tbuckley/cabot-search huggingface dataset:
Innovations in research and clinical care using patient‐generated health data
Authors: Heather S. L. Jim, Aasha I. Hoogland, Naomi C. Brownstein, Anna Barata, Adam P. Dicker, Hans Knoop, Brian D. Gonzalez, Randa Perkins, Dana Rollison, Scott M. Gilbert, Ronica Nanda, Anders Berglund, Ross Mitchell, Peter A. S. Johnstone
Journal: CA A Cancer Journal for Clinicians (2020)

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.
Ex Vivo Production of Transfusable Red Blood Cells at Large Scale from Cord Blood CD34+ Cells Using a Coculture System with Human Telomerase Catalytic Subunit (hTERT)-Transfected Human Stromal Cells at Early Phase and with Acitivated Macrophage from Cord Blood CD34+ Cells at Late Phase.
Authors: Akihito Fujimi, Takuya Matsunaga, Masayoshi Kobune, Yutaka Kawano, Ikuta Tanaka, Naofumi Takemoto, Takehide Akiyama, Hirofumi Hamada, Yoshiro Niitsu
Journal: Blood (2004)
Interleukin 17 and senescent cells regulate the foreign body response to synthetic material implants in mice and humans
Authors: Liam Chung, David R. Maestas, Andriana Lebid, Ashlie Mageau, Gedge D. Rosson, Xinqun Wu, Matthew T. Wolf, Ada J. Tam, Isabel Vanderzee, Xiaokun Wang, James I. Andorko, Hong Zhang, Radhika Narain, Kaitlyn Sadtler, Hongni Fan, Daniela Čiháková, Claude Jourdan Le Saux, Franck Housseau, Drew M. Pardoll, Jennifer H. Elisseeff
Journal: Science Translational Medicine (2020)

Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyzed fibrotic capsules surrounding surgically excised human breast implants from 12 individuals. We found increased numbers of interleukin 17 (IL17)-producing γδ+ T cells and CD4+ T helper 17 (TH17) cells as well as senescent stromal cells in the fibrotic capsules. Further analysis in a murine model demonstrated an early innate IL17 response to implanted synthetic material (polycaprolactone) particles that was mediated by innate lymphoid cells and γδ+ T cells. This was followed by a chronic adaptive CD4+ TH17 cell response that was antigen dependent. Synthetic materials with varying chemical and physical properties implanted either in injured muscle or subcutaneously induced similar IL17 responses in mice. Mice deficient in IL17 signaling established that IL17 was required for the fibrotic response to implanted synthetic materials and the development of p16INK4a senescent cells. IL6 produced by senescent cells was sufficient for the induction of IL17 expression in T cells. Treatment with a senolytic agent (navitoclax) that killed senescent cells reduced IL17 expression and fibrosis in the mouse implant model. Discovery of a feed-forward loop between the TH17 immune response and the senescence response to implanted synthetic materials introduces new targets for therapeutic intervention in the foreign body response.
TG101348, An Orally Bioavailable JAK2-Selective Inhibitor, Potently Inhibits KITD816V and FIP1L1-PDGFRA in Vitro
Authors: Jaya Kittur, Terra L Lasho, Joseph H Butterfield, Jolene Shorr, Ayalew Tefferi, Animesh D. Pardanani
Journal: Blood (2008)
Comparison Between the Performance of Quantitative Flow Ratio and Perfusion Imaging for Diagnosing Myocardial Ischemia
Authors: Pepijn A. van Diemen, Roel S. Driessen, Rolf A. Kooistra, Wynand J. Stuijfzand, Pieter G. Raijmakers, Ronald Boellaard, Stefan P. Schumacher, Michiel J. Bom, Henk Everaars, Ruben W. de Winter, Peter M. van de Ven, Johan H. Reiber, James K. Min, Jonathan A. Leipsic, Juhani Knuuti, Richard S. Underwood, Albert C. van Rossum, Ibrahim Danad, Paul Knaapen
Journal: JACC. Cardiovascular imaging (2020)
RNAi-Based Gene Therapy Rescues Developmental and Epileptic Encephalopathy in a Genetic Mouse Model
Authors: Osasumwen V. Aimiuwu, Allison M. Fowler, Megha Sah, Jia Jie Teoh, Ayla Kanber, Nettie K. Pyne, Sabrina Petri, Chana Rosenthal-Weiss, Mu Yang, Scott Q. Harper, Wayne N. Frankel
Journal: Molecular Therapy (2020)

