tbuckley/cabot-search huggingface dataset:
Alzheimer’s disease associated isoforms of human CD33 distinctively modulate microglial cell responses in 5XFAD mice
Authors: Ghazaleh Eskandari-Sedighi, Madeline Crichton, Sameera Zia, Erik Gomez-Cardona, Leonardo M. Cortez, Zain H. Patel, Kei Takahashi-Yamashiro, Chris D. St. Laurent, Gaurav Sidhu, Susmita Sarkar, Vivian Aghanya, Valerie L. Sim, Qiumin Tan, Olivier Julien, Jason R. Plemel, Matthew S. Macauley
Journal: Molecular Neurodegeneration (2024)

Abstract Microglia play diverse pathophysiological roles in Alzheimer’s disease (AD), with genetic susceptibility factors skewing microglial cell function to influence AD risk. CD33 is an immunomodulatory receptor associated with AD susceptibility through a single nucleotide polymorphism that modulates mRNA splicing, skewing protein expression from a long protein isoform (CD33M) to a short isoform (CD33m). Understanding how human CD33 isoforms differentially impact microglial cell function in vivo has been challenging due to functional divergence of CD33 between mice and humans. We address this challenge by studying transgenic mice expressing either of the human CD33 isoforms crossed with the 5XFAD mouse model of amyloidosis and find that human CD33 isoforms have opposing effects on the response of microglia to amyloid-β (Aβ) deposition. Mice expressing CD33M have increased Aβ levels, more diffuse plaques, fewer disease-associated microglia, and more dystrophic neurites compared to 5XFAD control mice. Conversely, CD33m promotes plaque compaction and microglia-plaque contacts, and minimizes neuritic plaque pathology, highlighting an AD protective role for this isoform. Protective phenotypes driven by CD33m are detected at an earlier timepoint compared to the more aggressive pathology in CD33M mice that appears at a later timepoint, suggesting that CD33m has a more prominent impact on microglia cell function at earlier stages of disease progression. In addition to divergent roles in modulating phagocytosis, scRNAseq and proteomics analyses demonstrate that CD33m + microglia upregulate nestin, an intermediate filament involved in cell migration, at plaque contact sites. Overall, our work provides new functional insights into how CD33, as a top genetic susceptibility factor for AD, modulates microglial cell function. Graphical Abstract
Nano-Sensitizer with Self-Amplified Drug Release and Hypoxia Normalization Properties Potentiates Efficient Chemoradiotherapy of Pancreatic Cancer
Authors: Shuchen Yu, Yitong Jiang, Qian Li, Mengmeng Li, Jiamin Su, Shicong Lai, Zhihua Gan, Zhenshan Ding, Qingsong Yu
Journal: Biomaterials (2024)
Microbial diagnostics in periodontal diseases
Authors: Daniel Manoil, Ana Parga, Nagihan Bostanci, Georgios N. Belibasakis
Journal: Periodontology 2000 (2024)

Microbial analytical methods have been instrumental in elucidating the complex microbial etiology of periodontal diseases, by shaping our understanding of subgingival community dynamics. Certain pathobionts can orchestrate the establishment of dysbiotic communities that can subvert the host immune system, triggering inflammation and tissue destruction. Yet, diagnosis and management of periodontal conditions still rely on clinical and radiographic examinations, overlooking the well-established microbial etiology. This review summarizes the chronological emergence of periodontal etiological models and the co-evolution with technological advances in microbial detection. We additionally review the microbial analytical approaches currently accessible to clinicians, highlighting their value in broadening the periodontal assessment. The epidemiological importance of obtaining culture-based antimicrobial susceptibility profiles of periodontal taxa for antibiotic resistance surveillance is also underscored, together with clinically relevant analytical approaches to guide antibiotherapy choices, when necessary. Furthermore, the importance of 16S-based community and shotgun metagenomic profiling is discussed in outlining dysbiotic microbial signatures. Because dysbiosis precedes periodontal damage, biomarker identification offers early diagnostic possibilities to forestall disease relapses during maintenance. Altogether, this review highlights the underutilized potential of clinical microbiology in periodontology, spotlighting the clinical areas most conductive to its diagnostic implementation for enhancing prevention, treatment predictability, and addressing global antibiotic resistance.
Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine
Authors: Liu-Xi Chu, Wen-Jia Wang, Xin-Pei Gu, Ping Wu, Chen Gao, Quan Zhang, Jia Wu, Da-Wei Jiang, Jun-Qing Huang, Xin-Wang Ying, Jia-Men Shen, Yi Jiang, Li-Hua Luo, Jun-Peng Xu, Yi-Bo Ying, Hao-Man Chen, Ao Fang, Zun-Yong Feng, Shu-Hong An, Xiao-Kun Li, Zhou-Guang Wang
Journal: Military Medical Research (2024)

Abstract Aging and regeneration represent complex biological phenomena that have long captivated the scientific community. To fully comprehend these processes, it is essential to investigate molecular dynamics through a lens that encompasses both spatial and temporal dimensions. Conventional omics methodologies, such as genomics and transcriptomics, have been instrumental in identifying critical molecular facets of aging and regeneration. However, these methods are somewhat limited, constrained by their spatial resolution and their lack of capacity to dynamically represent tissue alterations. The advent of emerging spatiotemporal multi-omics approaches, encompassing transcriptomics, proteomics, metabolomics, and epigenomics, furnishes comprehensive insights into these intricate molecular dynamics. These sophisticated techniques facilitate accurate delineation of molecular patterns across an array of cells, tissues, and organs, thereby offering an in-depth understanding of the fundamental mechanisms at play. This review meticulously examines the significance of spatiotemporal multi-omics in the realms of aging and regeneration research. It underscores how these methodologies augment our comprehension of molecular dynamics, cellular interactions, and signaling pathways. Initially, the review delineates the foundational principles underpinning these methods, followed by an evaluation of their recent applications within the field. The review ultimately concludes by addressing the prevailing challenges and projecting future advancements in the field. Indubitably, spatiotemporal multi-omics are instrumental in deciphering the complexities inherent in aging and regeneration, thus charting a course toward potential therapeutic innovations.
Living in my own skin: dermatological concerns and gender-affirming care as a trans person with neurofibromatosis type 1
Authors: Alex Barbieri, Jeremy Orloff, Nicholas Gulati, Rebecca M Brown
Journal: British Journal of Dermatology (2024)

We provide patient and clinician perspectives on the dermatological outcomes of patients with neurofibromatosis type 1 (NF1) seeking gender-affirming hormone therapy. This perspectives article speaks to the psychosocial challenges that patients with NF1 may face due to the visible signs and symptoms of their disease. The theoretical role that hormones may play in the development of cutaneous neurofibromas is also addressed.
Novel Multifunctional Meta‐Surface Plasmon Resonance Chip Microplate for High‐Throughput Molecular Screening
Authors: Youqian Chen, Huazhi Zhang, Rui Li, Hongli Fan, Junjie Huang, Rui Zhou, Shaoping Yin, Gang L. Liu, Liping Huang
Journal: Advanced Healthcare Materials (2024)

The utilization of surface plasmon resonance (SPR) sensors for real-time label-free molecular interaction analysis is already being employed in the fields of in vitro diagnostics and biomedicine. However, the widespread application of SPR technology is hindered by its limited detection throughput and high cost. To address this issue, this study introduces a novel multifunctional MetaSPR high-throughput microplate biosensor featuring 3D nanocups array structure, aiming to achieve high-throughput screening with a reduced cost and enhanced speed. Different types of MetaSPR sensors and analytical detection methods have been developed for accurate antibody subtype identification, epitope binding, affinity determination, antibody collocation, and quantitative detection， greatly promoting the screening and analysis of early-stage antibody drugs. The MetaSPR platform combined with nano-enhanced particles amplifies the detection signal and improves the detection sensitivity, making it more convenient, sensitive, and efficient than traditional ELISA. The findings demonstrate that the MetaSPR biosensor is a new practical technology detection platform that can improve the efficiency of biomolecular interaction studies with unlimited potential for new drug development.
Metabolome-wide Mendelian randomization for age at menarche and age at natural menopause
Authors: Mojgan Yazdanpanah, Nahid Yazdanpanah, Isabel Gamache, Ken Ong, John R. B. Perry, Despoina Manousaki
Journal: Genome Medicine (2024)

The role of metabolism in the variation of age at menarche (AAM) and age at natural menopause (ANM) in the female population is not entirely known. We aimed to investigate the causal role of circulating metabolites in AAM and ANM using Mendelian randomization (MR). We combined MR with genetic colocalization to investigate potential causal associations between 658 metabolites and AAM and between 684 metabolites and ANM. We extracted genetic instruments for our exposures from four genome-wide association studies (GWAS) on circulating metabolites and queried the effects of these variants on the outcomes in two large GWAS from the ReproGen consortium. Additionally, we assessed the mediating role of the body mass index (BMI) in these associations, identified metabolic pathways implicated in AAM and ANM, and sought validation for selected metabolites in the Avon Longitudinal Study of Parents and Children (ALSPAC). Our analysis identified 10 candidate metabolites for AAM, but none of them colocalized with AAM. For ANM, 76 metabolites were prioritized (FDR-adjusted MR P-value ≤ 0.05), with 17 colocalizing, primarily in the glycerophosphocholines class, including the omega-3 fatty acid and phosphatidylcholine (PC) categories. Pathway analyses and validation in ALSPAC mothers also highlighted the role of omega and polyunsaturated fatty acids levels in delaying age at menopause. Our study suggests that metabolites from the glycerophosphocholine and fatty acid families play a causal role in the timing of both menarche and menopause. This underscores the significance of specific metabolic pathways in the biology of female reproductive longevity.
Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults
Authors: Wanchun Xu, Amanda Lauren Lee, Cindy Lo Kuen Lam, Goodarz Danaei, Eric Yuk Fai Wan
Journal: Annals of Internal Medicine (2024)

There is little consensus on using statins for primary prevention of cardiovascular diseases (CVDs) and all-cause mortality in adults aged 75 years or older due to the underrepresentation of this population in randomized controlled trials.
Real-world experience of commercial relmacabtagene autoleucel (relma-cel) for relapsed/refractory central nervous system lymphoma: a multicenter retrospective analysis of patients in China
Authors: Wenyan Yu, Liang Huang, Heng Mei, Yuhua Li, Ting Niu, Dehui Zou, Yao Liu, Huilai Zhang, Peng Liu, Jianqiu Wu, Zhi Wang, Hui Li, Qingqing Cai, Jian-qing Mi
Journal: Journal for ImmunoTherapy of Cancer (2024)

Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the "real-world" use of relma-cel, especially for patients with CNS involvement.
Multifunctional fluorescence/photoacoustic bimodal imaging of γ-glutamyltranspeptidase in liver disorders under different triggering conditions
Authors: Kai Wang, Xu-Yang Chen, Ren-Wei-Yang Zhang, Ying Yue, Xiao-Lin Wen, Yu-Shun Yang, Chen-Yang Han, Yuan Ma, Hong-Ji Liu, Hai-Liang Zhu
Journal: Biomaterials (2024)
Distinctive multicellular immunosuppressive hubs confer different intervention strategies for left- and right-sided colon cancers
Authors: Bingxin Liu, Shuwei Li, Yifei Cheng, Peng Song, Menghuan Xu, Zhengyi Li, Wei Shao, Junyi Xin, Zan Fu, Dongying Gu, Mulong Du, Zhengdong Zhang, Meilin Wang
Journal: Cell Reports Medicine (2024)

Primary colon cancers arising from the left and right sides exhibit distinct clinical and molecular characteristics. Sidedness-associated heterogeneity relies intricately on the oncogenic properties of cancer cells and multicellular interactions in tumor microenvironments. Here, combining transcriptomic profiling of 426,863 single cells from 105 colon cancer patients and validation with spatial transcriptomics and large-scale histological analysis, we capture common transcriptional heterogeneity patterns between left- and right-sided malignant epithelia through delineating two side-specific expression meta-programs. The proliferation stemness meta-program is notably enriched in left-sided malignant epithelia that colocalize with Mph-PLTP cells, activated regulatory T cells (Tregs), and exhausted CD8-LAYN cells, constituting the glucose metabolism reprogramming niche. The immune secretory (IS) meta-program exhibits specific enrichment in right-sided malignant epithelia, especially in smoking patients with right-sided colon cancer. The IShigh malignant epithelia spatially localize in hypoxic regions and facilitate immune evasion through attenuating Mph-SPP1 cell antigen presentation and recruiting innate-like cytotoxicity-reduced CD8-CD161 cells.
Salmonella Typhimurium expansion in the inflamed murine gut is dependent on aspartate derived from ROS-mediated microbiota lysis
Authors: Woongjae Yoo, Nicolas G. Shealy, Jacob K. Zieba, Teresa P. Torres, Madi Baltagulov, Julia D. Thomas, Catherine D. Shelton, Anna G. McGovern, Nora J. Foegeding, Erin E. Olsan, Mariana X. Byndloss
Journal: Cell Host & Microbe (2024)

Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation. AspA-dependent growth advantage was abolished in the gut of germ-free mice and restored in gnotobiotic mice colonized with members of the classes Bacteroidia and Clostridia. Reactive oxygen species (ROS) produced during the host response caused lysis of commensal microbes, resulting in the release of microbiota-derived aspartate that was used by S. Tm, in concert with nitrate-dependent anaerobic respiration, to outcompete commensal Enterobacteriaceae. Our findings demonstrate the role of microbiota-derived amino acids in driving respiration-dependent S. Tm expansion during colitis.
Application and internal validation of lung ultrasound score in COVID-19 setting: The ECOVITA observational study
Authors: L. Rinaldi, M. Lugarà, V. Simeon, F. Perrotta, C. Romano, C. Iadevaia, C. Sagnelli, L. Monaco, C. Altruda, M.C. Fascione, L. Restivo, U. Scognamiglio, N. Laganà, R. Nevola, G. Oliva, M.G. Coppola, C. Acierno, F. Masini, E. Pinotti, E. Allegorico, S. Tamburrini, G. Vitiello, M. Niosi, M.L. Burzo, G. Franci, A. Perrella, G. Signoriello, V. Frusci, S. Mancarella, G. Loche, G.F. Pellicano, M. Berretta, G. Calabria, L. Pietropaolo, F.G. Numis, N. Coppola, A. Corcione, R. Marfella, L.E. Adinolfi, A. Bianco, F.C. Sasso, I. de Sio
Journal: Pulmonology (2024)

The severe acute respiratory syndrome Coronarovirus-2 associated still causes a significant number of deaths and hospitalizations mainly by the development of respiratory failure. We aim to validate lung ultrasound score in order to predict mortality and the severity of the clinical course related to the need of respiratory support. In this prospective multicenter hospital-based cohort study, all adult patients with diagnosis of SARS-CoV-2 infection, performed by real-time reverse transcription polymerase chain reaction were included. Upon admission, all patients underwent blood gas analysis and lung ultrasound by expert operators. The acquisition of ultrasound scan was performed on 12 peculiar anatomic landmarks of the chest. Lung ultrasound findings were classified according to a scoring method, ranging 0 to 3: Score 0: normal A-lines. Score 1: multiple separated B-lines. Score 2: coalescent B-lines, alteration of pleural line. Score 3: consolidation area. One thousand and seven patients were included in statistical analysis (male 62.4 %, mean age 66.3). Oxygen support was needed in 811 (80.5 %) patients. The median ultrasound score was 24 and the risk of having more invasive respiratory support increased in relation to higher values score computed. Lung ultrasound score showed negative strong correlation (rho: -0.71) with the P/F ratio and a significant association with in-hospital mortality (OR 1.11, 95 %CI 1.07–1.14; p < 0.001), even after adjustment with the following variables (age, sex, P/F ratio, SpO2, lactate, hypertension, chronic renal failure, diabetes, and obesity). The novelty of this research corroborates and validates the 12-field lung ultrasound score as tool for predicting mortality and severity clinical course in COVID-19 patients. Baseline lung ultrasound score was associated with in-hospital mortality and requirement of intensive respiratory support and predict the risk of IOT among COVID-19 patients.
Exploring Delayed Pediatric Diagnoses in Emergency Department—Reply
Authors: Kenneth A. Michelson, Chris A. Rees, Richard G. Bachur
Journal: JAMA Pediatrics (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Exploring Delayed Pediatric Diagnoses in Emergency Department
Authors: Serena Yun-Chen Tsai, Kevin Sheng-Kai Ma
Journal: JAMA Pediatrics (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Patterns of Adverse Childhood Experiences and Neurocognitive Development
Authors: Jing Yu, Denise L. Haynie, Stephen E. Gilman
Journal: JAMA Pediatrics (2024)

Importance Early life adversity is associated with higher risk of many adult health problems, including mental illness, substance abuse, suicide attempt, and chronic diseases. Many previous studies investigated adversities one at a time or investigated the health toll associated with the cumulative number of adversities. Objective To examine the co-occurrence of adversities among children and how specific patterns of adversities are associated with neurocognitive development. Design, Setting, and Participants This cohort study used data from the Collaborative Perinatal Project (CPP), which enrolled a national sample of women during pregnancy and followed their offspring to ages 7 to 8 years, between 1959 and 1974. The CPP was a community-based study conducted in 12 US medical centers. The CPP sample was ascertained through prenatal clinics and is diverse with respect to race and socioeconomic status. Data analysis was performed from August 2023 to March 2024. Exposures A latent class analysis was conducted of 12 adverse childhood experiences that occurred between birth and 7 years to identify common patterns of childhood adversities. Main Outcomes and Measures Five neurocognitive tests were used to measure children’s visual-motor, sensory-motor, auditory-vocal, intelligence quotient, and academic skills. Results The analysis sample included 49 853 offspring (25 226 boys [50.6%]); 24 436 children (49.0%) had low probability of experiencing any adversity, whereas the remaining half were classified into 5 groups reflecting distinct patterns of childhood adversities: parental harshness and neglect, 1625 children (3.3%); parental separation and poverty, 8731 children (17.5%); family instability, 3655 children (7.3%); family loss, instability, and poverty, 1505 children (3.0%); and crowded housing and poverty, 9901 children (19.9%). Children in 4 of these groups had lower neurocognitive scores than children with a low probability of experiencing adversity, with standardized mean differences ranging from −0.07 (95% CI, −0.11 to −0.03) to −0.86 (95% CI, −1.06 to −0.65). Conclusions and Relevance These findings suggest that adverse childhood experiences are associated with deficits in children’s neurocognitive functions. It is important to understand the complexity in children’s exposure to adversity and the resulting developmental consequences, as well as the underlying mechanisms, to help support children exposed to adversity and foster healthier and resilient trajectories of development.