tbuckley/cabot-search huggingface dataset:
A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclinical models
Authors: Nikole L. Warner, Jacob Archer, Stephanie Park, Garima Singh, Kathryn M. McFadden, Taishi Kimura, Katrina Nicholes, Adrian Simpson, Jason T. Kaelber, David W. Hawman, Heinz Feldmann, Amit P. Khandhar, Peter Berglund, Matthew R. Vogt, Jesse H. Erasmus
Journal: Science Translational Medicine (2024)

The recent emergence and rapid response to severe acute respiratory syndrome coronavirus 2 was enabled by prototype pathogen and vaccine platform approaches, driven by the preemptive application of RNA vaccine technology to the related Middle East respiratory syndrome coronavirus. Recently, the National Institutes of Allergy and Infectious Diseases identified nine virus families of concern, eight enveloped virus families and one nonenveloped virus family, for which vaccine generation is a priority. Although RNA vaccines have been described for a variety of enveloped viruses, a roadmap for their use against nonenveloped viruses is lacking. Enterovirus D68 was recently designated a prototype pathogen within the family Picornaviridae of nonenveloped viruses because of its rapid evolution and respiratory route of transmission, coupled with a lack of diverse anti-enterovirus vaccine approaches in development. Here, we describe a proof-of-concept approach using a clinical stage RNA vaccine platform that induced robust enterovirus D68–neutralizing antibody responses in mice and nonhuman primates and prevented upper and lower respiratory tract infections and neurological disease in mice. In addition, we used our platform to rapidly characterize the antigenic diversity within the six genotypes of enterovirus D68, providing the necessary data to inform multivalent vaccine compositions that can elicit optimal breadth of neutralizing responses. These results demonstrate that RNA vaccines can be used as tools in our pandemic-preparedness toolbox for nonenveloped viruses.
Semisynthetic guanidino lipoglycopeptides with potent in vitro and in vivo antibacterial activity
Authors: Emma van Groesen, Elma Mons, Ioli Kotsogianni, Melina Arts, Kamaleddin H. M. E. Tehrani, Nicola Wade, Vladyslav Lysenko, Floor M. Stel, Jordy T. Zwerus, Stefania De Benedetti, Alexander Bakker, Parichita Chakraborty, Mario van der Stelt, Dirk-Jan Scheffers, Jairo Gooskens, Wiep Klaas Smits, Kirsty Holden, Peter S. Gilmour, Joost Willemse, Christopher A. Hitchcock, J. G. Coen van Hasselt, Tanja Schneider, Nathaniel I. Martin
Journal: Science Translational Medicine (2024)

Gram-positive bacterial infections present a major clinical challenge, with methicillin- and vancomycin-resistant strains continuing to be a cause for concern. In recent years, semisynthetic vancomycin derivatives have been developed to overcome this problem as exemplified by the clinically used telavancin, which exhibits increased antibacterial potency but has also raised toxicity concerns. Thus, glycopeptide antibiotics with enhanced antibacterial activities and improved safety profiles are still necessary. We describe the development of a class of highly potent semisynthetic glycopeptide antibiotics, the guanidino lipoglycopeptides, which contain a positively charged guanidino moiety bearing a variable lipid group. These glycopeptides exhibited enhanced in vitro activity against a panel of Gram-positive bacteria including clinically relevant methicillin-resistant
In vivo Bruton’s tyrosine kinase inhibition attenuates alcohol-associated liver disease by regulating CD84-mediated granulopoiesis
Authors: Prashanth Thevkar Nagesh, Yeonhee Cho, Yuan Zhuang, Mrigya Babuta, Marti Ortega-Ribera, Radhika Joshi, Veronika Brezani, Arman Patel, Aditi Ashish Datta, Viliam Brezani, Yun-Cheng Hsieh, Adriana Ramos, Jeeval Mehta, Christopher Copeland, Eleni Kanata, Zhenghui Gordon Jiang, Ioannis Vlachos, John Asara, Gyongyi Szabo, Ramon Bataller, Craig J. McClain, Arun Sanya, Mack C. Mitchell, Srinivasan Dasarathy, Vijay H. Shah, Naga Chalasani, Samer Gawrieh, Wanzhu Tu, Bruce Barton
Journal: Science Translational Medicine (2024)

