tbuckley/cabot-search huggingface dataset:
Association of Sociodemographic Factors With Immunotherapy Receipt for Metastatic Melanoma in the US
Authors: Justin T. Moyers, Amie Patel, Wendy Shih, Gayathri Nagaraj
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Strides to improve survival in metastatic melanoma have been made with the use of immunotherapeutic agents in the form of immune checkpoint inhibitors. <h3>Objective</h3> To examine the factors associated with immunotherapy receipt in patients with metastatic melanoma in the era of immune checkpoint inhibitors and the Patient Protection and Affordable Care Act. <h3>Design, Setting, and Participants</h3> This cohort study used data on 9882 patients with metastatic melanoma diagnosed from January 1, 2013, to December 31, 2016, from the National Cancer Database. Patients who did not have documentation regarding immunotherapy receipt were excluded. Data analysis was performed from July 1, 2019, to December 15, 2019. <h3>Exposure</h3> Receipt of immunotherapy. <h3>Main Outcomes and Measures</h3> The primary outcome was the association of receipt of immunotherapy as first-line therapy with sociodemographic factors. The secondary outcome was overall survival by receipt of immunotherapy. <h3>Results</h3> A total of 9512 patients (mean [SD] age, 65.1 [14.4] years; 6481 [68.1%] male; 9217 [96.9%] White) met the criteria for treatment analysis. A total of 3428 (36.0%) received immunotherapy, and 6084 (64.0%) did not. Increasing age (odds ratio [OR], 0.98; 95% CI, 0.97-0.98;<i>P</i> &lt; .001) and increasing Charlson-Deyo comorbidity index (OR, 0.86; 95% CI, 0.80-0.92;<i>P</i> &lt; .001) were associated with lower odds of receiving immunotherapy on regression analysis. Diagnosis in Medicaid expansion states (OR, 1.16; 95% CI, 1.05-1.27;<i>P</i> = .003), treatment at an academic or integrated cancer network program (OR, 1.59; 95% CI, 1.45-1.75;<i>P</i> &lt; .001), and residence within the highest quartile of high school graduation rate zip code area (OR, 1.31; 95% CI, 1.09-1.56;<i>P</i> = .003) were associated with an increased likelihood of receiving immunotherapy. Median overall survival was 10.1 months (95% CI, 9.6-10.6 months) among all patients. Patients who received first-line immunotherapy had a median overall survival of 18.4 months (95% CI, 16.6-20.1 months) compared with 7.5 months (95% CI, 7.0-7.9 months) (<i>P</i> &lt; .001) among patients who did not. <h3>Conclusions and Relevance</h3> In this cohort study, patients who received immunotherapy for metastatic melanoma had improved overall survival. Residence in Medicaid expansion states, younger age, low comorbidity index, care at academic medical centers or integrated network cancer programs, and residence in zip codes within the highest quartile of high school graduation were associated with an increased likelihood of receiving immunotherapy. Recognizing sociodemographic associations with treatment receipt is important to identify potential barriers to treatment.
Positive Correlation between Serum Tryglycerides and Pro-Inflammatory Cytokines in Hemorrhagic Fever with Renal Syndrome
Authors: Konstantin Kletenkov, Aygul Kh. Valiullina, Ekaterina V. Martynova, Oleg A. Gusev, Yuri Davidyuk, Ekaterina E. Garanina, Venera G. Shakirova, Ilsiyar M. Khaertynova, Vladimir A. Anokhin, Albert Rizvanov, Svetlana Khaiboullina
Journal: Blood (2017)
Abstract 664: BGB-10188, a highly selective PI3Kδ inhibitor with improved safety profile and superior anti-tumor activities in vivo
Authors: Xiao Yang, Xiaolong Yang, Xinxin Cui, Dan Su, Yue Wu, Xuebing Sun, Jingyuan Wang, Huichen Bai, Wei Wei, Jing Li, Xi Yuan, Ye Liu, Fan Wang, Zhiwei Wang, Lai Wang, Xuesong Liu, Xiaomin Song
Journal: Cancer Research (2020)

