tbuckley/cabot-search huggingface dataset:
Correlation, comparison, and combined analysis of Ki-67 and histological grade for early luminal breast cancer.
Authors: Yoichi Naito, Satoshi Fujii, Kuniaki Itoh, Masahiko Nezu, Nobuaki Matsubara, Masaoki Sasaki, Noriaki Wada, Kimiyasu Yoneyama, Hirofumi Mukai
Journal: Journal of Clinical Oncology (2012)

585 Background: Both Ki-67 and histological grade are established prognostic factors in patients with early breast cancer. Recent international expert consensus employs Ki-67 to classify luminal breast cancer, and histological grade is described as an alternative. We investigated the prognostic value of Ki-67, histological grade, and their combination. Methods: Patients with early breast cancer treated with surgery between January 2000 and December 2008 were retrospectively reviewed. Inclusion criteria were as follows: estrogen receptor positive, HER2 negative, available for Ki-67 and histological grade. Clinicopathological data were retrieved from medical records. Ki-67 labeling index was investigated using MIB-1 antibody and subdivided into three categories: low 0-9%; intermediate 10-19%; high &gt;20%. Histological grade was scored between 1 and 3. Disease-free survival (DFS) was defined as time from surgery to the first documented disease recurrence or death. Ki-67 categories and histological grade were analyzed respectively and then concomitantly for prognostic impact on DFS. Results: A total of 606 patients were included. Median age was 58 and 28.1% were over 65 years. 65.4% were postmenopausal women. Progesterone receptor was positive in 84.0% of patients. 29.6% received neoadjuvant or adjuvant chemotherapy. Number of lymph node metastasis was 0 in 70.0%, 1-3 in 21.3%, and &gt;4 in 8.7% of patients. Ki-67 categories and histological grade showed weak but significantly correlation (Spearman’s rho = 0.385, p&lt;0.001). High Ki-67 and histological grade 3 were correlated with worse prognosis to the same extent (HR 2.518, p = 0.002 and HR 2.541, p = 0.048, respectively). For combined analysis, patients represented concomitant with high Ki-67 and histological grade 3 showed worse prognosis compared with those with Ki-67 low and histological grade 1 (HR 3.137, p = 0.021). Conclusions: Ki-67 and histological grade were significantly but weakly correlated. Combined use of these two factors could better predict recurrence of early luminal breast cancer.
Outcome of germinal center B-cell type compared to non-germinal center/activated B-cell type diffuse large b-cell lymphoma as determined by immunohistochemistry using the Hans algorithm.
Authors: Neha Patil, Marian Girgis
Journal: Journal of Clinical Oncology (2020)

