tbuckley/cabot-search huggingface dataset:
STING activation reprograms the microenvironment to sensitize NF1-related malignant peripheral nerve sheath tumors for immunotherapy
Authors: Bandarigoda N. Somatilaka, Laasya Madana, Ali Sadek, Zhiguo Chen, Sanjay Chandrasekaran, Renee M. McKay, Lu Q. Le
Journal: Journal of Clinical Investigation (2024)

Neurofibromatosis Type 1 (NF1) is caused by mutations in the NF1 gene that encodes neurofibromin, a RAS GTPase-Activating Protein. Inactivating NF1 mutations cause hyperactivation of RAS-mediated signaling, resulting in development of multiple neoplasms, including Malignant Peripheral Nerve Sheath Tumors (MPNSTs). MPNSTs are an aggressive tumor and the main cause of mortality in NF1 patients. MPNSTs are difficult to resect and refractory to chemo- and radiotherapy, and no molecular therapies currently exist. Immune Checkpoint Blockade (ICB) is an approach to treat inoperable, undruggable cancers like MPNST, but successful outcomes require an immune cell-rich tumor microenvironment (TME). While MPNSTs are non-inflamed "cold" tumors, here, we turned MPNSTs into T cell-inflamed "hot" tumors by activating "stimulator of interferon genes" (STING) signaling. Mouse genetic and human xenograft MPNST models treated with STING agonist plus ICB exhibited growth delay via increased apoptotic cell death. This strategy offers a potential treatment regimen for MPNST.
Molecular and Clinical Determinants of Acquired Resistance and Treatment Duration for Targeted Therapies in Colorectal Cancer
Authors: Emily Harrold, Fergus Keane, Henry Walch, Joanne F. Chou, Jenna Sinopoli, Silvia Palladino, Duaa H. Al-Rawi, Kalyani Chadalavada, Paolo Manca, Sree Chalasani, Jessica Yang, Andrea Cercek, Jinru Shia, Marinela Capanu, Samuel F. Bakhoum, Nikolaus Schultz, Walid K. Chatila, Rona Yaeger
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Targeted therapies have improved outcomes for patients with metastatic colorectal cancer, but their impact is limited by rapid emergence of resistance. We hypothesized that an understanding of the underlying genetic mechanisms and intrinsic tumor features that mediate resistance to therapy will guide new therapeutic strategies and ultimately allow the prevention of resistance. Experimental Design: We assembled a series of 52 patients with paired pretreatment and progression samples who received therapy targeting EGFR (n = 17), BRAF V600E (n = 17), KRAS G12C (n = 15), or amplified HER2 (n = 3) to identify molecular and clinical factors associated with time on treatment (TOT). Results: All patients stopped treatment for progression and TOT did not vary by oncogenic driver (P = 0.5). Baseline disease burden (≥3 vs. &amp;lt;3 sites, P = 0.02), the presence of hepatic metastases (P = 0.02), and gene amplification on baseline tissue (P = 0.03) were each associated with shorter TOT. We found evidence of chromosomal instability (CIN) at progression in patients with baseline MAPK pathway amplifications and those with acquired gene amplifications. At resistance, copy-number changes (P = 0.008) and high number (≥5) of acquired alterations (P = 0.04) were associated with shorter TOT. Patients with hepatic metastases demonstrated both higher number of emergent alterations at resistance and enrichment of mutations involving receptor tyrosine kinases. Conclusions: Our genomic analysis suggests that high baseline CIN or effective induction of enhanced mutagenesis on targeted therapy underlies rapid progression. Longer response appears to result from a progressive acquisition of genomic or chromosomal instability in the underlying cancer or from the chance event of a new resistance alteration.
Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease
Authors: Ararat J. Ablooglu, Wei-Sheng Chen, Zhihui Xie, Abhishek Desai, Subrata Paul, Justin B. Lack, Linda A. Scott, A. Robin Eisch, Arkadiusz Z. Dudek, Samir M. Parikh, Kirk M. Druey
Journal: Journal of Clinical Investigation (2024)