Abstract Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes capable of phosphorylating phosphatidylinositol to phosphoinositides, which are important secondary messengers involved in various cell signaling and functions. PI3Kδ is one of four isoforms (PI3Kα, β, δ and γ) of the PI3K class I family. It is restrictively expressed in leukocytes. PI3Kδ is a key signal transduction component for normal and malignant B cells and also important for the homeostasis and function of T-regulatory cells (Treg), making it a promising target for treatment of both hematologic malignancies and solid tumors. BGB-10188 is a highly selective inhibitor of PI3Kδ, showing no significant inhibition over 376 protein kinases and 17 lipid kinases, and more than three-thousand folds selectivity over PI3Kα, PI3Kβ, and PI3Kγ. BGB-10188 potently inhibited PI3Kδ in biochemical, cellular and human whole blood assays with IC50s ranging from 1.7-16 nM. It also showed a long-lasting and strong target inhibition activity in mouse pharmacodynamics (PD) studies at doses as low as 10mg/kg. The elimination half-life (t1/2) of BGB-10188 in plasma was 12.6 hours and 10.4 hours in rats and dogs, respectively. BGB-10188 showed significant antitumor effects in different types of B cell Lymphoma xenograft models. The liver toxicities of BGB-10188 were evaluated in mice and significantly improved safety margin was observed for BGB-10188 in comparison with other PI3Kδ inhibitors. In summary, BGB-10188 is a novel PI3Kδ inhibitor with high selectivity, potency and improved safety profile shown in preclinical studies, which is promising and warrants the testing of the compound in human. Citation Format: Xiao Yang, Xiaolong Yang, Xinxin Cui, Dan Su, Yue Wu, Xuebing Sun, Jingyuan Wang, Huichen Bai, Wei Wei, Jing Li, Xi Yuan, Ye Liu, Fan Wang, Zhiwei Wang, Lai Wang, Xuesong Liu, Xiaomin Song. BGB-10188, a highly selective PI3Kδ inhibitor with improved safety profile and superior anti-tumor activities in vivo [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 664.
Antisense Inhibition of Prekallikrein to Control Hereditary Angioedema
Authors: Danny M. Cohn, Nicholas J. Viney, Lauré M. Fijen, Eugene Schneider, Veronica J. Alexander, Shuting Xia, Gwendolyn E. Kaeser, Charvi Nanavati, Brenda F. Baker, Richard S. Geary, Marcel Levi, Joost C.M. Meijers, Erik S.G. Stroes
Journal: New England Journal of Medicine (2020)

Hereditary angioedema is characterized by recurrent and unpredictable episodes of subcutaneous and mucosal swelling that can be life threatening. IONIS-PKK-LRx is a ligand-conjugated antisense oligonucleotide designed for receptor-mediated delivery to hepatocytes. In a compassionate-use pilot study, two patients with severe bradykinin-mediated angioedema were initially administered weekly subcutaneous injections of the unconjugated parent drug, IONIS-PKKRx, for 12 to 16 weeks, after which they received IONIS-PKK-LRx at a dose of 80 mg every 3 to 4 weeks for 7 to 8 months. Treatment was accompanied by a reduction in the angioedema attack rate. (Funded by Amsterdam UMC.).
Abstract 2858: Comparative surface proteomic analysis of human breast cancer cell lines
Authors: Betsy Benton, Sergei Snovida, Katherine Herting, Kay Opperman, Barbara Kaboord
Journal: Cancer Research (2020)

Abstract Enrichment of cell surface proteins is commonly performed by biotinylation using amine-based chemistry; however, this method is often associated with intracellular labeling and difficulty distinguishing the true cell surface proteins from background contaminants. We developed a robust cell surface protein isolation method using amine-based chemistry that is compatible with mass spectrometry (MS). We applied this methodology to evaluate the surface proteomes of three breast cancer cell lines, including hormone responsive MCF-7 cells, and two triple negative breast cancer cell lines (TNBC), BT549 and Hs5789T. Thermo Scientific™ Tandem Mass Tag (TMT) Reagents, combined with high pH reverse phase fractionation of the labeled peptides, were used to multiplex protein identification and quantitative analyses by tandem MS. A heat map of enriched proteins from the three cell lines showed clearly distinct banding patterns of clustered protein groups. Relative quantitative differences in several classes of enriched proteins were observed, including tyrosine kinases, G-Protein-Coupled Receptors (GPCRs), and cell adhesion proteins. The tyrosine kinase EGFR was found to be more highly expressed in TNBC cell lines compared with MCF-7 cells. In contrast, the receptor tyrosine-protein kinase erbB-3 was found to be significantly higher in the MCF-7 cells compared with the TNBC cells. Several GPCRs were identified and found to vary across the three cell lines, including Frizzled 7 which is an emerging target for cancer therapy. Multiple cell adhesion proteins were also identified, including neural cell adhesion molecule L1 which promotes migration of MCF7 cells. Where possible, the data set was found to be consistent with literature reports. In conclusion, we have developed a highly sensitive method for cell surface proteomic analyses that can be effectively used to identify differences in cell types as well as for biomarker discovery and potential drug therapy targets. Citation Format: Betsy Benton, Sergei Snovida, Katherine Herting, Kay Opperman, Barbara Kaboord. Comparative surface proteomic analysis of human breast cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2858.
Influenza-negative influenza-like illness (fnILI) Z-score as a proxy for incidence and mortality of COVID-19
Authors: Fatima N. Mirza, Amyn A. Malik, Chandra Couzens, Saad B. Omer
Journal: Journal of Infection (2020)