e20076 Background: Classification of diffuse large B cell lymphoma (DLBCL) takes into consideration - cell of origin, germinal center B-cell (GCB) vs non germinal center/activated B-cell type (non-GCB/ABC), since its determination by gene expression profiling predicts prognosis when treated with standard therapy. In this report we evaluated impact of choice of therapy and stem cell transplant (SCT) on the outcome of GBC and ABC subtype determined by immunohistochemistry (IHC) using Hans algorithm. Methods: We reviewed pathology reports DLBCL patients diagnosed from 2009 - 2016. For GCB and non-GCB/ABC patients data was collected including demographics, stage, initial and subsequent chemo, response and SCT. Results: Out of total 267 patients with DLBCL Per Hans algorithm, 117 (43.8%) were GCB, 94 (35.2%) ABC. GCB group - Median age at diagnosis was 65 years. 65% were older than 60 years. 27% Double expressors (DE). Frontline therapy was R-CHOP in 67.5% patients. 38% received other chemo - BR, hyperCVAD, RICE, RCVP. 26% patients had multiple lines of treatment. Average duration of first remission was 2.6 years. Complete response (CR) was achieved in 53% patients. Partial response (PR) in 27%. Median survival was 84.8 months. 12% underwent SCT. After SCT - 8 achieved CR, 3 PR, and 1 in PD. ABC group - Median age at diagnosis was 67 years. 67% were older than 60 years. DE were 19%. Frontline therapy was R-CHOP in 78% patients. 20% received other chemo. 21% needed multiple lines of treatment. CR was achieved in 76%. Median survival was 59.2 month. Median duration of remission for patients who received R-CHOP was 2 years and 1.25 years for other chemo. 7.4% had SCT - 5 auto and 2 allo. Conclusions: GCB and non-GCB/ABC DLBCL identified by IHC who received R-CHOP as induction had better outcome than who received other chemo. GCB had better overall survival compared to non-GCB/ABC. Median duration of first remission was 2 to 2.6 years and 30% patients received multiple lines of therapy. Only 15% patients underwent SCT – 66% achieved CR in GCB and 85% in ABC. Clinical trials adding newer agents and better stratifying patients who benefit from SCT are warranted. [Table: see text]
2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: long-term follow-up of a multicentre, randomised trial
Authors: Deborah Utjés, Jonas Malmstedt, Jüri Teras, Krzysztof Drzewiecki, Hans Petter Gullestad, Christian Ingvar, Hanna Eriksson, Peter Gillgren
Journal: The Lancet (2019)
Combinational protective therapy for spinal cord injury medicated by sialic acid-driven and polyethylene glycol based micelles
Authors: Xiao-Juan Wang, Gao-Feng Shu, Xiao-Ling Xu, Chen-Han Peng, Chen-Ying Lu, Xing-Yao Cheng, Xiang-Chao Luo, Jie Li, Jing Qi, Xu-Qi Kang, Fei-Yang Jin, Min-Jiang Chen, Xiao-Ying Ying, Jian You, Yong-Zhong Du, Jian-Song Ji
Journal: Biomaterials (2019)
Myocardial Infarction as a Clinical End Point in Research
Authors: Andrew P. DeFilippis, Khurram Nasir, Michael J. Blaha
Journal: Circulation Research (2019)

R eflecting the greater understanding of the many di- verse causes of myocardial injury, international consensus definition of myocardial injury now includes nonischemic causes of myocardial injury and several etiologically distinct subtypes of myocardial infarction (MI).It is time that all ongoing prospective cohorts and clinical trials systematically differentiate and report on all the etiologically distinct types of myocardial injury.Such reporting will undoubtedly advance the fundamental understanding of the epidemiology of myocardial injury events, including differing risk factor associations, allowing better prediction, prevention, and pharmacotherapies for all identified subtypes of myocardial injury eventsincluding all subtypes of MI.
Abstract 14366: Cardiac Magnetic Resonance Derived Late Gadolinium Enhancement Replacement Fibrosis and Extracellular Volume Significance in the Detection of Diastolic Dysfunction
Authors: Kongkiat Chaikriangkrai, Juan C Lopez-Mattei, Mohamad Ghosn, Mohamed El-Beheary, Dipan J Shah, Sherif F Nagueh
Journal: Circulation (2013)

Background: Cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) is considered the gold standard for detection of replacement fibrosis (RF). Newer CMR techniques also allow asses...
Ефективна інфузійна терапія лікарських уражень печінки та підшлункової залози у хворих на туберкульоз легень
Authors: N.B. Gubergrits, O.Ye. Klochkov, P.G. Fomenko
Journal: GASTROENTEROLOGY (2013)

Автори обстежили 328 хворих з туберкульозом легень, у яких внаслідок поліхіміотерапії розвинулися лікарський гепатит і лікарський панкреатит. У пацієнтів сформувався синдром метаболічної інтоксикації, що супроводжувалося підвищенням рівня «середніх молекул» у крові. Під впливом лікування з використанням для інфузійної терапії препарату янтарної кислоти вдалося досягти не лише вірогідного зниження цього показника, але і його нормалізації.
Abstract 4122: The regulatory mechanism of PD-L1 level through ER-associated degradation
Authors: Jong-Ho Cha, Wen-Hao Yang, Weiya Xia, Yongkun Wei, Li-Chuan Chan, Chia-Wei Li, Heng-Huan Lee, Mien-Chie Hung
Journal: Cancer Research (2019)

