tbuckley/cabot-search huggingface dataset:
Mesothelin-specific CAR-T cell therapy that incorporates an HLA-gated safety mechanism selectively kills tumor cells
Authors: Talar Tokatlian, Grace E Asuelime, Jee-Young Mock, Breanna DiAndreth, Shruti Sharma, Dora Toledo Warshaviak, Mark E Daris, Kristian Bolanos, Breanna L Luna, Martin S Naradikian, Kiran Deshmukh, Agnes E Hamburger, Alexander Kamb
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Mesothelin (MSLN) is a classic tumor-associated antigen that is expressed in lung cancer and many other solid tumors. However, MSLN is also expressed in normal mesothelium which creates a significant risk of serious inflammation for MSLN-directed therapeutics. We have developed a dual-receptor (Tmod™) system that exploits the difference between tumor and normal tissue in a subset of patients with defined heterozygous gene loss (LOH) in their tumors. Methods T cells engineered with the MSLN CAR Tmod construct described here contain (1) a novel MSLN-activated CAR and (2) an HLA-A*02-gated inhibitory receptor (blocker). A*02 binding is intended to override T-cell cytotoxicity, even in the presence of MSLN. The Tmod system is designed to treat heterozygous HLA class I patients, selected for HLA LOH. When A*02 is absent from tumors selected for LOH, the MSLN Tmod cells are predicted to mediate potent killing of the MSLN(+)A*02(−) malignant cells. Results The sensitivity of the MSLN Tmod cells is comparable with a benchmark MSLN CAR-T that was active but toxic in the clinic. Unlike MSLN CAR-T cells, the Tmod system robustly protects surrogate “normal” cells even in mixed-cell populations in vitro and in a xenograft model. The MSLN CAR can also be paired with other HLA class I blockers, supporting extension of the approach to patients beyond A*02 heterozygotes. Conclusions The Tmod mechanism exemplified by the MSLN CAR Tmod construct provides an alternative route to leverage solid-tumor antigens such as MSLN in safer, more effective ways than previously possible.
Spatio-temporal directed acyclic graph learning with attention mechanisms on brain functional time series and connectivity
Authors: Shih-Gu Huang, Jing Xia, Liyuan Xu, Anqi Qiu
Journal: Medical Image Analysis (2022)

