tbuckley/cabot-search huggingface dataset:
A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture
Authors: Sanjiban Chakrabarty, William F. Quiros-Solano, Maayke M.P. Kuijten, Ben Haspels, Sandeep Mallya, Calvin Shun Yu Lo, Amr Othman, Cinzia Silvestri, Anja van de Stolpe, Nikolas Gaio, Hanny Odijk, Marieke van de Ven, Corrina M.A. de Ridder, Wytske M. van Weerden, Jos Jonkers, Ronald Dekker, Nitika Taneja, Roland Kanaar, Dik C. van Gent
Journal: Cancer Research (2021)

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. SIGNIFICANCE: The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.
Long-Term Follow-up of the Combination of Low-Intensity Chemotherapy Plus Inotuzumab Ozogamicin with or without Blinatumomab in Patients with Relapsed-Refractory Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia
Authors: Fadi Haddad, Hagop Kantarjian, Nicholas J. Short, Koji Sasaki, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Richard E. Champlin, Tapan M. Kadia, Koichi Takahashi, Naval Daver, Joseph D. Khoury, Jeffrey L. Jorgensen, Sa A Wang, Jovitta Jacob, Rebecca Garris, Susan M. O'Brien, Elias J. Jabbour
Journal: Blood (2021)
Evaluation of a Stepped Care Approach to Manage Depression and Diabetes Distress in Patients with Type 1 Diabetes and Type 2 Diabetes: Results of a Randomized Controlled Trial (ECCE HOMO Study)
Authors: Andreas Schmitt, Bernhard Kulzer, André Reimer, Christian Herder, Michael Roden, Thomas Haak, Norbert Hermanns
Journal: Psychotherapy and Psychosomatics (2021)

Depression is a common and serious complication of diabetes. Treatment approaches addressing the specific demands of affected patients are scarce.The aim of this work was to test whether a stepped care approach for patients with diabetes and depression and/or diabetes distress yields greater depression reduction than treatment-as-usual.Two-hundred and sixty patients with diabetes and elevated depressive symptoms (CES-D ≥16) and/or elevated diabetes distress (PAID ≥40) were randomized to stepped care for depression or diabetes treatment-as-usual. The primary outcome was the rate of meaningful depression reduction at the 12-month follow-up according to the HAMD (score <9 or reduction by ≥50%). Secondary outcomes were changes in depression scores (HAMD/CES-D), diabetes distress (PAID), diabetes acceptance (AADQ), well-being (WHO-5), quality of life (EQ-5D/SF-36), self-care behavior (SDSCA/DSMQ), HbA1c, and biomarkers of inflammation.One-hundred and thirty-one individuals were assigned to stepped care and 129 to treatment-as-usual. Overall, 15.4% were lost to follow-up. Meaningful depression reduction was observed in 80.2 versus 51.2% in stepped care versus treatment-as-usual (p < 0.001, intention-to-treat analysis). Of the secondary measures, the HAMD (∆ -3.2, p < 0.001), WHO-5 (∆ 1.5, p = 0.007), and AADQ (∆ -1.0, p = 0.008) displayed significant treatment effects, while effects on CES-D (∆ -2.3, p = 0.065), PAID (∆ -3.5, p = 0.109), and SDSCA (∆ 0.20, p = 0.081) were not significantly different. Both groups showed comparable changes in EQ-5D/SF-36, DSMQ, HbA1c, and biomarkers of inflammation (all p ≥ 0.19).The stepped care approach improved depression, well-being, and acceptance. The results support that increasing treatment intensity on demand is effective and can help provide more optimal treatment. The inclusion of diabetes-specific interventions may be beneficial for patients with diabetes and elevated depression.
Highlights from this issue
Authors: The Triumvirate
Journal: Thorax (2021)

The Triumvirate "Remember, remember the 5th of November: gunpowder, treason and plot!"As this issue of Thorax drops on your doormat, UK readers are preparing for Guy Fawkes night, when we remember a foiled attempt to blow up parliament and we burn an effigy of Guy Fawkes on bonfires around the country.Treason is still to be found in the UK respiratory landscape with a plot by the tobacco giant, Phillip Morris, to take over the inhaler manufacturer Vectura.The plot seems unlikely to be foiled at the last minute and we are not aware of any plans to burn effigies of the CEO of Phillip Morris this year…
<i>QuickStats:</i> Age-Adjusted Death Rates* for Female Breast Cancer,† by State — National Vital Statistics System, United States, 2019§
Authors: Sibeso Joyner
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Abbreviation: DC = District of Columbia.* Data were age-adjusted to the 2000 U.S. standard population.The 2019 U.S. breast cancer death rate was 19.4 per 100,000 population.† Breast cancer deaths were those with International Classification of Diseases, Tenth Revision underlying cause of death code C50.§ Rates are displayed by a Jenks classification for U.S. states and DC, which creates categories that minimize within-group variation and maximize between-group variation.In 2019, the age-adjusted rate of female breast cancer deaths in the United States was 19.4 per 100,000 population.Jurisdictions in the highest category for breast cancer death rates were DC (24.5),Nevada (23.7),Nebraska (22.4), Kentucky (22.2),Louisiana (22.0), and Mississippi (22.0).Those in the lowest category were North Dakota (14.8),Massachusetts (15.3),Vermont (16.2),Connecticut (16.8),Wyoming (17.2),Minnesota (17.5),Colorado (17.6), Wisconsin (17.6), and Maine (17.7).
Abstract 11112: Impact of Changes in Clinical Practice Guidelines on Survival Outcomes After Traumatic Out-of-Hospital Cardiac Arrest
Authors: Zainab Alqudah, Ziad Nehme, Brett Williams, Alaa Oteir, Karen L Smith
Journal: Circulation (2021)

Aim: In this study, we examine the impact of a trauma-based resuscitation protocol on survival outcomes following emergency medical services (EMS) witnessed traumatic out-of-hospital cardiac arrest (OHCA). Methods: We included EMS-witnessed OHCAs arising from trauma and occurring between 2008 and 2019. In December 2016, a new resuscitation protocol for traumatic OHCA was introduced prioritizing the treatment of potentially reversible causes before conventional cardiopulmonary resuscitation. The effect of the new protocol on survival outcomes was assessed using adjusted multivariable logistic regression models. Results: Paramedics attempted resuscitation on 490 patients, with 341 (69.6%) and 149 (30.4%) occurring during the control and intervention periods, respectively. A reduction in the proportion of cases receiving cardiopulmonary resuscitation and epinephrine administration were found in the intervention period compared to the control period, whereas trauma-based interventions increased significantly, including blood administration (pre-arrest: 17.9% vs 3.7%; intra-arrest: 24.1% vs 2.7%), splinting (pre-arrest: 38.6% vs 17.1%; intra-arrest: 20.7% vs 5.2%), and finger thoracostomy (pre-arrest: 13.1% vs 0.6%; intra-arrest: 22.8% vs 0.9%), respectively, with p-values &lt;0.001 for all comparisons. After adjustment, the trauma-based resuscitation protocol was not associated with an improvement in survival to hospital discharge (AOR 1.29, 95% CI: 0.51-3.23), event survival (AOR 0.72, 95% CI: 0.41-1.28) or prehospital return of spontaneous circulation (AOR 0.63, 95% CI: 0.39-1.03). Conclusion: In our region, the introduction of a trauma-based resuscitation protocol led to an increase in the delivery of almost all trauma interventions; however, this did not translate into better survival outcomes following EMS-witnessed traumatic OHCA.
A transcriptional biosensor to monitor single cancer cell therapeutic responses by bioluminescence microscopy
Authors: Audrey Champagne, Pallavi Jain, Lauriane Vélot, Julie Riopel, Véronique Lefebvre, Bertrand Neveu, Frédéric Pouliot
Journal: Theranostics (2021)

When several life-prolonging drugs are indicated for cancer treatment, predictive drug-response tumor biomarkers are essential to guide management. Most conventional biomarkers are based on bulk tissue analysis, which cannot address the complexity of single-cell heterogeneity responsible for drug resistance. Therefore, there is a need to develop alternative drug response predictive biomarker approaches that could directly interrogate single-cell and whole population cancer cell drug sensitivity. In this study, we report a novel method exploiting bioluminescence microscopy to detect single prostate cancer (PCa) cell response to androgen receptor (AR)-axis-targeted therapies (ARAT) and predict cell population sensitivity. Methods: We have generated a new adenovirus-delivered biosensor, PCA3-Cre-PSEBC-ITSTA, which combines an integrated two-step transcriptional amplification system (ITSTA) and the activities of the prostate cancer antigen 3 (PCA3) and modified prostate-specific antigen (PSEBC) gene promoters as a single output driving the firefly luciferase reporter gene. This system was tested on PCa cell lines and on primary PCa cells. Single cells, exposed or not to ARAT, were dynamically imaged by bioluminescence microscopy. A linear discriminant analysis (LDA)-based method was used to determine cell population sensitivities to ARAT. Results: We show that the PCA3-Cre-PSEBC-ITSTA biosensor is PCa-specific and can dynamically monitor single-cell AR transcriptional activity before and after ARAT by bioluminescence microscopy. After biosensor transduction and bioluminescence microscopy single-cell luminescence dynamic quantification, LDA analysis could discriminate the cell populations overall ARAT sensitivity despite heterogeneous single-cell responses. Indeed, the biosensor could detect a significant decrease in AR activity following exposure to conventional ARAT in hormone-naive primary PCa cells, while in castration-resistant PCa patients, treatment response correlated with the observed clinical ARAT resistance. Conclusion: The exploitation of bioluminescence microscopy and multi-promoter transcriptionally-regulated biosensors can aptly define the overall treatment response of patients by monitoring live single cell drug response from primary cancer tissue. This approach can be used to develop predictive biomarkers for drug response in order to help clinicians select the best drug combinations or sequences for each patient.
Abstract 13213: The Prognostic Role of Serum Neutrophil Gelatinase Associated Lipocalin in Out of Hospital Cardiac Arrest Patients Who Underwent Targeted Temperature Management
Authors: Changjoo An, Jung Soo Park, Changshin Kang, Yeonho You
Journal: Circulation (2021)

This study investigated the prognostic value of serum neutrophil gelatinase-associated lipocalin (NGAL) in patients treated with targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). The study included 85 comatose adult patients with OHCA who underwent TTM between May 2018 and December 2020. Serum NGAL and neuron-specific enolase (NSE) were measured at 24-h intervals until 72 h after return of spontaneous circulation (ROSC). The primary outcome was neurological status at 3 months after OHCA. Forty-nine patients (57.6%) had a poor neurological outcome; NGAL levels at all time points measured were significantly higher in these patients than in those with a good outcome (p&lt;0.01). NGAL showed lower maximal sensitivity (95% CI) under a false-positive rate of 0% for the primary outcome compared with NSE (18.2% [95% CI 8.2-32.7] vs. 66.7% [95% CI 50.5-80.4]). Combination of NGAL with NSE at 48 h showed the highest sensitivity (69.1% [95% CI 52.9-82.4]) and had the highest AUC (0.91 [95% CI 0.81-0.96]) for a poor outcome. The prognostic performance of NGAL alone was inadequate at all time points. However, NGAL obtained at 24 and 48 h after ROSC showed improved sensitivity when combined with NSE. NGAL should be considered as an additional biomarker to improve accuracy for prognostication in these patients.