Severe alcohol-associated hepatitis (AH) is a life-threatening form of alcohol-associated liver disease. Liver neutrophil infiltration is a hallmark of AH, yet the effects of alcohol on neutrophil functions remain elusive. Identifying therapeutic targets to reduce neutrophil-mediated liver damage is essential. Bruton’s tyrosine kinase (BTK) plays an important role in neutrophil development and function; however, the role of BTK in AH is unknown. Using RNA sequencing of circulating neutrophils, we found an increase in Btk expression ( P = 0.05) and phosphorylated BTK (pBTK) in patients with AH compared with healthy controls. In vitro, physiologically relevant doses of alcohol resulted in a rapid, TLR4-mediated induction of pBTK in neutrophils. In a preclinical model of AH, administration of a small-molecule BTK inhibitor (evobrutinib) or myeloid-specific Btk knockout decreased proinflammatory cytokines and attenuated neutrophil-mediated liver damage. We found that pBTK was essential for alcohol-induced bone marrow granulopoiesis and liver neutrophil infiltration. In vivo, BTK inhibition or myeloid-specific Btk knockout reduced granulopoiesis, circulating neutrophils, liver neutrophil infiltration, and liver damage in a mouse model of AH. Mechanistically, using liquid chromatography–tandem mass spectrometry, we identified CD84 as a kinase target of BTK, which is involved in granulopoiesis. In vitro, CD84 promoted alcohol-induced interleukin-1β and tumor necrosis factor–α in primary human neutrophils, which was inhibited by CD84-blocking antibody treatment. Our findings define the role of BTK and CD84 in regulating neutrophil inflammation and granulopoiesis, with potential therapeutic implications in AH.
Engineered exosomes with a photoinducible protein delivery system enable CRISPR-Cas–based epigenome editing in Alzheimer’s disease
Authors: Jihoon Han, Jae Hoon Sul, Jeongmi Lee, Eunae Kim, Hark Kyun Kim, Minshik Chae, Jeein Lim, Jongho Kim, Chanhee Kim, Jun-Sik Kim, Yoonsuk Cho, Jae Hyung Park, Yong Woo Cho, Dong-Gyu Jo
Journal: Science Translational Medicine (2024)

Effective intracellular delivery of therapeutic proteins can potentially treat a wide array of diseases. However, efficient delivery of functional proteins across the cell membrane remains challenging. Exosomes are nanosized vesicles naturally secreted by various types of cells and may serve as promising nanocarriers for therapeutic biomolecules. Here, we engineered exosomes equipped with a photoinducible cargo protein release system, termed mMaple3-mediated protein loading into and release from exosome (MAPLEX), in which cargo proteins can be loaded into the exosomes by fusing them with photocleavable protein (mMaple3)–conjugated exosomal membrane markers and subsequently released from the exosomal membrane by inducing photocleavage with blue light illumination. Using this system, we first induced transcriptional regulation by delivering octamer-binding transcription factor 4 and SRY-box transcription factor 2 to fibroblasts in vitro. Second, we induced in vivo gene recombination in Cre reporter mice by delivering Cre recombinase. Last, we achieved targeted epigenome editing in the brains of 5xFAD and 3xTg-AD mice, two models of Alzheimer’s disease. Administration of MAPLEXs loaded with β-site amyloid precursor protein cleaving enzyme 1 ( Bace1 )–targeting single guide RNA–incorporated dCas9 ribonucleoprotein complexes, coupled with the catalytic domain of DNA methyltransferase 3A, resulted in successful methylation of the targeted CpG sites within the Bace1 promoter. This approach led to a significant reduction in Bace1 expression, improved recognition memory impairment, and reduced amyloid pathology in 5xFAD and 3xTg-AD mice. These results suggest that MAPLEX is an efficient intracellular protein delivery system that can deliver diverse therapeutic proteins for multiple diseases.
Hepatic arterial infusion chemotherapy plus targeted therapy and immunotherapy versus systemic chemotherapy for advanced intrahepatic cholangiocarcinoma: a retrospective cohort study
Authors: Zhikai Zheng, Jiongliang Wang, Tianqing Wu, Minrui He, Yangxun Pan, Juncheng Wang, Jinbin Chen, Dandan Hu, Li Xu, Yaojun Zhang, Minshan Chen, Zhongguo Zhou
Journal: International Journal of Surgery (2024)

