tbuckley/cabot-search huggingface dataset:
Dietary Sodium and Blood Pressure
Authors: Thomas C. Keyserling, Veeral M. Saraiya, Alice S. Ammerman
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Screening Recommendations and Treatments for Postpartum Depression
Authors: Itamar Nitzan, Raylene Philips, Robert D. White
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis
Authors: Jinlin Zhu, Jialin Yin, Jing Chen, Mingyi Hu, Wenwei Lu, Hongchao Wang, Hao Zhang, Wei Chen
Journal: Gut Microbes (2024)

Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.
Conserved long noncoding RNA TILAM promotes liver fibrosis through interaction with PML in HSCs
Authors: Cheng Sun, Chan Zhou, Kaveh Daneshvar, Amel Ben Saad, Arcadia J. Kratkiewicz, Benjamin J. Toles, Nahid Arghiani, Anja Hess, Jennifer Y. Chen, Joshua V. Pondick, Samuel R. York, Wenyang Li, Sean P. Moran, Stefan D. Gentile, Raza Ur Rahman, Zixiu Li, Peng Zhou, Robert P. Sparks, Tim Habboub, Byeong-Moo Kim, Michael Y. Choi, Silvia Affo, Robert F. Schwabe, Yury V. Popov, Alan C. Mullen
Journal: Hepatology (2024)

Background and Aims: Fibrosis is the common end point for all forms of chronic liver injury, and the progression of fibrosis leads to the development of end-stage liver disease. Activation of HSCs and their transdifferentiation into myofibroblasts results in the accumulation of extracellular matrix proteins that form the fibrotic scar. Long noncoding RNAs regulate the activity of HSCs and provide targets for fibrotic therapies. Approach and Results: We identified long noncoding RNA TILAM located near COL1A1 , expressed in HSCs, and induced with liver fibrosis in humans and mice. Loss-of-function studies in human HSCs and human liver organoids revealed that TILAM regulates the expression of COL1A1 and other extracellular matrix genes. To determine the role of TILAM in vivo, we annotated the mouse ortholog ( Tilam ), generated Tilam- deficient green fluorescent protein-reporter mice, and challenged these mice in 2 different models of liver fibrosis. Single-cell data and analysis of single-data and analysis of Tilam-deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Tilam -deficient reporter mice revealed that Tilam is induced in murine HSCs with the development of fibrosis in vivo. Furthermore, loss of Tilam expression attenuated the development of fibrosis in the setting of in vivo liver injury. Finally, we found that TILAM interacts with promyelocytic leukemia nuclear body scaffold protein to regulate a feedback loop by which TGF-β2 reinforces TILAM expression and nuclear localization of promyelocytic leukemia nuclear body scaffold protein to promote the fibrotic activity of HSCs. Conclusions: TILAM is activated in HSCs with liver injury and interacts with promyelocytic leukemia nuclear body scaffold protein to drive the development of fibrosis. Depletion of TILAM may serve as a therapeutic approach to combat the development of end-stage liver disease.
Diurnal rhythmicity of infant fecal microbiota and metabolites: A randomized controlled interventional trial with infant formula
Authors: Nina Heppner, Sandra Reitmeier, Marjolein Heddes, Michael Vig Merino, Leon Schwartz, Alexander Dietrich, Markus List, Michael Gigl, Chen Meng, Daan R. van der Veen, Melanie Schirmer, Karin Kleigrewe, Hélène Omer, Silke Kiessling, Dirk Haller
Journal: Cell Host & Microbe (2024)

Microbiota assembly in the infant gut is influenced by diet. Breastfeeding and human breastmilk oligosaccharides promote the colonization of beneficial bifidobacteria. Infant formulas are supplemented with bifidobacteria or complex oligosaccharides, notably galacto-oligosaccharides (GOS), to mimic breast milk. To compare microbiota development across feeding modes, this randomized controlled intervention study (German Clinical Trial DRKS00012313) longitudinally sampled infant stool during the first year of life, revealing similar fecal bacterial communities between formula- and breast-fed infants (N = 210) but differences across age. Infant formula containing GOS sustained high levels of bifidobacteria compared with formula containing B. longum and B. breve or placebo. Metabolite and bacterial profiling revealed 24-h oscillations and circadian networks. Rhythmicity in bacterial diversity, specific taxa, and functional pathways increased with age and was strongest following breastfeeding and GOS supplementation. Circadian rhythms in dominant taxa were further maintained ex vivo in a chemostat model. Hence, microbiota rhythmicity develops early in life and is impacted by diet.
Race-specific coregulatory and transcriptomic profiles associated with DNA methylation and androgen receptor in prostate cancer
Authors: Swathi Ramakrishnan, Eduardo Cortes-Gomez, Sarah R. Athans, Kristopher M. Attwood, Spencer R. Rosario, Se Jin Kim, Donald E. Mager, Emily G. Isenhart, Qiang Hu, Jianmin Wang, Anna Woloszynska
Journal: Genome Medicine (2024)

