tbuckley/cabot-search huggingface dataset:
Abstract 8771: Asialoerythropoietin, a Nonerythropoietic Derivative of Erythropoietin, Displays Broad Anti-Heart Failure Activity
Authors: Toshiaki Takeyama, Genzou Takemura, Hiromitsu Kanamori, Atsushi Ogino, Tomonori Kawaguchi, Takatomo Watanabe, Kentaro Morishita, Akiko Tsujimoto, Kazuko Goto, Takako Fujiwara, Hisayoshi Fujiwara, Shinya Minatoguchi
Journal: Circulation (2011)

Accumulating evidence suggests cardioprotective effect of erythropoietion (EPO) in experiments, but EPO has some unwanted effects. We investigated effect of asialoerythropoietin (AEPO), a nonerythrogenic derivative of EPO, on 3 different models of heart failure: doxorubicin (DOX)-induced cardiomyopathy, post-large myocardial infarction (MI), and dilated cardiomyopathy in δ-sarcoglycan deficient mouse (Sgcd-null). Accoding to echocardiography and cardiac catheterization, a single intraperitoneal injection of DOX (15 mg/kg) induced an established heart failure in mice 2 weeks later, to which AEPO (1500 U/kg, twice a week, for 2 weeks) was administered. Left ventricular dysfunction was attenuated in the AEPO-treated group (ejection fraction: 71±3% vs. 50±1% in controls). The AEPO-treated heart showed less myocardial fibrosis, inflammatory cell infiltration, and atrophic degeneration of cardiomyocytes accompanying restored expression of GATA-4 and sarcomeric proteins. Among downstream signals of EPO receptor, DOX inactivated ERK in the heart, of which activity AEPO restored. Next, in the mice with large sized, 6-week-old MI, a marked left ventricular dysfunction with adverse remodeling was apparent. AEPO treatment for the subsequent 4 weeks mitigated the further progression of dysfunction and remodeling (ejection fraction: 37±2% vs. 26±3% in controls), accompanying reduced myocardial fibrosis. ERK and Akt were activated in the MI bearing hearts, which were furthermore augmented by AEPO. AEPO activated STAT3, too. Finally, AEPO was administered to 25 weeks old Sgcd-null mice with decreased left ventricular contractility, for the subsequent 5 weeks. Left ventricular dysfunction and dilatation were mitigated (ejection fraction: 71±1% vs. 52±0.4% in controls), accompanying reduced myocardial fibrosis and furthermore compensative hypertrophy. ERK was inactivated, and Akt was activated in the heart of Sgcd null mice. AEPO restored the ERK activity, and furthermore activated Akt. Neither polycythemia nor splenomegaly was noted in any groups. In conclusion, AEPO displays broad anti-heart failure activity regardless of the etiology of heart failure through distinct molecular signals.
Simplifying Survivorship Care Planning: A Randomized Controlled Trial Comparing 3 Care Plan Delivery Approaches
Authors: Claire Snyder, Youngjee Choi, Amanda L Blackford, Jennifer DeSanto, Nancy Mayonado, Susan Rall, Sharon White, Janice Bowie, David E Cowall, Fabian Johnston, Robert L Joyner, Joan Mischtschuk, Kimberly S Peairs, Elissa Thorner, Phuoc T Tran, Antonio C Wolff, Katherine C Smith