Background: To improve the prognosis of advanced intrahepatic cholangiocarcinoma (iCCA), we retrospectively compared the effect and safety of combined hepatic arterial infusion chemotherapy (HAIC), targeted therapy and immunotherapy with systemic chemotherapy (SC) in unresectable iCCA patients. Methods: We retrospectively enrolled 202 advanced iCCA patients treated with SC or targeted therapy, immunotherapy, and FOLFOX-HAIC combined between March 2015 and June 2023 at our institution. 202 patients were divided into two groups based on the therapeutic regimens. Baseline characteristics and prognosis were reviewed and analyzed. Results: After 1-to-1 propensity score matching, 76 patients were included in each group. The triple combination therapy group demonstrated longer median overall survival (OS, 20.77 vs. 14.83 months, P =0.047), progression-free survival (PFS, 9.07 vs. 6.23 mo, P &lt;0.001), intrahepatic PFS (11.03 vs. 6.73 mo, P &lt;0.001), extrahepatic PFS (11.37 vs. 7.13 months, P =0.0064), and a higher objective response rate (35.5% vs. 14.5%, P =0.003) than the SC group. Fever, thrombocytopenia, elevated ALT, elevated AST, hypoalbuminemia, and hyperbilirubinemia were more common adverse events (AEs) in the triple combination therapy group, while fatigue and anemia were more prevalent in the SC group ( P &lt;0.05). For grades 3-4 AEs, the rates of elevated ALT were higher in the triple combination group ( P =0.028). Conclusions: Compared with SC, triple combination therapy comprising HAIC, targeted therapy and immunotherapy appears to be an effective and safe treatment for advanced iCCA.
A machine learning model utilizing delphian lymph node characteristics to predict contralateral central lymph node metastasis in papillary thyroid carcinoma: A prospective multicenter study
Authors: Jia-ling He, Yu-zhao Yan, Yan Zhang, Jin-sui Li, Fei Wang, Yi You, Wei Liu, Ying Hu, Ming-Hao Wang, Qing-wen Pan, Yan Liang, Ming-shijing Ren, Zi-wei Wu, Kai You, Yi Zhang, Jun Jiang, Peng Tang
Journal: International Journal of Surgery (2024)

Background: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. Methods: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. Results: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. Conclusions: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.
E-Cigarette Use in Adolescents and Adults—A <i>JAMA</i> Collection
Authors: Tracy A. Lieu, Kirsten Bibbins-Domingo
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
Associations of High BMI and Excessive Gestational Weight Gain With Pregnancy Outcomes in Women With Type 1 Diabetes: A Systematic Review and Meta-analysis
Authors: Nooria Atta, Anuli Ezeoke, Clive J. Petry, Laura C. Kusinski, Claire L. Meek
Journal: Diabetes Care (2024)

The increased risk of pregnancy complications in type 1 diabetes is mainly attributed to maternal hyperglycemia. However, it is unclear whether other potentially modifiable factors also contribute to risk in this population.
Use of Financial Incentives to Promote Adolescent Type 1 Diabetes Self-management: A Pilot Randomized Controlled Trial
Authors: Faisal S. Malik, Tom Chen, Maria Manzueta, Joyce P. Yi-Frazier, Catherine Pihoker, Jessica L. LeBlanc, Seema K. Shah, Davene R. Wright
Journal: Diabetes Care (2024)