Abstract Programmed death ligand-1 (PD-L1) is an important immune checkpoint molecule that allows cancer cells to evade immune surveillance. Further, the PD-L1 level is relatively higher in tumor tissues compared to normal tissues. Thus, the PD-L1/PD-1 axis has served as primary target for cancer immunotherapy. However, the regulatory mechanisms of PD-L1 level are not fully understood. Here, we demonstrated that the ER-associated degradation (ERAD) mechanism of PD-L1 through cross-talking between phosphorylation and glycosylation. We discover that AMP-activated protein kinase (AMPK) activated by metformin directly binds with PD-L1 in the ER lumen and phosphorylates Ser 195 of PD-L1. The Ser 195 phosphorylation induces abnormal mannose-rich glycan structures of PD-L1 through excessive ER trimming process. PD-L1 with abnormal glycan structures is occupied by ER quality check components in the ER and finally degraded through ERAD pathway. We provide new insights to understand cancer immune checkpoints by identifying a new regulatory mechanism of PD-L1 and these findings can be used to improve the efficacy of previous cancer immunotherapy for the PD-L / PD-1 axis. Citation Format: Jong-Ho Cha, Wen-Hao Yang, Weiya Xia, Yongkun Wei, Li-Chuan Chan, Chia-Wei Li, Heng-Huan Lee, Mien-Chie Hung. The regulatory mechanism of PD-L1 level through ER-associated degradation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4122.
Low Relapse Rate in Younger Patients ≤ 60 Years Old with Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML) Treated with Crenolanib and Cytarabine/Anthracycline Chemotherapy
Authors: Eunice S. Wang, Martin S. Tallman, Richard M. Stone, Roland B. Walter, Chatchada Karanes, Vinay Jain, Robert H. Collins
Journal: Blood (2017)
Abstract 3345: Making the link between breastfeeding and breast cancer risk reduction among Hispanic women of childbearing age
Authors: Karoline Sondgeroth, Rosalba Ruiz-Holguin, Joe Padilla, Rebeca Ramos, Rebecca Palacios
Journal: Cancer Research (2019)

Abstract Background/Purpose. Breast Cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer related deaths for women in Texas (TX). In the border county of El Paso, TX, the breast cancer incidence and mortality rates are higher for Hispanic women relative to all races combined. Evidence indicates that breastfeeding can be protective against BC by (1) limiting breast cells’ ability to act abnormally, (2) lowering estrogen levels, and (3) promoting healthier lifestyle choices. Research also indicates that the longer a woman breastfeeds, the lower her risk of developing BC. Unfortunately, among all infants born in TX in 2015, only 48% were exclusively breastfed for up to 3 months and only 24.1% were exclusively breastfed for up to 6 months. The goal of the Breastfeeding Breast Cancer Connection Program (BFBCCP) is to increase intent to breastfeed among Hispanic women of childbearing age (18-44 years) by providing a brief education intervention focused on the importance of breastfeeding and BC prevention. Methods. Study participants included 50 Hispanic women of childbearing age living at the El Paso Housing Authority in El Paso, TX. The study consisted of an intervention group (n=25) and a control group (n=25). The control group received only educational brochures about breastfeeding, whereas, the intervention group received an educational presentation about the importance of breastfeeding and BC prevention. Measures assessed in this study included: 1) knowledge of breastfeeding and BC 2) attitudes towards breastfeeding in the workplace, and 3) behavioral intentions to breastfeed. All measures were assessed via a pre and post self-report survey in the participants preferred language. Results/Findings. Overall, Hispanic women participating in the BFBCCP learned more about the importance of breastfeeding, particularly as it relates to BC prevention, reported greater levels of intent to breastfeed, and reported more positive attitudes towards breastfeeding in the workplace compared to the control group. Given their high BC incidence and mortality rates, Hispanic women in the TX border region would benefit from interventions like BFCCP that promote exclusive breastfeeding for a duration of six mos. to one year as a means of reducing their BC risk. The next step is to assess the efficacy of the BFCCP in increasing breastfeeding completion and duration among pregnant Hispanic women. Citation Format: Karoline Sondgeroth, Rosalba Ruiz-Holguin, Joe Padilla, Rebeca Ramos, Rebecca Palacios. Making the link between breastfeeding and breast cancer risk reduction among Hispanic women of childbearing age [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3345.
Abstract 2325: Long term time-course monitoring of NK cell-mediated ADCC using the Celigo Image Cytometer
Authors: Leo L. Chan, Lucas Ferrari De Andrade, Charles A. Thomas, Dmitry Kuksin, Kai Wucherpfennig
Journal: Cancer Research (2019)

Abstract Antibody-dependent cell-mediated cytotoxicity (ADCC) assay has been widely performed for immuno-oncological research. Traditionally, ADCC assays are conducted by measuring the amount of released Chromium, calcein AM, or Lactate dehydrogenase (LDH) molecules after the target cancer cells are killed by effector/antibody pair. These methods can be inaccurate due to indirect measurement of supernatant at the end point of 4 hour, however, there is a need to characterize the effects of antibody-dependent cytotoxicity for longer than 72 hours. Previously, we have demonstrated an image-based ADCC detection method using the Celigo Image Cytometer, where the target cells are stained with calcein AM and other tracer dyes to monitor cell count or viability. However, the fluorescence of these dyes can significantly diminish within a 48 hour time frame. In this work, we demonstrated the time-course monitoring of NK cell-mediated ADCC of A375 cells in the presence or absence of IL2 and antibodies for 76 hours. First, A375-ZsGreen cells were seeded into a 96-well plate with and without target antibodies. Next, NK cells with and without IL2 were added to the wells at 10:1, 5:1, 2:1, and 1:1 E:T ratios. The co-culture was allowed to incubate for 76 hours and the image cytometer was used to scan and analyze at times 0, 3, 4, 6, 24, 27, 30, 51, 74, and 76 hours. The software was able to count individual cells as well as confluence % at each time point by segmenting highly fluorescent objects in the images. We were able to show time-dependent ADCC killing with decrease in ZsGreen positive cells as the read-out. In addition, the uniformity of cell killing can be observed in the Celigo obtained whole well images. One of the most important findings was that there was regrowth of target cells after the initial 30 hours of cell killing, indicating the activated NK cells without antibodies did not eradicate the cancer cells. Therefore, the ability to perform long term time-course monitoring of ADCC is highly important to better characterize the effects of target antibodies on cell killing function. Citation Format: Leo L. Chan, Lucas Ferrari De Andrade, Charles A. Thomas, Dmitry Kuksin, Kai Wucherpfennig. Long term time-course monitoring of NK cell-mediated ADCC using the Celigo Image Cytometer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2325.
Abstract 4292: Molecular mechanism of APIO-EE-7 suppresses cell metastasis by targeting Aurora B in osteosarcoma
Authors: Guoguo Jin, Jitian Li, Zhiping Guo, Junyan Teng, Xiaoling Li, Zhenjiang Zhao
Journal: Cancer Research (2019)