We develop a deep learning framework, spatio-temporal directed acyclic graph with attention mechanisms (ST-DAG-Att), to predict cognition and disease using functional magnetic resonance imaging (fMRI). This ST-DAG-Att framework comprises of two neural networks, (1) spatio-temporal graph convolutional network (ST-graph-conv) to learn the spatial and temporal information of functional time series at multiple temporal and spatial graph scales, where the graph is represented by the brain functional network, the spatial convolution is over the space of this graph, and the temporal convolution is over the time dimension; (2) functional connectivity convolutional network (FC-conv) to learn functional connectivity features, where the functional connectivity is derived from embedded multi-scale fMRI time series and the convolutional operation is applied along both edge and node dimensions of the brain functional network. This framework also consists of an attention component, i.e., functional connectivity-based spatial attention (FC-SAtt), that generates a spatial attention map through learning the local dependency among high-level features of functional connectivity and emphasizing meaningful brain regions. Moreover, both the ST-graph-conv and FC-conv networks are designed as feed-forward models structured as directed acyclic graphs (DAGs). Our experiments employ two large-scale datasets, Adolescent Brain Cognitive Development (ABCD, n=7693) and Open Access Series of Imaging Study-3 (OASIS-3, n=1786). Our results show that the ST-DAG-Att model is generalizable from cognition prediction to age prediction. It is robust to independent samples obtained from different sites of the ABCD study. It outperforms the existing machine learning techniques, including support vector regression (SVR), elastic net's mixture with random forest, spatio-temporal graph convolution, and BrainNetCNN.
The Steroid Therapy and Outcome of Parapneumonic Pleural Effusions (STOPPE): A Pilot Randomized Trial
Authors: Deirdre B. Fitzgerald, Grant W. Waterer, Charley Budgeon, Ranjan Shrestha, Edward T. Fysh, Sanjeevan Muruganandan, Christopher Stanley, Tajalli Saghaie, Arash Badiei, Calvin Sidhu, Hilman Harryanto, Victor Duong, Maree Azzopardi, David Manners, Norris S. H. Lan, Natalia D. Popowicz, Carolyn J. Peddle-McIntyre, Najib M. Rahman, Catherine A. Read, Ai Ling Tan, Seng Khee Gan, Kevin Murray, Y. C. Gary Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Pleural effusion commonly complicates community-acquired pneumonia and is associated with intense pleural inflammation. Whether antiinflammatory treatment with corticosteroids improves outcomes is unknown. Objectives: To assess the effects of corticosteroids in an adult population with pneumonia-related pleural effusion. Methods: The STOPPE (Steroid Therapy and Outcome of Parapneumonic Pleural Effusions) trial was a pilot, multicenter, double-blinded, placebo-controlled, randomized trial involving six Australian centers. Patients with community-acquired pneumonia and pleural effusion were randomized (2:1) to intravenous dexamethasone (4 mg twice daily for 48 h) or placebo and followed for 30 days. Given the diverse effects of corticosteroids, a comprehensive range of clinical, serological, and imaging outcomes were assessed in this pilot trial (ACTRN12618000947202). Measurements and Main Results: Eighty patients were randomized (one withdrawn before treatment) and received dexamethasone (n = 51) or placebo (n = 28). This pilot trial found no preliminary evidence of benefits of dexamethasone in improving time to sustained (>12 h) normalization of vital signs (temperature, oxygen saturations, blood pressure, heart, and respiratory rates): median, 41.0 (95% confidence interval, 32.3-54.5) versus 27.8 (15.4-49.5) hours in the placebo arm (hazard ratio, 0.729 [95% confidence interval, 0.453-1.173]; P = 0.193). Similarly, no differences in C-reactive protein or leukocyte counts were observed, except for a higher leukocyte count in the dexamethasone group at Day 3. Pleural drainage procedures were performed in 49.0% of dexamethasone-treated and 42.9% of placebo-treated patients (P = 0.60). Radiographic pleural opacification decreased over time with no consistent intergroup differences. Mean duration of antibiotic therapy (22.4 [SD, 15.4] vs. 20.4 [SD, 13.8] d) and median hospitalization (6.0 [interquartile range, 5.0-10.0] vs. 5.5 [interquartile range, 5.0-8.0] d) were similar between the dexamethasone and placebo groups. Serious adverse events occurred in 25.5% of dexamethasone-treated and 21.4% of placebo-treated patients. Transient hyperglycemia more commonly affected the dexamethasone group (15.6% vs. 7.1%). Conclusions: Systemic corticosteroids showed no preliminary benefits in adults with parapneumonic effusions. Clinical trial registered with www.anzctr.org.au (ACTRN12618000947202).
Effectiveness of Face Mask or Respirator Use in Indoor Public Settings for Prevention of SARS-CoV-2 Infection — California, February–December 2021
Authors: Kristin L. Andrejko, Jake M. Pry, Jennifer F. Myers, Nozomi Fukui, Jennifer L. DeGuzman, John Openshaw, James P. Watt, Joseph A. Lewnard, Seema Jain, Yasmine Abdulrahim, Camilla M. Barbaduomo, Miriam I. Bermejo, Julia Cheunkarndee, Adrian F. Cornejo, Savannah Corredor, Najla Dabbagh, Zheng N. Dong, Ashly Dyke, Anna T. Fang, Diana Felipe, Paulina M. Frost, Timothy Ho, Mahsa H. Javadi, Amandeep Kaur, Amanda Lam, Sophia S. Li, Monique Miller, Jessica Ni, Hyemin Park, Diana J. Poindexter, Helia Samani, Shrey Saretha, Maya Spencer, Michelle M. Spinosa, Vivian H. Tran, Nikolina Walas, Christine Wan, Erin Xavier
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