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Survivorship care plans seek to improve the transition to survivorship, but the required resources present implementation barriers. This randomized controlled trial aimed to identify the simplest, most effective approach for survivorship care planning. Methods Stage 1-3 breast, colorectal, and prostate cancer patients aged 21 years or older completing treatment were recruited from an urban-academic and rural-community cancer center. Participants were randomly assigned, stratified by recruitment site and cancer type 1:1:1 to a mailed plan, plan delivered during a 1-time transition visit, or plan delivered during a transition visit plus 6-month follow-up visit. Health service use data were collected from participants and medical records for 18 months. The primary outcome, receipt of all plan-recommended care, was compared across intervention arms using logistic regression adjusting for cancer type and recruitment site, with P less than .05 considered statistically significant. Results Of 378 participants randomly assigned, 159 (42.1%) were breast, 142 (37.6%) prostate, and 77 (20.4%) colorectal cancer survivors; 207 (54.8%) from the academic site and 171 (45.2%) from the community site; 316 were analyzable for the primary outcome. There was no difference across arms in the proportion of participants receiving all plan-recommended care: 45.2% mail, 50.5% 1-visit, 42.7% 2-visit (2-sided P = .60). Adherence by cancer type for mail, 1-visit, and 2-visit, respectively, was 52.2%, 53.3%, and 40.0% for breast cancer; 48.6%, 64.1%, and 57.1% for prostate cancer; and 23.8%, 19.0%, and 26.1% for colorectal cancer. There were no statistically significant interactions by recruitment site or cancer type. Conclusions This study did not find differences in receipt of recommended follow-up care by plan delivery approach. Feasibility and other factors may determine the best approach for survivorship care planning.
p28-functionalized PLGA nanoparticles loaded with gefitinib reduce tumor burden and metastases formation on lung cancer
Authors: Ana Rita Garizo, Flávia Castro, Cláudia Martins, Andreia Almeida, Tiago P. Dias, Fábio Fernardes, Cristina C. Barrias, Nuno Bernardes, Arsénio M. Fialho, Bruno Sarmento
Journal: Journal of Controlled Release (2021)
Estrogen Promotes Resistance to Bevacizumab in Murine Models of NSCLC
Authors: Sonia A. Patel, Matthew H. Herynk, Tina Cascone, Babita Saigal, Monique B. Nilsson, Hai Tran, Sumankalai Ramachandran, Lixia Diao, Jing Wang, Xiuning Le, John Minna, Ignacio I. Wistuba, John V. Heymach
Journal: Journal of Thoracic Oncology (2021)
Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study
Authors: Seung Won Lee, Jinhee Lee, Sung Yong Moon, Hyun Young Jin, Jee Myung Yang, Shuji Ogino, Mingyang Song, Sung Hwi Hong, Ramy Abou Ghayda, Andreas Kronbichler, Ai Koyanagi, Louis Jacob, Elena Dragioti, Lee Smith, Edward Giovannucci, I-Min Lee, Dong Hoon Lee, Keum Hwa Lee, Youn Ho Shin, So Young Kim, Min Seo Kim, Hong-Hee Won, Ulf Ekelund, Jae Il Shin, Dong Keon Yon
Journal: British Journal of Sports Medicine (2021)

To determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea.Data regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020.Out of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500-1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses.Adults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.
Associations of Early-Life Threat and Deprivation With Executive Functioning in Childhood and Adolescence
Authors: Dylan Johnson, Julia Policelli, Min Li, Alyna Dharamsi, Qiaochu Hu, Margaret A. Sheridan, Katie A. McLaughlin, Mark Wade
Journal: JAMA Pediatrics (2021)

Many studies have demonstrated an association between early-life adversity (ELA) and executive functioning in children and adolescents. However, the aggregate magnitude of this association is unknown in the context of threat and deprivation types of adversity and various executive functioning domains.To test the hypothesis that experiences of deprivation are more strongly associated with reduced executive functioning compared with experiences of threat during childhood and adolescence.Embase, ERIC, MEDLINE, and PsycInfo databases were searched from inception to December 31, 2020. Both forward and reverse snowball citation searches were performed to identify additional articles.Articles were selected for inclusion if they (1) had a child and/or adolescent sample, (2) included measures of ELA, (3) measured executive functioning, (4) evaluated the association between adversity and executive functioning, (5) were published in a peer-reviewed journal, and (6) were published in the English language. No temporal or geographic limits were set. A 2-reviewer, blinded screening process was conducted.PRISMA guidelines were used to guide data extraction and article diagnostics (for heterogeneity, small study bias, and p-hacking). Article quality was assessed, and data extraction was performed by multiple independent observers. A 3-level meta-analytic model with a restricted maximum likelihood method was used. Moderator analyses were conducted to explore heterogeneity.Primary outcomes included measures of the 3 domains of executive functioning: cognitive flexibility, inhibitory control, and working memory.A total of 91 articles were included, representing 82 unique cohorts and 31 188 unique individuals. Deprivation, compared with threat, was associated with significantly lower inhibitory control (F1,90 = 5.69; P = .02) and working memory (F1,54 = 5.78; P = .02). No significant difference was observed for cognitive flexibility (F1,36 = 2.38; P = .12). The pooled effect size of the association of inhibitory control with deprivation was stronger (Hedges g = -0.43; 95% CI, -0.57 to -0.29) compared with threat (Hedges g = -0.27; 95% CI, -0.46 to -0.08). The pooled effect size of the association of working memory with deprivation was stronger (Hedges g = -0.54; 95% CI, -0.75 to -0.33) compared with threat (Hedges g = -0.28; 95% CI, -0.51 to -0.05).Experiences of both threat and deprivation in childhood and adolescence were associated with reduced executive functioning, but the association was stronger for exposure to deprivation. Efforts to address the consequences of ELA for development should consider the associations between specific dimensions of adversity and specific developmental outcomes.
O2-1 Datopotamab Deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in patients with advanced NSCLC: Updated results of TROPION-PanTumor01 phase 1 study*
Authors: Toshio Shimizu, Aaron E. Lisberg, Jacob M. Sands, Jonathan Greenberg, Penny Phillips, Naoyuki Tajima, Yui Kawasaki, Jessie Gu, Fumiaki Kobayashi, Noboru Yamamoto, Melissa Johnson, Funda Meric-Bernstam, Kiyotaka Yoh, Edward B. Garon, Rebecca S. Heist, Alexander Spira
Journal: Annals of Oncology (2021)
The Impact of Sedentary Lifestyle, High-fat Diet, Tobacco Smoke, and Alcohol Intake on the Hematopoietic Stem Cell Niches
Authors: Katja Kaastrup, Kirsten Grønbæk
Journal: HemaSphere (2021)

Hematopoietic stem and progenitor cells maintain hematopoiesis throughout life by generating all major blood cell lineages through the process of self-renewal and differentiation. In adult mammals, hematopoietic stem cells (HSCs) primarily reside in the bone marrow (BM) at special microenvironments called “niches.” Niches are thought to extrinsically orchestrate the HSC fate including their quiescence and proliferation. Insight into the HSC niches mainly comes from studies in mice using surface marker identification and imaging to visualize HSC localization and association with niche cells. The advantage of mouse models is the possibility to study the 3-dimensional BM architecture and cell interactions in an intact traceable system. However, this may not be directly translational to human BM. Sedentary lifestyle, unhealthy diet, excessive alcohol intake, and smoking are all known risk factors for various diseases including hematological disorders and cancer, but how do lifestyle factors impact hematopoiesis and the associated niches? Here, we review current knowledge about the HSC niches and how unhealthy lifestyle may affect it. In addition, we summarize epidemiological data concerning the influence of lifestyle factors on hematological disorders and malignancies.
Covid-19: NICE issues guidance on vaccine induced immune thrombocytopenia and thrombosis
Authors: Jacqui Wise
Journal: BMJ (2021)

Patients who are acutely unwell with suspected vaccine induced immune thrombocytopenia and thrombosis (VITT) should be referred immediately to the emergency department, says new rapid guidance from the National Institute for Health and Care Excellence (NICE).1

However, a full blood count should be performed in primary care if the patient is not acutely unwell and if same day results can be obtained. If these blood tests show a low platelet count the patient should be referred to the emergency department on the same day.

