tbuckley/cabot-search huggingface dataset:
β2-microglobulin triggers NLRP3 inflammasome activation in tumor-associated macrophages to promote multiple myeloma progression
Authors: Daniel Hofbauer, Dimitrios Mougiakakos, Luca Broggini, Mario Zaiss, Maike Büttner-Herold, Christian Bach, Bernd Spriewald, Frank Neumann, Savita Bisht, Jens Nolting, Robert Zeiser, Shaima’a Hamarsheh, Martin Eberhardt, Julio Vera, Cristina Visentin, Chiara Maria Giulia De Luca, Fabio Moda, Stefan Haskamp, Cindy Flamann, Martin Böttcher, Katrin Bitterer, Simon Völkl, Andreas Mackensen, Stefano Ricagno, Heiko Bruns
Journal: Immunity (2021)
SO-28 Effect of prior bevacizumab treatment in BRAF V600E-mutant metastatic colorectal cancer: Overall survival with encorafenib + cetuximab +/- binimetinib in BEACON CRC
Authors: D. Aderka, S. Kopetz, A. Grothey, E. Van Cutsem, R. Yaeger, H. Wasan, T. Yoshino, J. Desai, F. Ciardiello, A. Golden, M. Edwards, J. Tabernero
Journal: Annals of Oncology (2021)
Omission of Radiotherapy in Older Adults With Early-Stage Breast Cancer
Authors: Varun Kumar Chowdhry
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Organelle-inspired supramolecular nanomedicine to precisely abolish liver tumor growth and metastasis
Authors: Jie Zhan, Yuhan Wang, Shaodan Ma, Qin Qin, Ling Wang, Yanbin Cai, Zhimou Yang
Journal: Bioactive Materials (2021)

Organelles are responsible for the efficient storage and transport of substances in living systems. A myriad of extracellular vesicles (EVs) acts as a bridge to exchange signaling molecules in cell-cell communication, and the highly dynamic tubulins and actins contribute to efficient intracellular substance transport. The inexhaustible cues of natural cargo delivery by organelles inspire researchers to explore the construction of biomimetic architectures for "smart" delivery carriers. Herein, we report a 10-hydroxycamptothecin (HCPT)-peptide conjugate HpYss that simulates the artificial EV-to-filament transformation process for precise liver cancer therapy. Under the sequential stimulus of extracellular alkaline phosphatase (ALP) and intracellular glutathione (GSH), HpYss proceeds via tandem self-assembly with a morphological transformation from nanoparticles to nanofibers. The experimental phase diagram elucidates the influence of ALP and GSH contents on the self-assembled nanostructures. In addition, the dynamic transformation of organelle-mimetic architectures that are formed by HpYss in HepG2 cells enables the efficient delivery of the anticancer drug HCPT to the nucleus, and the size-shape change from extracellular nanoparticles (50-100 nm) to intracellular nanofibers (4-9 nm) is verified to be of key importance for nuclear delivery. Nuclear targeting of HpYss amplifies apoptosis, thus significantly enhancing the inhibitory effect of HCPT (>10-fold) to HepG2 cells. Benefitting from the spatiotemporally controlled nanostructures, HpYss exhibited deep penetration, enhanced accumulation, and long-term retention in multicellular spheroid and xenograft models, potently abolishing liver tumor growth and preventing lung metastasis. We envision that our organelle-mimicking delivery strategy provides a novel paradigm for designing nanomedicine to cancer therapy.
Expanding Evidence for Clinical Care of Older Adults
Authors: Michael A. Steinman, Cynthia M. Boyd, Kenneth E. Schmader
Journal: JAMA (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 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
Discovery of Donor Genotype Associated with Long-Term Survival of Patients with Hematopoietic Stem Cell Transplantation in Refractory Acute Myeloid Leukemia
Authors: Chan-Young Ock, Heewon Seo, Dae-Yoon Kim, Inho Kim, Sung-Soo Yoon, Ju Han Kim, Youngil Koh
Journal: Blood (2017)
P16-6 Tumor infiltrating lymphocyte and leukocyte ratios as metastatic predictor in HER2 positive luminal type breast cancer
Authors: I Gede Wikania Wira Wiguna, Sinta Wiranata, Ni Putu Sri Indrani Remitha, I Gusti Ayu Stiti Sadvika, Putu Anda Tusta Adiputra, Desak Made Wihandani, I Gede Putu Supadmanaba
Journal: Annals of Oncology (2021)
Entering a labyrinth of COVID-19 stories
Authors: Peter Ranscombe
Journal: The Lancet Infectious Diseases (2021)

Figures have sat at the heart of the SARS-CoV-2 pandemic, from the percentages by which vaccines reduce the risk of developing a severe case of COVID-19 through to the rising numbers of cases, hospitalisations, and deaths given on the nightly news bulletins. In all that focus on the hard data, sometimes the very human stories behind the pandemic can be drowned out. This year's Edinburgh Science Festival put those personal reflections front and centre during a walking tour entitled Life in the COVID Bubble: Voices from the Frontline of Critical Care.
Covid-19: Lessons from UK’s pandemic response “cannot wait” for government inquiry, say MPs
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The lifetime cost of the UK government’s response to the covid-19 pandemic reached £372bn by May 2021 and will expose the taxpayer to “significant financial risks for decades to come,” a parliamentary committee has warned.

In two hard hitting reports the House of Commons Public Accounts Committee pinpointed an “unacceptably high” waste in areas such as the procurement of personal protective equipment, a “repeated failure to provide a full rationale for key decisions,” and poor communication of government guidelines as key initial lessons from the UK’s pandemic response.12

Although the government has promised to begin a public inquiry into its handling of the pandemic in spring 2022, the committee said this could take years to complete. “We are clear that the …
Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics
Authors: Arbel Artzy-Schnirman, Sivan Arber Raviv, Ofri Doppelt Flikshtain, Jeny Shklover, Netanel Korin, Adi Gross, Boaz Mizrahi, Avi Schroeder, Josué Sznitman
Journal: Advanced Drug Delivery Reviews (2021)
The Role of the Axis TGF-β1/Mir-382-5p/SOD2 in the Induction of Oxidative Stress in CD34+ Hematopoietic Stem/Progenitor Cells from Primary Myelofibrosis
Authors: Chiara Rossi, Roberta Zini, Samantha Ruberti, Sebastiano Rontauroli, Zelia Prudente, Greta Barbieri, Elisa Bianchi, Simona Salati, Elena Genovese, Carmela Mannarelli, Paola Guglielmelli, Enrico Tagliafico, Vittorio Rosti, Giovanni Barosi, Alessandro M. Vannucchi, Rossella Manfredini
Journal: Blood (2017)
Changes in Health-Related Quality of Life After Transient Ischemic Attack
Authors: Irene L. Katzan, Andrew Schuster, Lynn Daboul, Christine Doherty, Sidra Speaker, Ken Uchino, Brittany Lapin
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Numerous studies have found that patients diagnosed with TIA have decreased health-related quality of life, which has been interpreted as suggesting that patients with TIA have residual symptoms after the event. Studies assessing health status in the same patients before and after an event are lacking but may allow a direct determination of the association of TIA with postevent health status. <h3>Objective</h3> To examine patient-reported health before transient ischemic attack (TIA) among individuals diagnosed with this event and evaluate change in patient-reported health after the event overall and by TIA characterization subgroups. <h3>Design, Setting, and Participants</h3> This cohort study was conducted among 236 patients with a clinical diagnosis of TIA from October 2015 to December 2017 in a large US health system that collects a patient-reported outcome measure in ambulatory setting as part of routine care. Included patients had patient-reported global health scale assessments completed as part of routine care before and after a TIA event. Data were analyzed from March through July 2020. <h3>Main Outcomes and Measures</h3> The main outcome was Patient-Reported Outcome Measurement Information System Global Health (PROMIS GH) scale score before and after TIA. A change of 5 or more points in this score is considered clinically relevant. The secondary outcomes included change in patient-reported global health by clinical impression of the probability of a TIA event, pattern of neurological deficits, and short-term risk of stroke, as assessed by the ABCD2 score. <h3>Results</h3> Among 263 patients who experienced TIA, mean (SD) age was 67.9 (13.4) years and 138 (52.5%) were women. The median (interquartile range) time between patient-reported global health scores was 152 (94-284) days. Mean (SD) baseline patient-reported global physical health and mental health scale summary scores were 43.4 (8.2) and 47.7 (9.7), respectively, and were statistically significantly decreased compared with the general population mean (SD) scores of 50 (10;<i>P</i> &lt; .001) for physical and mental health. The difference between physical health summary score among study participants and the general population was clinically relevant. Mean (SD) summary scores were not statistically significantly different after the event compared with before the event overall (physical health: 44.1 [8.2], for a mean [SE] improvement of 0.65 [0.38] points;<i>P</i> = .09; mental health: 47.4 [9.1], for a mean [SE] worsening of 0.25 [0.38] points;<i>P</i> = .51) or within subgroups. <h3>Conclusions and Relevance</h3> These findings suggest that impaired health status among patients diagnosed with TIA reflect, at least in part, an impaired premorbid state of health. This study did not find that TIA events were associated with worsening of health status overall or within subgroups.
Polymeric nanoparticle mediated inhibition of miR-21 with enhanced miR-124 expression for combinatorial glioblastoma therapy
Authors: Yuanyuan Liu, Meng Zheng, Mingzhu Jiao, Chengnan Yan, Sen Xu, Qiuli Du, Marco Morsch, Jinlong Yin, Bingyang Shi
Journal: Biomaterials (2021)
Gain-of-function mutation in ubiquitin ligase KLHL24 causes desmin degradation and dilatation in hiPSC-derived engineered heart tissues
Authors: Mathilde C.S.C. Vermeer, Maria C. Bolling, Jacqueline M. Bliley, Karla F. Arevalo Gomez, Mario G. Pavez-Giani, Duco Kramer, Pedro H. Romero-Herrera, B. Daan Westenbrink, Gilles F.H. Diercks, Maarten P. van den Berg, Adam W. Feinberg, Herman H.W. Silljé, Peter van der Meer
Journal: Journal of Clinical Investigation (2021)

The start codon c.1A>G mutation in KLHL24, encoding ubiquitin ligase KLHL24, results in the loss of 28 N-terminal amino acids (KLHL24-ΔN28) by skipping the initial start codon. In skin, KLHL24-ΔN28 leads to gain of function, excessively targeting intermediate filament keratin-14 for proteasomal degradation and ultimately causing epidermolysis bullosa simplex (EBS). The majority of patients with EBS are also diagnosed with dilated cardiomyopathy (DCM), but the pathological mechanism in the heart is unknown. As desmin is the cardiac homolog of keratin-14, we hypothesized that KLHL24-ΔN28 leads to excessive degradation of desmin, resulting in DCM. Dynamically loaded engineered heart tissues (dyn-EHTs) were generated from human-induced pluripotent stem cell–derived (hiPSC-derived) cardiomyocytes from 2 patients and 3 nonfamilial controls. Ten-fold lower desmin protein levels were observed in patient-derived dyn-EHTs, in line with diminished desmin levels detected in patients' explanted heart. This was accompanied by tissue dilatation, impaired mitochondrial function, decreased force values, and increased cardiomyocyte stress. HEK293 transfection studies confirmed KLHL24-mediated desmin degradation. KLHL24 RNA interference or direct desmin overexpression recovered desmin protein levels, restoring morphology and function in patient-derived dyn-EHTs. To conclude, presence of KLHL24-ΔN28 in cardiomyocytes leads to excessive degradation of desmin, affecting tissue morphology and function, which can be prevented by restoring desmin protein levels.
O1-4 Survival time of nivolumab treatment in advanced gastric cancer from real-world data of the DELIVER trial (JACCRO GC-08)
Authors: Atsushi Ishiguro, Eisuke Inoue, Yasuhiro Sakamoto, Ryohei Kawabata, Yusuke Akamaru, Yosuke Kito, Masazumi Takahashi, Jin Matsuyama, Hiroshi Yabusaki, Akitaka Makiyama, Takahisa Suzuki, Masahiro Tsuda, Hisateru Yasui, Hisato Kawakami, Ryo Matoba, Kei Muro, Takako Eguchi Nakajima, Wataru Ichikawa, Masashi Fujii, Yu Sunakawa
Journal: Annals of Oncology (2021)
Genetic Risk for Overall Cancer and the Benefit of Adherence to a Healthy Lifestyle
Authors: Meng Zhu, Tianpei Wang, Yanqian Huang, Xiaoyu Zhao, Yuqing Ding, Mengyi Zhu, Mengmeng Ji, Cheng Wang, Juncheng Dai, Rong Yin, Lin Xu, Hongxia Ma, Qingyi Wei, Guangfu Jin, Zhibin Hu, Hongbing Shen
Journal: Cancer Research (2021)

