tbuckley/cabot-search huggingface dataset:
Immune evasion of dormant disseminated tumor cells is due to their scarcity and can be overcome by T cell immunotherapies
Authors: Erica T. Goddard, Miles H. Linde, Shivani Srivastava, Grant Klug, Tamer B. Shabaneh, Santino Iannone, Candice A. Grzelak, Sydney Marsh, Alessandra I. Riggio, Ryann E. Shor, Ian L. Linde, Marissa Guerrero, Joshua R. Veatch, Annelise G. Snyder, Alana L. Welm, Stanley R. Riddell, Cyrus M. Ghajar
Journal: Cancer Cell (2024)
Distinct spatiotemporal dynamics of CD8+ T cell-derived cytokines in the tumor microenvironment
Authors: Mirjam E. Hoekstra, Maarten Slagter, Jos Urbanus, Mireille Toebes, Nadine Slingerland, Iris de Rink, Roelof J.C. Kluin, Marja Nieuwland, Ron Kerkhoven, Lodewyk F.A. Wessels, Ton N. Schumacher
Journal: Cancer Cell (2024)

Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines and chemokines. While signaling of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding of the spatiotemporal behavior of these cytokines is limited. Here, we describe a single cell transcriptome-based approach to infer which signal(s) an individual cell has received. We demonstrate that, contrary to expectations, CD8+ T cell-derived IFNγ is the dominant modifier of the TME relative to TNFα. Furthermore, we demonstrate that cell pools that show abundant IFNγ sensing are characterized by decreased expression of transforming growth factor β (TGFβ)-induced genes, consistent with IFNγ-mediated TME remodeling. Collectively, these data provide evidence that CD8+ T cell-secreted cytokines should be categorized into local and global tissue modifiers, and describe a broadly applicable approach to dissect cytokine and chemokine modulation of the TME.
Reduction in Breast Cancer Death With Adjuvant Chemotherapy Among US Women According to Race, Ethnicity, and the 21-Gene Recurrence Score
Authors: Hsiao-Ching Huang, Gregory S. Calip, Jennifer Weiss, Yael Simons, V.K. Gadi, Oana C. Danciu, Garth H. Rauscher, Kent F. Hoskins
Journal: Journal of the National Comprehensive Cancer Network (2024)

Background: We previously showed the 21-gene breast recurrence score (RS) has lower prognostic accuracy for non-Hispanic Black (NHB) compared with non-Hispanic White (NHW) women with estrogen receptor (ER)–positive/HER2-negative breast cancer. The purpose of this study was to determine the clinical validity of the RS for predicting chemotherapy benefit as recommended in the current NCCN Guidelines for Breast Cancer among women from diverse racial/ethnic groups. Methods: Using the SEER Oncotype database, we estimated propensity score–weighted hazard ratios (HRs) and 95% confidence intervals for breast cancer death with chemotherapy for women with ER-positive/HER2-negative, AJCC stages I–II, axillary node–negative, invasive breast cancer according to race/ethnicity. Results: We included 6,033 (8.2%) Asian/Pacific Islander (API), 5,697 (7.8%) NHB, 6,688 (9.1%) Hispanic, and 54,945 (74.9%) NHW women. Breast cancer death was reduced with chemotherapy for NHB (HR, 0.48, 95% CI, 0.28–0.81), Hispanic (HR, 0.48; 95% CI, 0.25–0.94), and NHW (HR, 0.80; 95% CI, 0.65–0.99) women with an RS of 26 to 100. There was a nonsignificant reduction for API women (HR, 0.59; 95% CI, 0.28–1.24). For women with an RS of 11 to 25, there was no reduction in death for any racial/ethnic group. Among women aged ≤50 years, the reduction in breast cancer death with chemotherapy differed according to race (NHB: HR, 0.37 [95% CI, 0.20–0.67]; NHW: HR, 0.56 [95% CI, 0.44–0.74]; P interaction for chemotherapy * race &lt;.0499). An exploratory subgroup analysis found that young NHB women may benefit from chemotherapy at a lower RS cutoff than other women. Conclusions: The RS was clinically validated as a predictive biomarker for NHB, Hispanic, and NHW women with ER-positive, axillary node-negative breast cancer, but it may underestimate the benefit of chemotherapy for young NHB women. If this finding is confirmed, the RS cutoff for recommending adjuvant chemotherapy for young NHB women with ER-positive, axillary node-negative breast cancer may need to be lower than for other women.
Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration
Authors: Xuting Zhang, Wansi Zhong, Rui Xue, Haidi Jin, Xiaoxian Gong, Yuhui Huang, Fujian Chen, Mozi Chen, Liqun Gu, Yebo Ge, Xiaodong Ma, Bifeng Zhong, Mengjie Wang, Haitao Hu, Zhicai Chen, Shenqiang Yan, Yi Chen, Xin Wang, Xiaoling Zhang, Dongjuan Xu, Yuping He, Minfang Lou, Aiju Wang, Xiong Zhang, Li Ma, Xiaodong Lu, Jianer Wang, Qiong Lou, Ping’an Qian, Guomin Xie, Xiaofen Zhu, Songbin He, Jin Hu, Xiongjie Wen, Yan Liu, Yanwen Wang, Jingjing Fu, Weinv Fan, David Liebeskind, Changzheng Yuan, Min Lou
Journal: JAMA Neurology (2024)