Abstract Osteosarcoma is one of the most prevalent malignant bone tumors in children and adolescents and has the characteristics of early metastasis, rapid progression and poor prognosis. Although with the advancement in techniques and treatment increasing the survival rates up to 60%, the prognosis remains poor for most patients with metastatic or recurrent osteosarcoma. Identifying the molecular mechanism and developing therapeutic agents for metastasis is urgent. Aurora B kinase play a key role in mitosis and have been reported to be associated with cancer metastasis. However, the role of Aurora kinase in osteosarcoma is still unclear. In this study, we identified a novel compound, referred to as APIO-EE-7, which inhibits growth and colony formation and induces apoptosis in osteosarcoma. Using computer modeling, we found that APIO-EE-7 can interact with Aurora B at ATP-binding pocket. Treatment with APIO-EE-7 can increase EMT marker expression level of E-cadherin and decrease N-cadherin, vimentin and survivin expression. Importantly, APIO-EE-7 dramatically attenuated tumor incidence and volume in osteosarcoma metastasis mouse model. Our findings suggest that APIO-EE-7 is a potential therapeutic agent against osteosarcoma metastasis by targeting Aurora B, which provides hope for rapid clinic translation. Citation Format: Guoguo Jin, Jitian Li, Zhiping Guo, Junyan Teng, Xiaoling Li, Zhenjiang Zhao. Molecular mechanism of APIO-EE-7 suppresses cell metastasis by targeting Aurora B in osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4292.
Evidence‐based treatments for rosacea based on phenotype approach
Authors: E.J. Zuuren, Z. Fedorowicz, J. Tan, M.M.D. Linden, B.W.M. Arents, B. Carter, L. Charland
Journal: British Journal of Dermatology (2019)

Rosacea is a common, chronic skin condition causing flushing, redness, red pimples and pus‐filled spots (pustules) on the face. It affects about 1‐20% of people worldwide. Rosacea can also cause inflammation of the eyes/eyelids (ocular rosacea) and thickening of the skin, especially the nose (rhinophyma). Although the cause of rosacea is unclear, treatments are available for this distressing disease. This review from the Netherlands, U.K. and Canada aimed to find out which treatments are effective for rosacea. The authors included data from 152 studies. For reducing redness, brimonidine and oxymetazoline worked from three up to 12 hours after being applied. For reducing pimples and pustules with topical (applied to the skin) treatments, azelaic acid, ivermectin and metronidazole were effective and safe. Ivermectin was slightly more effective than metronidazole. Minocycline foam also showed a large reduction in pimples and pustules. With oral (taken by mouth) antibiotics, tetracycline, doxycycline 40 mg or minocycline 45 mg reduced the number of pimples and pustules. Doxycycline 40 mg was likely as effective as 100 mg, with fewer side effects like diarrhoea and nausea. Oral minocycline 100 mg was as effective as doxycycline 40 mg. Azithromycin may be as effective as 100 mg doxycycline. Isotretinoin 0.25 mg/kg decreased pimples and pustules by 90%, and increased quality of life and patients’ satisfaction. Isotretinoin 0.3 mg/kg appeared to be slightly more effective than 50‐100 mg doxycycline. However, isotretinoin is known to cause serious birth defects, so pregnancy must be avoided when using it. For treating dilated blood vessels, laser therapy and intense pulsed light therapy were both effective, but these studies had limited data. In ocular rosacea, ciclosporin 0.05% ophthalmic emulsion increased quality of life and improved the amount/quality of tears, and was slightly more effective than oral doxycycline. Omega‐3 fatty acids likely improve dry eyes and tear gland function.
Risks of stillbirth and neonatal death with advancing gestation at term: A systematic review and meta-analysis of cohort studies of 15 million pregnancies
Authors: Javaid Muglu, Henna Rather, David Arroyo-Manzano, Sohinee Bhattacharya, Imelda Balchin, Asma Khalil, Basky Thilaganathan, Khalid S. Khan, Javier Zamora, Shakila Thangaratinam
Journal: PLoS Medicine (2019)

Background Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age. Methods and findings We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990–October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome. Conclusions Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks. Systematic review registration PROSPERO CRD42015013785
Abstract 17538: Low Serum Sodium Values on Longitudinal Follow-Up Are Associated With Adverse Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Tasnim F Imran, Katherine E Kurgansky, Yash R Patel, Ariela R Orkaby, Robert R Mclean, Yuk-Lam Ho, Kelly Cho, David R Gagnon, J Michael Gaziano, Luc Djousse, Jacob Joseph
Journal: Circulation (2017)

Objective: to examine whether repeated measures of serum sodium are associated with mortality and hospitalization in a large national cohort of patients with heart failure with preserved ejection f...