tbuckley/cabot-search huggingface dataset:
Assessment of Prevalence, Awareness, and Characteristics of Isolated Systolic Hypertension Among Younger and Middle-Aged Adults in China
Authors: Shiwani Mahajan, Fang Feng, Shuang Hu, Yuan Lu, Aakriti Gupta, Karthik Murugiah, Yan Gao, Jiapeng Lu, Jiamin Liu, Xin Zheng, Erica S. Spatz, Haibo Zhang, Harlan M. Krumholz, Jing Li
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Isolated systolic hypertension (ISH) is increasing in prevalence among young and middle-aged adults. However, most studies of ISH are limited to older individuals, and a substantial knowledge gap exists regarding younger adults with ISH. <h3>Objective</h3> To assess the prevalence, awareness, and characteristics of ISH among younger and middle-aged adults in China. <h3>Design, Setting, and Participants</h3> This cross-sectional study was performed as part of the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project, which enrolled 3.1 million community residents aged 35 to 75 years from all of the 31 provinces in China between December 15, 2014, and May 15, 2019. The present analysis included only participants younger than 50 years. Data were analyzed from May to November 2019. <h3>Main Outcomes and Measures</h3> Prevalence and awareness of ISH (defined as systolic blood pressure of 140 mm Hg or higher and diastolic blood pressure of less than 90 mm Hg) and individual characteristics of participants with ISH. <h3>Results</h3> Among 898 929 participants aged 35 to 49 years, the mean (SD) age was 43.8 (3.9) years; 548 657 participants (61.0%) were women, and 235 138 participants (26.2%) had hypertension. Of those with hypertension, 62 819 participants (26.7%; 95% CI, 26.5%-26.9%) had ISH (mean [SD] age, 45.0 [3.5] years; 41 417 women [65.9%]), and 54 463 of those with ISH (86.7%; 95% CI, 86.4%-87.0%) had not received treatment. The prevalence of ISH was higher among individuals who were older, were female, were farmers, resided in the eastern region of China, and had an educational level of primary school or lower. Women and older individuals were more likely to have ISH than to be normotensive or to have other hypertension subtypes. Participants who were obese, currently used alcohol, had diabetes, and experienced previous cardiovascular events were more likely to have other types of hypertension and less likely to have normotension than to have ISH. Among the 54 463 participants with ISH who had not received treatment, only 3682 individuals (6.8%; 95% CI, 6.6%-7.0%) were aware of having hypertension, and awareness rates remained low even among those with systolic blood pressure of 160 mm Hg or higher (7135 individuals [13.1%; 95% CI, 12.4%-13.9%]). <h3>Conclusions and Relevance</h3> In this study, ISH was identified in 1 of 4 young and middle-aged adults with hypertension in China, most of whom remained unaware of having hypertension. These results highlight the increasing need for better guidance regarding the management of ISH in this population.
Correspondence on ‘Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities’
Authors: Johan Rönnelid, Örjan Dahlström, Charlotte Dahle, Christopher Sjöwall
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the recent work by Johnson and colleagues regarding their evaluation of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in early disease across patient groups with different ethnic background.1 Their work is important since SLE remains clinically heterogeneous, possibly due to underlying molecular diversity,2 and various sets of criteria may not necessarily perform equally well within all different populations or sexes.

To challenge new sets of classification criteria by using retrieved clinical and laboratory data from cases with confirmed disease and cases with suspected disease, and compare their performance with older classification grounds is fair, reasonable and important. In 2015, we applied the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria to 243 patients with confirmed SLE from our regional cohort and 55 control subjects with possible systemic autoimmune disease and presence of ≥1 SLE-related autoantibody. We concluded that SLICC-12 had advantages compared with older criteria with regard to diagnostic sensitivity, whereas we found the diagnostic specificity to be surprisingly low.3

Last year, we performed a similar evaluation …
Re: Enhanced Quality and Effectiveness of Transurethral Resection of Bladder Tumour in Non–muscle-invasive Bladder Cancer: A Multicentre Real-world Experience from Scotland’s Quality Performance Indicators Programme
Authors: Sławomir Poletajew, Wojciech Krajewski, Romuald Zdrojowy, Piotr Kryst
Journal: European Urology (2020)
RADT-12. DISEASE CHARACTERISTICS IN ACUTE SEIZURE FOLLOWING RADIOTHERAPY FOR BRAIN METASTASES
Authors: Rebecca Levin-Epstein, Stephen Tenn, Dan Ruan, Safiya Lahlaf, Brian Chu, Seung Lee, Michael Steinberg, Isaac Yang, Nader Pouratian, Won Kim, John Hegde, Tania Kaprealian
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Acute seizure following radiotherapy (RT) for brain metastases is an infrequent but significant adverse event that has not been well-described. Prophylactic antiepileptic drug (AED) or steroid therapy is not recommended for asymptomatic lesions. However, there is minimal data incorporating individualized factors into acute seizure risk-assessment with respect to RT. METHODS We retrospectively examined patients treated for brain metastases with any RT modality from 2013-2020 who experienced acute post-treatment seizure, which we defined as within 4 weeks post-RT. RESULTS Twenty patients experienced acute seizure at median 2 days post-treatment (range 0-27); 15 (75%) within 7 days and 7 (35%) on day 0 (radiosurgery date or during fractionated RT). Seizures occurred after radiosurgery (n=9, 45%), fractionated stereotactic RT (n=3, 15%), whole-brain RT (n=5, 25%), and post-operative RT (n=3, 15%). All RT encompassed at least one supratentorial lesion; 11 (55%) had &amp;gt;1 lesion treated. Median lesion size was 23mm (range 7-51mm). Moderate-to-severe perilesional edema was present in 12 (60%) and hemorrhage in 8 (40%) cases. Seizures occurred despite AED therapy in 8 (40%) overall; 5/8 (63%) were hemorrhagic and 7/8 (88%) had moderate-to-severe edema. Nine (45%) patients receiving steroids developed seizures. Primary pathologies were: melanoma (5), non-small cell lung (5), renal cell carcinoma (4), breast (3), colon (1), Merkel cell (1), and thyroid (1). Patients with melanoma who developed acute seizure had mainly non-hemorrhagic (80%), small lesions (median 9mm), not receiving AED (0%) or steroid (20%) therapy. CONCLUSIONS In acute post-RT seizure, lesions were predominantly supratentorial, &amp;gt;23mm, and had moderate-to-severe edema. Breakthrough seizures were common in edematous and/or hemorrhagic lesions. However, acute seizure also occurred with smaller, non-hemorrhagic melanoma lesions not receiving AED therapy. A larger series is needed to further evaluate these identified characteristics in acute seizure, and whether prophylactic therapy may be appropriate.
Recent Progress in Magnetically Actuated Microrobots for Targeted Delivery of Therapeutic Agents
Authors: Junhee Choi, Junsun Hwang, Jin‐young Kim, Hongsoo Choi
Journal: Advanced Healthcare Materials (2020)

Abstract Therapeutic agents, such as drugs and cells, play an essential role in virtually every treatment of injury, illness, or disease. However, the conventional practices of drug delivery often result in undesirable side effects caused by drug overdose and off‐target delivery. In the case of cell delivery, the survival rate of the transplanted cells is extremely low and difficulties with the administration route of cells remain a problem. Recently, magnetically actuated microrobots have started offering unique opportunities in targeted therapeutic delivery due to their tiny size and ability to access hard‐to‐reach lesions in a minimally invasive manner; considerable advances in this regard have been made over the past decade. Here, recent progress in magnetically actuated microrobots, developed for targeted drug/cell delivery, is presented, with a focus on their design features and mechanisms for controlled therapeutic release. Additionally, the practical challenges faced by the microrobots, and future research directions toward the swift bench‐to‐bedside translation of the microrobots are addressed.
MODL-19. DIPG HARBOUR ALTERATIONS TARGETABLE BY MEK INHIBITORS, WITH ACQUIRED RESISTANCE MECHANISMS OVERCOME BY COMBINATORIAL UP- OR DOWN-STREAM INHIBITION
Authors: Elisa Izquierdo, Diana Carvalho, Alan Mackay, Sara Temelso, Jessica K R Boult, Valeria Molinari, Mark Stubbs, Sarita Depani, Patricia O’Hare, Simon P Robinson, Michael Hubank, Darren Hargrave, Chris Jones
Journal: Neuro-Oncology (2020)

Abstract The survival of children with DIPG remains dismal, with new treatments desperately needed. In the era of precision medicine, targeted therapies represent an exciting treatment opportunity, yet resistance can rapidly emerge, playing an important role in treatment failure. In a prospective biopsy-stratified clinical trial (BIOMEDE), we combined detailed molecular profiling (methylation BeadArray, exome, RNAseq, phospho-proteomics) linked to drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. We identified a high degree of in vitro sensitivity to the MEK inhibitor trametinib (GI50 16-50nM) in samples which harboured genetic alterations targeting the MAPK pathway, including the non-canonical BRAF_G469V mutation, and those affecting PIK3R1. Treatment of PDX models and the patient with trametinib at relapse, however, failed to elicit a significant response. We generated trametinib-resistant clones (62-188-fold, GI50 2.4–5.2µM) in the BRAF_G469V model through continuous drug exposure, and identified acquired mutations in MEK1/2 (MEK1_K57N, MEK1_I141S and MEK2_I115N) with sustained pathway up-regulation. These cells showed the hallmarks of mesenchymal transition, with overexpression of key proteins involved in invasion/migration, such as collagen-family proteins, integrins, MMPs and AHNAK2, amongst others. Resistant clones were conversely sensitive to the upstream receptor tyrosine kinase inhibitor dasatinib (GI50 36-93nM), and combinations of trametinib with dasatinib and the downstream ERK inhibitor ulixertinib showed synergistic effects in vitro. These data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatments likely to be required for meaningful clinical translation.
Utility of Preoperative Computed Tomography Scans for Coronavirus Disease in a Cancer Treatment Center
Authors: Yukinori Ozaki, Jun Masuda, Akemi Kataoka, Katsunori Oikado, Natsue Uehiro, Lina Inagaki, Chieko Kato, Hidetomo Morizono, Toshimi Takano, Takayuki Ueno, Shinji Ohno
Journal: Cancer Cell (2020)
Nitroglycerin Hits the Nerve: Role for Mitochondrial Aldehyde Dehydrogenase?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Ulrich Hink, Mohamed-Saiel S. Alhamdani, Thomas Münzel
Journal: Journal of the American College of Cardiology (2008)
BIOM-30. DECREASED B CELL AND ALTERED CD4+ T CELL SUBSET RATIO PREDICT FAVORABLE RESPONSE TO RUXOLINITIB IN HIGH-GRADE GLIOMAS
Authors: Yasmeen Rauf, Xuefei Jia, Justin Lathia, David Peereboom, Manmeet Ahluwalia
Journal: Neuro-Oncology (2020)

Abstract Altered cellular growth and suppression of anti-tumor immune response collectively drive progression and therapeutic resistance of high-grade gliomas (HGGs), suggesting that successful treatments will likely target these key mechanisms. Janus-associated kinase (JAK)-STAT pathway comprises one such therapeutic node, as STAT3 signaling is upregulated in proliferating glioma cells and immunosuppressive cell types. We performed retrospective analysis on 13 HGG patients treated with the JAK1/2 inhibitor ruxolinitib in combination with radiation or radiation plus temozolomide in a Phase I setting (NCT03514069). Disease progression and treatment response was determined based on the Response Assessment in Neuro-Oncology (RANO) criteria. Peripheral blood mononuclear cells (PBMCs) cells were collected from patients prior to treatment, and 2- 4- and 6-week time points to characterize early immunological changes that are indicative of treatment response with flow cytometry. 6 patients responded favorably, define as progression-free survival &amp;gt;6 months. Investigation of myeloid and lymphoid cell populations revealed no differences in dendritic cell, myeloid-derived suppressor cell and CD8+ T cell subset frequencies in blood. Similarly, expression of checkpoint inhibitors PD-1, TIGIT, CTLA-4 and TIM3 were not altered with ruxolinitib treatment. However, there was a ~2-fold reduction in the frequency of peripheral B cells in favorable responders at 4-week time point, whereas the levels remained stable in non-responders (p&amp;lt;0.05). In addition, while 5 out of 7 non-responders had increased CD4+ T cells by 4-weeks, 5 out of 6 responders had stable or reduced CD4+ T cells. This effect was driven by reduction in immunosuppressive regulatory T cells (Tregs) as the relative ratio of immunostimulatory T helper 1 (Th1)-to-Treg ratio was 3-fold higher in responders compared to non-responders. These results support evaluation of B and CD4+ T cells in the peripheral blood as biomarkers to identify HGG patients likely to benefit from such approach.
Development and deployment of a biomaterial tracking and management (BTMTM) software system into anatomic pathology practice to support tissueprocurement and research activities
Authors: Mark D. Tuthill, Azadeh Stark, Azita Sharif, Richard J. Zarbo
Journal: Cancer Research (2004)

5226   The direction of research in genomic and proteomic medicine highlights the value of institutionally based biospecimens and data repositories and the unique roles of pathology and informatics for their development, integration and management. To facilitate researchers’ access to an institutionally based biospecimen facility, we developed a real-time, web-based tracking and management software system with inquiry functionality. This application enables pathology personnel to rapidly accession and track tissue samples as well as supports real-time, HIPAA compliant queries from researchers looking for samples. The system is currently deployed on a Dell PowerEdge server running Windows 2000 Server operating system. Internet services are provided through Microsoft Internet Information Server. The BTM™ is capable of working with any relational database management system. Our implementation uses MS-SQL. Application coding was managed with a variety of tools but ultimately generates JavaScript and Microsoft active server pages (ASP). Windows OS Client workstations require only Microsoft Internet Explorer as well as bar code printer and scanner drivers. The design, development, and implementation have occurred in 3 discrete phases: pilot systems development; operational systems deployment and integration; and enterprise and interfacing. Currently, we have completed pilot testing of most system components. The second phase of the project is now under way, with integration of the software into the clinical workflow allowing specimens to be added to the repository as they are received. Steps include installation of workstations in the surgical pathology gross dissection areas. Implementation of the BTM™ is occurring in conjunction with implementation of an AP-LIS that will utilize the same workstation hardware. The Enterprise Interface phase of the project focuses on interfaces between the BTM™, and the AP-LIS, eliminating effort and error due to duplicate entry of data at sample accession. This final step will require a highly coordinated, team approach on the part of Pathology Informatics, Henry Ford Health System information technology and our commercial partners. Completion of this project over the next two years will link our clinical information systems to the BTM™ allowing for an efficient and reliable system for tracking and managing tissue specimens. Simultaneously, tightly securing data, patient confidentiality and support researchers needs to mine tissue banks for appropriate sample selection.
CTIM-14. PELAREOREP AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) WITH STANDARD CHEMORADIOTHERAPY/ADJUVANT TEMOZOLOMIDE FOR GLIOBLASTOMA MULTIFORME (GBM) PATIENTS: REOGLIO PHASE I TRIAL RESULTS
Authors: Jessica Kendall, Anthony Chalmers, Catherine McBain, Alan Melcher, Adel Samson, Rachel Phillip, Sarah Brown, Susan Short
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Oncolytic viruses represent a novel treatment approach in GBM through oncolytic targeting as well as local immune activation. We designed a phase Ib, open-label study of intravenous reovirus (pelareorep) with GM-CSF alongside standard chemoradiotherapy to assess safety and tolerability. METHODS 15 patients with newly diagnosed GBM were treated with GM-CSF 50mg subcutaneously (days 1–3) and pelareorep (days 4–5) in weeks 1 and 4 of chemoradiotherapy, and week 1 of adjuvant temozolomide course: 7 patients received 1x1010TCID50 (dose level 1); 8 received 3x1010TCID50 (dose level 2). The primary objective was to determine the maximum tolerated dose of pelareorep and GM-CSF with standard chemoradiotherapy. Secondary objectives were to gain preliminary assessment of the activity of the combination and assess treatment compliance. RESULTS 1 dose limiting toxicity (DLT) and 20 SAEs were experienced overall; median number of SAEs per patient was 2. Commonest SAEs were nervous system disorders, predominantly seizures. SARs included fever/flu-like episodes (n=5), fall (n=1) and headache (n=1). Two SUSARs occurred in dose level 2, classed as vascular disorders manifesting as hypotension episodes – one was a DLT. Suspected relationship of SARs: pelareorep (n=6); temozolomide (n=1); radiotherapy (n=1); all study drugs (n=1). 87% of patients (n=13) completed chemoradiotherapy without unplanned delays. Adjuvant treatment was delayed in 21% of cycles overall, with the majority due to inadequate haematology/biochemistry values (44% of delays). Pelareorep was omitted in 4 instances in 4 patients during chemoradiotherapy and omitted in 4 instances in 3 patients during adjuvant treatment. CONCLUSION We present the first clinical data using intravenous pelareorep with GM-CSF alongside standard chemoradiotherapy in patients with GBM, suggesting that the combination is tolerable. Further analysis is underway and efficacy results will be ready for presentation at the conference. This work was supported by CRUK, The Brain Tumour Charity, Yorkshire Cancer Research and Oncolytics Biotech Inc.
Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy
Authors: Ahmet Yilmaz, Hanwei Cui, Michael A. Caligiuri, Jianhua Yu
Journal: Journal of Hematology & Oncology (2020)

Natural killer (NK) cells are a critical component of the innate immune system. Chimeric antigen receptors (CARs) re-direct NK cells toward tumor cells carrying corresponding antigens, creating major opportunities in the fight against cancer. CAR NK cells have the potential for use as universal CAR cells without the need for human leukocyte antigen matching or prior exposure to tumor-associated antigens. Exciting data from recent clinical trials have renewed interest in the field of cancer immunotherapy due to the potential of CAR NK cells in the production of "off-the-shelf" anti-cancer immunotherapeutic products. Here, we provide an up-to-date comprehensive overview of the recent advancements in key areas of CAR NK cell research and identify under-investigated research areas. We summarize improvements in CAR design and structure, advantages and disadvantages of using CAR NK cells as an alternative to CAR T cell therapy, and list sources to obtain NK cells. In addition, we provide a list of tumor-associated antigens targeted by CAR NK cells and detail challenges in expanding and transducing NK cells for CAR production. We additionally discuss barriers to effective treatment and suggest solutions to improve CAR NK cell function, proliferation, persistence, therapeutic effectiveness, and safety in solid and liquid tumors.
CBIO-19. LOW GLOBAL HISTONE H4 ACETYLATION LEVELS REVEAL CANDIDATE QUIESCENT CELL POPULATIONS IN GLIOMA AND DISTINGUISH TUMORS BY GRADE
Authors: Anca Mihalas, Heather Feldman, Anoop Patel, Patrick Paddison
Journal: Neuro-Oncology (2020)

Abstract Current standard of care therapy for glioblastoma (GBM) includes cytoreduction followed by ablative therapies that target rapidly dividing cell types. However, the presence of quiescent-like/G0 states, therefore, represents a natural reservoir of tumor cells that are resistant to current treatments. Quiescence or G0 phase is a reversible state of “stasis” cells enter in response to developmental or environmental cues. To gain insight into how glioblastoma cells might regulate G0-like states, we performed a genome-wide CRISPR-Cas9 screen in patient-derived GBM stem-like cells (GSCs) harboring a G0-reporter to identify genes that when inhibited trap GSCs in G0-like states. Among the top screen hits were members of the Tip60/KAT5 histone acetyltransferase complex, which targets both histones (e.g., H4) and non-histone proteins for acetylation. NuA4 functions as a transcriptional activator, whose activities are coordinated with MYC in certain contexts, and also participates in DNA double-strand break repair by facilitating chromatin opening. However, currently little is known about the roles for NuA4 complex in GBM biology. Through modeling KAT5 function in GSC in vitro cultures and in vivo tumors, we find that KAT5 inhibition causes cells to arrest in a G0-like state with high p27 levels, G1-phase DNA content, low protein synthesis rates, low rRNA rates, lower metabolic rate, suppression of cell cycle gene expression, and low histone H4 acetylation. Interestingly, partial inhibition of KAT5 activity slows highly aggressive tumor growth, while increasing p27hi H4-aclow populations. Remarkably, we that low grade gliomas have significantly higher H4-aclow subpopulations and generally lower H4-ac levels than aggressive grade IV tumors. Taken together, our results suggest that NuA4/KAT5 activity may play a key role in quiescence ingress/egress in glioma and that targeting its activity in high grade tumors may effectively “down grade” them, thus, increase patient survival.
A Pigmented Lung Perivascular Epithelioid Cell Tumor
Authors: Ilaria Onorati, Marianne Kambouchner, Emmanuel Martinod
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"A Pigmented Lung Perivascular Epithelioid Cell Tumor." American Journal of Respiratory and Critical Care Medicine, 203(8), pp. 1023–1024