Clarkson disease (monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome, ISCLS) is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. Specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here we characterize an autonomous vascular endothelial defect in ISCLS that is recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs are functionally hyper-responsive to permeability-inducing factors like VEGF and histamine in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of N(γ)-nitro-L-arginine methyl ester (L-NAME) ameliorates vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyper-activation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach.
Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients With Exsanguinating Hemorrhage
Authors: Kyosuke Kamijo, Yosuke Matsumura
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
Primary Care Interventions to Prevent Child Maltreatment
Authors: Meera Viswanathan, Caroline Rains, Laura C. Hart, Emma Doran, Nila Sathe, Kesha Hudson, Rania Ali, Daniel E. Jonas, Roger Chou, Adam J. Zolotor
Journal: JAMA (2024)

Importance Child maltreatment is associated with serious negative physical, psychological, and behavioral consequences. Objective To review the evidence on primary care–feasible or referable interventions to prevent child maltreatment to inform the US Preventive Services Task Force. Data Sources PubMed, Cochrane Library, and trial registries through February 2, 2023; references, experts, and surveillance through December 6, 2023. Study Selection English-language, randomized clinical trials of youth through age 18 years (or their caregivers) with no known exposure or signs or symptoms of current or past maltreatment. Data Extraction and Synthesis Two reviewers assessed titles/abstracts, full-text articles, and study quality, and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures Directly measured reports of child abuse or neglect (reports to Child Protective Services or removal of the child from the home); proxy measures of abuse or neglect (injury, visits to the emergency department, hospitalization); behavioral, developmental, emotional, mental, or physical health and well-being; mortality; harms. Results Twenty-five trials (N = 14 355 participants) were included; 23 included home visits. Evidence from 11 studies (5311 participants) indicated no differences in likelihood of reports to Child Protective Services within 1 year of intervention completion (pooled odds ratio, 1.03 [95% CI, 0.84-1.27]). Five studies (3336 participants) found no differences in removal of the child from the home within 1 to 3 years of follow-up (pooled risk ratio, 1.06 [95% CI, 0.37-2.99]). The evidence suggested no benefit for emergency department visits in the short term (&amp;amp;lt;2 years) and hospitalizations. The evidence was inconclusive for all other outcomes because of the limited number of trials on each outcome and imprecise results. Among 2 trials reporting harms, neither reported statistically significant differences. Contextual evidence indicated (1) widely varying practices when screening, identifying, and reporting child maltreatment to Child Protective Services, including variations by race or ethnicity; (2) widely varying accuracy of screening instruments; and (3) evidence that child maltreatment interventions may be associated with improvements in some social determinants of health. Conclusion and Relevance The evidence base on interventions feasible in or referable from primary care settings to prevent child maltreatment suggested no benefit or insufficient evidence for direct or proxy measures of child maltreatment. Little information was available about possible harms. Contextual evidence pointed to the potential for bias or inaccuracy in screening, identification, and reporting of child maltreatment but also highlighted the importance of addressing social determinants when intervening to prevent child maltreatment.
Primary Care Interventions to Prevent Child Maltreatment
Authors: Michael J. Barry, Wanda K. Nicholson, Michael Silverstein, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Carlos Roberto Jaén, M. (Tonette) Krousel-Wood, Sei Lee, Li Li, Goutham Rao, John M. Ruiz, James J. Stevermer, Joel Tsevat, Sandra Millon Underwood, Sarah Wiehe
Journal: JAMA (2024)