The use of face masks or respirators (N95/KN95) is recommended to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Well-fitting face masks and respirators effectively filter virus-sized particles in laboratory conditions (2,3), though few studies have assessed their real-world effectiveness in preventing acquisition of SARS-CoV-2 infection (4). A test-negative design case-control study enrolled randomly selected California residents who had received a test result for SARS-CoV-2 during February 18-December 1, 2021. Face mask or respirator use was assessed among 652 case-participants (residents who had received positive test results for SARS-CoV-2) and 1,176 matched control-participants (residents who had received negative test results for SARS-CoV-2) who self-reported being in indoor public settings during the 2 weeks preceding testing and who reported no known contact with anyone with confirmed or suspected SARS-CoV-2 infection during this time. Always using a face mask or respirator in indoor public settings was associated with lower adjusted odds of a positive test result compared with never wearing a face mask or respirator in these settings (adjusted odds ratio [aOR] = 0.44; 95% CI = 0.24-0.82). Among 534 participants who specified the type of face covering they typically used, wearing N95/KN95 respirators (aOR = 0.17; 95% CI = 0.05-0.64) or surgical masks (aOR = 0.34; 95% CI = 0.13-0.90) was associated with significantly lower adjusted odds of a positive test result compared with not wearing any face mask or respirator. These findings reinforce that in addition to being up to date with recommended COVID-19 vaccinations, consistently wearing a face mask or respirator in indoor public settings reduces the risk of acquiring SARS-CoV-2 infection. Using a respirator offers the highest level of personal protection against acquiring infection, although it is most important to wear a mask or respirator that is comfortable and can be used consistently.
Bioinspired porous microspheres for sustained hypoxic exosomes release and vascularized bone regeneration
Authors: Yike Gao, Zuoying Yuan, Xiaojing Yuan, Zhuo Wan, Yingjie Yu, Qi Zhan, Yuming Zhao, Jianmin Han, Jianyong Huang, Chunyang Xiong, Qing Cai
Journal: Bioactive Materials (2022)

Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated regenerative potential for cell-free bone tissue engineering, nevertheless, certain challenges, including the confined therapeutic potency of exosomes and ineffective delivery method, are still persisted. Here, we confirmed that hypoxic precondition could induce enhanced secretion of exosomes from stem cells from human exfoliated deciduous teeth (SHEDs) via comprehensive proteomics analysis, and the corresponding hypoxic exosomes (H-Exo) exhibited superior potential in promoting cellular angiogenesis and osteogenesis via the significant up-regulation in focal adhesion, VEGF signaling pathway, and thyroid hormone synthesis. Then, we developed a platform technology enabling the effective delivery of hypoxic exosomes with sustained release kinetics to irregular-shaped bone defects via injection. This platform is based on a simple adsorbing technique, where exosomes are adsorbed onto the surface of injectable porous poly(lactide-co-glycolide) (PLGA) microspheres with bioinspired polydopamine (PDA) coating (PMS-PDA microspheres). The PMS-PDA microspheres could effectively adsorb exosomes, show sustained release of H-Exo for 21 days with high bioactivity, and induce vascularized bone regeneration in 5-mm rat calvarial defect. These findings indicate that the hypoxic precondition and PMS-PDA porous microsphere-based exosome delivery are efficient in inducing tissue regeneration, hence facilitating the clinical translation of exosome-based therapy.
Phenotype-directed Therapy with Mepolizumab for Urban Children with Exacerbation-Prone Asthma
Authors: Daniel Jackson, Leonard Bacharier, Peter Gergen, Lisa Gagalis, Miguel Villarreal, Michelle Gill, Andrew Liu, Rebecca Gruchalla, Robin Cohen, Melanie Makhija, Gurjit Khurana Hershey, Michael Sherenian, Katherine Rivera-Spoljaric, Jeffrey Stokes, Edward Zoratti, Stephen Teach, Meyer Kattan, Cynthia Visness, Patrice Becker, James Gern, Christine Sorkness, William Busse, Matthew Altman
Journal: Journal of Allergy and Clinical Immunology (2022)
TCT-240: PLATINUM QCA: A Prospective, Multicenter Trial Assessing Clinical, Angiographic, and Intravascular Ultrasound Outcomes (9 Months) with the Novel Platinum-Chromium Thin-Strut PROMUS Element Everolimus-Eluting Stent in De Novo Coronary Stenoses
Journal: Journal of the American College of Cardiology (2010)
A call to action for translational sciences in COVID-19 and future pandemics
Authors: Kanny K. Wan, Danielle Davis, Taylor N. Lee, Stephanie L. Ford-Scheimer, Antonio L. Andreu, Florence Bietrix, Justin Bryans, Marco T. Castro, Nobuyoshi Chiba, Jessica M. Faupel-Badger, Brittany Haynes, Ryutaro Hirasawa, Carlos M. Morel, Thiago Moreno L. Souza, David Morrow, Trent Munro, Stuart Newman, Anton E. Ussi, Poliana B. Zorzal, Matthew D. Hall, Donald C. Lo, Christine M. Cutillo
Journal: Nature Reviews Drug Discovery (2022)
T Cell Responses to the Microbiota
Authors: Ivaylo I. Ivanov, Timur Tuganbaev, Ashwin N. Skelly, Kenya Honda
Journal: Annual Review of Immunology (2022)

