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Leveraging archival cerebrospinal fluid samples for genetic insights from cell-free DNA [Editorial]

Miller, Alexandra M; Bale, Tejus A
PMID: 38427323
ISSN: 1934-6638
CID: 5770612

Alignment of brain embeddings and artificial contextual embeddings in natural language points to common geometric patterns

Goldstein, Ariel; Grinstein-Dabush, Avigail; Schain, Mariano; Wang, Haocheng; Hong, Zhuoqiao; Aubrey, Bobbi; Schain, Mariano; Nastase, Samuel A; Zada, Zaid; Ham, Eric; Feder, Amir; Gazula, Harshvardhan; Buchnik, Eliav; Doyle, Werner; Devore, Sasha; Dugan, Patricia; Reichart, Roi; Friedman, Daniel; Brenner, Michael; Hassidim, Avinatan; Devinsky, Orrin; Flinker, Adeen; Hasson, Uri
Contextual embeddings, derived from deep language models (DLMs), provide a continuous vectorial representation of language. This embedding space differs fundamentally from the symbolic representations posited by traditional psycholinguistics. We hypothesize that language areas in the human brain, similar to DLMs, rely on a continuous embedding space to represent language. To test this hypothesis, we densely record the neural activity patterns in the inferior frontal gyrus (IFG) of three participants using dense intracranial arrays while they listened to a 30-minute podcast. From these fine-grained spatiotemporal neural recordings, we derive a continuous vectorial representation for each word (i.e., a brain embedding) in each patient. Using stringent zero-shot mapping we demonstrate that brain embeddings in the IFG and the DLM contextual embedding space have common geometric patterns. The common geometric patterns allow us to predict the brain embedding in IFG of a given left-out word based solely on its geometrical relationship to other non-overlapping words in the podcast. Furthermore, we show that contextual embeddings capture the geometry of IFG embeddings better than static word embeddings. The continuous brain embedding space exposes a vector-based neural code for natural language processing in the human brain.
PMCID:10980748
PMID: 38553456
ISSN: 2041-1723
CID: 5645352

In vivo mapping of hippocampal venous vasculature and oxygenation using susceptibility imaging at 7T

Li, Chenyang; Buch, Sagar; Sun, Zhe; Muccio, Marco; Jiang, Li; Chen, Yongsheng; Haacke, E Mark; Zhang, Jiangyang; Wisniewski, Thomas M; Ge, Yulin
Mapping the small venous vasculature of the hippocampus in vivo is crucial for understanding how functional changes of hippocampus evolve with age. Oxygen utilization in the hippocampus could serve as a sensitive biomarker for early degenerative changes, surpassing hippocampal tissue atrophy as the main source of information regarding tissue degeneration. Using an ultrahigh field (7T) susceptibility-weighted imaging (SWI) sequence, it is possible to capture oxygen-level dependent contrast of submillimeter-sized vessels. Moreover, the quantitative susceptibility mapping (QSM) results derived from SWI data allow for the simultaneous estimation of venous oxygenation levels, thereby enhancing the understanding of hippocampal function. In this study, we proposed two potential imaging markers in a cohort of 19 healthy volunteers aged between 20 and 74 years. These markers were: 1) hippocampal venous density on SWI images and 2) venous susceptibility (Δχvein) in the hippocampus-associated draining veins (the inferior ventricular veins (IVV) and the basal veins of Rosenthal (BVR) using QSM images). They were chosen specifically to help characterize the oxygen utilization of the human hippocampus and medial temporal lobe (MTL). As part of the analysis, we demonstrated the feasibility of measuring hippocampal venous density and Δχvein in the IVV and BVR at 7T with high spatial resolution (0.25 × 0.25 × 1 mm3). Our results demonstrated the in vivo reconstruction of the hippocampal venous system, providing initial evidence regarding the presence of the venous arch structure within the hippocampus. Furthermore, we evaluated the age effect of the two quantitative estimates and observed a significant increase in Δχvein for the IVV with age (p = 0.006, r2 = 0.369). This may suggest the potential application of Δχvein in IVV as a marker for assessing changes in atrophy-related hippocampal oxygen utilization in normal aging and neurodegenerative diseases such as AD and dementia.
PMID: 38554779
ISSN: 1095-9572
CID: 5645402

Racial/Ethnic Differences in Long-COVID-Associated Symptoms among Pediatrics Population: Findings from Difference-in-differences Analyses in RECOVER Program

Chen, Yong; Zhang, Dazheng; Zhang, Bingyu; Wu, Qiong; Zhou, Ting; Tong, Jiayi; Lu, Yiwen; Chen, Jiajie; Wang, Huiyuan; Chisolm, Deena; Jhaveri, Ravi; Kenney, Rachel; Rothman, Russel; Rao, Suchitra; Williams, David; Hornig, Mady; Morris, Jeffrey; Forrest, Christopher
Racial/ethnic differences are associated with the potential symptoms and conditions of post-acute sequelae SARS-CoV-2 infection (PASC) in adults. These differences may exist among children and warrant further exploration. We conducted a retrospective cohort study for children and adolescents under the age of 21 from the thirteen institutions in the RECOVER Initiative. The cohort is 225,723 patients with SARS-CoV-2 infection or COVID-19 diagnosis and 677,448 patients without SARS-CoV-2 infection or COVID-19 diagnosis between March 2020 and October 2022. The study compared minor racial/ethnic groups to Non-Hispanic White (NHW) individuals, stratified by severity during the acute phase of COVID-19. Within the severe group, Asian American/Pacific Islanders (AAPI) had a higher prevalence of fever/chills and respiratory symptoms, Hispanic patients showed greater hair loss prevalence in severe COVID-19 cases, while Non-Hispanic Black (NHB) patients had fewer skin symptoms in comparison to NHW patients. Within the non-severe group, AAPI patients had increased POTS/dysautonomia and respiratory symptoms, and NHB patients showed more cognitive symptoms than NHW patients. In conclusion, racial/ethnic differences related to COVID-19 exist among specific PASC symptoms and conditions in pediatrics, and these differences are associated with the severity of illness during acute COVID-19.
PMCID:10996810
PMID: 38585924
ISSN: 2693-5015
CID: 5746052

Proteomics from compartment-specific APEX2 labeling in Mycobacterium tuberculosis reveals Type VII secretion substrates in the cell wall

Jaisinghani, Neetika; Previti, Mary L; Andrade, Joshua; Askenazi, Manor; Ueberheide, Beatrix; Seeliger, Jessica C
The cell wall of mycobacteria plays a key role in interactions with the environment. Its ability to act as a selective filter is crucial to bacterial survival. Proteins in the cell wall enable this function by mediating the import and export of diverse metabolites, from ions to lipids to proteins. Identifying cell wall proteins is an important step in assigning function, especially as many mycobacterial proteins lack functionally characterized homologues. Current methods for protein localization have inherent limitations that reduce accuracy. Here we showed that although chemical labeling of live cells did not exclusively label surface proteins, protein tagging by the engineered peroxidase APEX2 within live Mycobacterium tuberculosis accurately identified the cytosolic and cell wall proteomes. Our data indicate that substrates of the virulence-associated Type VII ESX secretion system are exposed to the periplasm, providing insight into the currently unknown mechanism by which these proteins cross the mycobacterial cell envelope.
PMID: 37967559
ISSN: 2451-9448
CID: 5644222

The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people

Jacobs, Tovia; Jacobson, Sean R; Fortea, Juan; Berger, Jeffrey S; Vedvyas, Alok; Marsh, Karyn; He, Tianshe; Gutierrez-Jimenez, Eugenio; Fillmore, Nathanael R; Bubu, Omonigho M; Gonzalez, Moses; Figueredo, Luisa; Gaggi, Naomi L; Plaska, Chelsea Reichert; Pomara, Nunzio; Blessing, Esther; Betensky, Rebecca; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj; Glodzik, Lidia; Wisniewski, Thomas M; Leon, Mony J; Osorio, Ricardo S; Ramos-Cejudo, Jaime
BACKGROUND/UNASSIGNED:(p-tau), as well as the trajectories of these CSF measures obtained longitudinally. RESULTS/UNASSIGNED:A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. CONCLUSIONS/UNASSIGNED:in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.
PMID: 38559231
ISSN: 2693-5015
CID: 5728992

Glia trigger endocytic clearance of axonal proteins to promote rodent myelination

Bekku, Yoko; Zotter, Brendan; You, Changjiang; Piehler, Jacob; Leonard, Warren J; Salzer, James L
Axons undergo striking changes in their content and distribution of cell adhesion molecules (CAMs) and ion channels during myelination that underlies the switch from continuous to saltatory conduction. These changes include the removal of a large cohort of uniformly distributed CAMs that mediate initial axon-Schwann cell interactions and their replacement by a subset of CAMs that mediate domain-specific interactions of myelinated fibers. Here, using rodent models, we examine the mechanisms and significance of this removal of axonal CAMs. We show that Schwann cells just prior to myelination locally activate clathrin-mediated endocytosis (CME) in axons, thereby driving clearance of a broad array of axonal CAMs. CAMs engineered to resist endocytosis are persistently expressed along the axon and delay both PNS and CNS myelination. Thus, glia non-autonomously activate CME in axons to downregulate axonal CAMs and presumptively axo-glial adhesion. This promotes the transition from ensheathment to myelination while simultaneously sculpting the formation of axonal domains.
PMID: 38309265
ISSN: 1878-1551
CID: 5627032

Multinodular and Vacuolating Neuronal Tumor-like Lesion of the Spinal Cord: Two Case Reports

Schollaert, Joris; Van der Planken, David; Mampaey, Sam; Breen, Matthew; Foo, Farng-Yang; Jain, Rajan; Van Goethem, Johan W M
We describe 2 cases of a spinal cord lesion with imaging features closely resembling those described in supratentorial multinodular and vacuolating neuronal tumor (MVNT) or infratentorial multinodular and vacuolating posterior fossa lesions of unknown significance. Multiple well-delineated nonenhancing T2-hyperintense intramedullary cystic ovoid nodules were visualized within the white matter of the spinal cord, including some immediately abutting the gray matter. No alterations in signal intensity or morphology were detected in a follow-up. Moreover, no relevant clinical symptoms attributable to the lesions were present. We describe these lesions as presumed MVNT, and we therefore use the term MVNT-like spinal cord lesions.
PMID: 38331962
ISSN: 1936-959x
CID: 5632462

Sex Differences in Outcomes of Acute Myocardial Injury After Stroke

Rosso, Michela; Stengl, Helena; Ganeshan, Ramanan; Hellwig, Simon; Klammer, Markus G; von Rennenberg, Regina; Böhme, Sophie; Nolte, Christian H; Audebert, Heinrich J; Endres, Matthias; Kasner, Scott E; Scheitz, Jan F
BACKGROUND:Sex differences in presentation, treatment, and prognosis of cardiovascular disorders are well recognized. Although an association between acute myocardial injury and mortality after ischemic stroke has been demonstrated, it is unclear whether prevalence and outcome of poststroke acute myocardial injury differ between women and men. METHODS AND RESULTS/RESULTS:=0.024). Statistically significant associations between acute myocardial injury and outcomes were observed in women (7-day in-hospital mortality: adjusted odds ratio [aOR], 3.2 [95% CI, 1.07-9.3]; in-hospital mortality: aOR, 3.3 [95% CI, 1.4-7.6]; modified Rankin Scale score at discharge: aOR, 1.6 [95% CI, 1.1-2.4]) but not in men. The implementation of sex-specific cutoffs did not increase the prognostic value of acute myocardial injury for unfavorable outcomes. CONCLUSIONS:The prevalence of acute myocardial injury after ischemic stroke and its association with mortality and greater disability might be sex-dependent. REGISTRATION/BACKGROUND:URL: https://www.clinicaltrials.gov; Unique identifier: NCT03892226.
PMCID:10944046
PMID: 38410952
ISSN: 2047-9980
CID: 5806082

The past, present, and future of the brain imaging data structure (BIDS)

Poldrack, Russell A; Markiewicz, Christopher J; Appelhoff, Stefan; Ashar, Yoni K; Auer, Tibor; Baillet, Sylvain; Bansal, Shashank; Beltrachini, Leandro; Benar, Christian G; Bertazzoli, Giacomo; Bhogawar, Suyash; Blair, Ross W; Bortoletto, Marta; Boudreau, Mathieu; Brooks, Teon L; Calhoun, Vince D; Castelli, Filippo Maria; Clement, Patricia; Cohen, Alexander L; Cohen-Adad, Julien; D'Ambrosio, Sasha; de Hollander, Gilles; de la Iglesia-Vayá, María; de la Vega, Alejandro; Delorme, Arnaud; Devinsky, Orrin; Draschkow, Dejan; Duff, Eugene Paul; DuPre, Elizabeth; Earl, Eric; Esteban, Oscar; Feingold, Franklin W; Flandin, Guillaume; Galassi, Anthony; Gallitto, Giuseppe; Ganz, Melanie; Gau, Rémi; Gholam, James; Ghosh, Satrajit S; Giacomel, Alessio; Gillman, Ashley G; Gleeson, Padraig; Gramfort, Alexandre; Guay, Samuel; Guidali, Giacomo; Halchenko, Yaroslav O; Handwerker, Daniel A; Hardcastle, Nell; Herholz, Peer; Hermes, Dora; Honey, Christopher J; Innis, Robert B; Ioanas, Horea-Ioan; Jahn, Andrew; Karakuzu, Agah; Keator, David B; Kiar, Gregory; Kincses, Balint; Laird, Angela R; Lau, Jonathan C; Lazari, Alberto; Legarreta, Jon Haitz; Li, Adam; Li, Xiangrui; Love, Bradley C; Lu, Hanzhang; Marcantoni, Eleonora; Maumet, Camille; Mazzamuto, Giacomo; Meisler, Steven L; Mikkelsen, Mark; Mutsaerts, Henk; Nichols, Thomas E; Nikolaidis, Aki; Nilsonne, Gustav; Niso, Guiomar; Norgaard, Martin; Okell, Thomas W; Oostenveld, Robert; Ort, Eduard; Park, Patrick J; Pawlik, Mateusz; Pernet, Cyril R; Pestilli, Franco; Petr, Jan; Phillips, Christophe; Poline, Jean-Baptiste; Pollonini, Luca; Raamana, Pradeep Reddy; Ritter, Petra; Rizzo, Gaia; Robbins, Kay A; Rockhill, Alexander P; Rogers, Christine; Rokem, Ariel; Rorden, Chris; Routier, Alexandre; Saborit-Torres, Jose Manuel; Salo, Taylor; Schirner, Michael; Smith, Robert E; Spisak, Tamas; Sprenger, Julia; Swann, Nicole C; Szinte, Martin; Takerkart, Sylvain; Thirion, Bertrand; Thomas, Adam G; Torabian, Sajjad; Varoquaux, Gael; Voytek, Bradley; Welzel, Julius; Wilson, Martin; Yarkoni, Tal; Gorgolewski, Krzysztof J
The Brain Imaging Data Structure (BIDS) is a community-driven standard for the organization of data and metadata from a growing range of neuroscience modalities. This paper is meant as a history of how the standard has developed and grown over time. We outline the principles behind the project, the mechanisms by which it has been extended, and some of the challenges being addressed as it evolves. We also discuss the lessons learned through the project, with the aim of enabling researchers in other domains to learn from the success of BIDS.
PMID: 39308505
ISSN: 2837-6056
CID: 5802782