To evaluate whether financial incentives lead to improvement in self-management behaviors and glycemia in adolescents with type 1 diabetes (T1D).
Abstract P263: Biomarkers of Dairy Fatty Acids and Incidence of Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Marcia C de Oliveira Otto, Jennifer A Nettleton, Rozenn N Lemaitre, Lyn Steffen Steffen, Daan Kromhout, Stephen S Rich, Michael Y Tsai, David R Jacobs, Jr., Dariush Mozaffarian
Journal: Circulation (2013)

Background: Evidence on the role of dairy fat intake in cardiovascular health has been mixed and inconclusive. Most prior large studies have used self-reported measures of dietary intake and focused on relatively racially homogeneous populations. Circulating biomarkers of dairy fat in a multi-ethnic cohort provide objective measures of dairy fat intake and facilitate conclusions relevant to populations with different diets and susceptibility to CVD. Aims: To evaluate plasma phospholipid fatty acids 15:0, trans-16:1n-7 and 14:0 as objective markers of dairy fat and prospectively assess their associations with incident CVD and CHD in the Multi-Ethnic Study of Atherosclerosis (MESA). We hypothesized that circulating biomarkers of dairy fat would be inversely associated with CVD risk. Methods: We evaluated 2,837 U.S. adults 45-84 years of age at baseline (2000-2002), evenly distributed across four race-ethnic groups (Caucasians, Hispanics, African and Chinese Americans), in whom plasma phospholipid fatty acid levels were measured using validated gas-chromatography. Adjudicated CVD (MI, resuscitated cardiac arrest, definite and probable angina, stroke, and CVD death; n=189) and CHD (MI, resuscitated cardiac arrest, CHD death; n=141) were identified through 2010 during cohort examinations and follow-up calls. We also evaluated the influence of potential mediators of the associations of interest including BMI, diabetes, hypertension, HDL-C and LDL-C. Results: Self-reported intakes of whole-fat dairy and butter had the strongest association with 15:0. Self-reported dairy fat intake was more weakly associated with 14:0 and trans 16:1n7. In multivariate models including demographics, lifestyle and dietary habits (e.g. intakes of red meat, fiber, fruits, vegetables), each SD-unit of 15:0 was associated with a 19% lower CVD risk (HR and 95% CI: 0.81 [0.68,0.98]) and a 26% lower CHD risk (HR and 95% CI: 0.74 [0.60,0.92]). Associations were strengthened after mutual adjustment for 14:0 and trans16:1n-7. Results were similar after adjustment for potential mediators. Plasma phospholipid 14:0 and trans16:1n-7 were not significantly associated with incident CVD or CHD in MESA. Results were similar across the 4 race-ethnicities. Conclusion: Plasma phospholipid 15:0, a biomarker of dairy fat, was inversely associated with incident CVD and CHD. Our data support the need for further investigation of CVD effects of dairy fat, dairy-specific fatty acids, and dairy products in general.
Bioinspired multifunctional cellulose film: In situ bacterial capturing and killing for managing infected wounds
Authors: Chengcheng Li, Ya-Xuan Zhu, Ying Yang, Wanting Miao, Xiaotong Shi, Ke-Fei Xu, Zi-Heng Li, Huining Xiao, Fu-Gen Wu
Journal: Bioactive Materials (2024)

Bacterial infection of cutaneous wounds can easily lead to occurrence of chronic wounds and even more serious diseases. Therefore, multifunctional, biodegradable, and reusable wound dressings that can quickly manage wound infection and promote wound healing are urgently desired. Herein, inspired by the "capturing and killing" action of
Dissecting Out a Rare Mutation, STAT: Features of <i>STAT3</i>-Mutant Myeloid Neoplasms
Authors: Michael J. Hochman, David A. Frank
Journal: Clinical Cancer Research (2024)

