tbuckley/cabot-search huggingface dataset:
The number of people exposed to water stress in relation to how much water is reserved for the environment: a global modelling study
Authors: Davy Vanham, Lorenzo Alfieri, Martina Flörke, Stefania Grimaldi, Valerio Lorini, Ad de Roo, Luc Feyen
Journal: The Lancet Planetary Health (2021)

Increasing human demand for water and changes in water availability due to climate change threatens water security worldwide. Additionally, exploitation of water resources induces stress on freshwater environments, leading to biodiversity loss and reduced ecosystem services. We aimed to conduct a spatially detailed assessment of global human water stress for low to high environmental flow (EF) protection.In this modelling study, we used the LISFLOOD model to generate daily natural flows without anthropogenic water use for 1980-2018. On the basis of these flows, we selected three EF methods (EF with high ecological protection [EFPROT], EF with minimum flow requirements [EFMIN], and variable monthly flow [EFVMF]) to calculate monthly EFs. We assessed monthly consumptive water use for industry, agricultural crops, livestock, municipalities, and energy production for 2010. We then estimated the corresponding number of people under water stress per month on a global and national level using a spatially detailed population database for 2010.We estimate that 3·2 billion (EFPROT), 2·4 billion (EFVMF), and 2·2 billion (EFMIN) people lived under water stress for at least 1 month per year, corresponding to 46%, 35%, and 32% of the world's population in 2010, respectively. Around 80% of people living under water stress lived in Asia; in particular, India, Pakistan, and northeast China. Compared with EFMIN, imposing EFPROT globally would have put between 710 million (March) to 1 billion (June) additional people under water stress on a monthly basis, whereas this would have been 72 million (August) to 218 million (April) additional people if EFVMF were imposed.Ensuring high ecological protection would put nearly half of the world's population (3·2 billion people) under water stress for at least 1 month per year. Policy makers and water managers have to make an important trade-off when allocating limited water resources between direct human needs and the environment. A better understanding of local ecosystem needs is crucial to alleviating current and future human water stress, while sustaining healthy ecosystems.None.
Predictive Value for Increased Factor XIa and Plasma Kallikrein Activity in Acute Venous Thromboembolism
Authors: Magdolna Nagy, Alejandro Pallares Robbles, Mayken Visser, Vincent Ten Cate, Thomas Knoeck, Arina J. Ten Cate-Hoek, Hugo ten Cate, Philipp Wild, Henri M.H. Spronk
Journal: Blood (2021)
TEMPO: A Phase 2, Randomized, Open-Label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects with Indolent Non Hodgkin Lymphoma (iNHL)
Authors: Vladimir I. Vorobyev, Dok Hyun Yoon, Maciej Kaźmierczak, Sebastian Grosicki, Corrado Tarella, Angelo Genua, Jin Seok Kim, Debra Litwak, David Cohan, Ian W. Flinn, Pier Luigi Zinzani, Leo I. Gordon
Journal: Blood (2021)
Multicenter Prospective Evaluation of Diagnostic Potential of Flow Cytometric Aberrancies in Myelodysplastic Syndromes
Authors: Wolfgang Kern, Theresia M. Westers, Frauke Bellos, Marie C Bene, Peter Bettelheim, Lisa Eidenschink Brodersen, Kate Burbury, Sung-Chao Chu, Matthew Cullen, Matteo Della Porta, Alan Stewart Dunlop, Ulrika Johansson, Sergio Matarraz, Uta Oelschlaegel, Kiyoyuki Ogata, Anna Porwit, Frank W. M. B. Preijers, Katherina Psarra, Leonie Saft, Dolores Subirá, Elisabeth Weiss, Arjan A. Van de Loosdrecht
Journal: Blood (2021)
Circular RNA circ-FoxO3 attenuates blood-brain barrier damage by inducing autophagy during ischemia/reperfusion
Authors: Zhenguo Yang, Cheng Huang, Xueyi Wen, Wenlin Liu, Xiaoxiong Huang, Yufeng Li, Jiankun Zang, Zean Weng, Dan Lu, Chi Kwan Tsang, Keshen Li, Anding Xu
Journal: Molecular Therapy (2021)

Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R. Upregulation of circ-FoxO3 and autophagic flux were detected in brain microvessel endothelial cells in patients with hemorrhagic transformation and in mice models with middle cerebral artery occlusion/reperfusion. In vivo and in vitro studies indicated that circ-FoxO3 alleviated BBB damage principally by autophagy activation. Mechanistically, we found that circ-FoxO3 inhibited mTORC1 activity mainly by sequestering mTOR and E2F1, thus promoting autophagy to clear cytotoxic aggregates for improving BBB integrity. These results demonstrate that circ-FoxO3 plays a novel role in protecting against BBB damage, and that circ-FoxO3 may be a promising therapeutic target for neurological disorders associated with BBB damage.
