inguinal graft infection, and 3 for graft infection in thoracic aorta. Six (23%) were emergently performed. Two (7.7%) died within 30 days postoperatively, both following in situ replacement of an infected aortoiliac graft, corresponding to a 20% mortality in this subgroup. The incidence of reinfections was 19.2%; one each in the mycotic aneurysm group, the aortoiliac graft infection group, and the thoracic graft infection group. After 90 days, two patients were diagnosed with aorto-enteric fistula. All involved surgeons could easily identify available suitable homografts, and within 2 h have homografts of acceptable quality and requested dimensions. The establishment of the Danish Cardiovascular Homograft Biobank was straightforward and effectively serves cardiovascular procedures performed 24/7. Additionally, the initial experiences seem comparable to others experiences.

Collective use center is an organization or structural unit with unique resource providing access to this resource for internal and third-party users. Collective use centers are a relatively new phenomenon in bioresource collections, especially collections of human biological material due to some ethical and legal issues. At the same time, the demand for human biological material continues to grow in fundamental and applied researches. The collective use center «Bioresource collection of tissues and cell cultures of tumors of the human nervous system for fundamental and applied researches» has worked since October 14, 2022. This center has access to unique collection of the Laboratory of Neurosurgical Anatomy and Conservation of Human Biological Tissues of the Burdenko Neurosurgical Center.
OBJECTIVE: To analyze the experience of collective use center and biobank of the Burdenko Neurosurgical Center compared to national and international data on functioning of collective use centers specializing in tumors of the human central nervous system.
METHODS: We reviewed the PubMed and e-Library databases using the following keywords: core facilities brain tumors, repository of collective use brain tumors, biobank of CNS tumors, central nervous system tumor collection centers. We also analyzed the organizations registered on the portal of scientific and technical infrastructure of the Russian Federation.
RESULTS: We analyzed 275 publications devoted to collective use centers and biobanks. These biobanks do not position themselves as collective use centers but actively realize biological material for researches. Structure of institutions presented on the portal of scientific and technical infrastructure of the Russian Federation is characterized. The collective use center «Bioresource collection of tissues and cell cultures of tumors of the human nervous system for fundamental and applied researches» has access to biobank of the Burdenko Neurosurgical Center. To date, the biobank contains more than 8478 aliquots of tumor tissue frozen at ultra-low temperature (-196°C) and obtained from 1993 patients. Considering available data, we established the basic principles of work in collective use centers with bioresource collections.
CONCLUSIONS: Collective use centers with bioresource collections of tumors of the central nervous system are rare. There is only one collective use center organized at the Burdenko Neurosurgical Center on the portal of scientific and technical infrastructure of the Russian Federation. At the same time, there is an urgent need to increase their number and activity in Russia and other countries worldwide. You can use the resource of brain tumor collections by leaving a request on the official website of this organization in the «Collective use center» section.
Центр коллективного пользования (ЦКП) — это организация или структурное подразделение располагающие уникальным ресурсом и обеспечивающие доступ к этому ресурсу для внутренних и сторонних пользователей. ЦКП представляет собой относительно новое явление в сфере реализации биоресурсных коллекций, особенно коллекций биологического материала, полученного от человека, ввиду ряда этических и правовых вопросов. При этом спрос на биологический материал человека продолжает расти как при фундаментальных, так и при прикладных исследованиях. ЦКП «Биоресурсная коллекция тканей и клеточных культур опухолей нервной системы человека для фундаментальных и прикладных исследований» функционирует с 14.10.22 и имеет доступ к уникальной коллекции лаборатории нейрохирургической анатомии и консервации биологических тканей человека ФГАУ «Национальный медицинский исследовательский центр нейрохирургии им. акад. Н.Н. Бурденко» Минздрава России (НМИЦН).
UNASSIGNED: Проанализировать опыт работы ЦКП и биобанка НМИЦН, сопоставить его с отечественными и мировыми данными в области функционирования ЦКП, специализирующихся на работе с образцами опухолей центральной нервной системы человека.
UNASSIGNED: В рамках исследования произведен поиск публикаций, представленных в базах данных PubMed и eLibrary, по ключевым словам: «core facilities brain tumors», «repository of collective use brain tumors», «biobank of CNS tumors», «центры коллективного пользования опухолей центральной нервной системы». Изучены также организации, зарегистрированные на портале научно-технической инфраструктуры Российской Федерации.
UNASSIGNED: Всего проанализировано 275 публикаций, посвященных ЦКП и биобанкам, которые, не позиционируя себя как ЦКП, при этом активно реализуют хранящийся у них биологический материал для научных исследований. Охарактеризована структура учреждений, представленных на портале научно-технической инфраструктуры Российской Федерации. ЦКП «Биоресурсная коллекция тканей и клеточных культур опухолей нервной системы человека для фундаментальных и прикладных исследований» имеет доступ к коллекции биобанка НМИЦН. На сегодняшний день в биобанке насчитывается более 8478 аликвот опухолевой ткани, замороженных при сверхнизкой температуре (–196 °C), полученных от 1993 пациентов. На основании полученных данных сформулированы основные принципы деятельности ЦКП биоресурсными коллекциями.
UNASSIGNED: ЦКП биоресурсными коллекциями опухолей центральной нервной системы — редкое явление. На портале научно-технической инфраструктуры РФ зарегистрирован только ЦКП, организованный на базе НМИЦН. При этом имеется острая потребность в увеличении их количества и активности в России и других странах мира. Воспользоваться ресурсом коллекции опухолей головного мозга НМИЦН можно, оставив заявку на официальном сайте организации в разделе ЦКП.

BACKGROUND: Epidemiological studies have consistently shown an inverse association between cigarette smoking and Parkinson\'s disease. Literature indicates that both current and former smokers have a reduced risk of developing PD compared to non-smokers. If smoking protects against Parkinson\'s disease risk or, conversely, smoking habit is abated due to the disease itself, according to the reverse causation, is still an unsolved question.
METHODS: 118 patients from the UK Brain Bank with an alive clinical diagnosis of Parkinson\'s disease were enrolled. Post-mortem validation served as the gold standard for diagnosis to divide the population into true positive and false positive groups. Patient charts were reviewed to extract smoking exposure information and statistical analyses were conducted to determine the odds associated with smoking in the two diagnostic groups.
RESULTS: Among alive clinically diagnosed patients with Parkinson\'s disease, 53 % had no smoking exposure. In the True Positive group, 58 % had no smoking exposure, while this proportion was lower in the False Positive group at 46 %. The Odds Ratio for the association between smoking exposure and the two groups was 0.63 (95 % CI: 0.32-1.37). The Chi-square test yielded a p-value of 0.2804.
CONCLUSIONS: Our findings emphasize the role of smoking exposure in Parkinson\'s diagnosis. The results indicate that the observed association is not specific to idiopathic Parkinson\'s disease but rather a broader phenomenon encompassing various parkinsonian disorders. This suggests a potential common neuroprotective effect of smoking, shared risk factors, or supports the reverse causation hypothesis where parkinsonian symptoms reduce smoking exposure.

The liver is a highly specialized organ involved in regulating systemic metabolism. Understanding metabolic reprogramming of liver disease is key in discovering clinical biomarkers, which relies on robust tissue biobanks. However, sample collection and storage procedures pose a threat to obtaining reliable results, as metabolic alterations may occur during sample handling. This study aimed to elucidate the impact of pre-analytical delay during liver resection surgery on liver tissue metabolomics. Patients were enrolled for liver resection during which normal tissue was collected and snap-frozen at three timepoints: before transection, after transection, and after analysis in Pathology. Metabolomics analyses were performed using 1H Nuclear Magnetic Resonance (NMR) and Liquid Chromatography-Mass Spectrometry (LC-MS). Time at cryopreservation was the principal variable contributing to differences between liver specimen metabolomes, which superseded even interindividual variability. NMR revealed global changes in the abundance of an array of metabolites, namely a decrease in most metabolites and an increase in β-glucose and lactate. LC-MS revealed that succinate, alanine, glutamine, arginine, leucine, glycerol-3-phosphate, lactate, AMP, glutathione, and NADP were enhanced during cryopreservation delay (all p<0.05), whereas aspartate, iso(citrate), ADP, and ATP, decreased (all p<0.05). Cryopreservation delays occurring during liver tissue biobanking significantly alter an array of metabolites. Indeed, such alterations compromise the integrity of metabolomic data from liver specimens, underlining the importance of standardized protocols for tissue biobanking in hepatology.

Multiple sclerosis (MS) is a heterogeneous neurological disorder with regards to clinical presentation and pathophysiology. Here, we investigated the heterogeneity of MS by performing an exploratory factor analysis on quantitative and qualitative neuropathology data collected for 226 MS donors in the Netherlands Brain Bank autopsy cohort. Three promising dimensions were identified and subsequently validated with clinical, neuropathological, and genetic data. Dimension 1 ranged from a predominance of remyelinated and inactive lesions to extensive pathological changes, higher proportions of active and mixed lesions, and foamy microglia morphology. This pattern was positively correlated with more severe disease, the presence of B and T cells, and neuroaxonal damage. Scoring high on dimension 2 was associated with active lesions, reactive sites, and the presence of nodules. These donors had less severe disease, a specific pattern of cortical lesions, and MS risk variants in the human leukocyte antigen region, the latter indicating a connection between disease onset and this neuropathological dimension. Donors scoring high on dimension 3 showed increased lesional pathology with relatively more mixed and inactive lesions and ramified microglia morphology. This pattern was associated with longer disease duration, subpial cortical lesions, less involvement of the adaptive immune system, and less axonal damage. Taken together, the three dimensions may represent (1) demyelination and immune cell activity associated with pathological and clinical progression, (2) microglia (re)activity and possibly lesion initiation, and (3) loss of lesion activity and scar formation. Our findings highlight that a thorough understanding of the interplay between multiple pathological characteristics is crucial to understand the heterogeneity of MS pathology, as well as its association with genetic predictors and disease outcomes. The scores of donors on the dimensions can serve as an important starting point for further disentanglement of MS heterogeneity and translation into observations and interventions in living cohorts with MS.

Toward the translation of allogeneic cell therapy products, cell banks are needed not only to manufacture the final human product but also during the preclinical evaluation of an animal-based analogous cellular product (ACP). These cell banks need to be established at both the master cell bank (MCB) level and the working cell bank (WCB) level. Inasmuch as most of the development of cell therapy products is at academic centers, it is imperative that academic researchers understand how to establish MCBs and WCBs within an academic environment. To illustrate this process, using articular cartilage as the model, a cell bank for an ACP was developed (MCBs at passage 2, WCBs at passage 5) to produce self-assembled neocartilage for preclinical evaluation (constructs at passage 7). The cell bank system is estimated to be able to produce between 160 000 and 400 000 constructs for each of the six MCBs. Overall, the ACP cell bank yielded constructs that are analogous to the intended human product, which is critical toward conducting preclinical evaluations of the ACP for inclusion in an Investigational New Drug application to the FDA.

The New South Wales Brain Tissue Resource Centre is a human brain bank that provides top-quality brain tissue for cutting-edge neuroscience research spanning various conditions from alcohol use disorder to neurodegenerative diseases. However, the conventional practice of preserving brain tissue in formalin poses challenges for immunofluorescent staining primarily due to the formalin\'s tendency, over time, to create cross-links between antigens, which can obscure epitopes of interest. In addition, researchers can encounter issues such as spectral bleeding, limitations in using multiple colors, autofluorescence, and cross-reactivity when working with long-term formalin-fixed brain tissue. The purpose of the study was to test chromogen-based double immunolabeling to negate the issues with immunofluorescent staining. Colocalization of antigens was explored using chromogens 3-amino-9-ethylcarbazole (AEC) and 3,3,-diaminobenzidine in a sequential staining procedure where the AEC signal was eliminated by alcohol treatment. Combinations of 2 or 3 primary antibodies from the same or different species were trialed successfully with this protocol. The colocalization of antigens was also demonstrated with pseudocoloring that mimicked immunofluorescence staining. This staining technique increases the utility of archival formalin-fixed tissue samples.

This Viewpoint discusses the death of a patient caused by unregulated biological products and efforts to encourage federal government oversight of such products.