The transcription factor STAT3 drives the expression of genes promoting cellular proliferation, survival, and pluripotency. The description of STAT3 mutations and their clinical correlates in myeloid neoplasms, such as acute myeloid leukemia and myelodysplastic syndromes, raises new insights into both the pathogenesis and the targeted therapy of these diseases. See related article by Ye et al., p. 4681.
Intraoperative Oxygen Treatment, Oxidative Stress, and Organ Injury Following Cardiac Surgery
Authors: Marcos G. Lopez, Matthew S. Shotwell, Cassandra Hennessy, Mias Pretorius, David R. McIlroy, Melissa J. Kimlinger, Eric H. Mace, Tarek Absi, Ashish S. Shah, Nancy J. Brown, Frederic T. Billings, Robert Deegan, Susan S. Eagle, Antonio Hernandez, Brian J. Gelfand, Miklos D. Kertai, Meredith Kingeter, Ryan LeFevre, Frederic W. Lombard, Michael F. Mantinan, Kelly K. Mishra, Andrew D. Shaw, Kara K. Siegrist, Ban Sileshi, Robert E. Freundlich, Jonathan P. Wanderer
Journal: JAMA Surgery (2024)

Liberal oxygen (hyperoxia) is commonly administered to patients during surgery, and oxygenation is known to impact mechanisms of perioperative organ injury.
Surgeon Type and Anastomotic Leaks in Ovarian Cancer
Authors: Alexandra C. Istl, Nerlyne Desravines, Ugwuji N. Maduekwe
Journal: JAMA Surgery (2024)

For patients with advanced ovarian cancer, cytoreductive surgery (CRS) and platinum-based chemotherapy are pillars of treatment.1 Optimal completeness of cytoreduction, which may necessitate multivisceral resections, aims to achieve minimal residual disease and improve oncologic outcomes.2,3
Neonatal Mortality Disparities by Gestational Age in European Countries
Authors: Victor Sartorius, Marianne Philibert, Kari Klungsoyr, Jeannette Klimont, Katarzyna Szamotulska, Zeljka Drausnik, Petr Velebil, Laust Mortensen, Mika Gissler, Jeanne Fresson, Jan Nijhuis, Wei-Hong Zhang, Karin Källén, Tonia A. Rihs, Vlad Tica, Ruth Matthews, Lucy Smith, Jennifer Zeitlin, Alex Farr, Sophie Alexander, Judith Racapé, Gisèle Vandervelpen, Vasos Coutellas, Theopisti Kyprianou, Jitka Jirova, Luule Sakkeus, Liili Abuladze, Béatrice Blondel, Annick Vilain, Mélanie Durox, Guenther Heller, István Sziller, Johanna Gunnarsdóttir, Helga Sól Ólafsdóttir, Izabela Sikora, Sinead O'Hara, Karen Kearns, Marina Cuttini, Marzia Loghi, Rosaria Boldrini, Marilena Pappagal, Stefano Marchetti, Serena Donati, Janis Misins, Irisa Zile-Velika, Jelena Isakova, Aline Lecomte, Jessica Pastore, Daniel Álvarez, Miriam Gatt, PW Achterberg, Lisa Broeders, Rupali Akerkar, Hilde Engjom, Ewa Mierzejewska, Henrique Barros, Lucian Puscasiu, Mihaela-Alexandra Budianu, Alexandra Cucu, Vlad Tica, Miha Lučovnik, Ivan Verdenik, Maria Fernandez Elorriaga, Oscar Zurriaga, Adela Recio Alcaide, Anastasia Nyman, Alison Macfarlane, Sonya Scott, Kirsten Monteath, Siobhan Morgan, Craig Thomas, Sinead Magill, Greg Ceely
Journal: JAMA Network Open (2024)

There are wide disparities in neonatal mortality rates (NMRs, deaths <28 days of life after live birth per 1000 live births) between countries in Europe, indicating potential for improvement. Comparing country-specific patterns of births and deaths with countries with low mortality rates can facilitate the development of effective intervention strategies.
Rethinking Anticoagulation for Left Atrial Appendage Closure
Authors: Vinay Guduguntla, Kristen K. Patton
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal