tbuckley/cabot-search huggingface dataset:
Abstract PD12-07: Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study
Authors: Soojeong Choi, Jae ho Jeong, Jinhong Jung, Young Jae Lee, Jong Won Lee, Beom Seok Ko, Byung Ho Son, Sei Hyun Ahn, Yura Lee, Hee jeong Kim, Il Yong Chung
Journal: Cancer Research (2021)

Abstract BackgroundBreast cancer survivors who taking tamoxifen as adjuvant therapy have been reported to have more endometrial lesions. According to guidelines, a gynecological assessment is recommended for postmenopausal women, but there is no mention of premenopausal women. The purpose of this study is to compare the risk of endometrial cancer by age at diagnosis, and to investigate frequencies of gynecological exam in breast cancer patients taking tamoxifen in South Korea. MethodsA nationwide retrospective cohort study was conducted using South Korea Health Insurance Review and Assessment Service claims data. Between 2010 and 2015, a total of 60,545 (mean follow-up, 66.0 months) newly diagnosed female breast cancer survivors were included. Endometrial evaluation and Dilatation &amp; Curettage (D&amp;C) proportion were analyzed by age at diagnosis. The incidence of endometrial cancer and benign lesions were calculated as incident cases per person-year and analyzed with the Kaplan-Meier method. ResultsThe 26,374 patients who taking tamoxifen were divided into four groups by age at diagnosis. The incidence rate of endometrial cancer per 1,000 person-years was 1.13 and 1.45 for age range 50-59 and over 60 and 0.62 and 0.82 for in age under 40 and range 40-49. However, D&amp;C proportion did not all differ from 10 to 11% in each subgroup. ConclusionsThis nationwide cohort study showed that the risk of endometrial cancer in premenopausal breast cancer women taking tamoxifen was lower than that of postmenopausal women. However, the invasive diagnostic procedure such as aspiration, biopsy, polypectomy and D&amp;C was proceeding at a level that makes no difference with those in postmenopausal women. Citation Format: Soojeong Choi, Jae ho Jeong, Jinhong Jung, Young Jae Lee, Jong Won Lee, Beom Seok Ko, Byung Ho Son, Sei Hyun Ahn, Yura Lee, Hee jeong Kim, Il Yong Chung. Incidences of endometrial events and frequencies of endometrial invasive diagnostic procedures in breast cancer survivors on tamoxifen: A nationwide study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-07.
Inhibition of tumor growth by an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1.
Authors: Hiroshi Yagi, Masakazu Ueda, Hiromitsu Jinnno, Koichi Aiura, Masaharu Seno, Hiroko Tada, Hidenori Yamada, Masaki Kitajima
Journal: Cancer Research (2006)

5123  Background: Human pancreatic ribonuclease-1 (RNase1) does not exhibit its cytotoxicity due to their ability to degrade RNA molecules unless it is artificially internalized into the cytosol. Furthermore, once it encounters the cytosolic RNase inhibitor (RI), the activity of RNase1 is seriously reduced. To study the cytotoxic potential of RNase toward malignant tumor by reducing the angiogenesis, the basic fibroblast growth factor (bFGF) sequence was inserted into RNase1 at the RI binding site using a gene fusion technique. Methods: We investigated whether fusion bFGF-RNase affects tumor angiogenesis and malignant tumor growth in vivo. Female BALB/c (nu/nu) mice (6wk old) were injected intradermally with human A431 squamous cell carcinoma cells (one site per mouse and eight per group). Beginning the day after tumor cell inoculation, mice were injected intraperitoneally with bFGF-RNase and PBS. After injection bFGF-RNase and PBS were continuously infused by infusional osmotic pump for a week. The smallest and largest tumor diameters were measured every day and tumor volumes were calculated. 10 days after first injection, mice were sacrificed and tumors were excised and embedded. Tumor data were analysed by two-sided unpaired t test. Results: Tumorigenesis assays demonstrated that systemic treatment by continuous subcutaneous injection after high dose intraperitoneal injection of this fusion protein markedly inhibited the growth of the human A431. And no apparent signs of toxicity were observed during the fusion protein therapy. Conclusions: This result showed that the fusion protein inhibits tumor angiogenesis in vivo that can be expected to be a potent anti tumor agent.
Estimated impact of the pneumococcal conjugate vaccine on pneumonia mortality in South Africa, 1999 through 2016: An ecological modelling study
Authors: Jackie Kleynhans, Stefano Tempia, Kayoko Shioda, Anne von Gottberg, Daniel M. Weinberger, Cheryl Cohen
Journal: PLoS Medicine (2021)

Background Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions. Methods and findings We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged &lt;1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related. Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged &lt;19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates. Conclusions This study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to &lt;19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children.
Drug Nanotargeting for Treating Vascular Dementia and Alzheimer's Disease
Authors: D'Arrigo Joseph S.
Journal: Alzheimers Disease & Dementia (2021)

Microvascular endothelial dysfunction precedes, often by decades, the cognitive decline associated with Alzheimer's disease. Hence, preservation of a healthy cerebrovascular endothelium can be an important therapeutic target. By incorporating appropriate drug(s) into biobased (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier.
What Can Administrative Data Teach Us About Racial/Ethnic Disparities in Atrial Fibrillation Management?
Authors: Faisal M. Merchant
Journal: JAMA Network Open (2021)

Lauren A. Eberly, MD, MPH; Lohit Garg, MD; Lin Yang, MS; Timothy M. Markman, MD; Ashwin S. Nathan, MD, MS; Nwamaka D. Eneanya, MD, MPH; Sanjay Dixit, MD; Francis E. Marchlinski, MD; Peter W. Groeneveld, MD, MS; David S. Frankel, MD
Pituitary adenylate cyclase-activating polypeptide promotes cutaneous dendritic cell functions in contact hypersensitivity
Authors: Yasuo Yamamoto, Atsushi Otsuka, Yoshihiro Ishida, Lai San Wong, Judith A. Seidel, Yumi Nonomura, Chisa Nakashima, Saeko Nakajima, Akihiko Kitoh, Takashi Nomura, Teruki Dainichi, Tetsuya Honda, Wataru Amano, Noriko Konishi, Mikio Hayashi, Mutsuyoshi Matsushita, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2021)
Clinicopathologic and Genomic Analysis of <i>TP53</i>-Mutated Endometrial Carcinomas
Authors: Amir Momeni-Boroujeni, Wissam Dahoud, Chad M. Vanderbilt, Sarah Chiang, Rajmohan Murali, Eric V. Rios-Doria, Kaled M. Alektiar, Carol Aghajanian, Nadeem R. Abu-Rustum, Marc Ladanyi, Lora H. Ellenson, Britta Weigelt, Robert A. Soslow
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Copy number–high endometrial carcinomas were described by The Cancer Genome Atlas as high-grade endometrioid and serous cancers showing frequent copy-number alterations (CNA), low mutational burden (i.e., non-hypermutant), near-universal TP53 mutation, and unfavorable clinical outcomes. We sought to investigate and compare the clinicopathologic and molecular characteristics of non-hypermutant TP53-altered endometrial carcinomas of four histologic types. Experimental Design: TP53-mutated endometrial carcinomas, defined as TP53-mutant tumors lacking microsatellite instability or pathogenic POLE mutations, were identified (n = 238) in a cohort of 1,239 endometrial carcinomas subjected to clinical massively parallel sequencing of 410–468 cancer-related genes. Somatic mutations and CNAs (n = 238), and clinicopathologic features were determined (n = 185, initial treatment planning at our institution). Results: TP53-mutated endometrial carcinomas encompassed uterine serous (n = 102, 55.1%), high-grade endometrial carcinoma with ambiguous features/not otherwise specified (EC-NOS; n = 44, 23.8%), endometrioid carcinomas of all tumor grades (n = 28, 15.1%), and clear cell carcinomas (n = 11, 5.9%). PTEN mutations were significantly more frequent in endometrioid carcinomas, SPOP mutations in clear cell carcinomas, and CCNE1 amplification in serous carcinomas/EC-NOS; however, none of these genomic alterations were exclusive to any given histologic type. ERBB2 amplification was present at similar frequencies across TP53-mutated histologic types (7.7%–18.6%). Although overall survival was similar across histologic types, serous carcinomas presented more frequently at stage IV, had more persistent and/or recurrent disease, and reduced disease-free survival. Conclusions: TP53-mutated endometrial carcinomas display clinical and molecular similarities across histologic subtypes. Our data provide evidence to suggest performance of ERBB2 assessment in all TP53-mutated endometrial carcinomas. Given the distinct clinical features of serous carcinomas, histologic classification continues to be relevant.
Dominant mutations in MIEF1 affect mitochondrial dynamics and cause a singular late onset optic neuropathy
Authors: Majida Charif, Yvette C. Wong, Soojin Kim, Agnès Guichet, Catherine Vignal, Xavier Zanlonghi, Philippe Bensaid, Vincent Procaccio, Dominique Bonneau, Patrizia Amati-Bonneau, Pascal Reynier, Dimitri Krainc, Guy Lenaers
Journal: Molecular Neurodegeneration (2021)

Abstract Inherited optic neuropathies are the most common mitochondrial diseases, leading to neurodegeneration involving the irreversible loss of retinal ganglion cells, optic nerve degeneration and central visual loss. Importantly, properly regulated mitochondrial dynamics are critical for maintaining cellular homeostasis, and are further regulated by MIEF1 (mitochondrial elongation factor 1) which encodes for MID51 (mitochondrial dynamics protein 51), an outer mitochondrial membrane protein that acts as an adaptor protein to regulate mitochondrial fission. However, dominant mutations in MIEF1 have not been previously linked to any human disease. Using targeted sequencing of genes involved in mitochondrial dynamics, we report the first heterozygous variants in MIEF1 linked to disease, which cause an unusual form of late-onset progressive optic neuropathy characterized by the initial loss of peripheral visual fields. Pathogenic MIEF1 variants linked to optic neuropathy do not disrupt MID51’s localization to the outer mitochondrial membrane or its oligomerization, but rather, significantly disrupt mitochondrial network dynamics compared to wild-type MID51 in high spatial and temporal resolution confocal microscopy live imaging studies. Together, our study identifies dominant MIEF1 mutations as a cause for optic neuropathy and further highlights the important role of properly regulated mitochondrial dynamics in neurodegeneration.
Considerations of the proximate mechanisms and ultimate functions of disgust will improve our understanding of cleansing effects
Authors: Joshua M. Tybur, Debra Lieberman
Journal: Behavioral and Brain Sciences (2021)

To understand the consequences of cleansing, Lee and Schwarz favor a grounded procedures perspective over recently developed disgust theory. We believe that this position stems from three errors: (1) interpreting cleansing effects as broader than they are; (2) not detailing the proximate mechanisms underlying disgust; and (3) not detailing adaptive function versus system byproducts when developing the grounded procedures perspective.
Study of clinical determinants in prescribing capecitabine in patients receiving first-line therapy for metastatic colorectal cancer under 'real practice' conditions in Belgium and Luxemburg
Authors: E.j.r. Joossens, Kalantan H. Rezaei, M. De Man, Jacques Dumont, F. Geurs, Didier Verhoeven, A. Bols, Bart Neyns
Journal: Annals of Oncology (2007)
FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a <i>FLT3</i> Mutation
Authors: E. Dianne Pulte, Kelly J. Norsworthy, Yaping Wang, Qing Xu, Hisham Qosa, Ramadevi Gudi, Donna Przepiorka, Wentao Fu, Olanrewaju O. Okusanya, Kirsten B. Goldberg, R. Angelo De Claro, Ann T. Farrell, Richard Pazdur
Journal: Clinical Cancer Research (2021)

On November 28, 2018, the FDA approved gilteritinib (Xospata; Astellas), a small-molecule FMS-like tyrosine kinase 3 (FLT3) inhibitor, for treatment of relapsed or refractory acute myeloid leukemia with a FLT3 mutation as detected by an FDA-approved test. In the ADMIRAL study, patients were randomized 2:1 to receive gilteritinib or standard chemotherapy and stratified by response to first-line treatment and intensity of prespecified chemotherapy. Efficacy was established on interim analysis on the basis of complete remission (CR) + CR with partial hematologic recovery (CRh) rate, duration of CR + CRh, and conversion from transfusion dependence to transfusion independence in 138 patients in the gilteritinib arm. With median follow-up of 4.6 months [95% confidence interval (CI), 2.8-15.8 months] at interim analysis, the CR + CRh rate was 21% (95% CI, 15%-29%), median duration of CR + CRh was 4.6 months (range, 0.1-15.8+), and conversion from transfusion dependence to transfusion independence was 31%. Revised labeling approved on May 29, 2019 included the results of the final analysis, showing an improvement in overall survival (OS) with gilteritinib compared with chemotherapy (HR, 0.64; 95% CI, 0.49-0.83; one-sided P = 0.0004; median OS, 9.3 vs. 5.6 months). The OS benefit was observed in both high and low chemotherapy intensity subgroups. Labeling includes a boxed warning for differentiation syndrome and warnings for posterior reversible encephalopathy syndrome, QT prolongation, pancreatitis, and embryo-fetal toxicity. Safe use requires frequent monitoring of electrocardiograms and blood chemistries. Assessments of long-term safety are pending.
Adaptive and Constitutive Activations of Malic Enzymes Confer Liver Cancer Multilayered Protection Against Reactive Oxygen Species
Authors: Derek Lee, Misty Shuo Zhang, Felice Ho‐Ching Tsang, Macus Hao‐Ran Bao, Iris Ming‐Jing Xu, Robin Kit‐Ho Lai, David Kung‐Chun Chiu, Aki Pui‐Wah Tse, Cheuk‐Ting Law, Cerise Yuen‐Ki Chan, Vincent Wai‐Hin Yuen, Noreen Nog‐Qin Chui, Irene Oi‐Lin Ng, Chun‐Ming Wong, Carmen Chak‐Lui Wong
Journal: Hepatology (2021)

HCC undergoes active metabolic reprogramming. Reactive oxygen species (ROS) are excessively generated in cancer cells and are neutralized by NADPH. Malic enzymes (MEs) are the less studied NADPH producers in cancer.We found that ME1, but not ME3, was regulated by the typical oxidative stress response pathway mediated by kelch-like ECH associated protein 1/nuclear factor erythroid 2-related factor (NRF2). Surprisingly, ME3 was constitutively induced by superenhancers. Disruption of any ME regulatory pathways decelerated HCC progression and sensitized HCC to sorafenib. Therapeutically, simultaneous blockade of NRF2 and a superenhancer complex completely impeded HCC growth. We show that superenhancers allow cancer cells to counteract the intrinsically high level of ROS through constitutively activating ME3 expression. When HCC cells encounter further episodes of ROS insult, NRF2 allows cancer cells to adapt by transcriptionally activating ME1.Our study reveals the complementary regulatory mechanisms which control MEs and provide cancer cells multiple layers of defense against oxidative stress. Targeting both regulatory mechanisms represents a potential therapeutic approach for HCC treatment.
Engineering extracellular vesicles with platelet membranes fusion enhanced targeted therapeutic angiogenesis in a mouse model of myocardial ischemia reperfusion
Authors: Qiyu Li, Yanan Song, Qiaozi Wang, Jing Chen, Jinfeng Gao, Haipeng Tan, Su Li, Yuan Wu, Hongbo Yang, Hanwei Huang, Yang Yu, Yao Li, Ning Zhang, Zheyong Huang, Zhiqing Pang, Juying Qian, Junbo Ge
Journal: Theranostics (2021)

Therapeutic angiogenesis is one promising strategy for the treatment of ischemic heart disease, which is the leading cause of death globally. In recent years, extracellular vesicles (EVs) have quickly gained much attention as a cell-free approach to stimulate angiogenesis. However, clinical applications of EVs are limited by their insufficient targeting capability. Herein, we introduce a method to enhance therapeutic angiogenesis based on platelet membrane-engineered EVs.Platelet-mimetic EVs (P-EVs) were fabricated by fusing the membranes of EVs with platelet membranes by extrusion. A mouse model of myocardial ischemia reperfusion (MI/R) was established and injected with PBS, EVs, and P-EVs to evaluate their targeting ability and therapeutic angiogenesis efficacy.P-EVs inherited the adhesive proteins and natural targeting ability to injured vasculature of platelets and retained the pro-angiogenic potential of EVs. In the MI/R model, P-EVs preferentially accumulated in the injured endothelium of the ischemic hearts and enhanced the angiogenesis potency of EVs.This engineering strategy to modify pre-isolated EVs with platelet membranes by membrane fusion bestows EVs with the targeting ability of platelets and offers an exciting opportunity to design other targeted EVs fused with cell membranes from different sources for therapeutic angiogenesis.
Correction: Angiokines Associated with Outcomes after Sunitinib or Everolimus Treatment in Patients with Non–Clear Cell Renal Cell Carcinoma
Authors: Andrew J. Armstrong, Andrew B. Nixon, Andrea Carmack, Qian Yang, Tim Eisen, Walter M. Stadler, Robert J. Jones, Jorge A. Garcia, Ulka N. Vaishampayan, Joel Picus, Robert E. Hawkins, John D. Hainsworth, Christian K. Kollmannsberger, Theodore F. Logan, Igor Puzanov, Lisa M. Pickering, Christopher W. Ryan, Andrew Protheroe, Daniel J. George, Susan Halabi
Journal: Clinical Cancer Research (2021)

In earlier versions of [this article][1] ([1][2]) that were published online on February 16, 2021 and March 23, 2021, three errors were made during analysis of the angiokines dataset. First, 89 patients were reported in the article, and the correct sample size was 99 patients. Second, there was a
Grounded procedures of connection are not created equal
Authors: Daniel Wentzel, Benjamin von Walter, Philipp Scharfenberger
Journal: Behavioral and Brain Sciences (2021)

Lee and Schwarz propose that grounded procedures can also be related to connection rather than separation. Drawing on consumer behavior research, we point to different grounded procedures of connection - in terms of the motor actions involved, their salient properties, and their motivational conditions - and discuss how procedures of separation may be affected by the procedures of connection that precede them.
Author Correction: Clonal hematopoiesis in patients with rheumatoid arthritis
Authors: Paula Savola, Sofie Lundgren, Mikko A. I. Keränen, Henrikki Almusa, Pekka Ellonen, Marjatta Leirisalo-Repo, Tiina Kelkka, Satu Mustjoki
Journal: Blood Cancer Journal (2021)

A Correction to this paper has been published: https://doi.org/10.1038/s41408-021-00427-1
Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease
Authors: Alfred K. Cheung, Tara I. Chang, William C. Cushman, Susan L. Furth, Fan Fan Hou, Joachim H. Ix, Gregory A. Knoll, Paul Muntner, Roberto Pecoits-Filho, Mark J. Sarnak, Sheldon W. Tobe, Charles R.V. Tomson, Lyubov Lytvyn, Jonathan C. Craig, David J. Tunnicliffe, Martin Howell, Marcello Tonelli, Michael Cheung, Amy Earley, Johannes F.E. Mann
Journal: Kidney International (2021)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.