Efferocytosis induces macrophage proliferation to help resolve tissue injury
Authors: Brennan D Gerlach, Patrick B Ampomah, Arif Yurdagul, Chuang Liu, Max C Lauring, Xiaobo Wang, Canan Kasikara, Na Kong, Jinjun Shi, Wei Tao, Ira Tabas
Journal: Cell Metabolism (2021)
Regulation of Multidrug Resistance 1 Transcription and Chemoresistance by the Mixed Lineage Leukemia 1 Protein
Authors: Hairong Huo, Pellegrino G Magro, Eva C Pietsch, Brijesh B Patel, Kathleen W Scotto
Journal: Cancer Research (2010)

The multidrug resistance 1 gene (MDR1) encodes P-glycoprotein (Pgp), a member of the ATP-binding cassette (ABC) transporter family that confers tumor drug resistance by actively effluxing a number of anti-tumor agents. We have previously shown that MDR1 transcription is regulated by epigenetic events such as histone acetylation, and have identified the histone acetylase P/CAF and the transcription factor NF-Y as the factors mediating the enzymatic and DNA anchoring functions, respectively, at the MDR1 promoter. It has also been shown that MDR1 activation is accompanied by increased methylation on lysine 4 of histone H3 (H3K4). In this study, we have further the investigation of histone methylation in MDR1 regulation and function. We show that the Mixed Lineage Leukemia 1 (MLL1) protein, a histone methyltransferase specific for H3K4, is required for MDR1 promoter methylation, as knockdown of MLL1 resulted in a decrease in MDR1 expression. The regulation of MDR1 by MLL1 has functional consequences in that downregulation of MLL1 led to increased retention of the Pgp-specific substrate DIOC2(3), as well as increased cellular sensitivity to several Pgp substrates. Regulation of MDR1 by MLL1 was dependent on the CCAAT box within the proximal MDR1 promoter, similar to what we had shown for MDR1 promoter acetylation, and also requires NF-Y. Finally, overexpression of the most prevalent MLL fusion protein, MLL-AF4, led to increased MDR1 expression. This is the first identification of a histone methyltransferase and its leukemogenic rearrangement that regulates expression of an ABC drug transporter, suggesting a new target for circumvention of tumor multidrug resistance.
Identification of Small Molecules That Induce Therapeutic Levels of Fetal Hemoglobin for Treatment of Sickle Cell Disease By Pairing Machine Learning with High-Resolution Single Cell RNA Sequencing Maps of Adult and Fetal Human Erythropoiesis
Authors: Mauricio Cortes, Anthony J Monti, Sunny Sun, Orna Lynch, Youli Xia, Sarah Lin, Michael Malamas, Scott Steelman, Sriram Krishnamoorthy, Morag Stewart, Effie Tozzo
Journal: Blood (2021)
Hard tissue stability after guided bone regeneration: a comparison between digital titanium mesh and resorbable membrane
Authors: Songhang Li, Junyi Zhao, Yu Xie, Taoran Tian, Tianxu Zhang, Xiaoxiao Cai
Journal: International Journal of Oral Science (2021)

Guided bone regeneration (GBR) uses resorbable and non-resorbable membranes as biological barriers. This study compared the differences in hard tissue stability between GBR using evidence-based digital titanium mesh and resorbable collagen membranes during implant placement. A total of 40 patients (65 implant sites) were enrolled and divided into two groups: resorbable membrane and digital titanium mesh groups. The alveolar bone was analyzed at two- and three-dimensional levels using cone-beam computed tomography and by reconstructing and superimposing the hard tissues at four time points: preoperatively, postoperatively, before second-stage surgery, and 1 year after loading. The use of digital titanium mesh showed less alveolar bone resorption in vertical and horizontal directions two-dimensionally before the second-stage surgery and 1 year after loading. Regarding volumetric stability, the percentage of resorption after 6 months of healing with resorbable membrane coverage reached 37.5%. However, it was only 23.4% with titanium mesh. Although postoperative bone volume was greater at all labial sites with resorbable membrane than with digital titanium mesh, after substantial bone resorption within 1 year of loading, the labial bone thickness at the upper part of implants was thinner with resorbable membrane than with digital titanium mesh. Furthermore, digital titanium meshes made according to ideal bone arch contour reduced soft tissue irritation, and the exposure rate was only 10%. Therefore, although both resorbable membrane and digital titanium mesh in GBR were able to successfully reconstruct the bone defect, digital titanium meshes were better at maintaining the hard tissue volume in the osteogenic space.
