tbuckley/cabot-search huggingface dataset:
An Antioxidant Nanoparticle Enhances Exercise Performance in Rat High‐intensity Running Models
Authors: Takuto Toriumi, Ahram Kim, Shoichi Komine, Ikuru Miura, Suminori Nagayama, Hajime Ohmori, Yukio Nagasaki
Journal: Advanced Healthcare Materials (2021)

Abstract Although the adverse effects of excessively generated reactive oxygen species (ROS) on the body during aerobic exercise have been debated, there are few reports on the remarkable effects of the application of conventional antioxidants on exercise performance. The conventional antioxidants could not enhance exercise performance due to their rapid excretion from the body and serious adverse effects on the cellular respiratory system. In this study, impact of the original antioxidant self‐assembling nanoparticle, redox‐active nanoparticle (RNP), is investigated on the exercise performance of rats during running experiments. With an increase in the dose of the administered RNP, the all‐out time of the rat running extends in a dose‐dependent manner. In contrast, with an increase in the dose of the low‐molecular‐weight (LMW) antioxidant, the all‐out running time of the rats decreases. The control group and LMW antioxidant treated group decrease in the number of red blood cells (RBCs) and increase oxidative stress after running. However, the RNP group maintains a similar RBC level and oxidative stress as that of the sedentary group. The results suggest that RNP, which shows long‐blood circulation without disturbance of mitohormesis, effectively removes ROS from the bloodstream to suppresses RBC oxidative stress and damage, thus improving exercise performance.
Letter to the editor: Hypoxia kinetics and histology in combined radiotherapy and oxidative phosphorylation inhibition effects on antitumor immunity
Authors: Daan F Boreel, Paul N Span, Johan Bussink
Journal: Journal for ImmunoTherapy of Cancer (2021)

In response to the recent paper by Chen et al investigating the triple combination of oxidative phosphorylation inhibition, immunotherapy and radiotherapy, we would like to stress that after irradiation, a strong reduction in hypoxia (within 24 hours) can be followed by a strong increase (several days). This is especially the case with larger fraction sizes of radiation therapy, which are often applied in combination with immunotherapy, and is likely to be tumor dependent. All together this may strongly affect the synergistic effect of such a triple combination therapy.
Effects of Scaffold Fiber Orientation on Quality of In-Situ Tissue Engineered Heart Valves
Authors: M. Uiterwijk, A. I. P. M. Smits, D. van Geemen, B. R. van Klarenbosch, S. Dekker, M. J. M. Cramer, J. W. van Rijswijk, E. B. Lurier, M. C. P. Brugmans, A. W. Bosman, P. F. Grundeman, C. V. C. Bouten, J. Kluin
Journal: Circulation (2018)

Introduction:In situ tissue engineering (TE) of heart valves uses readily available acellular synthetic biodegradable scaffolds that transform in vivo in autologous living valves. This study hypothesized that scaffold fiber orientation that resembles native collagen alignment (i.e. anisotropic) results in superior valve function, mechanical properties, and matrix formation during in situ TE.Methods: Trileaflet heart valve scaffolds of biodegradable ureidopyrimidinone (UPy)-polymers with anisotropic (n=10; fibers in circumferential direction) or isotropic (n=10) fiber orientation were produced and implanted in the pulmonary position in sheep. Functional evaluation with echocardiography was performed. Explants (1, 6 and 12 months) were analyzed to evaluate cellularity, extracellular matrix formation and organization, and mechanical propertiesResults: Seventeen animals survived the entire follow-up time and showed functional valves. Consistently higher-pressure gradients were observed for valves in the anisotropic group (not significant at 12 months). Macroscopic analysis revealed pliable leaflets, with no evident differences between the groups. In both groups, fiber resorption was not completed after 12 months and most pronounced at the cell-rich base. Matrix organization did not show apparent differences between the groups, nor in quantity nor in orientation. Notably, anisotropic valves were stiffer in circumferential direction prior to implantation, which already was negated after 1 month of implantation.Conclusions:In situ TE of pulmonary valves demonstrated sustained functionality up to 12 months. Surprisingly, the predefined scaffold fiber organization did not result in significant differences in the newly formed matrix orientation. Apparently, other cues seem to overrule the effect of predefined fiber organization, limiting our possibilities to guide matrix formation by changing scaffold fiber orientation.
The use of 3D printed models on trainee and patient experience for partial nephrectomies.
Authors: E. Reilly Scott, Samuel Morano, Andrea Quinn, Erica Mann, Michelle Ho, Alice Karp, Kaitlyn Boyd, Abhay Singh, Thenappan Chandrasekar, Mark Jonathan Mann, Edouard John Trabulsi, Vishal Desai, Costas D. Lallas
Journal: Journal of Clinical Oncology (2021)