NICE says that although VITT is extremely rare, with 14.2 cases per …
Nutritional Interventions and the Gut Microbiome in Children
Authors: Saurabh Mehta, Samantha L. Huey, Daniel McDonald, Rob Knight, Julia L. Finkelstein
Journal: Annual Review of Nutrition (2021)

The gut microbiome plays an integral role in health and disease, and diet is a major driver of its composition, diversity, and functional capacity. Given the dynamic development of the gut microbiome in infants and children, it is critical to address two major questions: (a) Can diet modify the composition, diversity, or function of the gut microbiome, and (b) will such modification affect functional/clinical outcomes including immune function, cognitive development, and overall health? We synthesize the evidence on the effect of nutritional interventions on the gut microbiome in infants and children across 26 studies. Findings indicate the need to study older children, assess the whole intestinal tract, and harmonize methods and interpretation of findings, which are critical for informing meaningful clinical and public health practice. These findings are relevant for precision health, may help identify windows of opportunity for intervention, and may inform the design and delivery of such interventions.
Antiviral antibody responses to systemic administration of an oncolytic RNA virus: the impact of standard concomitant anticancer chemotherapies
Authors: Victoria Roulstone, David Mansfield, Robert J Harris, Katie Twigger, Christine White, Johann de Bono, James Spicer, Sophia N Karagiannis, Richard Vile, Hardev Pandha, Alan Melcher, Kevin Harrington
Journal: Journal for ImmunoTherapy of Cancer (2021)

Oncolytic reovirus therapy for cancer induces a typical antiviral response to this RNA virus, including neutralizing antibodies. Concomitant treatment with cytotoxic chemotherapies has been hypothesized to improve the therapeutic potential of the virus. Chemotherapy side effects can include immunosuppression, which may slow the rate of the antiviral antibody response, as well as potentially make the patient more vulnerable to viral infection.Reovirus neutralizing antibody data were aggregated from separate phase I clinical trials of reovirus administered as a single agent or in combination with gemcitabine, docetaxel, carboplatin and paclitaxel doublet or cyclophosphamide. In addition, the kinetics of individual antibody isotypes were profiled in sera collected in these trials.These data demonstrate preserved antiviral antibody responses, with only moderately reduced kinetics with some drugs, most notably gemcitabine. All patients ultimately produced an effective neutralizing antibody response.Patients' responses to infection by reovirus are largely unaffected by the concomitant drug treatments tested, providing confidence that RNA viral treatment or infection is compatible with standard of care treatments.
Direct identification of neoantigen-specific TCRs from tumor specimens by high-throughput single-cell sequencing
Authors: Yong-Chen Lu, Zhili Zheng, Frank J Lowery, Jared J Gartner, Todd D Prickett, Paul F Robbins, Steven A Rosenberg
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Recognition of neoantigens by T cells plays a major role in cancer immunotherapy. Identification of neoantigen-specific T-cell receptors (TCRs) has become a critical research tool for studying T cell-mediated responses after immunotherapy. In addition, neoantigen-specific TCRs can be used to modify the specificity of T cells for T cell-based therapies targeting tumor-specific mutations. Although several techniques have been developed to identify TCR sequences, these techniques still require a significant amount of labor, making them impractical in the clinical setting. Methods Thanks to the availability of high-throughput single-cell sequencing, we developed a new process to isolate neoantigen-specific TCR sequences. This process included the isolation of tumor-infiltrating T cells from a tumor specimen and the stimulation of T cells by neoantigen-loaded dendritic cells, followed by single-cell sequencing for TCR and T-cell activation markers, interferon-γ and interleukin-2. Results In this study, potential neoantigen-specific TCRs were isolated from three melanoma and three colorectal tumor specimens. These TCRs were then synthesized and transduced into autologous T cells, followed by testing the recognition of neoantigens. A total of 28 neoantigen-specific TCRs were identified by this process. If identical TCR sequences were detected from two or more single cells, this approach was highly reliable (100%, 19 out of 19 TCRs). Conclusion This single-cell approach provides an efficient process to isolate antigen-specific TCRs for research and clinical applications.
Major incident declared at two London hospitals after severe flooding
Authors: Shaun Griffin
Journal: BMJ (2021)

One of England’s largest hospital trusts was forced to declare a major incident at two hospitals it runs in east London after severe flooding affected patient care.

