tbuckley/cabot-search huggingface dataset:
Engineered neutrophil apoptotic bodies ameliorate myocardial infarction by promoting macrophage efferocytosis and inflammation resolution
Authors: Lili Bao, Geng Dou, Ran Tian, Yajie Lv, Feng Ding, Siying Liu, Ruifeng Zhao, Lu Zhao, Jun Zhou, Lin Weng, Yan Dong, Bei Li, Shiyu Liu, Xin Chen, Yan Jin
Journal: Bioactive Materials (2021)

Inflammatory response plays a critical role in myocardial infarction (MI) repair. The neutrophil apoptosis and subsequent macrophage ingestion can result in inflammation resolution and initiate regeneration, while the therapeutic strategy that simulates and enhances this natural process has not been established. Here, we constructed engineered neutrophil apoptotic bodies (eNABs) to simulate natural neutrophil apoptosis, which regulated inflammation response and enhanced MI repair. The eNABs were fabricated by combining natural neutrophil apoptotic body membrane which has excellent inflammation-tropism and immunoregulatory properties, and mesoporous silica nanoparticles loaded with hexyl 5-aminolevulinate hydrochloride (HAL). The eNABs actively targeted to macrophages and the encapsulated HAL simultaneously initiated the biosynthesis pathway of heme to produce anti-inflammatory bilirubin after intracellular release, thereby further enhancing the anti-inflammation effects. In in vivo studies, the eNABs efficiently modulated inflammation responses in the infarcted region to ameliorate cardiac function. This study demonstrates an effective biomimetic construction strategy to regulate macrophage functions for MI repair.
Dengue and Chikungunya seroprevalence in waste pickers from the largest Latin American open-air dump
Authors: Évelin Mota Cassemiro, Daiani Cristina Cilião-Alves, Drielly Rodrigues Moura, Svetoslav Nanev Slavov, Tatyane de Souza Cardoso Quintão, James Alexander Scott, Carla Pintas Marques, Marcos Takashi Obara, Wildo Navegantes de Araújo, Vanessa Resende Nogueira Cruvinel, Rodrigo Haddad
Journal: Journal of Infection (2021)
Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response
Authors: Jeong A. Park, Linlin Wang, Nai-Kong V. Cheung
Journal: Journal of Hematology & Oncology (2021)

Tumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesis, growth, proliferation, and metastasis, while derailing the host anti-tumor response. TME impedes bispecific antibody (BsAb) or chimeric antigen receptor (CAR)-driven T cells infiltration, survival, and cytotoxic efficacy. Modulating tumor infiltrating myeloid cells (TIMs) could potentially improve the efficacy of BsAb. We evaluated the effects of TIM modulation on BsAb-driven T cell infiltration into tumors, their persistence, and in vivo anti-tumor response. Anti-GD2 BsAb and anti-HER2 BsAb built on IgG-[L]-scFv platform were tested against human cancer xenografts in BALB-Rag2-/-IL-2R-γc-KO (BRG) mice. Depleting antibodies specific for polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic MDSC (M-MDSC), and tumor associated macrophage (TAM) were used to study the role of each TIM component. Dexamethasone, an established anti-inflammatory agent, was tested for its effect on TIMs. BsAb-driven T cells recruited myeloid cells into human tumor xenografts. Each TIM targeting therapy depleted cells of interest in blood and in tumors. Depletion of PMN-MDSCs, M-MDSCs, and particularly TAMs was associated with enhanced T cell infiltration into tumors, significantly improving tumor control and survival in multiple cancer xenograft models. Dexamethasone premedication depleted monocytes in circulation and TAMs in tumors, enhanced BsAb-driven T cell infiltration, and anti-tumor response with survival benefit. Reducing TIMs markedly enhanced anti-tumor effects of BsAb-based T cell immunotherapy by improving intratumoral T cell infiltration and persistence. TAM depletion was more effective than PMN- or M-MDSCs depletion at boosting the anti-tumor response of T cell engaging BsAb.
Abstract 15880: Phenotype of Super-Responders to Stem Cell Therapy for Non-Ischemic Dilated Cardiomyopathy
Authors: Angela C Rieger, Victoria Florea, Bryon A Tompkins, Makoto Natsumeda, Ana M Landin, Courtney Premer, Ivonne H Schulman, Joshua M Hare
Journal: Circulation (2017)