Child maltreatment, which includes child abuse and neglect, can have profound effects on health, development, survival, and well-being throughout childhood and adulthood. The prevalence of child maltreatment in the US is uncertain and likely underestimated. In 2021, an estimated 600 000 children were identified by Child Protective Services as experiencing abuse or neglect and an estimated 1820 children died of abuse and neglect. The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate benefits and harms of primary care-feasible or referable behavioral counseling interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of maltreatment. Children and adolescents younger than 18 years who do not have signs or symptoms of or known exposure to maltreatment. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of primary care interventions to prevent child maltreatment in children and adolescents younger than 18 years without signs or symptoms of or known exposure to maltreatment. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care interventions to prevent child maltreatment. (I statement).
Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients With Exsanguinating Hemorrhage
Authors: Boris Kessel, Horer Tal, Adenauer Marinho de Oliveira Góes
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
Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients With Exsanguinating Hemorrhage
Authors: Constantinos Tingerides, Paul Walker
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
Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients With Exsanguinating Hemorrhage—Reply
Authors: Jan O. Jansen, Graeme S. MacLennan, Marion K. Campbell
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
Serum S100B Level in the Management of Pediatric Minor Head Trauma
Authors: Damien Bouvier, Aymeric Cantais, Alban Laspougeas, Fleur Lorton, Yannick Plenier, Maria Cottier, Philippe Fournier, Antoine Tran, Emilie Moreau, Julie Durif, Catherine Sarret, Charline Mourgues, Franck Sturtz, Jean-Baptiste Oudart, Juliette Raffort, Philippe Gonzalo, Jean-Paul Cristol, Damien Masson, Bruno Pereira, Vincent Sapin
Journal: JAMA Network Open (2024)

Importance Minor head trauma (HT) is one of the most common causes of hospitalization in children. A diagnostic test could prevent unnecessary hospitalizations and cranial computed tomographic (CCT) scans. Objective To evaluate the effectiveness of serum S100B values in reducing exposure to CCT scans and in-hospital observation in children with minor HT. Design, Setting, and Participants This multicenter, unblinded, prospective, interventional randomized clinical trial used a stepped-wedge cluster design to compare S100B biomonitoring and control groups at 11 centers in France. Participants included children and adolescents 16 years or younger (hereinafter referred to as children) admitted to the emergency department with minor HT. The enrollment period was November 1, 2016, to October 31, 2021, with a follow-up period of 1 month for each patient. Data were analyzed from March 7 to May 29, 2023, based on the modified intention-to-treat and per protocol populations. Interventions Children in the control group had CCT scans or were hospitalized according to current recommendations. In the S100B biomonitoring group, blood sampling took place within 3 hours after minor HT, and management depended on serum S100B protein levels. If the S100B level was within the reference range according to age, the children were discharged from the emergency department. Otherwise, children were treated as in the control group. Main Outcomes and Measures Proportion of CCT scans performed (absence or presence of CCT scan for each patient) in the 48 hours following minor HT. Results A total of 2078 children were included: 926 in the control group and 1152 in the S100B biomonitoring group (1235 [59.4%] boys; median age, 3.2 [IQR, 1.0-8.5] years). Cranial CT scans were performed in 299 children (32.3%) in the control group and 112 (9.7%) in the S100B biomonitoring group. This difference of 23% (95% CI, 19%-26%) was not statistically significant ( P = .44) due to an intraclass correlation coefficient of 0.32. A statistically significant 50% reduction in hospitalizations (95% CI, 47%-53%) was observed in the S100B biomonitoring group (479 [41.6%] vs 849 [91.7%]; P &amp;amp;lt; .001). Conclusions and Relevance In this randomized clinical trial of effectiveness of the serum S100B level in the management of pediatric minor HT, S100B biomonitoring yielded a reduction in the number of CCT scans and in-hospital observation when measured in accordance with the conditions defined by a clinical decision algorithm. Trial Registration ClinicalTrials.gov Identifier: NCT02819778
Resuscitative Endovascular Balloon Occlusion of the Aorta in Patients With Exsanguinating Hemorrhage
Authors: Brian Chin, Heli Patel, Adel Elkbuli
Journal: JAMA (2024)