Heavy rainfall across London and parts of southeast England on Sunday 25 July caused London’s Barts Health Group to declare a major incident on Monday 26 July after flooding affected the delivery of services at Whipps Cross …
Choriocapillaris: Fundamentals and advancements
Authors: Raphael Lejoyeux, Jennifer Benillouche, Joshua Ong, Marie-Hélène Errera, Ethan A. Rossi, Sumit R. Singh, Kunal K. Dansingani, Susana da Silva, Debasish Sinha, José-Alain Sahel, K. Bailey Freund, SriniVas R. Sadda, Gerard A. Lutty, Jay Chhablani
Journal: Progress in Retinal and Eye Research (2021)
Addressing a Missing Link in Emergency Preparedness: New Insights on the Ethics of Care in Contingency Conditions from the Minnesota COVID Ethics Collaborative
Authors: Joel T. Wu, Debra A. DeBruin, Susan M. Wolf, Thomas Klemond, Erin S. DeMartino
Journal: The American Journal of Bioethics (2021)

This article is referred to by:Ethics Frameworks and Beyond—Advancing Our Understanding of the Contingency Phase to Improve Health Care Quality During Public Health Emergencies
Subacute small bowel obstruction or chronic large bowel obstruction
Authors: Marc Winslet, Kevin Barraclough, Gregor Campbell Hewson
Journal: BMJ (2021)

### What you need to know

A 48 year old woman presented to her general practitioner with a seven day history of colicky lower abdominal pain and vomiting. The intermittent colicky abdominal pain started first when it woke her from sleep. The next day she vomited twice. Her colicky abdominal pain continued, and she noted that it tended to occur about half an hour after eating. She continued vomiting once or twice a day. She reported no diarrhoea and had last opened her bowels six days earlier. On examination she was obese, had no abdominal scars, no abdominal hernias, had quiet bowel sounds, and non-specific generalised abdominal tenderness. There was no guarding or rebound tenderness. The rectum was empty. The general practitioner diagnosed constipation and prescribed a laxative. Three days later she was admitted to hospital with recurrent vomiting and dehydration. She was diagnosed with bowel obstruction due to a caecal carcinoma. 

Sub-acute small bowel obstruction implies an incomplete obstruction of the bowel lumen. Whereas patients with complete bowel obstruction rapidly become extremely unwell, patients with subacute small bowel obstruction or chronic large bowel obstruction may have colicky pain, abdominal distension and vomiting that are less pronounced …
P-47 5-fluorouracil bolus use in infusional regimens among oncologists: A survey by Brazilian Group of Gastrointestinal Tumors
Authors: R. Peixoto, A. Coutinho, R. Weschenfelder, G. Prolla, D. da Rocha Filho, A. Andrade, J. Rego, G. Dos Santos Fernandes, M. Crosara Teixeira, P. Hoff, M. Costa e Silva, R. Dienstmann, R. Riechelmann
Journal: Annals of Oncology (2021)
Myocardial Infarction Repair With iPS Induced by Human Stemness Factors
Authors: Timothy Nelson
Journal: Circulation (2009)

Abstract #3088 Timothy Nelson, Almudena Martinez-Fernandez, Satsuki Yamada, Carmen Perez-Terzic, Yasuhiro Ikeda, Andre Terzic, Mayo, Rochester, MN Timothy Nelson, 2009 Finalist and Presenting Author