Although direct detection of SARS-CoV2 in symptomatic or asymptomatic individuals is the ideal epidemiological tool for determining the burden of disease, the lack of availability of testing can preclude its wider implementation as a robust surveillance system. We correlated the use of the derivative influenza-negative influenza-like illness (fnILI) z-score from the US Centers for Disease Control and Prevention as a proxy for incident cases and disease-specific deaths. For every unit increase of fnILI z-score, the number of cases increased by 376.5 (95% CI [202.5, 550.5]) and number of deaths increased by 10.2 (95% CI [5.4, 15.0]). FnILI data may serve as an accurate outcome measurement to track the spread of COVID-19 infection and disease, and allow for informed and timely decision-making on public health interventions.
Abstract 317: Organoid and TIL co-culture system models the human tumor immune microenvironment and drug sensitivity
Authors: Yoshihisa Tokumaru, Masanori Oshi, Eriko Katsuta, Nobuhisa Matsuhashi, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe
Journal: Cancer Research (2020)

Abstract BACKGROUNDS: Host tumor immune microenvironment has been shown to play a critical role on the outcome of the breast cancer patient. Among the immune cells, tumor infiltrating lymphocytes (TILs) were shown to be a predictive biomarker for the efficacy of chemotherapy by clinical trials. Triple negative breast cancer (TNBC) is known to have high infiltration of TILs compared with other subtypes. TILs were reported to be associated with the response to doxorubicin and cyclophosphamide, and with better survival in breast cancer patients. Recently, there are accumulating evidences that organoids generated from patient tumors are useful as models for drug sensitivity pre-clinical trials. Here, we hypothesized that co-culture of TILs with organoids will mimic human tumor immune microenvironment and enhance the drug sensitivity. MATERIAL AND METHODS: GSE22226 that contains both clinical data and gene expression profile of untreated tumors was used as the breast cancer patient cohort that underwent neoadjuvant chemotherapy (NAC). Relative fractions of 22 types of infiltrating immune cells were estimated from tumor gene expression with the CIBERSORT method. Organoids of the same tumors grown as mouse xenografts were generated using standard methods. Organoids (1000/well of 96-w plate) were treated with doxorubicin (0.01-100 µM) for 2 days before addition of TILs of same patient (1-16 x103 per well). Cytotoxicity was assessed after another two days with the CellTiter-Glo 3D cell viability assay. RESULTS: We first assessed the clinical relevance of TILs in response outcome of NAC by utilizing the previously reported cohort, in which Adriamycin, Cyclophosphamide and Taxane were used. We found that the number of TILs were significantly higher in the patients that achieved pathological complete response (pCR) when compared with the ones that did not. We established 18 PDX models all of which are from TNBC and we successfully expanded TILS 7 of these patients. We derived 8 organoids from the patients. We performed the experiment of adding TILs to the organoids. TILs effectively killed organoids when TILs were cultured at 1:8 or 1:16 ratio. Furthermore, the killing of organoids by doxorubicin was enhanced by the addition of TILs. CONCLUSION: Amount of TILs associated with better outcome in NAC cohort. In pre-clinical setting, addition of TIL intensified the sensitivity of organoids to doxorubicin. Citation Format: Yoshihisa Tokumaru, Masanori Oshi, Eriko Katsuta, Nobuhisa Matsuhashi, Manabu Futamura, Kazuhiro Yoshida, Kazuaki Takabe. Organoid and TIL co-culture system models the human tumor immune microenvironment and drug sensitivity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 317.
10-Year Outcome of Chronic Myeloid Leukemia Patients Resistant to Frontline Imatinib
Authors: Simone Claudiani, Adi Shacham Abulafia, Ira Sabli, Richard Szydlo, Dragana Milojkovic, George Nesr, Renuka Palanicawander, George Nteliopoulos, Mary Alikian, Jamshid S Khorashad, Letizia Foroni, Jane F. Apperley
Journal: Blood (2017)
Evaluation of the latent tuberculosis screening and treatment strategy for asylum seekers in Stockholm, Sweden 2015–2018: a record linkage study of the care cascade
Authors: Joanna Nederby Öhd, Maria-Pia Hergens, Yauheni Luksha, Charlotte Buxbaum, Jad Shedrawy, Jerker Jonsson, Judith Bruchfeld, Knut Lönnroth
Journal: European Respiratory Journal (2020)

Introduction About 90% of active tuberculosis (TB) cases in Sweden are foreign born and are mainly due to latent TB infection (LTBI) reactivation. The aim of this study was to assess the current migrant LTBI screening programme with regards to test results and completion of the care cascade. Method A retrospective cohort of all 14173 individuals attending a health examination was established for the Stockholm Region 2015–2018 through record-linkage of data extracted from the Swedish Migration Authority and medical records. Screening results, referrals to specialist care and treatment initiation were ascertained through automated data extraction for the entire cohort. Detailed cascade steps, including treatment completion, were analysed through manual data extraction for a subsample of all persons referred to specialist care in the period 2016–2017. Results Of 5470 patients screened with an interferon-gamma release assay (IGRA), 1364 (25%) were positive, of whom 358 (26%) initiated LTBI treatment. An increased trend in IGRA-positivity was seen for increased age and TB-incidence in country of origin. Among the IGRA positive patients, 604 (44%) were referred to specialist care. Lower age was the main referral predictor. In the subsample of 443 patients referred to specialist care in 2016–2017, 386 (87%) were invited, of whom 366 (95%) attended. Of 251 patients (69%) recommended for LTBI treatment, 244 (97%) started such treatment and of those 221 (91%) completed it. Conclusion The low attrition in patient-dependent cascade steps shows that the voluntary approach works well. Low LTBI treatment attainment is due to the current conservative local treatment policy, which means the vast majority are IGRA-tested without an intention to treat for LTBI.
Is there a maximal effect of tranexamic acid in patients undergoing total knee arthroplasty? A randomized controlled trial
Authors: Yiting Lei, Jinwei Xie, Qiang Huang, Fuxing Pei
Journal: MedComm (2020)

Abstract The optimal dosing regimen of tranexamic acid (TXA) has not been determined in total knee arthroplasty (TKA). In this study, patients were randomized to receive a high initial‐dose (60 mg/kg) TXA before incision, followed by five doses 3, 6, 12, 18, and 24 hours later (A), or three doses 3, 12, and 24 hours later (B), or a single dose 3 hours later (C). The primary outcome was perioperative blood loss. Other outcomes such as, hemoglobin level, transfusion, the levels of fibrin (ogen) degradation products (FDP), D‐dimer, C‐reactive protein (CRP) and interleukin‐6 (IL‐6), coagulation parameters, and adverse events were also compared. The results showed that individuals in Groups A and B had reduced total and hidden blood loss (HBL), lower FDP, D‐dimer, CRP, and IL‐6 levels than in Group C. Such differences were also detected in HBL between Groups A and B. No differences were observed in other outcomes between Groups A and B. No differences were observed in coagulation parameters and adverse events among the three groups. In conclusion, a high initial‐dose (60 mg/kg) TXA before TKA followed by three doses can be sufficient to achieve maximal effects on total blood loss, fibrinolysis, and inflammation.
Association of COVID‐19 with skin diseases and relevant biologics: a cross‐sectional study using nationwide claim data in South Korea*
Authors: S.I. Cho, Y.E. Kim, S.J. Jo
Journal: British Journal of Dermatology (2020)

As the coronavirus disease 2019 (COVID-19) pandemic has spread, information about COVID-19 and skin disease or related biologics is still lacking.To identify the association between COVID-19 and skin diseases or biologics.A nationwide claim dataset relevant to COVID-19 in South Korea was analysed. This dataset included insurance claim data before and during COVID-19 treatment and clinical outcomes. Claim data related to skin diseases and relevant biologics were analysed to determine the association of COVID-19 with skin diseases and relevant biologics.The dataset contained a total of 234 427 individuals (111 947 male and 122 480 female) who underwent COVID-19 testing. Of them, 7590 (3·2%) were confirmed as having COVID-19, and 227 (3·0%) confirmed patients died. Among various skin diseases and biologics, no significant increase in the presence of specific skin diseases or exposure to biologics was observed in the COVID-19-positive group, even after adjusting for or matching covariates. The presence of skin diseases and exposure to biologics also did not seem to affect clinical outcomes including mortality.Underlying skin diseases did not appear to increase susceptibility to COVID-19 or mortality from COVID-19. Considering the risks and benefits, biologics for dermatological conditions might be continuously used during the COVID-19 pandemic.
AB0102 Antiphospholipid syndrome (aps) in children
Authors: ME Pombo, R Merino, D Pascual, MV Cuesta, A Aguado, J García-Consuegra
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate clinical features and management options of persistent antiphospholipid antibodies (aPL) in children. <h3>Methods</h3> Retrospective chart review of patients, seen between 1987 and 2000. <h3>Results</h3> Six patients with ages at diagnosis ranging from 9 to 13 years are presented. One of them with primary APS and 3 with SLE and asymptomatic aPL. The clinical manifestations are shown in the Table 1. All of the patients included were positive for lupus anticoagulant and all of them except the case 4 had positive tests for aCL and Aβ<sub>2GPI</sub>. <h3>Conclusion</h3> In paediatric patients with aPL, the risk of thrombosis, their recurrences and the management of oral anticoagulation may be different from adults.
Financial incentives to promote retention in care and viral suppression in adults with HIV initiating antiretroviral therapy in Tanzania: a three-arm randomised controlled trial
Authors: Carolyn A Fahey, Prosper F Njau, Emmanuel Katabaro, Rashid S Mfaume, Nzovu Ulenga, Natalino Mwenda, Patrick T Bradshaw, William H Dow, Nancy S Padian, Nicholas P Jewell, Sandra I McCoy
Journal: The Lancet HIV (2020)
Abstract 789: Development and validation of a capture based NGS assay that enables the detection of Epstein Barr virus from gastric cancer patients' tumor tissues
Authors: Yajie Hu, Bo Yang, Lei Wang, Shiyi Liu, Lei Liang, Jie Wang, Fugen Li, Yu Sun
Journal: Cancer Research (2020)

Abstract Background: Gastric cancer patients with positive test for Epstein Barr virus (EBV) in their tumors have been reported to benefit significantly from anti-PD-1 therapy. Current clinical testing relies on fluorescent in situ hybridization of EBV-encoded small RNA (EBER). NGS assays have been increasingly used in the clinical settings to make therapeutic recommendations to cancer patients due to its versatility in detecting various types of genomic alterations. Detecting EBV by NGS is highly desired. Method: DNA was extracted from the FFPE samples of 214 gastric cancer patients' tumors, and profiled by the comprehensive NGS assay. A classification algorithm was developed using 131 gastric cancer samples (EBV Pos, n = 31; EBV Neg, n = 100) with known EBV status derived from EBER. The algorithm and the predetermined cutoff was then applied to an independent sample set (EBV Pos, n = 30; EBV Neg, n = 53) to evaluate the test performance. Results: In the training set, we achieved a sensitivity of 93.5% at a specificity of 100%. In the validation set, we achieved a sensitivity of 93.3% at a specificity of 100%. Using the same algorithm and cutoff, in the patients with tumor content above 20%, we achieve a sensitivity of 97.9% at a specificity of 100%. Conclusion: We developed a method to detect EBV in gastric tumors' FFPE samples through a capture-based NGS assay. We also demonstrated strong concordance with an orthogonal assay (EBER) in detecting EBV. Citation Format: Yajie Hu, Bo Yang, Lei Wang, Shiyi Liu, Lei Liang, Jie Wang, Fugen Li, Yu Sun. Development and validation of a capture based NGS assay that enables the detection of Epstein Barr virus from gastric cancer patients' tumor tissues [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 789.