To the Editor We would like to highlight some concerns surrounding the study design and findings of the UK-REBOA randomized clinical trial1 that evaluated the effectiveness of REBOA and standard care compared with standard care alone.
A Decision Aid to Support Tubal Sterilization Decision-Making Among Pregnant Women
Authors: Sonya Borrero, Elizabeth A. Mosley, Michaella Wu, Christine Dehlendorf, Catherine Wright, Kaleab Z. Abebe, Nikki Zite
Journal: JAMA Network Open (2024)

Importance Tubal sterilization is common, especially among individuals with low income. There is substantial misunderstanding about sterilization among those who have undergone the procedure, suggesting suboptimal decision-making about a method that permanently ends reproductive capacity. Objective To test the efficacy of a web-based decision aid for improving tubal sterilization decision quality. Design, Setting, and Participants This randomized clinical trial conducted between March 2020 and November 2023 included English- or Spanish-speaking pregnant cisgender women aged 21 to 45 years who had Medicaid insurance and were contemplating tubal sterilization after delivery. Participants were recruited from outpatient obstetric clinics in 3 US cities. Intervention Participants were randomized 1:1 to usual care (control arm) or to usual care plus a web-based decision aid (MyDecision/MiDecisión) (intervention arm). The aid includes written, audio, and video information about tubal sterilization procedures; an interactive table comparing contraceptive options; values-clarifying exercises; knowledge checks; and a summary report. Main Outcomes and Measures The co–primary outcomes were tubal sterilization knowledge and decisional conflict regarding the contraceptive decision. Knowledge was measured as the percentage of correct responses to 10 true-false items. Decisional conflict was measured using the low-literacy Decision Conflict Scale, with lower scores on a range from 0 to 100 indicating less conflict. Results Among the 350 participants, mean (SD) age was 29.7 (5.1) years. Compared with the usual care group, participants randomized to the decision aid had significantly higher tubal sterilization knowledge (mean [SD] proportion of questions answered correctly, 76.5% [16.9%] vs 55.6% [22.6%]; P &amp;amp;lt; .001) and lower decisional conflict scores (mean [SD], 12.7 [16.6] vs 18.7 [20.8] points; P = .002). The greatest knowledge differences between the 2 groups were for items about permanence, with more participants in the intervention arm answering correctly that tubal sterilization is not easily reversible (90.1% vs 39.3%; odds ratio [OR], 14.2 [95% CI, 7.9-25.4]; P &amp;amp;lt; .001) and that the tubes do not spontaneously “come untied” (86.6% vs 33.7%; OR, 13.0 [95% CI, 7.6-22.4]; P &amp;amp;lt; .001). Conclusions and Relevance MyDecision/MiDecisión significantly improved tubal sterilization decision-making quality compared with usual care only. This scalable decision aid can be implemented into clinical practice to supplement practitioner counseling. These results are particularly important given the recent increase in demand for permanent contraception after the US Supreme Court decision overturning federal abortion protections. Trial Registration ClinicalTrials.gov Identifier: NCT04097717
<i>JAMA</i><i> Network Open</i>—The Year in Review, 2023
Authors: Stephan D. Fihn, Frederick P. Rivara
Journal: JAMA Network Open (2024)

With its advent in 2018, the publishers and editors of JAMA Network Open confronted the risky proposition as to whether a high-volume, open access journal could be successful while maintaining the same standards as the most highly respected medical journals.Now, 6 years on, the answer is clear.Submissions to the journal have grown steadily, reaching nearly 15 000 in 2023, 14% more than in 2022.The reach of the journal has become global.Two-thirds of submissions originate from 82 countries outside the United States, particularly China,
Prevalence and Risk Factors of Depression and Posttraumatic Stress Disorder After a Mass Shooting
Authors: Mohammed Abba-Aji, Angela Moreland, Salma M. Abdalla, Caitlin Rancher, Sandro Galea, Faraday Davies, Dean G. Kilpatrick
Journal: JAMA Network Open (2024)

This cross-sectional study examines the self-reported mental health outcomes of adults 4 years after witnessing and surviving the shooting at the Route 91 Harvest Music Festival in Las Vegas, Nevada.