Graft-Vs-Host Disease (GvHD) Prophylaxis with Post-Transplant Cyclophosphamide (PTCy) and Thymoglobulin (ATG) Are More Important Determinants of Cytomegalovirus (CMV) Reactivation after Allogeneic Hematopoietic Cell Transplantation (HCT) Than Ex-Vivo T-Cell Depletion in the Era of Pre-Emptive Therapy
Authors: Lip Leong Chong, Chelsea Chia, Yin Teng Koh, Yang Liang Boo, Chun Tsu Lee, Michelle Poon, Lip Kun Tan, Liang Piu Koh
Journal: Blood (2021)
A Phase 1/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma
Authors: Chunrui Li, Di Wang, Yongping Song, Jianyong Li, He Huang, Bing Chen, Jing Liu, Kai Hu, Hanyun Ren, Xi Zhang, Zhenyu Li, Dehui Zou, Qingsong Yin, Lijuan Chen, Yongxian HU, Yong Xu, Qian Cheng, Yuelu Guo, Yujun Dong, Li Gao, Aining Xu, Songbai Cai, Wen Wang, Ming Wu, Jue Wang, Liting Chen, Jianfeng Zhou, Lugui Qiu
Journal: Blood (2021)
Fatty Bone Marrow Positively Selects Pre-Leukemic HSPCs with a <i>DNMT3A-</i>mutation
Authors: Naama Zioni, Noa Chapal Ilani, Ekaterina Petrovich-Kopitman, Mehmet Saçma, Hartmut Geiger, Marina Scheller, Carsten Mueller-Tidow, Nathali Kaushansky, Liran I. Shlush
Journal: Blood (2021)
Abstract 10734: Assessment of Cardiovascular Disease and Mortality Among Black Patients with Gout
Authors: Harshith P chandrakumar, Anoop V Puskoor, Seeta Chillumuntala, Sara Sharif, Diego Cepeda Mora, Tanuj Gupta, Ashkan Tadayoni, Pelin Celiker, Stephanie Yakoubovitch, Andrew Tsai, Courtney Chiu, Anan Kazi, Michael Frielich, Ahmad Saleh, Seung Jae Moon, Kingsley Cruickshank, Julie Katz, Louis Salciccioli, isabel M McFarlane
Journal: Circulation (2021)

Introduction: While the association between gout and cardiovascular disease (CVD) has been extensively studied, scarce data is available for the Black population. We aimed to assess, in a predominantly Black urban population with gout, the prevalence of traditional CVD risk factors, CV outcomes, and the strength of the association between gout and CVD after adjusting for CVD risk factors. Hypothesis: Black patients with gout have higher CVD rates compared to a matched cohort without gout. Methods: Cross-sectional analysis of data obtained from the EMR of gout patients followed at our primary care clinics. Patients were identified by ICD codes and compared to age, sex and race matched non- gout cohort. Descriptive data was obtained, and logistic regression used to assess the strength of association between gout and CVD, before and after adjustment for CVD risk factors including obesity, DM, HTN, dyslipidemia and smoking. Results: There were 471 patients with gout with a mean age of 63.7 ± 0.5 years (mean ±SEM); 89% were Black, 63% were men, mean BMI was 31.3 ± 0.4 Kg/m 2 . HTN, DM and dyslipidemia were present in 89%, 46% and 52% respectively.Compared to controls, patients with gout had significantly higher rates of angina, arrythmia, CAD/stents, MI, CABG, CVA, and PVD. The odds ratio (OR) for CVD = 4.5 (3.3-6.2) (95% CI), p&lt;0.001 and OR =2.9 (1.9-4.5), p&lt;0.001 before and after adjustment for CVD risk factors respectively. There was a significantly higher mortality rate of 6.2 in gout vs 2.6 in the non- gout cohort, p &lt;0.01. Conclusion: Gout in a predominantly Black population confers three times the CVD risk and overall mortality compared to a race, age and sex-matched cohort.This risk appears greater compared to previously published data in whites (OR 1.25-1.55) (Choi HK et al Circulation 2007;116:894-900). Further research is needed to confirm our findings and to develop interventions to reduce morbidity and mortality among these vulnerable patients.