The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown.
COVID-19 Immunization Coverage Among People With Sickle Cell Disease
Authors: Hannah K. Peng, Kevin J. Dombkowski, Melissa A. Plegue, Krista Latta, Ryan Malosh, Melissa S. Creary, Sarah L. Reeves
Journal: JAMA Network Open (2024)

This cross-sectional study compares the completion of the primary COVID-19 vaccine series in Michigan residents with vs without sickle cell disease and by age group.
NALIRIFOX, FOLFIRINOX, and Gemcitabine With Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Cancer
Authors: Federico Nichetti, Simone Rota, Paolo Ambrosini, Chiara Pircher, Eleonora Gusmaroli, Michele Droz Dit Busset, Sara Pusceddu, Carlo Sposito, Jorgelina Coppa, Federica Morano, Filippo Pietrantonio, Maria Di Bartolomeo, Luigi Mariani, Vincenzo Mazzaferro, Filippo de Braud, Monica Niger
Journal: JAMA Network Open (2024)

The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
Error in Affiliation
Authors: Mr Zhang
Journal: JAMA Network Open (2024)

Lu Zhang, MPH; Ping Li, MPH; Qiaoyue Ge, MPH; Zeyuan Sun, MSc; Jiarui Cai, MA; Chenghan Xiao, PhD; Chuan Yu, PhD; Chiara Nosarti, PhD; Jiaqiang Liao, PhD; Zhenmi Liu, PhD
Risk Factors for Severe Maternal Morbidity Among Women Enrolled in Mississippi Medicaid
Authors: Shishir Maharjan, Swarnali Goswami, Yiran Rong, Terri Kirby, Dennis Smith, Catherine X. Brett, Eric L. Pittman, Kaustuv Bhattacharya
Journal: JAMA Network Open (2024)