Abstract Background Prostate cancer is a significant health concern, particularly among African American (AA) men who exhibit higher incidence and mortality compared to European American (EA) men. Understanding the molecular mechanisms underlying these disparities is imperative for enhancing clinical management and achieving better outcomes. Methods Employing a multi-omics approach, we analyzed prostate cancer in both AA and EA men. Using Illumina methylation arrays and RNA sequencing, we investigated DNA methylation and gene expression in tumor and non-tumor prostate tissues. Additionally, Boolean analysis was utilized to unravel complex networks contributing to racial disparities in prostate cancer. Results When comparing tumor and adjacent non-tumor prostate tissues, we found that DNA hypermethylated regions are enriched for PRC2/H3K27me3 pathways and EZH2/SUZ12 cofactors. Olfactory/ribosomal pathways and distinct cofactors, including CTCF and KMT2A, were enriched in DNA hypomethylated regions in prostate tumors from AA men. We identified race-specific inverse associations of DNA methylation with expression of several androgen receptor (AR) associated genes, including the GATA family of transcription factors and TRIM63 . This suggests that race-specific dysregulation of the AR signaling pathway exists in prostate cancer. To investigate the effect of AR inhibition on race-specific gene expression changes, we generated in-silico patient-specific prostate cancer Boolean networks. Our simulations revealed prolonged AR inhibition causes significant dysregulation of TGF-β, IDH1, and cell cycle pathways specifically in AA prostate cancer. We further quantified global gene expression changes, which revealed differential expression of genes related to microtubules, immune function, and TMPRSS2-fusion pathways, specifically in prostate tumors of AA men. Enrichment of these pathways significantly correlated with an altered risk of disease progression in a race-specific manner. Conclusions Our study reveals unique signaling networks underlying prostate cancer biology in AA and EA men, offering potential insights for clinical management strategies tailored to specific racial groups. Targeting AR and associated pathways could be particularly beneficial in addressing the disparities observed in prostate cancer outcomes in the context of AA and EA men. Further investigation into these identified pathways may lead to the development of personalized therapeutic approaches to improve outcomes for prostate cancer patients across different racial backgrounds.
A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis
Authors: Yimin Dong, Honglei Kang, Renpeng Peng, Zheming Liu, Fuben Liao, Shi-an Hu, Weizhong Ding, Pengju Wang, Pengchao Yang, Meipeng Zhu, Sibo Wang, Minglong Wu, Dawei Ye, Xin Gan, Feng Li, Kehan Song
Journal: Cell Metabolism (2024)
Carrier-free mRNA vaccine induces robust immunity against SARS-CoV-2 in mice and non-human primates without systemic reactogenicity
Authors: Saed Abbasi, Miki Matsui-Masai, Fumihiko Yasui, Akimasa Hayashi, Theofilus A. Tockary, Yuki Mochida, Shiro Akinaga, Michinori Kohara, Kazunori Kataoka, Satoshi Uchida
Journal: Molecular Therapy (2024)

Carrier-free naked mRNA vaccines may reduce the reactogenicity associated with delivery carriers; however, their effectiveness against infectious diseases has been suboptimal. To boost efficacy, we targeted the skin layer rich in antigen-presenting cells (APCs) and utilized a jet injector. The jet injection efficiently introduced naked mRNA into skin cells, including APCs in mice. Further analyses indicated that APCs, after taking up antigen mRNA in the skin, migrated to the lymph nodes (LNs) for antigen presentation. Additionally, the jet injection provoked localized lymphocyte infiltration in the skin, serving as a physical adjuvant for vaccination. Without a delivery carrier, our approach confined mRNA distribution to the injection site, preventing systemic mRNA leakage and associated systemic proinflammatory reactions. In mouse vaccination, the naked mRNA jet injection elicited robust antigen-specific antibody production over 6 months, along with germinal center formation in LNs and the induction of both CD4- and CD8-positive T cells. By targeting the SARS-CoV-2 spike protein, this approach provided protection against viral challenge. Furthermore, our approach generated neutralizing antibodies against SARS-CoV-2 in non-human primates at levels comparable to those observed in mice. In conclusion, our approach offers a safe and effective option for mRNA vaccines targeting infectious diseases. Carrier-free naked mRNA vaccines may reduce the reactogenicity associated with delivery carriers; however, their effectiveness against infectious diseases has been suboptimal. To boost efficacy, we targeted the skin layer rich in antigen-presenting cells (APCs) and utilized a jet injector. The jet injection efficiently introduced naked mRNA into skin cells, including APCs in mice. Further analyses indicated that APCs, after taking up antigen mRNA in the skin, migrated to the lymph nodes (LNs) for antigen presentation. Additionally, the jet injection provoked localized lymphocyte infiltration in the skin, serving as a physical adjuvant for vaccination. Without a delivery carrier, our approach confined mRNA distribution to the injection site, preventing systemic mRNA leakage and associated systemic proinflammatory reactions. In mouse vaccination, the naked mRNA jet injection elicited robust antigen-specific antibody production over 6 months, along with germinal center formation in LNs and the induction of both CD4- and CD8-positive T cells. By targeting the SARS-CoV-2 spike protein, this approach provided protection against viral challenge. Furthermore, our approach generated neutralizing antibodies against SARS-CoV-2 in non-human primates at levels comparable to those observed in mice. In conclusion, our approach offers a safe and effective option for mRNA vaccines targeting infectious diseases.
Author Correction: Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation
Authors: Yohei Kawana, Junta Imai, Yosuke M. Morizawa, Yoko Ikoma, Masato Kohata, Hiroshi Komamura, Toshihiro Sato, Tomohito Izumi, Junpei Yamamoto, Akira Endo, Hiroto Sugawara, Haremaru Kubo, Shinichiro Hosaka, Yuichiro Munakata, Yoichiro Asai, Shinjiro Kodama, Kei Takahashi, Keizo Kaneko, Shojiro Sawada, Tetsuya Yamada, Akira Ito, Kuniyasu Niizuma, Teiji Tominaga, Akihiro Yamanaka, Ko Matsui, Hideki Katagiri
Journal: Nature Biomedical Engineering (2024)
Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts
Authors: Yahaya A. Yabo, Pilar M. Moreno-Sanchez, Yolanda Pires-Afonso, Tony Kaoma, Bakhtiyor Nosirov, Andrea Scafidi, Luca Ermini, Anuja Lipsa, Anaïs Oudin, Dimitrios Kyriakis, Kamil Grzyb, Suresh K. Poovathingal, Aurélie Poli, Arnaud Muller, Reka Toth, Barbara Klink, Guy Berchem, Christophe Berthold, Frank Hertel, Michel Mittelbronn, Dieter H. Heiland, Alexander Skupin, Petr V. Nazarov, Simone P. Niclou, Alessandro Michelucci, Anna Golebiewska
Journal: Genome Medicine (2024)

Abstract Background A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials. Methods Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry, and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors. Results We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood–brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components. Conclusions Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment. Graphical Abstract
Combining multi-mode thermal therapy with IL-6 and IL-17A neutralization amplifies antitumor immunity to facilitate long-term survival in LLC1-bearing mice
Authors: Jiamin Zheng, Jincheng Zou, Yue Lou, Shicheng Wang, Zelu Zhang, Junjun Wang, Peishan Du, Yongxin Zhu, Jiaqi You, Yichen Yao, Yuankai Hao, Aili Zhang, Ping Liu
Journal: Med-X (2024)

Abstract Non-small cell lung cancer (NSCLC) is known for rapid development and chronic inflammation-induced immunosuppression. IL-6 and IL-17A are the essential cytokines that facilitate NSCLC progression and myeloid-derived suppressive cell (MDSC)-mediated evasion. IL-6 or IL-17A targeting, especially IL-6, shown outstanding efficacy in patient NSCLC controlling, but failed to completely eradicate tumor. The local tumor multi-mode thermal therapy developed in our prior research was demonstrated to stimulate systemic and durable tumor-specific immune response thereby promoting long-term tumor-free survival of mice and prolong the progression-free survival of patients, although the therapeutic efficacy was still affected by high-level preoperative MDSCs. To further improve the efficacy, in this study, IL-6 and IL-17A neutralization were combined with multi-mode thermal therapy in mouse LLC1 NSCLC model. Study revealed that combined with single cytokine neutralization only prolonged the survival time while triple combination therapy efficiently improved the survival rate. Additionally, triple combination therapy reduced the accumulation of MDSCs but promoted their maturation with strengthened activation and function of myeloid cells, thereby triggering a Th1-dominant-CD4 + T cell-response and enhancing the malignant cell-killing capacity of immune cells. Our study highlights the extraordinary efficacy of combining multi-mode thermal therapy with IL-6 and IL-17A neutralization, revealing a new strategy for refractory NSCLC patients. Graphical Abstract
NF-κB subunits RelA and c-Rel selectively control CD4+ T cell function in multiple sclerosis and cancer
Authors: Guilhem Lalle, Raphaëlle Lautraite, Khaled Bouherrou, Maud Plaschka, Aurora Pignata, Allison Voisin, Julie Twardowski, Marlène Perrin-Niquet, Pierre Stéphan, Sarah Durget, Laurie Tonon, Maude Ardin, Cyril Degletagne, Alain Viari, Laurence Belgarbi Dutron, Nathalie Davoust, Thomas S. Postler, Jingyao Zhao, Christophe Caux, Julie Caramel, Stéphane Dalle, Philippe A. Cassier, Ulf Klein, Marc Schmidt-Supprian, Roland Liblau, Sankar Ghosh, Yenkel Grinberg-Bleyer
Journal: The Journal of Experimental Medicine (2024)

The outcome of cancer and autoimmunity is often dictated by the effector functions of CD4+ conventional T cells (Tconv). Although activation of the NF-κB signaling pathway has long been implicated in Tconv biology, the cell-autonomous roles of the separate NF-κB transcription-factor subunits are unknown. Here, we dissected the contributions of the canonical NF-κB subunits RelA and c-Rel to Tconv function. RelA, rather than c-Rel, regulated Tconv activation and cytokine production at steady-state and was required for polarization toward the TH17 lineage in vitro. Accordingly, RelA-deficient mice were fully protected against neuroinflammation in a model of multiple sclerosis due to defective transition to a pathogenic TH17 gene-expression program. Conversely, Tconv-restricted ablation of c-Rel impaired their function in the microenvironment of transplanted tumors, resulting in enhanced cancer burden. Moreover, Tconv required c-Rel for the response to PD-1-blockade therapy. Our data reveal distinct roles for canonical NF-κB subunits in different disease contexts, paving the way for subunit-targeted immunotherapies.
Individuals with <i>JAK1</i> variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis
Authors: Michael E. Horesh, Marta Martin-Fernandez, Conor Gruber, Sofija Buta, Tom Le Voyer, Eve Puzenat, Harry Lesmana, Yiming Wu, Ashley Richardson, David Stein, Stephanie Hodeib, Mariam Youssef, Jacob A. Kurowski, Elizabeth Feuille, Luis A. Pedroza, Ramsay L. Fuleihan, Alexandria Haseley, Alain Hovnanian, Pierre Quartier, Jérémie Rosain, Georgina Davis, Daniel Mullan, O’Jay Stewart, Roosheel Patel, Angelica E. Lee, Rebecca Rubinstein, Leyla Ewald, Nikhil Maheshwari, Virginia Rahming, Ivan K. Chinn, James R. Lupski, Jordan S. Orange, Vanessa Sancho-Shimizu, Jean-Laurent Casanova, Noura S. Abul-Husn, Yuval Itan, Joshua D. Milner, Jacinta Bustamante, Dusan Bogunovic
Journal: The Journal of Experimental Medicine (2024)

Inborn errors of immunity lead to autoimmunity, inflammation, allergy, infection, and/or malignancy. Disease-causing JAK1 gain-of-function (GoF) mutations are considered exceedingly rare and have been identified in only four families. Here, we use forward and reverse genetics to identify 59 individuals harboring one of four heterozygous JAK1 variants. In vitro and ex vivo analysis of these variants revealed hyperactive baseline and cytokine-induced STAT phosphorylation and interferon-stimulated gene (ISG) levels compared with wild-type JAK1. A systematic review of electronic health records from the BioME Biobank revealed increased likelihood of clinical presentation with autoimmunity, atopy, colitis, and/or dermatitis in JAK1 variant-positive individuals. Finally, treatment of one affected patient with severe atopic dermatitis using the JAK1/JAK2-selective inhibitor, baricitinib, resulted in clinically significant improvement. These findings suggest that individually rare JAK1 GoF variants may underlie an emerging syndrome with more common presentations of autoimmune and inflammatory disease (JAACD syndrome). More broadly, individuals who present with such conditions may benefit from genetic testing for the presence of JAK1 GoF variants.