Introduction: The POSEIDON-DCM trial reported a marked increase in EF in non-ischemic dilated cardiomyopathy (NIDCM) patients receiving allogeneic mesenchymal stem cells, with half of the patients ...
急性冠動脈症候群(ACS)患者の臨床転帰に及ぼすプロトンポンプ阻害剤(PPI)及びCYP2C19多型性
Authors: Hokimoto Seiji, Yamamoto Koichiro, Chitose Tadasuke, Ono Takamichi, Kaikita Koichi, Tsujita Kenichi, Nakagawa Kazuko, Sumida Hitoshi, Sugiyama Seigo, Ogawa Hisao
Journal: Circulation (2011)
Associations of Preoperative Frailty With Cancer and Noncancer Deaths of Older Adults Following Surgery for Cancer—Reply
Authors: Tyler R. Chesney, Julie Hallet
Journal: JAMA Surgery (2021)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
P-126 Atezolizumab plus bevacizumab for patients with advanced hepatocellular carcinoma and chronic hepatitis B virus infection with high viral load
Authors: S. Chen, H. Lai, H. Tsou, Y. Shao, C. Chang, T. Su, T. Liu, L. Chen, A. Cheng, C. Hsu
Journal: Annals of Oncology (2021)
Covering Tracheostomies Reduces Viral Spread to Health Care Staff
Authors: Anita Slomski
Journal: JAMA (2021)

Alexandra J. Berges, BS; Ioan A. Lina, MD; Rafael Ospino, BS; Hsiu-Wen Tsai, PhD; Michael J. Brenner, MD; Vinciya Pandian, PhD; Ana M. Rule, PhD; Alexander T. Hillel, MD
Additive effects of variants of unknown significance in replication repair-associated DNA polymerase genes on mutational burden and prognosis across diverse cancers
Authors: Jieer Ying, Lin Yang, Jiani C Yin, Guojie Xia, Minyan Xing, Xiaoxi Chen, Jiaohui Pang, Yong Wu, Hua Bao, Xue Wu, Yang Shao, Lingjun Zhu, Xiangdong Cheng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Defects in replication repair-associated DNA polymerases often manifest an ultra-high tumor mutational burden (TMB), which is associated with higher probabilities of response to immunotherapies. The functional and clinical implications of different polymerase variants remain unclear. Methods Targeted next-generation sequencing using a 425-cancer gene panel, which covers all exonic regions of three polymerase genes ( POLE , POLD1 , and POLH ), was conducted in a cohort of 12,266 patients across 16 different tumor types from January 2017 to January 2019. Prognostication of POL variant-positive patients was performed using a cohort of 4679 patients from the The Cancer Genome Atlas (TCGA) datasets. Results The overall prevalence of somatic and germline polymerase variants was 4.2% (95% CI 3.8% to 4.5%) and 0.7% (95% CI 0.5% to 0.8%), respectively, with highest frequencies in endometrial, urinary, prostate, and colorectal cancers (CRCs). While most germline polymerase variants showed no clear functional consequences, we identified a candidate p.T466A affecting the exonuclease domain of POLE, which might be underlying the early onset in a case with childhood CRC. Low frequencies of known hot-spot somatic mutations in POLE were detected and were associated with younger age, the male sex, and microsatellite stability. In both the panel and TCGA cohorts, POLE drivers exhibited high frequencies of alterations in genes in the DNA damage and repair (DDR) pathways, including BRCA2 , ATM , MSH6 , and ATR . Variants of unknown significance (VUS) of different polymerase domains showed variable penetrance with those in the exonuclease domain of POLE and POLD1 displaying high TMB. VUS in POL genes exhibited an additive effect as carriers of multiple VUS had exponentially increased TMB and prolonged overall survival. Similar to cases with driver mutations, the TMB-high POL VUS samples showed DDR pathway involvement and polymerase hypermutation signatures. Combinatorial analysis of POL and DDR pathway status further supported the potential additive effects of POL VUS and DDR pathway genes and revealed distinct prognostic subclasses that were independent of cancer type and TMB. Conclusions Our results demonstrate the pathogenicity and additive prognostic value of POL VUS and DDR pathway gene alterations and suggest that genetic testing may be warranted in patients with diverse solid tumors.
Activating a collaborative innate-adaptive immune response to control metastasis
Authors: Lijuan Sun, Tim Kees, Ana Santos Almeida, Bodu Liu, Xue-Yan He, David Ng, Xiao Han, David L. Spector, Iain A. McNeish, Phyllis Gimotty, Sylvia Adams, Mikala Egeblad
Journal: Cancer Cell (2021)
Temporal multi-omics identifies LRG1 as a vascular niche instructor of metastasis
Authors: Mahak Singhal, Nicolas Gengenbacher, Ashik Ahmed Abdul Pari, Miki Kamiyama, Ling Hai, Bianca J. Kuhn, David M. Kallenberg, Shubhada R. Kulkarni, Carlotta Camilli, Stephanie F. Preuß, Barbara Leuchs, Carolin Mogler, Elisa Espinet, Eva Besemfelder, Danijela Heide, Mathias Heikenwalder, Martin R. Sprick, Andreas Trumpp, Jeroen Krijgsveld, Matthias Schlesner, Junhao Hu, Stephen E. Moss, John Greenwood, Hellmut G. Augustin
Journal: Science Translational Medicine (2021)

A temporal systems biology screen of premetastatic endothelial cells identified LRG1 as a therapeutic target for restricting metastases.
Call for emergency action to limit global temperature increases, restore biodiversity and protect health
Authors: Lukoye Atwoli, Abdullah H Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel GM Olde Rikkert, Eric J Rubin, Peush Sahni, Richard Smith, Nicholas J Talley, Sue Turale, Damián Vázquez
Journal: Annals of the Rheumatic Diseases (2021)

> Wealthy nations must do much more, much faster.

The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (Conference of the Parties (COP)26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature and protect health.

Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with COVID-19, we cannot wait for the pandemic to pass to rapidly reduce emissions.

Reflecting the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory.

The risks to health of increases above 1.5°C are now well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical infections, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4 

Global heating is also contributing to the decline in …
Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series
Authors: Grace Hsin-Min Wang, Kenneth K C Man, Wei-Hung Chang, Tzu-Chi Liao, Edward Chia-Cheng Lai
Journal: BMJ (2021)

Abstract Objective To evaluate the association between the use of antipsychotic drugs and cholinesterase inhibitors and the risk of falls and fractures in elderly patients with major neurocognitive disorders. Design Self-controlled case series. Setting Taiwan’s National Health Insurance Database. Participants 15 278 adults, aged ≥65, with newly prescribed antipsychotic drugs and cholinesterase inhibitors, who had an incident fall or fracture between 2006 and 2017. Prescription records of cholinesterase inhibitors confirmed the diagnosis of major neurocognitive disorders; all use of cholinesterase inhibitors was reviewed by experts. Main outcome measures Conditional Poisson regression was used to derive incidence rate ratios and 95% confidence intervals for evaluating the risk of falls and fractures for different treatment periods: use of cholinesterase inhibitors alone, antipsychotic drugs alone, and a combination of cholinesterase inhibitors and antipsychotic drugs, compared with the non-treatment period in the same individual. A 14 day pretreatment period was defined before starting the study drugs because of concerns about confounding by indication. Results The incidence of falls and fractures per 100 person years was 8.30 (95% confidence interval 8.14 to 8.46) for the non-treatment period, 52.35 (48.46 to 56.47) for the pretreatment period, and 10.55 (9.98 to 11.14), 10.34 (9.80 to 10.89), and 9.41 (8.98 to 9.86) for use of a combination of cholinesterase inhibitors and antipsychotic drugs, antipsychotic drugs alone, and cholinesterase inhibitors alone, respectively. Compared with the non-treatment period, the highest risk of falls and fractures was during the pretreatment period (adjusted incidence rate ratio 6.17, 95% confidence interval 5.69 to 6.69), followed by treatment with the combination of cholinesterase inhibitors and antipsychotic drugs (1.35, 1.26 to 1.45), antipsychotic drugs alone (1.33, 1.24 to 1.43), and cholinesterase inhibitors alone (1.17, 1.10 to 1.24). Conclusions The incidence of falls and fractures was high in the pretreatment period, suggesting that factors other than the study drugs, such as underlying diseases, should be taken into consideration when evaluating the association between the risk of falls and fractures and use of cholinesterase inhibitors and antipsychotic drugs. The treatment periods were also associated with a higher risk of falls and fractures compared with the non-treatment period, although the magnitude was much lower than during the pretreatment period. Strategies for prevention and close monitoring of the risk of falls are still necessary until patients regain a more stable physical and mental state.