363 Background: 3D printing is a growing tool in surgical education due to the ability to visualize organs, tissue, and masses from multiple angles before operating on a patient. Previous studies using highly detailed and expensive 3D models costing between $1,000-250 per model have been shown to enhance patient and trainee comprehension of tumor characteristics, goals of surgery, and planned surgical procedure for partial nephrectomies. In our study we aim to use simpler and less expensive models in a greater range of patients receiving partial nephrectomies to determine the use of 3D models in patient, resident, and fellow education. Methods: 3D models of the effected kidney, mass, renal artery, and renal vein were created using preoperative imaging of undergoing partial nephrectomies at Thomas Jefferson University Hospital (TJUH) costing $35 per model. Residents and fellows filled out 3 surveys assessing their surgical plan and their confidence in the chosen plan at 3 time points: 1) Before seeing the model, 2) After seeing the model before surgery, and 3) After surgery. Ten patients filled out 2 surveys about their understanding of the kidney, their disease, the surgery they will undergo, and the risks involved with surgery before and after seeing the model. Results: Based on surveys to assess for surgical plan and confidence given to resident and fellow surgeons before and after seeing the 3D model, confidence significantly increased. Surveys given after surgery assessing anatomic and surgical comprehension found that resident and fellow surgeons rated the helpfulness of the models on their anatomical comprehension 7.6 out of 10 and the help of the models on their surgical confidence 7 out of 10. Patient understanding of their kidney, disease, and surgery significantly increased after seeing the 3D model, but the risks associated with surgery did not significantly increase. The extent that the model helped the patients learn about the kidney, their disease, the surgery, and the risks related to surgery were rated an average of 8.33, 9.67, 9.5, and 8.83 out of 10, respectively. Conclusions: Patient-specific 3D models for partial nephrectomies increase resident and fellow confidence in surgical approach and helped patients learn about their disease and feel comfortable going into surgery. Thus, it is important to continue to explore 3D models as an educational tool for both trainees and patients and potentially include 3D models as part of the standard of care. Further research could continue to explore the utility of 3D models as a pre-operative educational tool for both patients and trainees in other surgical fields.
ECMO as a Bridge to Left Ventricular Assist Device or Heart Transplantation
Authors: Ersilia M. DeFilippis, Kevin Clerkin, Lauren K. Truby, Michael Francke, Justin Fried, Amirali Masoumi, A. Reshad Garan, Maryjane A. Farr, Hiroo Takayama, Koji Takeda, Nir Uriel, Veli K. Topkara
Journal: JACC Heart Failure (2021)
241P NAB-paclitaxelasthird-linetherapyafterfailureof gemcitabineand5-fluorouracil(5-FU)basedcombinationsin advancedgallbladdercancerpatients
Authors: V. Goel, V. Talwar, N. Patnaik, S. Raina, S. Singh
Journal: Annals of Oncology (2016)
Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice
Authors: Jing Qu, Shan-Zhong Yang, Yi Zhu, Ting Guo, Victor J. Thannickal, