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arXiv 2024年

作者： Ding, Jun-En Yang, Shihao Zilverstand, Anna Kulkarni, Kaustubh R. Gu, Xiaosi Liu, Fegn School of Systems and Enterprises Stevens Institute of Technology Hoboken United States Department of Psychiatry and Behavioral Sciences University of Minnesota MinneapolisMN55414 United States Medical Scientist Training Program The Icahn School of Medicine at Mount Sinai NY10027 United States Psychiatry and Neuroscience and directs the Center for Computational Psychiatry at Mount Sinai New York CityNY United States

The excessive consumption of marijuana can induce substantial psychological and social consequences. In this investigation, we propose an elucidative framework termed high-order graph attention neural networks (HOGANN) for the classification of Marijuana addiction, coupled with an analysis of localized brain network communities exhibiting abnormal activities among chronic marijuana users. HOGANN integrates dynamic intrinsic functional brain networks, estimated from functional magnetic resonance imaging (fMRI), using graph attention-based long short-term memory (GAT-LSTM) to capture temporal network dynamics. We employ a high-order attention module for information fusion and message passing among neighboring nodes, enhancing the network community analysis. Our model is validated across two distinct data cohorts, yielding substantially higher classification accuracy than benchmark algorithms. Furthermore, we discern the most pertinent subnetworks and cognitive regions affected by persistent marijuana consumption, indicating adverse effects on functional brain networks, particularly within the dorsal attention and frontoparietal networks. Intriguingly, our model demonstrates superior performance in cohorts exhibiting prolonged dependence, implying that prolonged marijuana usage induces more pronounced alterations in brain networks. The model proficiently identifies craving brain maps, thereby delineating critical brain regions for analysis. © 2024, CC BY.

关键词： Graph neural networks

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Mycotic aneurysm of the left main coronary artery producing acute coronary occlusion and purulent pericarditis

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International Journal of Cardiology 2007年第3期114卷 E81-E82页

作者： Westover, Kenneth Benedick, Bruce Stanford University School of Medicine Medical Scientist Training Program Stanford CA 94305 United States Stanford University School of Medicine Department of Medicine Palo Alto CA 94304 770 Welch Road #100 United States

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Cerebral hemodynamics and pseudo-continuous arterial spin labeling considerations in adults with sickle cell anemia

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NMR in Biomedicine 2017年第2期30卷 101002/nbm3681页

作者： Juttukonda, Meher R. Jordan, Lori C. Gindville, Melissa C. Davis, Larry T. Watchmaker, Jennifer M. Pruthi, Sumit Donahue, Manus J. Department of Radiology and Radiological Sciences Vanderbilt University Medical Center NashvilleTN United States Department of Pediatrics Division of Pediatric Neurology Vanderbilt Medical Center NashvilleTN United States Medical Scientist Training Program Vanderbilt University NashvilleTN United States Department of Neurology Vanderbilt University Medical Center NashvilleTN United States Department of Psychiatry Vanderbilt University Medical Center NashvilleTN United States

Sickle cell anemia (SCA) is a genetic disorder resulting in reduced oxygen carrying capacity and elevated stroke risk. Pseudo-continuous arterial spin labeling (pCASL) measures of cerebral blood flow (CBF) may have relevance for stroke risk assessment;however, the effects of elevated flow velocity and reduced bolus arrival time (BAT) on CBF quantification in SCA patients have not been thoroughly characterized, and pCASL model parameters used in healthy adults are often applied to patients with SCA. Here, cervical arterial flow velocities and pCASL labeling efficiencies were computed in adults with SCA (n = 19) and age- and race-matched controls without sickle trait (n = 7) using pCASL in sequence with phase contrast MR angiography (MRA). Controls (n = 7) and a subgroup of patients (n = 8) also underwent multi-post-labeling-delay pCASL for BAT assessment. Mean flow velocities were elevated in SCA adults (velocity = 28.3 ± 4.1 cm/s) compared with controls (velocity = 24.5 ± 3.8 cm/s), and mean pCASL labeling efficiency (α) was reduced in SCA adults (α = 0.72) relative to controls (α = 0.91). In patients, mean whole-brain CBF from phase contrast MRA was 91.8 ± 18.1 ml/100 g/min, while mean pCASL CBF when assuming a constant labeling efficiency of 0.86 was 75.2 ± 17.3 ml/100 g/min (p 1 variation. In conclusion, BAT variation influences pCASL quantification less than elevated cervical arterial velocity and labeling efficiency variation in SCA adults;thus, a lower labeling efficiency (α = 0.72) or subject-specific labeling efficiency should be incorporated for SCA patients. Copyright © 2017 John Wiley & Sons, Ltd.

关键词： Flow velocity

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Therapeutic Targeting of Follicular Helper T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells

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SSRN 2019年

作者： Reighard, Seth D. Cranert, Stacey A. Rangel, Kelly M. Ali, Ayad Gyurova, Ivayla E. de la Cruz-Lynch, Arthur T. Tuazon, Jasmine A. Kottyan, Leah C. Smith, David F. Brunner, Hermine I. Waggoner, Stephen N. Center for Autoimmune Genomics & Etiology Cincinnati Children’s Hospital Medical Center Medical Scientist Training Program University of Cincinnati College of Medicine Immunology Graduate Training Program University of Cincinnati College of Medicine Division of Developmental Biology Cincinnati Children’s Hospital Medical Center Pathobiology and Molecular Medicine Graduate Program University of Cincinnati College of Medicine Department of Pediatrics University of Cincinnati College of Medicine Division of Pediatric Otolaryngology - Head & Neck Surgery Cincinnati Children’s Hospital Medical Center Division of Pulmonary and Sleep Medicine Cincinnati Children’s Hospital Medical Center Department of Otolaryngology - Head & Neck Surgery University of Cincinnati College of Medicine Division of Rheumatology Cincinnati Children’s Hospital Medical Center

Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. Unfortunately, no clinical interventions are currently available for selective depletion of TFH cells to alleviate these disease conditions. We engineered a novel chimeric antigen receptor (CAR) that facilitates specific targeting of cells highly expressing human programmed cell death protein 1 (PD-1), a cardinal feature of TFH cells. CAR-expressing natural killer (NK) cells robustly degranulate in response to PD-1, resulting in discriminatory elimination of human tonsil TFH cells while sparing other T and B-cell subsets. Given that CAR NK cells are emerging as a safe and effective alternative to CAR T cells in cancer immunotherapy, our results suggest a new, clinically-translatable application of CAR NK cells for selective depletion of pathogenic TFH cells in specific disease states. © 2019, The Authors. All rights reserved.

关键词： Diseases

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Durable T cell immunity to COVID-19 vaccines in MS patients on B cell depletion therapy

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npj Vaccines 2025年第1期10卷 1-10页

作者： Davis-Porada, Julia Tozlu, Ceren Aiello, Claudia Apostolidis, Sokratis A. Bar-Or, Amit Bove, Riley Espinoza, Diego A. Ferreira Brito, Sugeidy Jacobs, Dina Kakara, Mihir Onomichi, Kaho Ricci, Adelle Sabatino, Joseph J. Walker, Elizabeth Wherry, E. John Zhang, Lili Zhu, Wen Xia, Zongqi De Jager, Philip Wesley, Sarah Flanagan Straus Farber, Rebecca Farber, Donna L. Department of Microbiology and Immunology Columbia University Irving Medical Center New York NY United States Medical Scientist Training Program Columbia University Irving Medical Center New York NY United States Department of Radiology Weill Cornell Medicine New York NY United States Institute for Immunology and Immune Health University of Pennsylvania Perelman School of Medicine Philadelphia PA United States Division of Rheumatology Department of Medicine University of Pennsylvania Perelman School of Medicine Philadelphia PA United States Center for Neuroinflammation and Experimental Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA United States Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia PA United States UCSF Weill Institute for Neuroscience Department of Neurology University of California San Francisco San Francisco CA United States Immunology Graduate Group Perelman School of Medicine University of Pennsylvania Philadelphia PA United States Department of Neurology Columbia University Vagelos College of Physicians and Surgeons Neurology Columbia Multiple Sclerosis Center and Center for Translational & Computational Neuroimmunology New York NY United States Department of Neurology NYU Grossman School of Medicine New York NY United States Department of Neurology University of Pittsburgh Pittsburgh PA United States Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA United States Department of Surgery Columbia University Irving Medical Center New York NY United States

Immune-mediated protection generated to COVID-19 mRNA vaccines is associated with anti-Spike (S) protein neutralizing antibodies. However, humoral immunity is compromised in B cell depleting (BCD) therapies, used to treat autoimmune diseases such as Multiple Sclerosis (MS). To study the effect of BCD on the durability and protective efficacy of vaccine-induced immunity, we evaluated S-reactive antibodies and T cell responses 1–70 weeks post-vaccination in MS cohorts treated with BCD compared to non-BCD therapies from four centers. BCD-treated participants had significantly reduced antibody levels and enhanced frequencies of S-reactive CD4+ and CD8+ memory T cells to COVID-19 vaccination compared to the non-BCD group, with some variations among different BCD formulations. T cell memory responses persisted up to 14 months post-vaccination in both BCD and non-BCD cohorts, who experienced similar clinical protection from COVID-19. Together, our results establish a critical role for T cell-mediated immunity in anti-viral protection independent of humoral immunity. © The Author(s) 2025.

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Development of 3D-printing composite inks based on photoreactive cartilage extracellular matrix and gelatin nanoparticles

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Bioprinting 2023年 36卷

作者： Hogan, Katie J. Perez, Marissa R. Öztatlı, Hayriye Si, Sophia Wang, Ziwen Jiang, Emily Y. Diba, Mani Garipcan, Bora Mikos, Antonios G. Department of Bioengineering Rice University Houston 77030 TX United States Baylor College of Medicine Medical Scientist Training Program Houston 77030 TX United States Institute of Biomedical Engineering Boğaziçi University İstanbul Turkey

Decellularized extracellular matrix (dECM)-based materials possess innate biochemical cues to drive cell recruitment and differentiation and are of interest for cartilage tissue engineering. While 3D-printing (3DP) provides a means for achieving the precise architecture needed for cartilage tissue engineering, dECM hydrogels have proven difficult to translate to 3DP due to low viscosity and weak mechanical properties. In this study, a cartilage dECM (cdECM, 3 w/v%) was combined with varied amounts of gelatin nanoparticles (GNPs;10, 12.5, 15 w/v%) to form novel hydrogel-colloidal composite materials for 3DP. The addition of GNPs increased the viscosity and rheological properties of the cdECM hydrogel in a dose-dependent manner, directly improving the printability of cdECM 3DP inks. Additionally, functionalization of both materials yielded a UV-crosslinkable material for post-printing crosslinking, and increased GNP content increased post-UV storage moduli with 15 w/v% GNPs yielding a storage modulus 26x greater than that of cdECM alone. 3DP construct swelling and degradation were decreased as a function of increased UV-crosslinking dosage (0, 1.5, and 3 J/cm²). After 14 d of swelling in PBS, construct non-porous area was increased by ∼40 % and pore area was increased by ∼30 % for uncrosslinked (0 J/cm²) constructs versus highly crosslinked (3 J/cm²) constructs. Roughly 40 % higher mass retention was observed across GNP content groups for 3 J/cm² versus 0 J/cm² UV exposure after 14 d of enzymatic degradation, showing the potential for tuning physicochemical properties via UV exposure. Likewise, the retention of key biochemical components of cdECM over the course of degradation was evaluated. Sulfated glycosaminoglycans, a key reservoir for tissue-specific growth factors, were found to be retained within scaffolds over 14 d of degradation and to be released relative to construct degradation and UV-crosslinking. The

关键词： 3D-printing Cartilage tissue engineering Colloidal gel Decellularized extracellular matrix

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Spotlight on the small

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Science 2014年第6198期345卷 738页

作者： Michael Shen The author is at the NYU Medical Scientist Training Program New York NY 10016 USA.

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Increasing Expression of the Retinoic X Receptor-B During Malignant Melanoma Progression

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Journal of Cutaneous Pathology 2008年第1期32卷

作者： S.J. McAlhany J.A. Reed Medical Scientist Training Program and Department of Pathology Baylor College of Medicine Houston TX.

Retinoic X receptor-b (RXR-b) is a heterodimerization partner for vitamin D receptor (VDR). 1,25-dihydroxyvitamin D3 activation of VDR leads to growth inhibition in numerous cell lines, including some melanoma lines. Evaluation of VDR and RXR-b expression in vivo in melanocytic neoplasms will increase our understanding of this pathways potential role in growth control. Previous studies in our laboratory showed decreased VDR expression in superficially invasive melanoma, and progressive loss of expression in deeply invasive melanomas and metastatic melanomas (MET). We next sought to evaluate RXR-b expression. Twenty-eight melanocytic neoplasms including 8 melanomas in situ (MIS), 9 primary invasive melanomas (PIM), and 11 MET were evaluated for RXR-b expression by immunohistochemistry. Nuclear labeling was assessed as 0 (0%), 1+(<5%), 2+(>5% but <50%), or 3+(>=50%). A significant increase in RXR-b expression from low (0–1+) to high (>1+) was found when comparing MIS to PIM and MET (chi2 p < 0.05). These data suggest: 1) potential loss of 1,25-dihydroxyvitamin D3 induced growth inhibition during melanoma progression may be due to decreased VDR expression without concomitant loss of RXR-b; and 2) increased RXR-b expression during melanoma progression may offer selective advantage through alternative signaling pathways.

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Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain (vol 86, pg 511, 2020)

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NATURE neuroscience 2020年第10期23卷 1308-1308页

作者： Marschallinger, Julia Iram, Tal Zardeneta, Macy Lee, Song E. Lehallier, Benoit Haney, Michael S. Pluvinage, John V. Mathur, Vidhu Hahn, Oliver Morgens, David W. Kim, Justin Tevini, Julia Felder, Thomas K. Wolinski, Heimo Bertozzi, Carolyn R. Bassik, Michael C. Aigner, Ludwig Wyss-Coray, Tony Department of Neurology and Neurological Sciences School of Medicine Stanford University Stanford CA USA Paul F. Glenn Center for the Biology of Aging Stanford University School of Medicine Stanford CA USA Institute of Molecular Regenerative Medicine Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS) Paracelsus Medical University Salzburg Austria Department of Genetics School of Medicine and Chemistry Engineering and Medicine for Human Health (ChEM-H) Stanford University Stanford CA USA Medical Scientist Training Program Stanford University School of Medicine Stanford CA USA Department of Chemistry Stanford ChEM-H and Howard Hughes Medical Institute Stanford University Stanford CA USA Department of Laboratory Medicine Paracelsus Medical University Salzburg Austria Obesity Research Unit Paracelsus Medical University Salzburg Austria Institute of Molecular Biosciences BioTechMed-Graz University of Graz Graz Austria Stanford Neurosciences Institute Stanford University Stanford CA USA Department of Veterans Affairs Palo Alto CA USA

Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call ‘lipid-droplet-accumulating microglia’ (LDAM), are defective in phagocytosis, produce high levels of reactive oxygen species and secrete proinflammatory cytokines. RNA-sequencing analysis of LDAM revealed a transcriptional profile driven by innate inflammation that is distinct from previously reported microglial states. An unbiased CRISPR–Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin (GRN), are causes of autosomal-dominant forms of human neurodegenerative diseases. We therefore propose that LDAM contribute to age-related and genetic forms of neurodegeneration.

关键词： Cellular neuroscience Cognitive ageing Glial biology

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Large-scale identification of secreted and membrane-associated gene products using DNA microarrays

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Nature Genetics 1999年第3期23卷 41-41页

作者： Max Diehn Medical Scientist Training Program & Department of Biochemistry Stanford University School of Medicine Stanford USA

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