<i>HLF</i>expression defines the human hematopoietic stem cell state
Authors: Bernhard Lehnertz, Jalila Chagraoui, Tara MacRae, Elisa Tomellini, Sophie Corneau, Nadine Mayotte, Isabel Boivin, Aurélie Durand, Deanne Gracias, Guy Sauvageau
Journal: Blood (2021)
Phenotypic Expression and Outcomes in Individuals With Rare Genetic Variants of Hypertrophic Cardiomyopathy
Authors: Antonio de Marvao, Kathryn A. McGurk, Sean L. Zheng, Marjola Thanaj, Wenjia Bai, Jinming Duan, Carlo Biffi, Francesco Mazzarotto, Ben Statton, Timothy J.W. Dawes, Nicolò Savioli, Brian P. Halliday, Xiao Xu, Rachel J. Buchan, A. John Baksi, Marina Quinlan, Paweł Tokarczuk, Upasana Tayal, Catherine Francis, Nicola Whiffin, Pantazis I. Theotokis, Xiaolei Zhang, Mikyung Jang, Alaine Berry, Antonis Pantazis, Paul J.R. Barton, Daniel Rueckert, Sanjay K. Prasad, Roddy Walsh, Carolyn Y. Ho, Stuart A. Cook, James S. Ware, Declan P. O’Regan
Journal: Journal of the American College of Cardiology (2021)

BACKGROUND Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population.OBJECTIVES The goal of this study was to compare lifetime outcomes and cardiovascular phenotypes according to the presence of rare variants in sarcomere-encoding genes among middle-aged adults.METHODS This study analyzed whole exome sequencing and cardiac magnetic resonance imaging in UK Biobank participants stratified according to sarcomere-encoding variant status. RESULTSThe prevalence of rare variants (allele frequency <0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n ¼ 5,712; 1 in 35), and the prevalence of variants pathogenic or likely pathogenic for HCM (SARC-HCM-P/LP) was 0.25% (n ¼ 493; 1 in 407).SARC-HCM-P/LP variants were associated with an increased risk of death or major adverse cardiac events compared with controls (hazard ratio: 1.69; 95% confidence interval [CI]: 1.38-2.07;P < 0.001), mainly due to heart failure endpoints (hazard ratio: 4.23; 95% CI: 3.07-5.83;P < 0.001).In 21,322 participants with both cardiac magnetic resonance imaging and whole exome sequencing, SARC-HCM-P/LP variants were associated with an asymmetric increase in left ventricular maximum wall thickness (10.9 AE 2.7 mm vs 9.4 AE 1.6 mm; P < 0.001), but hypertrophy ($13 mm) was only present in 18.4% (n ¼ 9 of 49; 95% CI: 9%-32%).SARC-HCM-P/LP variants were still associated with heart failure after adjustment for wall thickness (hazard ratio: 6.74; 95% CI: 2.43-18.7;P < 0.001).CONCLUSIONS In this population of middle-aged adults, SARC-HCM-P/LP variants have low aggregate penetrance for overt HCM but are associated with an increased risk of adverse cardiovascular outcomes and an attenuated cardiomyopathic phenotype.Although absolute event rates are low, identification of these variants may enhance risk stratification beyond familial disease.
Hepatocyte-derived exosomes from early onset obese mice promote insulin sensitivity through miR-3075
Authors: Yudong Ji, Zhenlong Luo, Hong Gao, Felipe Castellani Gomes Dos Reis, Gautam Bandyopadhyay, Zhongmou Jin, Kameswari Ananthakrishnan Manda, Roi Isaac, Meixiang Yang, Wenxian Fu, Wei Ying, Jerrold M. Olefsky
Journal: Nature Metabolism (2021)
Microfluidic Tandem Mechanical Sorting System for Enhanced Cancer Stem Cell Isolation and Ingredient Screening
Authors: Yuanyuan Jia, Peiliang Shen, Tao Yan, Weijia Zhou, Jia Sun, Xin Han
Journal: Advanced Healthcare Materials (2021)

Abstract Robust isolation of cancer stem cells (CSCs) in a high‐throughput, label‐free manner is critical for understanding tumor heterogeneity and developing therapeutic strategies targeting CSCs. Cell‐mechanics‐based microfluidic sorting systems provide efficient and specific platforms for investigation of stem cell‐like characteristics on the basis of cell deformability and cell‐substrate adhesion properties. In the present study, a microfluidic tandem mechanical sorting system is developed to enrich CSCs with high flexibility and low adhesive capacity. In the integrated microfluidic system, cancer cells are driven by hydrodynamic forces to flow continuously through two featured devices, which are functionalized with sequentially variable microbarriers and surface‐coated fluid mixing microchannels, respectively. Collected deformable and low‐adhesive cancer cells exhibit enhanced stem cell‐like properties with higher stemness and metastasis capacity both in vitro and in vivo, compared with each single device separation. Using these devices, bioactive natural compound screening targeting CSCs is performed and a potent therapeutic compound isoliquiritigenin from licorice is identified to inhibit the lung cancer stem cell phenotype. Taken together, this microfluidic tandem mechanical sorting system can facilitate drug screening targeting CSCs and the analysis of signals regulating CSC function in drug resistance.
Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma
Authors: David G. Maloney, John Kuruvilla, Fei Fei Liu, Ana Kostic, Yeonhee Kim, Ashley Bonner, Yixie Zhang, Christopher P. Fox, Guillaume Cartron
Journal: Journal of Hematology & Oncology (2021)

In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL).Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor.The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56-3.49] and 1.21 [0.56-2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44-1.49] and 0.95 [0.58-1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01-0.07] and 0.08 [0.01-0.67], respectively) and study-specific neurological events (0.16 [0.08-0.33] and 0.05 [0.02-0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor.After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL.NCT02631044 and NCT02348216.
Liver transplantation for non-resectable colorectal liver metastases: the International Hepato-Pancreato-Biliary Association consensus guidelines
Authors: Glenn K Bonney, Claire Alexandra Chew, Peter Lodge, Joleen Hubbard, Karim J Halazun, Pavel Trunecka, Paolo Muiesan, Darius F Mirza, John Isaac, Richard W Laing, Shridhar Ganpathi Iyer, Cheng Ean Chee, Wei Peng Yong, Mark Dhinesh Muthiah, Fabrizio Panaro, Juan Sanabria, Axel Grothey, Keymanthri Moodley, Ian Chau, Albert C Y Chan, Chih Chi Wang, Krishna Menon, Gonzalo Sapisochin, Morten Hagness, Svein Dueland, Pål-Dag Line, René Adam
Journal: The Lancet. Gastroenterology & hepatology (2021)