55P Neoantigen-reactive CD8 T-cells experience broadened and activated recognition profile following PD-L1 blockade and 1000-fold neoantigen-specific expansion using ImmPACT scaffolds
Authors: J. Sejerø Holm, S.A. Funt, S.A. Tvingsholm, A. Borch, D.F. Bajorin, S. Reker Hadrup
Journal: Annals of Oncology (2021)
Microbial metabolite delta-valerobetaine is a diet-dependent obesogen
Authors: Ken H. Liu, Joshua A. Owens, Bejan Saeedi, Catherine E. Cohen, Moriah P. Bellissimo, Crystal Naudin, Trevor Darby, Samuel Druzak, Kristal Maner-Smith, Michael Orr, Xin Hu, Jolyn Fernandes, Mary Catherine Camacho, Sarah Hunter-Chang, David VanInsberghe, Chunyu Ma, Thota Ganesh, Samantha M. Yeligar, Karan Uppal, Young-Mi Go, Jessica A. Alvarez, Miriam B. Vos, Thomas R. Ziegler, Michael H. Woodworth, Colleen S. Kraft, Rheinallt M. Jones, Eric Ortlund, Andrew S. Neish, Dean P. Jones
Journal: Nature Metabolism (2021)
Safety, Tolerability, PK/PD and Preliminary Efficacy of NKTR-255, a Novel IL-15 Receptor Agonist, in Patients with Relapsed/Refractory Hematologic Malignancies
Authors: Nina Shah, Alan Tan, Elizabeth Budde, Craig C. Hofmeister, Andrew J. Cowan, Miguel-Angel Perales, Taewoong Choi, Hayder Saeed, Julio C. Chavez, Jing C. Ye, Mitchell S. Cairo, David A. Rizzieri, Gregory J. Orloff, Zachary Lee, Neha Dixit, Wildaliz Nieves, Qiang Zhao, Xiaoli Wang, Kazuharu Kai, Mario Q. Marcondes, Mary A. Tagliaferri, Jonathan Zalevsky, Krina K. Patel
Journal: Blood (2021)
Health-Related Quality of Life Measurement in Public Health
Authors: Robert M. Kaplan, Ron D. Hays
Journal: Annual Review of Public Health (2021)

Patient-reported outcomes are recognized as essential for the evaluation of medical and public health interventions. Over the last 50 years, health-related quality of life (HRQoL) research has grown exponentially from 0 to more than 17,000 papers published annually. We provide an overview of generic HRQoL measures used widely in epidemiological studies, health services research, population studies, and randomized clinical trials [e.g., Medical Outcomes Study SF-36 and the Patient-Reported Outcomes Measurement Information System (PROMIS®)-29]. In addition, we review methods used for economic analysis and calculation of the quality-adjusted life year (QALY). These include the EQ-5D, the Health Utilities Index (HUI), the self-administered Quality of Well-being Scale (QWB-SA), and the Health and Activities Limitation Index (HALex). Furthermore, we consider hybrid measures such as the SF-6D and the PROMIS-Preference (PROPr). The plethora of HRQoL measures has impeded cumulative science because incomparable measures have been used in different studies. Linking among different measures and consensus on standard HRQoL measurement should now be prioritized. In addition, enabling widespread access to common measures is necessary to accelerate future progress.