Developmental and epileptic encephalopathy (DEE) associated with de novo variants in the gene encoding dynamin-1 (DNM1) is a severe debilitating disease with no pharmacological remedy. Like most genetic DEEs, the majority of DNM1 patients suffer from therapy-resistant seizures and comorbidities such as intellectual disability, developmental delay, and hypotonia. We tested RNAi gene therapy in the Dnm1 fitful mouse model of DEE using a Dnm1-targeted therapeutic microRNA delivered by a self-complementary adeno-associated virus vector. Untreated or control-injected fitful mice have growth delay, severe ataxia, and lethal tonic-clonic seizures by 3 weeks of age. These major impairments are mitigated following a single treatment in newborn mice, along with key underlying cellular features including gliosis, cell death, and aberrant neuronal metabolic activity typically associated with recurrent seizures. Our results underscore the potential for RNAi gene therapy to treat DNM1 disease and other genetic DEEs where treatment would require inhibition of the pathogenic gene product.
Robot-assisted Cavectomy Versus Thrombectomy for Level II Inferior Vena Cava Thrombus: Decision-making Scheme and Multi-institutional Analysis
Authors: Taoping Shi, Qingbo Huang, Kan Liu, Songliang Du, Yang Fan, Luojia Yang, Cheng Peng, Dan Shen, Zhongxin Wang, Yu Gao, Liangyou Gu, Shaoxi Niu, Qing Ai, Hongzhao Li, Fengyong Liu, Qiuyang Li, Haiyi Wang, Aitao Guo, Bin Fu, Xiaojian Yang, Xuepei Zhang, Delin Wang, Dongwen Wang, Hongqian Guo, Hengping Li, Alberto Olivero, Xeng Inn Fam, Xin Ma, Baojun Wang, Xu Zhang
Journal: European Urology (2020)
Cancer cell-intrinsic expression of MHC II in lung cancer cell lines is actively restricted by MEK/ERK signaling and epigenetic mechanisms
Authors: Alexander J Neuwelt, Abigail K Kimball, Amber M Johnson, Benjamin W Arnold, Bonnie L Bullock, Rachael E Kaspar, Emily K Kleczko, Jeff W Kwak, Meng-Han Wu, Lynn E Heasley, Robert C Doebele, Howard Y Li, Raphael A Nemenoff, Eric T Clambey
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Programmed death 1/programmed death ligand 1 (PD-1/PD-L1) targeted immunotherapy affords clinical benefit in ~20% of unselected patients with lung cancer. The factor(s) that determine whether a tumor responds or fails to respond to immunotherapy remains an active area of investigation. We have previously defined divergent responsiveness of two KRAS-mutant cell lines to PD-1/PD-L1 blockade using an orthotopic, immunocompetent mouse model. Responsiveness to PD-1/PD-L1 checkpoint blockade correlates with an interferon gamma (IFNγ)-inducible gene signature and major histocompatibility complex class II (MHC II) expression by cancer cells. In the current study, we aim to identify therapeutic targets that can be manipulated in order to enhance cancer-cell-specific MHC II expression. Methods Responsiveness to IFNγ and induction of MHC II expression was assessed after various treatment conditions in mouse and human non-small cell lung cancer (NSCLC) cell lines using mass cytometric and flow cytometric analysis. Results Single-cell analysis using mass and flow cytometry demonstrated that IFNγ consistently induced PD-L1 and MHC class I (MHC I) across multiple murine and human NSCLC cell lines. In contrast, MHC II showed highly variable induction following IFNγ treatment both between lines and within lines. In mouse models of NSCLC, MHC II induction was inversely correlated with basal levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting potential mitogen-activated protein (MAP) kinase-dependent antagonism of MHC II expression. To test this, cell lines were subjected to varying levels of stimulation with IFNγ, and assessed for MHC II expression in the presence or absence of mitogen-activated protein kinase kinase (MEK) inhibitors. IFNγ treatment in the presence of MEK inhibitors significantly enhanced MHC II induction across multiple lung cancer lines, with minimal impact on expression of either PD-L1 or MHC I. Inhibition of histone deacetylases (HDACs) also enhanced MHC II expression to a more modest extent. Combined MEK and HDAC inhibition led to greater MHC II expression than either treatment alone. Conclusions These studies emphasize the active inhibitory role that epigenetic and ERK signaling cascades have in restricting cancer cell-intrinsic MHC II expression in NSCLC, and suggest that combinatorial blockade of these pathways may engender new responsiveness to checkpoint therapies.
Association of a Novel Protocol for Rapid Exclusion of Myocardial Infarction With Resource Use in a US Safety Net Hospital
Authors: Rebecca Vigen, Deborah B. Diercks, Ibrahim A. Hashim, Ambarish Pandey, Lin Zhong, Patricia Kutscher, Fernabelle Fernandez, Amy Yu, Bryan Bertulfo, Kyle Molberg, Jeffery C. Metzger, Jose Soto, Dergham Alzubaidy, Lorie Thibodeaux, Jose A. Joglar, Sandeep R. Das, James A. de Lemos
Journal: JAMA Network Open (2020)

<h3>Importance</h3> High-sensitivity cardiac troponin T (hs-cTnT) protocols for the evaluation of chest pain in the emergency department (ED) may reduce unnecessary resource use and overcrowding. <h3>Objective</h3> To determine whether the implementation of a novel hs-cTnT protocol, which incorporated troponin values drawn at 0, 1, and 3 hours after ED presentation and the modified HEART score (history, electrocardiogram, age, risk factors), was associated with improvements in resource use while maintaining safety. <h3>Design, Setting, and Participants</h3> This retrospective cohort study from Parkland Health and Hospital System, a large safety net hospital in Dallas, Texas, included data on 31 543 unique ED encounters in which patients underwent electrocardiographic and troponin testing from January 1, 2017, to October 16, 2018. The hs-cTnT protocol was implemented in December 2017. <h3>Main Outcomes and Measures</h3> Resource use outcomes included trends in ED dwell time, troponin to disposition decision time (the difference between the first troponin draw time and the time an order was placed for inpatient admission, admission to observation, or discharge), and final patient disposition. Safety outcomes included readmission for myocardial infarction and death. <h3>Results</h3> In 31 543 encounters, mean (SD) patient age was 54 (14.4) years and 14 675 patients (48%) were female. Department dwell time decreased by a mean of −1.09 (95% CI, −2.81 to 0.64) minutes per month in the preintervention period. The decline was steeper after the intervention (−4.69 [95% CI, −9.05 to −0.33] minutes per month) (<i>P</i>for interaction = .007). The troponin to disposition time was increasing in the preintervention period by 1.72 (95% CI, 1.08 to 2.36) minutes per month; postintervention, the mean difference increased more slowly (0.37 [95% CI, −1.25 to 1.99 minutes per month;<i>P</i>value for interaction = .007]). The proportion of patients discharged from the ED increased after the intervention (48% vs 54%,<i>P</i> &lt; .001). Thirty-day major adverse cardiac event rates were low and did not differ before and after the intervention. <h3>Conclusions and Relevance</h3> Implementation of a novel protocol incorporating serial hs-cTnT measurements over 3 hours with the Modified HEART Score was associated with reduction in ED dwell times and attenuation of temporal increases in time from troponin measurement to disposition. This or similar protocols to rule out myocardial infarction have the potential to reduce ED overcrowding and improve health care quality while maintaining safety.
William Brumfitt: pioneer of modern microbiology
Authors: Rebecca Wallersteiner
Journal: BMJ (2020)

Born in Ilkley, William Brumfitt was educated at Worksop College in Nottinghamshire, where he shone at science and enjoyed playing rugby. In his youth he played centre three quarter for Yorkshire.

His friend and colleague Jeremy Hamilton-Miller, who worked with him for more than 30 years, says, “Bill was a Yorkshireman and proud of it: his two elder brothers lived there, and he spoke often of the Moors and Dales, although he did not often visit, but he always referred to it as home.

“He was interviewed at St Mary’s Hospital Medical School, which has a long rugby tradition, by Lord Moran, and I gather the crucial question was, ‘What position do you play in rugby?’ His answer, ‘Fly half,’ was deemed satisfactory. He went on to play for the army, and for Gloucester, and was selected for an England trial.”

After qualifying, Brumfitt did his national service, during which he found time to write his MD thesis on iron deficiency anaemia. His PhD topic, researched in Alexander Fleming’s laboratory in the Wright-Fleming Institute, was a study of certain aspects of lysozyme.

He was appointed senior lecturer and …
Enhanced Levels of Apoptosis by Combination of Farnesyl Transferase Inhibition (Tipifarnib) and Proteasome Inhibition (Bortezomib) in Myeloma Cell Lines and Primary Myeloma Cells and Its Mechanistic Effects on Akt and Caspase Pathways.
Authors: Jonathan L. Kaufman, Ebenezer David2, Claire Torre3, Rajni Sinha4, Sagar Lonial5
Journal: Blood (2005)
Tashinone IIA Can Trigger the Apoptosis of a Megakaryocytic Cell Line CHRF- 288 through the TNFRSF9 Mediated Caspase-3 Activation Pathway
Authors: Chang Charlie Liu, LiangJie Vicky Wang, Min Zhou, JieYu Ye, Godfrey ChiFung Chan, Mo Yang
Journal: Blood (2008)
The Missing Waveform Information in the Orthogonal Electrocardiogram (Frank Leads)
Authors: F. KORNREICH
Journal: Circulation (1973)

The orthogonal electrocardiogram (Frank leads) is a reasonable compromise between the demands of practicability and diagnostic accuracy. The accuracy has been enhanced by the use of computerized multivariate statistical procedures. The work of the last two or three decades, however, has shown that these leads account for only part of the total available surface information. In this paper, the missing waveform information with respect to the Frank leads is quantitatively and systematically determined and a method of retrieval is worked out. The essence of this method rests on the empirical evidence obtained by testing each of the 126 surface electrocardiograms for the XYZ content. The results are analyzed by a least squares, best fit procedure. The poorly fitted curves are considered as additional waveform sources. The number and the sites of the additional information are determined on a test group of 207 patients. The "total" surface waveform information is found to be represented by nine surface leads. This set of waveforms is then tested on a control group consisting of 205 patients. An average resynthesis coefficient of 96% is reached. No further resynthesis is looked for because of the estimated noise level. Although the waveforms recorded at these sites represent the minimum number of unique building blocks capable of synthesizing any waveform on the body surface, they cannot predict the surface potential distribution at all surface points. This information is "total" as far as statistical procedures-performing discriminant analysis on time-functions—are concerned. This "total" waveform information consists of a set of electrocardiograms recorded in each individual at nine well-defined anatomical locations.
Covid-19: Disproportionate impact on ethnic minority healthcare workers will be explored by government
Authors: Abi Rimmer
Journal: BMJ (2020)

Preoperative localization of the parathyroids using <sup>99m</sup>Tc-sestamibi scanning has not yet been established as a routine diagnostic procedure for primary hyperparathyroidism. Several studies have demonstrated a variable degree of accuracy (70%–98%) in asymptomatic patients. <b>Methods:</b> We evaluated the accuracy of this technique in 64 patients who underwent scanning between January 2000 and January 2005 according to the clinical manifestations of the disease. <b>Results:</b> The study included 25 asymptomatic patients (group I), 18 nephrolithiasis patients without overt bone disease (group II), and 21 patients with severe bone involvement and osteitis fibrosa cystica (group III). Mean serum calcium in groups I, II, and III was 10.98 ± 0.02, 11.32 ± 0.17, and 13.35 ± 0.35 mg/dL, respectively. Mean serum parathyroid hormone in groups I, II, and III was 135.45 ± 13.50, 165.85 ± 15.06, and 579.6 ± 628.4 pg/mL, respectively. The <sup>99m</sup>Tc-sestamibi scan results were positive in 64% of the patients in group I, in 83% of those in group II, and in 100% of those in group III. Of the patients with severe bone disease, 70% showed increased uptake on the initial images, whereas in the other groups, increased uptake was seen only on the delayed images, as expected. <b>Conclusion:</b> Our data show a high degree of accuracy for the use of <sup>99m</sup>Tc-sestamibi scanning as a localizing procedure in severe primary hyperparathyroidism.
Chloroquine reduces Th17 cell differentiation by stimulating T-bet expression in T cells
Authors: Rodolfo Thome, Alexandra Boehm, Larissa Lumi Watanabe Ishikawa, Giacomo Casella, Jaqueline Munhoz, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad Rostami
Journal: Cellular and Molecular Immunology (2020)
Covid-19: Japan prepares to extend state of emergency nationwide as “untraceable” cases soar
Authors: Mun-Keat Looi
Journal: BMJ (2020)

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Managing high clinical suspicion COVID-19 inpatients with negative RT-PCR: a pragmatic and limited role for thoracic CT
Authors: Aniket N Tavare, Aaron Braddy, Simon Brill, Hannah Jarvis, Anand Sivaramakrishnan, Joseph Barnett, Dean D Creer, Samanjit S Hare
Journal: Thorax (2020)

As the COVID-19 pandemic sweeps across the UK there remain issues with reverse-transcription polymerase chain reaction (RT-PCR), the gold standard diagnostic method. Delays in obtaining results have been particularly problematic. Some patients, including those with high clinical suspicion of COVID-19, test falsely negative on initial RT-PCR test, sometimes requiring multiple subsequent tests to return an eventual positive result. Suggested possible reasons for this include: suboptimal clinical sampling techniques; variations in viral load; and manufacturer test kit sensitivity.1 With surging caseloads, managing these RT-PCR ‘negative’ patients is proving hugely challenging.

An emerging bottleneck to effective care is dealing with isolation capacity. Inpatients who are truly PCR negative can be moved to a non-isolation ward, thereby freeing up isolation beds for COVID-19 positive patients and also reducing risk of nosocomial virus transmission. Patients with high index clinical suspicion of COVID-19, but who test negative on initial RT-PCR test, continue to be managed with respiratory isolation precautions, often undergoing repeat PCR testing. However, this means further delay while awaiting subsequent test results. Against this backdrop, an effective pathway to deal with negative COVID-19 RT-PCR results in the setting of high clinical probability is urgently needed.

A further important concern is developing regarding deisolation on patient discharge to either home or community care: a confirmed COVID-19 diagnosis - or confirmed alternative, non-COVID-19 diagnosis - is key to imparting advice to families and carers.

Imaging has been suggested as a potential solution to some of these problems. Most patients undergo chest radiograph (CXR) at presentation to hospital, with CXRs being hot-reported using a template …
Surgical spectral imaging
Authors: Neil T. Clancy, Geoffrey Jones, Lena Maier-Hein, Daniel S. Elson, Danail Stoyanov
Journal: Medical Image Analysis (2020)

Recent technological developments have resulted in the availability of miniaturised spectral imaging sensors capable of operating in the multi- (MSI) and hyperspectral imaging (HSI) regimes. Simultaneous advances in image-processing techniques and artificial intelligence (AI), especially in machine learning and deep learning, have made these data-rich modalities highly attractive as a means of extracting biological information non-destructively. Surgery in particular is poised to benefit from this, as spectrally-resolved tissue optical properties can offer enhanced contrast as well as diagnostic and guidance information during interventions. This is particularly relevant for procedures where inherent contrast is low under standard white light visualisation. This review summarises recent work in surgical spectral imaging (SSI) techniques, taken from Pubmed, Google Scholar and arXiv searches spanning the period 2013–2019. New hardware, optimised for use in both open and minimally-invasive surgery (MIS), is described, and recent commercial activity is summarised. Computational approaches to extract spectral information from conventional colour images are reviewed, as tip-mounted cameras become more commonplace in MIS. Model-based and machine learning methods of data analysis are discussed in addition to simulation, phantom and clinical validation experiments. A wide variety of surgical pilot studies are reported but it is apparent that further work is needed to quantify the clinical value of MSI/HSI. The current trend toward data-driven analysis emphasises the importance of widely-available, standardised spectral imaging datasets, which will aid understanding of variability across organs and patients, and drive clinical translation.
NRF2 activation promotes the recurrence of dormant tumour cells through regulation of redox and nucleotide metabolism
Authors: Douglas B. Fox, Nina Marie G. Garcia, Brock J. McKinney, Ryan Lupo, Laura C. Noteware, Rachel Newcomb, Juan Liu, Jason W. Locasale, Matthew D. Hirschey, James V. Alvarez
Journal: Nature Metabolism (2020)