tbuckley/cabot-search huggingface dataset:
Spatial profiling reveals association between WNT pathway activation and T-cell exclusion in acquired resistance of synovial sarcoma to NY-ESO-1 transgenic T-cell therapy
Authors: Katie M Campbell, Maneesha Thaker, Egmidio Medina, Anusha Kalbasi, Arun Singh, Antoni Ribas, Theodore Scott Nowicki
Journal: Journal for ImmunoTherapy of Cancer (2022)

Genetically engineered T-cell immunotherapies for adoptive cell transfer (ACT) have emerged as a promising form of cancer treatment, but many of these patients develop recurrent disease. Furthermore, delineating mechanisms of resistance may be challenging since the analysis of bulk tumor profiling can be complicated by spatial heterogeneity.
EFFECTS OF HABITUAL COFFEE CONSUMPTION ON INCIDENT CARDIOVASCULAR DISEASE, ARRHYTHMIA, AND MORTALITY: FINDINGS FROM UK BIOBANK
Authors: David Chieng, Rodrigo Canovas, Louise Segan, Hariharan Sugumar, Aleksandr Voskoboinik, Sandeep Prabhu, Liang-han Ling, Geoffrey Lee, Joseph B. Morton, David M. Kaye, Jonathan M. Kalman, Peter M. Kistler
Journal: Journal of the American College of Cardiology (2022)
Galacto-oligosaccharides as an anti-bacterial and anti-invasive agent in lung infections
Authors: Yang Cai, Jos P.M. van Putten, Myrthe S. Gilbert, Walter J.J. Gerrits, Gert Folkerts, Saskia Braber
Journal: Biomaterials (2022)

Emerging antimicrobial resistance in infections asks for novel intervention strategies. Galacto-oligosaccharides (GOS) might be attractive alternatives to antibiotics due to their anti-inflammatory and anti-adhesive properties. Mannheimia haemolytica is one of the major Pasteurellaceae associated with bovine lung infections. Using M. haemolytica, we demonstrated that GOS have the capacity to reduce bacterial viability and can be used as adjuvant to improve antibiotic efficacy. Using M. haemolytica-treated primary bronchial epithelial cells (PBECs) of calves, we identified the anti-adhesive and anti-invasive activities of GOS. The observed inhibition of cytokine/chemokine release and the prevention of airway epithelial barrier dysfunction in M. haemolytica-treated PBECs by GOS might be related to the downregulation of "toll-like receptor 4/nuclear factor-κB" pathway and the anti-invasive and anti-adhesive properties of GOS. Particularly, GOS lowered lipopolysaccharides- but not flagellin-induced cytokine/chemokine release in calf and human airway epithelial cells. Finally, we performed in vivo experiments in calves and demonstrated for the first time that intranasal application of GOS can relieve lung infections/inflammation and lower M. haemolytica positivity in the lungs without affecting clinical performance. These findings not only shed light on the anti-inflammatory mechanisms of GOS during lung infections, but GOS might also be a promising anti-bacterial agent for preventing (lung) infections.
Video-based physiologic monitoring: promising applications for the ICU and beyond
Authors: James A. Diao, Jayson S. Marwaha, Joseph C. Kvedar
Journal: npj Digital Medicine (2022)

The vital signs—temperature, heart rate, respiratory rate, and blood pressure—are indispensable in clinical decision-making. These metrics are widely used to identify physiologic decline and prompt investigation or intervention. Vital sign monitoring is particularly important in acute care settings, where patients are at higher risk and may require additional vigilance. Conventional contact-based devices, while widespread and generally reliable, can be inconvenient or disruptive to patients, families, and staff. Non-contact, video-based methods present a more flexible and information-dense alternative that may enable creative improvements to patient care. Still, these approaches are susceptible to several sources of bias and require rigorous clinical validation. A recent study by Jorge et al. demonstrates that video-based monitoring can reliably capture heart rate and respiratory rate and overcome many potential sources of bias in post-operative settings. This presents real-world evaluation of a practical, noninvasive, and continuous monitoring technology that had previously only been tested in controlled settings.
A Theoretical Framework for Human and Nonhuman Vocal Interaction
Authors: Gregg A. Castellucci, Frank H. Guenther, Michael A. Long
Journal: Annual Review of Neuroscience (2022)