61P IMpower110: Exploratory analyses of the impact of first-line (1L) atezolizumab on the efficacy of next-line of therapy in PD-L1–selected NSCLC
Authors: S.P. Patel, J.E. Reuss, K. Scilla, G. Giaccone, D.R. Spigel, C. Ngiam, Q. Zhu, I. Bara, B. Ding, R.S. Herbst
Journal: Annals of Oncology (2021)
Factors associated with the clinical outcome of patients with relapsed/refractory CD19<sup>+</sup> acute lymphoblastic leukemia treated with ARI-0001 CART19-cell therapy
Authors: Valentín Ortiz-Maldonado, Susana Rives, Marta Español-Rego, Anna Alonso-Saladrigues, Mercedes Montoro, Laura Magnano, Eva Giné, Mariona Pascal, Marina Díaz-Beyá, Maria Castella, Albert Català, Anna Faura, Luis Gerardo Rodríguez-Lobato, Aina Oliver-Caldes, Alexandra Martínez-Roca, Montserrat Rovira, E Azucena González-Navarro, Juan Ramón Ortega, Joan Cid, Miquel Lozano, Enric Garcia-Rey, Sara Fernández, Pedro Castro, Iolanda Jordan, Neus Villamor, Marta Aymerich, Montserrat Torrebadell, Àngela Deyà, Carlos Fernández de Larrea, Daniel Benitez-Ribas, Esteve Trias, Sara Varea, Gonzalo Calvo, Jordi Esteve, Alvaro Urbano-Ispizua, Manel Juan, Julio Delgado
Journal: Journal for ImmunoTherapy of Cancer (2021)

<h3>Abstract</h3> Serum antibodies IgM and IgG are elevated during COVID-19 to defend against viral attack. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their two-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense, and that high titers of IgM might not be favorable to COVID-19 recovery.
SOD2 V16A amplifies vascular dysfunction in sickle cell patients by curtailing mitochondria complex IV activity
Authors: Atinuke Dosunmu-Ogunbi, Shuai Yuan, Michael Reynolds, Luca Giordano, Subramaniam Sanker, Mara Sullivan, Donna Beer Stolz, Brett A. Kaufman, Katherine C. Wood, Yingze Zhang, Sruti Shiva, Seyed Mehdi Nouraie, Adam C. Straub
Journal: Blood (2021)
Lack of Attending Surgeon Scrubbed and Resident Autonomy Are Not Equivalent
Authors: Jonah J. Stulberg, Sasha D. Adams, Lillian S. Kao
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
QOLP-31. QUALITY OF LIFE OF PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA DURING TTFIELDS THERAPY IN ROUTINE CLINICAL CARE: FIRST RESULTS OF THE TIGER STUDY
Authors: Oliver Bähr, Ghazaleh Tabatabai, Rainer Fietkau, Roland Goldbrunner, Martin Glas
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE Current interdisciplinary treatment strategies for glioblastoma (GBM) outside clinical trials include maximally safe resection, followed by radiation and chemotherapy. The results of the positive phase III trial EF-14, adding Tumor Treating Fields (TTFields) to temozolomide (TMZ) maintenance therapy, brought an additional treatment method to clinical routine. The TIGER (TTFields In GErmany in Routine Clinical Care) study documents the use of TTFields in routine clinical care with a focus on health-related quality of life (HRQoL) within 4 months after starting therapy, treatment compliance and duration. METHODS This multi-center, prospective, non-interventional study in Germany (NCT03258021) included ndGBM patients eligible for TTFields therapy. Following their consent, patients received a comprehensive introduction to the therapy and baseline demographic data were collected. Information on TTFields therapy decision was evaluated based on a dedicated TTFields questionnaire at baseline in both arms; follow-up information on how patients handle the therapy was collected two months after TTFields treatment start. HRQoL was assessed in patients deciding for TTFields therapy at baseline and at 2 and 4 months using the EORTC-QLQ-C30/BN-20 questionnaires. RESULTS Between August 2017 and November 2019, 710 patients (259 female/451 male) were enrolled at 81 participating centers. The mean age was 58.5 years (range: 19.0-85.0; Cut-off: August 31, 2020). The overall baseline characteristics of the study group reflects a typical GBM population. Of these, 582 (82%) decided to start TTFields; 128 (18%) refused TTFields treatment. HRQoL did not decline during TTFields therapy except for itchy skin, comparable to the EF-14 trial. A detailed analysis of the cohort as well as their reported QoL will be presented. CONCLUSION The TIGER study is the largest non-interventional trial on the use of TTFields in routine clinical care. The use of TTFields in patients with ndGBM did not impair HRQoL during the follow-up period, except for more itchy skin.