Importance Mississippi has one of the highest rates of severe maternal morbidity (SMM) in the US, and SMMs have been reported to be more frequent among Medicaid-insured women. A substantial proportion of pregnant women in Mississippi are covered by Medicaid; hence, there is a need to identify potential risk factors for SMM in this population. Objective To examine the associations of health care access and clinical and sociodemographic characteristics with SMM events among Mississippi Medicaid–enrolled women who had a live birth. Design, Setting, and Participants A nested case-control study was conducted using 2018 to 2021 Mississippi Medicaid administrative claims database. The study included Medicaid beneficiaries aged 12 to 55 years who had a live birth and were continuously enrolled throughout their pregnancy period and 12 months after delivery. Individuals in the case group had SMM events and were matched to controls on their delivery date using incidence density sampling. Data analysis was performed from June to September 2022. Exposure Risk factors examined in the study included sociodemographic factors (age and race), health care access (distance from delivery center, social vulnerability index, and level of maternity care), and clinical factors (maternal comorbidity index, first-trimester pregnancy-related visits, and postpartum care). Main Outcomes and Measures The main outcome of the study was an SMM event. Adjusted odds ratio (aORs) and 95% CIs were calculated using conditional logistic regression. Results Among 13 485 Mississippi Medicaid–enrolled women (mean [SD] age, 25.0 [5.6] years; 8601 [63.8%] Black; 4419 [32.8%] White; 465 [3.4%] other race [American Indian, Asian, Hispanic, multiracial, and unknown]) who had a live birth, 410 (3.0%) were in the case group (mean [SD] age, 26.8 [6.4] years; 289 [70.5%] Black; 112 [27.3%] White; 9 [2.2%] other race) and 820 were in the matched control group (mean [SD] age, 24.9 [5.7] years; 518 [63.2%] Black; 282 [34.4%] White; 20 [2.4%] other race). Black individuals (aOR, 1.44; 95% CI, 1.08-1.93) and those with higher maternal comorbidity index (aOR, 1.27; 95% CI, 1.16-1.40) had higher odds of experiencing SMM compared with White individuals and those with lower maternal comorbidity index, respectively. Likewise, an increase of 100 miles (160 km) in distance between beneficiaries’ residence to the delivery center was associated with higher odds of experiencing SMM (aOR, 1.14; 95% CI, 1.07-1.20). Conclusions and Relevance The study findings hold substantial implications for identifying high-risk individuals within Medicaid programs and call for the development of targeted multicomponent, multilevel interventions for improving maternal health outcomes in this highly vulnerable population.
Evaluation of a Best-Practice Advisory for Primary Aldosteronism Screening
Authors: Suranut Charoensri, Linda Bashaw, Cheryl Dehmlow, Tammy Ellies, Jennifer Wyckoff, Adina F. Turcu
Journal: JAMA Internal Medicine (2024)

Primary aldosteronism (PA) is a common cause of secondary hypertension and an independent risk factor for cardiovascular morbidity and mortality. Fewer than 2% to 4% of patients at risk are evaluated for PA.
An Incarcerated Individual With Weight Loss and Interstitial Pulmonary Infiltrates
Authors: Nilesh Kapoor, Christina Dietz, Benjamin P. Buettner
Journal: JAMA (2024)

A man with HIV had syncopal episodes and hypoxemia after recent exposure to SARS-CoV-2; computed tomography revealed diffuse bilateral pulmonary micronodular opacities, a 2.2-cm nodule in the lingula, and mediastinal and hilar lymphadenopathy. What is the diagnosis and what would you do next?
Population-Based Trends in Complexity of Hospital Inpatients
Authors: Hiten Naik, Tyler M. Murray, Mayesha Khan, Daniel Daly-Grafstein, Guiping Liu, Barry O. Kassen, Jake Onrot, Jason M. Sutherland, John A. Staples
Journal: JAMA Internal Medicine (2024)

Clinical experience suggests that hospital inpatients have become more complex over time, but few studies have evaluated this impression.
Stepping Systematically Forward Toward Health Equity in Sickle Cell Disease
Authors: Anne M. Marsh, Marsha J. Treadwell
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
Trigeminal Ganglionopathy on Brain Magnetic Resonance Imaging—A Rare Etiology
Authors: Noel William Gomes, Rahul Tryambak Chakor, Swaleha Nadaf
Journal: JAMA Neurology (2024)

This case report describes a 56-year-old man with periorbital swelling and hyperpigmentation on the right side of the face and a hypopigmented patch on the anterior chest.
One CD4+TCR and One CD8+TCR Targeting Autochthonous Neoantigens Are Essential and Sufficient for Tumor Eradication
Authors: Steven P. Wolf, Vasiliki Anastasopoulou, Kimberley Drousch, Markus I. Diehl, Boris Engels, Poh Yin Yew, Kazuma Kiyotani, Yusuke Nakamura, Karin Schreiber, Hans Schreiber, Matthias Leisegang
Journal: Clinical Cancer Research (2024)