Vocal communication is a critical feature of social interaction across species; however, the relation between such behavior in humans and nonhumans remains unclear. To enable comparative investigation of this topic, we review the literature pertinent to interactive language use and identify the superset of cognitive operations involved in generating communicative action. We posit these functions comprise three intersecting multistep pathways: (a) the Content Pathway, which selects the movements constituting a response; (b) the Timing Pathway, which temporally structures responses; and (c) the Affect Pathway, which modulates response parameters according to internal state. These processing streams form the basis of the Convergent Pathways for Interaction framework, which provides a conceptual model for investigating the cognitive and neural computations underlying vocal communication across species.
GIANT LEFT ATRIAL MYXOMA WITH FUNCTIONAL SEVERE MITRAL VALVE STENOSIS: EARLY SURGICAL INTERVENTION IS CRITICALLY NEEDED
Authors: Tai Thien Tan Tri Truyen, Phuc Vu, Nghi Tran, Hanh-Nhi Le, Hai Duong Nguyen, An Bui, Nguyen Tran, Thao Nguyen, Chi Nguyen, Amandeep Goyal, Anh Tu Nguyen, Tuan Mai, Phillip Tran
Journal: Journal of the American College of Cardiology (2022)
Nanoprodrug ratiometrically integrating autophagy inhibitor and genotoxic agent for treatment of triple-negative breast cancer
Authors: Huifang Wang, Haoyu Bai, Jiafeng Wang, Xuefei Zhou, Hongda Chen, Liying Wang, Huiming Ren, Zimo Liu, Wei Zhuo, Zhuxian Zhou, Jianbin Tang, Zhijie Li, Jigang Wang, Youqing Shen, Tianhua Zhou, Xiangrui Liu
Journal: Biomaterials (2022)
TEMPORAL TRENDS AND OUTCOMES OF TACHYARRHYTHMIAS IN HOSPITALIZED PATIENTS WITH ACUTE PANCREATITIS
Authors: Alexander Dang, Christopher M. Nguyen, Rafael Cabello, Steven Mai, Marcus Ynalvez, Michelle Baliss, Mohamad Khaled Soufi, Ayman Elbadawi, Wissam Khalife, Rafic F. Berbarie
Journal: Journal of the American College of Cardiology (2022)
Assessment of Disease Status and Treatment Response With Artificial Intelligence−Enhanced Electrocardiography in Obstructive Hypertrophic Cardiomyopathy
Authors: Geoffrey H. Tison, Konstantinos C. Siontis, Sean Abreau, Zachi Attia, Priyanka Agarwal, Aarthi Balasubramanyam, Yunfan Li, Amy J. Sehnert, Jay M. Edelberg, Paul A. Friedman, Jeffrey E. Olgin, Peter A. Noseworthy
Journal: Journal of the American College of Cardiology (2022)
MACHINE LEARNING BASED PREDICTION OF CARDIAC-RELATED HOSPITALIZATION COSTS AT TIME OF DIAGNOSTIC IMAGING: DEMONSTRATION OF VALUE FROM MULTI-DOMAIN PHENOTYPIC DATA AT TIME OF CARDIOVASCULAR MRI
Authors: Lucy Lei, Steven Dykstra, Yoko Mikami, Aidan Cornhill, Alessandro Satriano, Derek S. Chew, Jacqueline A. Flewitt, Sandra Rivest, Rosa Sandonato, Michelle Seib, Carmen Lydell, Andrew G. Howarth, Hude Quan, Nowell Mark Fine, Joon Lee, James White
Journal: Journal of the American College of Cardiology (2022)
Granzyme B <sup>+</sup> CD4 T cells accumulate in the colon during chronic HIV-1 infection
Authors: Stephanie M. Dillon, Kaylee L. Mickens, Tezha A. Thompson, Emily H. Cooper, Sabrina Nesladek, Allison J. Christians, Moriah Castleman, Kejun Guo, Cheyret Wood, Daniel N. Frank, Katerina Kechris, Mario L. Santiago, Cara C. Wilson
Journal: Gut Microbes (2022)

Chronic HIV-1 infection results in the sustained disruption of gut homeostasis culminating in alterations in microbial communities (dysbiosis) and increased microbial translocation. Major questions remain on how interactions between translocating microbes and gut immune cells impact HIV-1-associated gut pathogenesis. We previously reported that in vitro exposure of human gut cells to enteric commensal bacteria upregulated the serine protease and cytotoxic marker Granzyme B (GZB) in CD4 T cells, and GZB expression was further increased in HIV-1-infected CD4 T cells. To determine if these in vitro findings extend in vivo, we evaluated the frequencies of GZB+ CD4 T cells in colon biopsies and peripheral blood of untreated, chronically infected people with HIV-1 (PWH). Colon and blood GZB+ CD4 T cells were found at significantly higher frequencies in PWH. Colon, but not blood, GZB+ CD4 T cell frequencies were associated with gut and systemic T cell activation and Prevotella species abundance. In vitro, commensal bacteria upregulated GZB more readily in gut versus blood or tonsil-derived CD4 T cells, particularly in inflammatory T helper 17 cells. Bacteria-induced GZB expression in gut CD4 T cells required the presence of accessory cells, the IL-2 pathway and in part, MHC Class II. Overall, we demonstrate that GZB+ CD4 T cells are prevalent in the colon during chronic HIV-1 infection and may emerge following interactions with translocated bacteria in an IL-2 and MHC Class II-dependent manner. Associations between GZB+ CD4 T cells, dysbiosis and T cell activation suggest that GZB+ CD4 T cells may contribute to gut HIV-1 pathogenesis.
Infection-induced lymphatic zippering restricts fluid transport and viral dissemination from skin
Authors: Madeline J. Churchill, Haley du Bois, Taylor A. Heim, Tenny Mudianto, Maria M. Steele, Jeffrey C. Nolz, Amanda W. Lund
Journal: The Journal of Experimental Medicine (2022)

Lymphatic vessels are often considered passive conduits that flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that infection-induced changes in lymphatic transport actively contribute to innate host defense. We demonstrate that cutaneous vaccinia virus infection by scarification activates dermal lymphatic capillary junction tightening (zippering) and lymph node lymphangiogenesis, which are associated with reduced fluid transport and cutaneous viral sequestration. Lymphatic-specific deletion of VEGFR2 prevented infection-induced lymphatic capillary zippering, increased fluid flux out of tissue, and allowed lymphatic dissemination of virus. Further, a reduction in dendritic cell migration to lymph nodes in the absence of lymphatic VEGFR2 associated with reduced antiviral CD8+ T cell expansion. These data indicate that VEGFR2-driven lymphatic remodeling is a context-dependent, active mechanism of innate host defense that limits viral dissemination and facilitates protective, antiviral CD8+ T cell responses.
Immunological and inflammatory changes after simplifying to dual therapy in virologically suppressed HIV-infected patients through week 96 in a randomized trial
Authors: María Trujillo-Rodríguez, Esperanza Muñoz-Muela, Ana Serna-Gallego, Yusnelkis Milanés-Guisado, Juan Manuel Praena-Fernández, Ana Isabel Álvarez-Ríos, Laura Herrera-Hidalgo, Montserrat Domínguez, Carmen Lozano, Gloria Romero-Vazquez, Cristina Roca, Nuria Espinosa, Alicia Gutiérrez-Valencia, Luis F. López-Cortés
Journal: Clinical Microbiology and Infection (2022)

To evaluate whether simplification of antiretroviral treatment to dual therapy (DT) negatively impacts immune recovery (IR), immune activation and inflammation (IA/I), and HIV reservoir.An open-label, single-centre, randomized controlled trial conducted in adult virologically suppressed HIV-infected patients on triple therapy (TT) with elvitegravir-cobicistat, emtricitabine and tenofovir alafenamide or dolutegravir (DTG), abacavir, and lamivudine (3TC). Participants were randomized to continue TT or switch to DTG, or darunavir/cobicistat (DRVc) plus 3TC. IR was assessed by CD4+/CD8+ ratio at 48 and 96 weeks. Changes in immune activation, proliferation, exhaustion, senescence, and apoptosis in CD4+ and CD8+ T cells, plasma sCD14, hsCRP, D-dimers, β2-microglobulin, IL-6, TNF-α and IP-10 levels, cell-associated HIV-DNA (CA-DNA), and unspliced HIV-RNA (usRNA) were also analysed.One hundred and fifty-one participants were enrolled. Fourteen patients did not complete the follow up. In the ITT and PP analysis, the IR was similar between the treatment arms. In the ITT analysis, the median increase in CD4+/CD8+ ratio was 0.10, 0.04, and 0.07 at week 48, and 0.09, 0.05, and 0.08 at week 96 for TT, DTG/3TC, and DRVc/3TC, respectively. After adjusting for confounding factors, the slopes of changes in CD4+/CD8+ ratio over time were independent of treatment (F = 1.699; p = 0.436) and related only to baseline values (F = 756.871; p = 0.000). There were no differences in IA/I, CA-DNA, or usRNA between treatment arms.Both IR and IA/I, CA-DNA, and usRNA were similar in the three treatment groups, regardless of maintaining TT or simplifying to DTG/3TC or DRVc/3TC in virologically suppressed HIV-infected patients.
Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial
Authors: Laurence Chu, Keith Vrbicky, David Montefiori, Wenmei Huang, Biliana Nestorova, Ying Chang, Andrea Carfi, Darin K. Edwards, Judy Oestreicher, Holly Legault, Frank J. Dutko, Bethany Girard, Rolando Pajon, Jacqueline M. Miller, Rituparna Das, Brett Leav, Roderick McPhee
Journal: Nature Medicine (2022)

Abstract Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6–8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 ( NCT04405076 ). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.7-fold (95% confidence interval (CI): 1.5, 1.9) higher than those at 28 days after the second injection of the primary series, which met the pre-specified non-inferiority criterion (primary immunogenicity objective) and might indicate a memory B cell response. The nAb titers against the Delta variant (B.1.617.2) (exploratory objective) at 1 month after the booster were 2.1-fold (95% CI: 1.8, 2.4) higher than those at 28 days after the second injection of the primary series. The seroresponse rate (95% CI (four-fold rise from baseline)) was 100% (98.7, 100.0) at 28 days after the booster compared to 98.3% (96.0, 99.4) after the primary series. The higher antibody titers at 28 days after the booster dose compared to 28 days after the second dose in the phase 3 COVE study were also observed in two assays for anti-spike IgG antibody measured by ELISA and by Meso Scale Discovery (MSD) Multiplex. The frequency of solicited local and systemic adverse reactions after the booster dose was similar to that after the second dose in the primary two-dose series of mRNA-1273 (50 µg or 100 µg); no new signals were observed in the unsolicited adverse events; and no serious adverse events were reported in the 1-month follow-up period. These results show that a booster injection of mRNA-1273 more than 6 months after completing the primary two-dose series is safe and elicited nAb titers that were statistically significantly higher than the peak titers detected after the primary vaccination series, suggesting that a booster dose of mRNA-1273 might result in increased vaccine effectiveness against infection and disease caused by SARS-CoV-2.
Forkhead Box Transcription Factors: Double-Edged Swords in Cancer
Authors: Maria Castaneda, Petra den Hollander, Sendurai A. Mani
Journal: Cancer Research (2022)

Abstract A plethora of treatment options exist for cancer therapeutics, but many are limited by side effects and either intrinsic or acquired resistance. The need for more effective targeted cancer treatment has led to the focus on forkhead box (FOX) transcription factors as possible drug targets. Forkhead factors such as FOXA1 and FOXM1 are involved in hormone regulation, immune system modulation, and disease progression through their regulation of the epithelial–mesenchymal transition. Forkhead factors can influence cancer development, progression, metastasis, and drug resistance. In this review, we discuss the various roles of forkhead factors in biological processes that support cancer as well as their function as pioneering factors and their potential as targetable transcription factors in the fight against cancer.
Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion
Authors: Leila Amini, Sara K. Silbert, Shannon L. Maude, Loretta J. Nastoupil, Carlos A. Ramos, Renier J. Brentjens, Craig S. Sauter, Nirali N. Shah, Mohamed Abou-el-Enein
Journal: Nature Reviews Clinical Oncology (2022)
RISK OF ATRIAL FIBRILLATION FOLLOWING PFO CLOSURE - A SYSTEMATIC REVIEW AND UMBRELLA META-ANALYSIS
Authors: David Pielykh, Chetna Dengri, Nishel Kothari, Greshaben Patel, Muhammad Imtiaz Tar, Aakash Baskar, Syed Nazeer Mahmood, Appala Peela, Urvish Patel, Amit Sharma
Journal: Journal of the American College of Cardiology (2022)
THE UTILITY OF VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION IN PATIENTS WITH ACUTE ISCHAEMIC VENTRICULAR SEPTAL DEFECT AND CARDIOGENIC SHOCK
Authors: Kevin Rajakariar, Daniel Gayed, Brendan Backhouse, John Dyett, Michael Rowe, Jaya Chandrasekhar
Journal: Journal of the American College of Cardiology (2022)
COMPARING SGLT2 INHIBITORS AGAINST SACUBITRIL/VALSARTAN IN HEART FAILURE: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Yao Neng Teo, Yao Hao Teo, Nicholas L. Syn, Celine Shuen Yin Yoong, Alex Jia Yang Cheong, Caitlin Fern Wee, Yoke-Ching Lim, Chi-Hang Lee, Tiong Cheng Yeo, Ping Chai, Raymond Ching-Chiew Wong, Weiqin Lim, Ching Hui Sia
Journal: Journal of the American College of Cardiology (2022)
Four-Week Mentalizing Imagery Therapy for Family Dementia Caregivers: A Randomized Controlled Trial with Neural Circuit Changes
Authors: Felipe A. Jain, Sergey V. Chernyak, Lisa D. Nickerson, Stefana Morgan, Rhiana Schafer, David Mischoulon, Richard Bernard-Negron, Maren Nyer, Cristina Cusin, Liliana Ramirez Gomez, Albert Yeung
Journal: Psychotherapy and Psychosomatics (2022)

Family caregivers of patients with dementia suffer a high burden of depression and reduced positive emotions. Mentalizing imagery therapy (MIT) provides mindfulness and guided imagery skills training to improve balanced mentalizing and emotion regulation.
Association of Trauma Center Designation With Postdischarge Survival Among Older Adults With Injuries
Authors: Molly P. Jarman, Ginger Jin, Joel S. Weissman, Arlene S. Ash, Jennifer Tjia, Ali Salim, Adil Haider, Zara Cooper
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Trauma centers improve outcomes for young patients with serious injuries. However, most injury-related hospital admissions and deaths occur in older adults, and it is not clear whether trauma center care provides the same benefit in this population. <h3>Objective</h3> To examine whether 30- and 365-day mortality of injured older adults is associated with the treating hospital's trauma center level. <h3>Design, Setting, and Participants</h3> This prospective, population-based cohort study used Medicare claims data from January 1, 2013, to December 31, 2016, for all fee-for-service Medicare beneficiaries 66 years or older with inpatient admission for traumatic injury in 2014 to 2015. Data analysis was performed from January 1 to June 31, 2021. Preinjury health was measured using 2013 claims, and outcomes were measured through 2016. The population was stratified by anatomical injury pattern. Propensity scores for level I trauma center treatment were estimated using the Abbreviated Injury Scale, age, and residential proximity to trauma center and then used to match beneficiaries from each trauma level (I, II, III, and IV/non-trauma centers) by injury type. <h3>Exposure</h3> Admitting hospital's trauma center level. <h3>Main Outcomes and Measures</h3> Case fatality rates (CFRs) at 30 and 365 days after injury, estimated in the matched sample using multivariable, hierarchical logistic regression models. <h3>Results</h3> A total of 433 169 Medicare beneficiaries (mean [SD] age, 82.9 [8.3] years; 68.4% female; 91.5% White) were included in the analysis. A total of 206 275 (47.6%) were admitted to non-trauma centers and 161 492 (37.3%) to level I or II trauma centers. Patients with isolated extremity fracture had the fewest deaths (365-day CFR ranged from 16.1% [95% CI, 11.2%-22.4%] to 17.4% [95% CI, 11.8%-24.6%] by trauma center status). Patients with both hip fracture and traumatic brain injury had the most deaths (365-day CFRs ranged from 33.4% [95% CI, 25.8%-42.1%] to 35.8% [95% CI, 28.9%-43.5%]). <h3>Conclusions and Relevance</h3> These findings suggest that older adults do not benefit from existing trauma center care, which is designed with younger patients in mind. There is a critical need to improve trauma care practices to address common injury mechanisms and types of injury in older adults.
Estimating the Effects of Soil Remediation on Children’s Blood Lead near a Former Lead Smelter in Omaha, Nebraska, USA
Authors: Dongni Ye, James S. Brown, David M. Umbach, John Adams, William Thayer, Mark H. Follansbee, Ellen F. Kirrane
Journal: Environmental Health Perspectives (2022)

Background: Lead exposures from legacy sources threaten children's health. Soil in Omaha, Nebraska, was contaminated by emissions from a lead smelter and refinery. The U.S. Environmental Protection Agency excavated and replaced contaminated soil at the Omaha Lead Superfund Site between 1999 and 2016. Objectives: The goal of this study was to assess the association of soil lead level (SLL) and soil remediation status with blood lead levels (BLLs) in children living near or on the site. Methods: We linked information on SLL at residential properties with children's BLLs and assigned remediation status to children's BLL measurements based on whether their measurements occurred during residence at remediated or unremediated properties. We examined the association of SLL and remediation status with elevated BLL (EBLL). We distinguished the roles of temporal trend and the intervention with time-by-intervention-status interaction contrasts. All analyses estimated odds ratios (ORs) with a generalized estimating equations approach to ensure robustness under the complex correlations among BLL measurements. All analyses controlled for relevant covariates including children's characteristics. Results: EBLL (>5μg/dL) was associated with both residential SLL [e.g., OR=2.00; 95% confidence interval (CI): 1.83, 2.19; >400–800 vs. ≤200 ppm] and neighborhood SLL [e.g., OR=1.85 (95% CI: 1.62, 2.11; >400–800 vs. ≤200 ppm)] before remediation but only with neighborhood SLL after remediation. The odds of EBLL were higher before remediation [OR 1.52 (95% CI: 1.34, 1.72)]. Similarly, EBLL was positively associated with preremediation status in our interaction analysis [interaction OR=1.18 (95%CI: 1.02, 1.37)]. Discussion: Residential and neighborhood SLLs were important predictors of EBLLs in children residing near or on this Superfund site. Neighborhood SLL remained a strong predictor following remediation. Our data analyses showed the benefit of soil remediation. Results from the interaction analyses should be interpreted cautiously due to imperfect correspondence of remediation times between remediation and comparison groups. https://doi.org/10.1289/EHP8657
CLO22-078: Dual-Tracer PET/CT-Targeted, mpMRI-Targeted, Systematic Biopsy, and Combined Biopsy for the Diagnosis of Prostate Cancer
Authors: Dong-Xu Qiu, Jian Li, Jin-Wei Zhang, Min-Feng Chen, Xiao-Mei Gao, Yong-Xiang Tang, Ye Zhang, Xiao-Ping Yi, Hong-ling Yin, Yu Gan, Gui-Lin Wang, Xiong-Bing Zu, Shuo Hu, Yi Cai
Journal: Journal of the National Comprehensive Cancer Network (2022)