A Phase1b Clinical Study of the Oral PI3Kδ Inhibitor, Linperlisib, in Patients with B-Cell Lymphomas
Authors: Lugui Qiu, Zhiming Li, Yunhong Huang, Ligen Liu, Lihong Liu, Ye Guo, Lan Deng, Haiyan Yang, Zhen CAI, Xu Ye, Zhen Wang, Hanying Bao, Zusheng Xu, Binghua Zheng
Journal: Blood (2021)
Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab Versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Evolve CLL/SLL Study (SWOG S1925; NCT#04269902)
Authors: Deborah M. Stephens, Anna Moseley, Brian T. Hill, John M. Pagel, Mazyar Shadman, Michael Fisch, Alexey V. Danilov, David Ng, Anthony R. Mato, Danielle M. Brander, Megan Othus, Steven Coutre, Susan M. O'Brien, Harry P. Erba
Journal: Blood (2021)
Safety and Efficacy of FT596, a First-in-Class, Multi-Antigen Targeted, Off-the-Shelf, iPSC-Derived CD19 CAR NK Cell Therapy in Relapsed/Refractory B-Cell Lymphoma
Authors: Veronika Bachanova, Armin Ghobadi, Krish Patel, Jae H Park, Ian W. Flinn, Prutha Shah, Carol Wong, Cara Bickers, Peter Szabo, Lilly Wong, Bahram Valamehr, Siminder Atwal, Yu-Waye Chu, Rebecca Elstrom, Paolo Strati
Journal: Blood (2021)
Single-Cell Multiomics Reveals Increased Plasticity, Resistant Populations and Stem-Cell-like Blasts in KMT2A-Rearranged Leukemia
Authors: Changya Chen, Wenbao Yu, Fatemeh Alikarami, Qi Qiu, Chia-hui Chen, Jennifer Flournoy, Peng Gao, Yasin Uzun, Li Fang, Yuxuan Hu, Qin Zhu, Kai Wang, Clara Libbrecht, Alex Felmeister, Isaiah Rozich, Yang-yang Ding, Stephen P Hunger, Hao Wu, Patrick A. Brown, Erin Guest, David M Barrett, Kathrin M. Bernt, Kai Tan
Journal: Blood (2021)
Abstract IA-001: Molecular subtypes and vulnerabilities in pancreatic cancer
Authors: Andrew Aguirre
Journal: Cancer Research (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with few effective treatment options. Understanding the molecular underpinnings of PDAC is critical to developing new biomarker strategies and therapeutic approaches for patients. In this talk, I will review our understanding of the genetics and biology of PDAC, including the major genomic subtypes and transcriptional programs of the disease. I will discuss how single-cell RNA sequencing has refined our understanding of subtype heterogeneity and evolution in the context of therapy and PDAC model systems. Moreover, I will discuss new KRAS inhibitors, their mechanisms of resistance and their potential to impact the treatment landscape for pancreatic cancer patients. Lastly, I will discuss our recent efforts to use functional genetic screening approaches to define new therapeutic targets in pancreatic cancer, highlighting our work on the VPS4A ATPase as a potential new target in tumors with 18q/SMAD4 deletion. Citation Format: Andrew Aguirre. Molecular subtypes and vulnerabilities in pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-001.
Heterogeneity of Diabetes: β-Cells, Phenotypes, and Precision Medicine: Proceedings of an International Symposium of the Canadian Institutes of Health Research’s Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases
Authors: William T. Cefalu, Dana K. Andersen, Guillermo Arreaza-Rubín, Christopher L. Pin, Sheryl Sato, C. Bruce Verchere, Minna Woo, Norman D. Rosenblum
Journal: Diabetes Care (2021)

One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes.
Integration of pre-exposure prophylaxis services into public HIV care clinics in Kenya: a pragmatic stepped-wedge randomised trial
Authors: Elizabeth M Irungu, Kenneth K Mugwanya, Nelly R Mugo, Elizabeth A Bukusi, Deborah Donnell, Josephine Odoyo, Elizabeth Wamoni, Sue Peacock, Jennifer F Morton, Kenneth Ngure, Mary Mugambi, Irene Mukui, Gabrielle O'Malley, Jared M Baeten
Journal: The Lancet Global Health (2021)

BackgroundSuccessful and sustainable models for HIV pre-exposure prophylaxis (PrEP) delivery in public health systems in Africa are needed. We aimed to evaluate the implementation of PrEP delivery integrated in public HIV care clinics in Kenya.MethodsAs part of Kenya's national PrEP roll-out, we conducted a stepped-wedge cluster-randomised pragmatic trial to catalyse scale-up of PrEP delivery integrated in 25 public HIV care clinics. We selected high-volume clinics in these regions (ie, those with a high number of people living with HIV enrolled in HIV care and treatment). Clinics (each representing a cluster) were stratified by region and randomly assigned to the order in which clinic staff would receive PrEP training and ongoing technical support using numbered opaque balls picked from a bag. There was no masking. PrEP provision was done by clinic staff without additional financial support. Data were abstracted from records of individuals initiating PrEP. The primary outcome was the number of people initiating PrEP per clinic per month comparing intervention to control periods. Other outcomes included PrEP continuation, adherence, and incident HIV infections. This trial is registered with ClinicalTrials.gov, NCT03052010.FindingsAfter the baseline period, which started in January, 2017, every month two to six HIV care clinics crossed over from control to intervention, until August, 2017, when all clinics were implementing the intervention. Of 4898 individuals initiating PrEP (27 during the control period and 4871 during the intervention period), 2640 (54%) were women, the median age was 31 years (IQR 25–39), and 4092 (84%) reported having a partner living with HIV. The mean monthly number of PrEP initiations per clinic was 0·1 (SD 0·5) before the intervention and 7·5 (2·7) after intervention introduction (rate ratio 23·7, 95% CI 14·2–39·5, p<0·0001). PrEP continuation was 57% at 1 month, 44% at 3 months, and 34% at 6 months, and 12% of those who missed a refill returned later for PrEP re-initiation. Tenofovir diphosphate was detected in 68 (96%) of 71 blood samples collected from a randomly selected subset of participants. Six HIV infections were observed over 2531 person-years of observation (incidence 0·24 cases per 100 person-years), three of which occurred at the first visit after PrEP initiation.InterpretationWe observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible.FundingNational Institute of Mental Health and Bill & Melinda Gates Foundation.
Abstract 11904: Heart Health for South Asians: Improved Cardiovascular Risk Factors and Outcomes With a Culturally Tailored Health Education Program
Authors: Paniz Vafaei, Seema Pursnani, Uma Vadlakonda, Chi-Mei Liu, yu chan
Journal: Circulation (2021)

Introduction: The Kaiser Permanente (KP) Northern California Heart Health for South Asians (HHSA) Program is a two-hour educational class offered at KP Santa Clara, California. The class provides culturally relevant lifestyle and dietary recommendations to South Asian patients, in an effort to reduce the known disproportionate burden of cardiovascular (CV) disease in this population. We aimed to evaluate the impact of the HHSA Program on CV risk factors and major adverse CV events (MACE). Methods: A retrospective cohort study identified 1517 participants of South Asian descent, age ≥ 18 years old from 2006-2019. We evaluated the change in individual risk factors with program attendance (median follow up of 6.9 years) for the following variables: systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), LDL, HDL, BMI, and HbA1c. We also performed a propensity matched analysis to evaluate differences in MACE including stroke, myocardial infarction (MI), coronary revascularization, and all-cause mortality. Results: Differences in individual risk factors are outlined in figure 1A and show a significant improvement in SBP, DBP, TG, LDL, HDL and HbA1c at follow up. In the propensity matched analysis, there was a statistically significant reduction in revascularization (OR 0.33, 95% CI 0.14-0.78, p= 0.011) and mortality (OR 0.41, 95% CI 0.22-0.79, p= 0.008), a trend towards reduction in stroke (OR 0.22 , 95% CI 0.05-1.03, p= 0.054), and no statistically significant difference in the rate of MI (OR 0.93 , 95% CI 0.43-1.98, p= 0.85) (Figure 1B). Conclusions: Our study demonstrates the efficacy of a culturally tailored South Asian health education program in improving CV risk factors and reducing MACE. The program highlights the importance and value of providing culturally tailored, motivational health education in primary CV disease prevention.