The immune system employs recognition tools to communicate with its microbial evolutionary partner. Among all the methods of microbial perception, T cells enable the widest spectrum of microbial recognition resolution, ranging from the crudest detection of whole groups of microbes to the finest detection of specific antigens. The application of this recognition capability to the crucial task of combatting infections has been the focus of classical immunology. We now appreciate that the coevolution of the immune system and the microbiota has led to development of a lush immunological decision tree downstream of microbial recognition, of which an inflammatory response is but one branch. In this review we discuss known T cell-microbe interactions in the gut and place them in the context of an algorithmic framework of recognition, context-dependent interpretation, and response circuits across multiple levels of microbial recognition resolution. The malleability of T cells in response to the microbiota presents an opportunity to edit immune response cellularity, identity, and functionality by utilizing microbiota-controlled pathways to promote human health.
Thinking Differently about Cancer Treatment Regimens
Authors: Jeff Settleman, João M. Fernandes Neto, René Bernards
Journal: Cancer Discovery (2021)

Abstract Summary: Most experimental cancer drugs ultimately fail during the course of clinical development, contributing to the high cost of the few that are granted regulatory approval. Moreover, approved drugs often deliver only modest clinical benefit to patients with advanced disease due to the development of resistance. Here, we discuss opportunities we consider promising to overcome drug resistance associated with interactions between signaling pathways and the presence of multiple coexisting cell states within tumors with distinct vulnerabilities. We highlight how understanding drug-resistance mechanisms can enable innovative treatment regimens that deliver longer-lasting benefit to patients.
Targeting Huntingtin Expression in Patients with Huntington’s Disease
Authors: Sarah J. Tabrizi, Blair R. Leavitt, G. Bernhard Landwehrmeyer, Edward J. Wild, Carsten Saft, Roger A. Barker, Nick F. Blair, David Craufurd, Josef Priller, Hugh Rickards, Anne Rosser, Holly B. Kordasiewicz, Christian Czech, Eric E. Swayze, Daniel A. Norris, Tiffany Baumann, Irene Gerlach, Scott A. Schobel, Erika Paz, Anne V. Smith, C. Frank Bennett, Roger M. Lane
Journal: New England Journal of Medicine (2019)

Huntington's disease is an autosomal-dominant neurodegenerative disease caused by CAG trinucleotide repeat expansion in HTT, resulting in a mutant huntingtin protein. IONIS-HTTRx (hereafter, HTTRx) is an antisense oligonucleotide designed to inhibit HTT messenger RNA and thereby reduce concentrations of mutant huntingtin. We conducted a randomized, double-blind, multiple-ascending-dose, phase 1-2a trial involving adults with early Huntington's disease. Patients were randomly assigned in a 3:1 ratio to receive HTTRx or placebo as a bolus intrathecal administration every 4 weeks for four doses. Dose selection was guided by a preclinical model in mice and nonhuman primates that related dose level to reduction in the concentration of huntingtin. The primary end point was safety. The secondary end point was HTTRx pharmacokinetics in cerebrospinal fluid (CSF). Prespecified exploratory end points included the concentration of mutant huntingtin in CSF. Of the 46 patients who were enrolled in the trial, 34 were randomly assigned to receive HTTRx (at ascending dose levels of 10 to 120 mg) and 12 were randomly assigned to receive placebo. Each patient received all four doses and completed the trial. Adverse events, all of grade 1 or 2, were reported in 98% of the patients. No serious adverse events were seen in HTTRx-treated patients. There were no clinically relevant adverse changes in laboratory variables. Predose (trough) concentrations of HTTRx in CSF showed dose dependence up to doses of 60 mg. HTTRx treatment resulted in a dose-dependent reduction in the concentration of mutant huntingtin in CSF (mean percentage change from baseline, 10% in the placebo group and -20%, -25%, -28%, -42%, and -38% in the HTTRx 10-mg, 30-mg, 60-mg, 90-mg, and 120-mg dose groups, respectively). Intrathecal administration of HTTRx to patients with early Huntington's disease was not accompanied by serious adverse events. We observed dose-dependent reductions in concentrations of mutant huntingtin. (Funded by Ionis Pharmaceuticals and F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02519036.).
Evaluation of HIV-1 Immunogen, an Immunologic Modifier, Administered to Patients Infected With HIV Having 300 to 549 × 10
Authors: Jennifer Goldblatt, B Med, Sci Oliver, F James, David Jones
Journal: JAMA (2001)

3.9%]; P = .46vs controls).A significantly greater rate of decrease was seen in fatigued patients (4.0% per repeat [2.1%-10.7%];PϽ.005 vs nonfatigued patients, PϽ.005 vs controls).A significant correlation was seen between fatigue severity and rate of decrease in muscle grip strength (r=0.69,PϽ.001 in patients; FIGURE).No association was found between muscle fatigability and liver disease severity (data not shown).Comment.Patients with PBC who complained of fatigue showed a markedly accelerated decrease in muscle function on repeat activity compared with both control subjects and nonfatigued patients.Moreover, there was a strong correlation between the rate at which grip strength is lost and the severity of the fatigue experienced by the patient, suggesting that peripheral muscle fatigability may contribute to the symptom complex experienced by some patients.The etiology of this abnormality in repeat muscle function remains unclear and there appears to be no simple relationship with liver disease severity.We could not exclude a volitional component to the decrease in repeat muscle function, although the finding of normal initial grip strength in the fatigued patients would argue against this.Further studies of peripheral muscle and neuromuscular junction function in PBC-related fatigue are warranted.If a significant peripheral motor system contribution to fatigue in PBC is confirmed, this may suggest new modalities of treatment for this troubling symptom.
Effect of three-month antimicrobial treatment with clarithromycin in acute non-Q wave coronary syndrome
Authors: Juha P. Sinisalo, Kimmo J. Mattila, Ville Valtonen, Olli Anttonen, Jukka Juvonen, John Melin, Helena Vuorinen-Markkola, Markku S. Nieminen
Journal: Journal of the American College of Cardiology (2002)
The correlation between sleep quality and the severity of allergic rhinitis in Korea
Authors: Sung-Woo Cho, Doo Hee Han, Dae Hyun Lim, Youn Ho Sheen, Kyung Suk Lee, Sun Hee Choi, In Hwan Oh, Yeong-Ho Rha, Chae-Seo Rhee
Journal: Journal of Allergy and Clinical Immunology (2022)
Le métabolisme de l'azoté: La physiologie des substances protéiques. II. Dégradation, synthèse, métabolisme intermédiaire
Journal: JAMA (1941)

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 Publications 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 2023 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
Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer
Authors: Annika Fendler, Scott T C Shepherd, Lewis Au, Mary Wu, Ruth Harvey, Andreas M Schmitt, Zayd Tippu, Benjamin Shum, Sheima Farag, Aljosja Rogiers, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, Karla Lingard, Mary Mangwende, Lucy Holt, Hamid Ahmod, Justine Korteweg, Tara Foley, Taja Barber, Andrea Emslie-Henry, Niamh Caulfield-Lynch, Fiona Byrne, Daqi Deng, Svend Kjaer, Ok-Ryul Song, Christophe Queval, Caitlin Kavanagh, Emma C Wall, Edward J Carr, Simon Caidan, Mike Gavrielides, James I MacRae, Gavin Kelly, Kema Peat, Denise Kelly, Aida Murra, Kayleigh Kelly, Molly O'Flaherty, Robyn L Shea, Gail Gardner, Darren Murray, Nadia Yousaf, Shaman Jhanji, Kate Tatham, David Cunningham, Nicholas Van As, Kate Young, Andrew J S Furness, Lisa Pickering, Rupert Beale, Charles Swanton, Sonia Gandhi, Steve Gamblin, David L V Bauer, George Kassiotis, Michael Howell, Emma Nicholson, Susanna Walker, James Larkin, Samra Turajlic
Journal: The Lancet (2022)
SURGICAL PRACTICE ON THE LOWER ANIMALS.
Journal: JAMA (1905)

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 Publications 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 2023 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
DOCK2 regulates antifungal immunity by regulating RAC GTPase activity
Authors: Xiaojian Ma, Xi Tan, Bingbing Yu, Wanwei Sun, Heping Wang, Huijun Hu, Yanyun Du, Ruirui He, Ru Gao, Qianwen Peng, Zhihui Cui, Ting Pan, Xiong Feng, Junhan Wang, Chengqi Xu, Bin Zhu, Wei Liu, Chenhui Wang
Journal: Cellular and Molecular Immunology (2022)