Abstract Purpose: To achieve eradication of solid tumors, we examined how many neoantigens need to be targeted with how many T-cell receptors (TCR) by which type of T cells. Experimental Design: Unmanipulated, naturally expressed (autochthonous) neoantigens were targeted with adoptively transferred TCR-engineered autologous T cells (TCR-therapy). TCR-therapy used CD8+ T-cell subsets engineered with TCRs isolated from CD8+ T cells (CD8+TCR-therapy), CD4+ T-cell subsets engineered with TCRs isolated from CD4+ T cells (CD4+TCR-therapy), or combinations of both. The targeted tumors were established for at least 3 weeks and derived from primary autochthonous cancer cell cultures, resembling natural solid tumors and their heterogeneity as found in humans. Results: Relapse was common with CD8+TCR-therapy even when targeting multiple different autochthonous neoantigens on heterogeneous solid tumors. CD8+TCR-therapy was only effective against homogenous tumors artificially derived from a cancer cell clone. In contrast, a combination of CD8+TCR-therapy with CD4+TCR-therapy, each targeting one neoantigen, eradicated large and established solid tumors of natural heterogeneity. CD4+TCR-therapy targeted a mutant neoantigen on tumor stroma while direct cancer cell recognition by CD8+TCR-therapy was essential for cure. In vitro data were consistent with elimination of cancer cells requiring a four-cell cluster composed of TCR-engineered CD4+ and CD8+ T cells together with antigen-presenting cells and cancer cells. Conclusions: Two cancer-specific TCRs can be essential and sufficient to eradicate heterogeneous solid tumors expressing unmanipulated, autochthonous targets. We demonstrate that simplifications to adoptive TCR-therapy are possible without compromising efficacy.
DMHPpp1r17 neurons regulate aging and lifespan in mice through hypothalamic-adipose inter-tissue communication
Authors: Kyohei Tokizane, Cynthia S. Brace, Shin-ichiro Imai
Journal: Cell Metabolism (2024)

Recent studies have shown that the hypothalamus functions as a control center of aging in mammals that counteracts age-associated physiological decline through inter-tissue communications. We have identified a key neuronal subpopulation in the dorsomedial hypothalamus (DMH), marked by Ppp1r17 expression (DMHPpp1r17 neurons), that regulates aging and longevity in mice. DMHPpp1r17 neurons regulate physical activity and WAT function, including the secretion of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), through sympathetic nervous stimulation. Within DMHPpp1r17 neurons, the phosphorylation and subsequent nuclear-cytoplasmic translocation of Ppp1r17, regulated by cGMP-dependent protein kinase G (PKG; Prkg1), affect gene expression regulating synaptic function, causing synaptic transmission dysfunction and impaired WAT function. Both DMH-specific Prkg1 knockdown, which suppresses age-associated Ppp1r17 translocation, and the chemogenetic activation of DMHPpp1r17 neurons significantly ameliorate age-associated dysfunction in WAT, increase physical activity, and extend lifespan. Thus, these findings clearly demonstrate the importance of the inter-tissue communication between the hypothalamus and WAT in mammalian aging and longevity control.
Protecting infants against RSV disease: an impact and cost-effectiveness comparison of long-acting monoclonal antibodies and maternal vaccination
Authors: David Hodgson, Neil Wilkins, Edwin van Leeuwen, Conall H. Watson, Jonathan Crofts, Stefan Flasche, Mark Jit, Katherine E. Atkins
Journal: The Lancet Regional Health - Europe (2024)

Two new products for preventing Respiratory Syncytial Virus (RSV) in young children have been licensed: a single-dose long-acting monoclonal antibody (la-mAB) and a maternal vaccine (MV). To facilitate the selection of new RSV intervention programmes for large-scale implementation, this study provides an assessment to compare the costs of potential programmes with the health benefits accrued. Using an existing dynamic transmission model, we compared maternal vaccination to la-mAB therapy against RSV in England and Wales by calculating the impact and cost-effectiveness. We calibrated a statistical model to the efficacy trial data to accurately capture their immune waning and estimated the impact of seasonal and year-round programmes for la-mAB and MV programmes. Using these impact estimates, we identified the most cost-effective programme across pricing and delivery cost assumptions. For infants under six months old in England and Wales, a year-round MV programme with 60% coverage would avert 32% (95% CrI 22–41%) of RSV hospital admissions and a year-round la-mAB programme with 90% coverage would avert 57% (95% CrI 41–69%). The MV programme has additional health benefits for pregnant women, which account for 20% of the population-level health burden averted. A seasonal la-mAB programme could be cost-effective for up to £84 for purchasing and administration (CCPA) and a seasonal MV could be cost-effective for up to £80 CCPA. This modelling and cost-effectiveness analysis has shown that both the long-acting monoclonal antibodies and the maternal vaccine could substantially reduce the burden of RSV disease in the infant population. Our analysis has informed JCVI's recommendations for an RSV immunisation programme to protect newborns and infants. National Institute for Health Research.
<i>Cryptosporidium</i> infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus
Authors: Valentin Greigert, Iti Saraav, Juhee Son, Yinxing Zhu, Denise Dayao, Avan Antia, Saul Tzipori, William H. Witola, Thaddeus S. Stappenbeck, Siyuan Ding, L. David Sibley
Journal: Gut Microbes (2024)

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen C. hominis and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for C. hominis using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of C. hominis in vitro including all life cycle stages. Cryptosporidium infection induced a strong interferon response from enterocytes, possibly driven, in part, by an endogenous dsRNA virus in the parasite. Prior infection with Cryptosporidium induced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.
A Genomic Link From Heart Failure to Atrial Fibrillation Risk: FOG2 Modulates a TBX5/GATA4-Dependent Atrial Gene Regulatory Network
Authors: Michael T. Broman, Rangarajan D. Nadadur, Carlos Perez-Cervantes, Ozanna Burnicka-Turek, Sonja Lazarevic, Anna Gams, Brigitte Laforest, Jeffrey D. Steimle, Sabrina Iddir, Zhezhen Wang, Linsin Smith, Stefan R. Mazurek, Harold E. Olivey, Pingzhu Zhou, Margaret Gadek, Kaitlyn M. Shen, Zoheb Khan, Joshua W.M. Theisen, Xinan H. Yang, Kohta Ikegami, Igor R. Efimov, William T. Pu, Christopher R. Weber, Elizabeth M. McNally, Eric C. Svensson, Ivan P. Moskowitz
Journal: Circulation (2024)

The relationship between heart failure (HF) and atrial fibrillation (AF) is clear, with up to half of patients with HF progressing to AF. The pathophysiological basis of AF in the context of HF is presumed to result from atrial remodeling. Upregulation of the transcription factor FOG2 (friend of GATA2; encoded by
Retraction: <i>In Vivo</i> Monitoring of Polycythemia Vera Development Reveals Carbonic Anhydrase 1 as a Potent Therapeutic Target
Authors: F Edmond, I Pasquier, W Plo, J.-L Vainchenker
Journal: Blood Cancer Discovery (2024)

This article (1) is being retracted at the request of the authors.When experiments in Fig. 4G-L and Supplementary Fig. S5 (G, H, I, andL) were repeated, the results did not reproduce a significant difference in the evolution of the allelic burden and in mouse survival in presence or absence of furosemide or acetazolamide.In addition, a reanalysis of the data used to produce the results shown in Fig. 4F and Supplementary Fig. S5C-S5F did not give convincing evidences for these results.
Increased cysteinyl-tRNA synthetase drives neuroinflammation in Alzheimer’s disease
Authors: Xiu-Hong Qi, Peng Chen, Yue-Ju Wang, Zhe-Ping Zhou, Xue-Chun Liu, Hui Fang, Chen-Wei Wang, Ji Liu, Rong-Yu Liu, Han-Kui Liu, Zhen-Xin Zhang, Jiang-Ning Zhou
Journal: Translational Neurodegeneration (2024)

Abstract Background Microglia-mediated neuroinflammation in Alzheimer’s disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. Methods Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. Results A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aβ plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. Conclusions The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.