Abstract Cancer site–specific polygenic risk scores (PRS) effectively identify individuals at high risk of individual cancers, but the effectiveness of PRS on overall cancer risk assessment and the extent to which a high genetic risk of overall cancer can be offset by a healthy lifestyle remain unclear. Here, we constructed an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific PRSs. Lifestyle was determined according to smoking, alcohol consumption, physical activity, body mass index, and diet. Cox regression by sex was used to analyze associations of genetic and lifestyle factors with cancer incidence using UK Biobank data (N = 442,501). Compared with participants at low genetic risk (bottom quintile of CPRS), those at intermediate (quintiles 2 to 4) or high (top quintile) genetic risk had HRs of 1.27 (95% confidence interval, 1.21–1.34) or 1.91 (1.81–2.02) for overall cancer, respectively, for men, and 1.21 (1.16–1.27) or 1.62 (1.54–1.71), respectively, for women. A joint effect of genetic and lifestyle factors on overall cancer risk was observed, with HRs reaching 2.99 (2.45–3.64) for men and 2.38 (2.05–2.76) for women with high genetic risk and unfavorable lifestyle compared with those with low genetic risk and favorable lifestyle. Among participants at high genetic risk, the standardized 5-year cancer incidence was significantly reduced from 7.23% to 5.51% for men and from 5.77% to 3.69% for women having a favorable lifestyle. In summary, individuals at high genetic risk of overall cancer can be identified by CPRS, and risk can be attenuated by adopting a healthy lifestyle. Significance: A new indicator of cancer polygenic risk score measures genetic risk for overall cancer, which could identify individuals with high cancer risk to facilitate decision-making about lifestyle modifications for personalized prevention.
Could lung bacterial dysbiosis predict ICU mortality in patients with extra-pulmonary sepsis? A proof-of-concept study
Authors: Beatriz Guillen-Guio, Tamara Hernandez-Beeftink, Laura Ciuffreda, Héctor Rodríguez-Pérez, David Domínguez, Adrian Baez-Ortega, Almudena Corrales, Raúl Hernández-Bisshopp, Jorge Arias, Luis Soto, David Viera Camacho, Gabriela Noemí González, Marina Soro, Elena Espinosa, Julia Alcoba-Florez, Rafaela González-Montelongo, Jesús Villar, Carlos Flores
Journal: Intensive Care Medicine (2020)
Abstract 14595: Radiographic Predictors of Operative Difficulty in Minimally Invasive Mitral Valve Surgery
Authors: Edward Y Chan, Gregory D Pearson, Jonathan A Yang, Dennis M Lumbao, Alexander Iribarne, Rachel Easterwood, Elisabeth M Sebesta, Faisal H Cheema, Craig R Smith, Michael Argenziano
Journal: Circulation (2011)

OBJECTIVE Selection of candidates for minimally invasive cardiac surgery (MICS) is largely dictated by individual surgeon preference, and based on subjective assessments of body size and shape. Poo...
Abstract 8232: Obesity-Related Arterial-Ventricular Stiffening in Children
Authors: Kenji Harada, Yukiko Harada, Manatomo Toyono
Journal: Circulation (2011)

Background: Obesity is associated with structural and functional changes in the heart. Increases in arterial, ventricular systolic, and ventricular diastolic elastance (stiffness) may contribute to the pathogenesis of cardiac dysfunction. However, there is little information on arterial-ventricular stiffness and coupling in obese children. The purpose of the study is to assess the relationship between body mass index (BMI) and arterial-ventricular stiffening and coupling in children. Methods: Echocardiography with tissue Doppler imaging was performed in 303 children aged 6 to 15 years (BMI 12 to 34kg/m2). Left ventricular (LV) end-diastolic volume, LV mass, transmitral peak flow velocity (E), and mitral annular myocardial velocity (Em) were measured. LV mass/volume ratio was calculated. Stroke volume (SV) was measured using aortic diameter and pulsed Doppler velocity profile. SV was indexed for body surface area (SVI). Effective arterial elastance (Ea) was estimated by end-systolic pressure/SVI. End-systolic elastance (Ees) was calculated by a modified single-beat method using systolic and diastolic blood pressure, stroke volume, ejection fraction, timing intervals, and an estimated normalized ventricular elastance at arterial end diastole. Operant Ed was calculated from Doppler indices reflective of atrial pressures (E/Em) and the diastolic filling volume (SV). Results: Ea, Ees, and Ed all increased significantly with BMI(r = 0.35, p &lt; 0.01, 0.26, p &lt; 0.01, and 0.15, p &lt; 0.05, respectively). Arterial-ventricular coupling (Ea/Ees ratio) did not change with BMI. LV mass/volume ratio was positively associated with increased BMI (r = 0.48, p &lt; 0.01). The increased LV mass/volume ratio was due to a greater increase in LV mass to LV end-diastolic volume. There were weak but significant relationships between LV mass/volume ratio and Ees (r = 0.14, p &lt; 0.05), Ea (r = 0.18, p &lt; 0.01), and Ed (r = 0.15, p &lt; 0.05). Conclusions: The present study suggests that higher BMI is associated with increases in arterial, ventricular systolic, and ventricular diastolic stiffness in children. This combined arterial-ventricular stiffening in obese children may contribute to the increased prevalence of later cardiovascular diseases.
MO2-2 Preclinical evaluation of androgen deprivation with JAK1/2 and PD-L1 inhibition in mouse Pten-deficient prostate cancer
Authors: Yurie Kura, Develasco Marco, Naomi Ando, Noriko Sako, Kazuko Sakai, Kazuto Nishio, Hirotsugu Uemura
Journal: Annals of Oncology (2021)
Decrease post-transplant relapse using donor-derived expanded NK-cells
Authors: Stefan O. Ciurea, Piyanuch Kongtim, Doris Soebbing, Prashant Trikha, Gregory Behbehani, Gabriela Rondon, Amanda Olson, Qaiser Bashir, Alison M. Gulbis, Kaur Indreshpal, Katayoun Rezvani, Elizabeth J. Shpall, Roland Bassett, Kai Cao, Andrew St Martin, Steven Devine, Mary Horowitz, Marcelo Pasquini, Dean A. Lee, Richard E. Champlin
Journal: Leukemia (2021)

Abstract In this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 × 10 5 –1 × 10 8 cells/kg/dose) were administered on days −2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database. After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% ( p = 0.014), and disease-free survival (DFS) was 66% vs. 44% ( p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 ( p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype. Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 ( https://clinicaltrials.gov/ct2/show/NCT01904136 ).
Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study
Authors: Zuguo Mei, O Yaw Addo, Maria Elena Jefferds, Andrea J Sharma, Rafael C Flores-Ayala, Gary M Brittenham
Journal: The Lancet Haematology (2021)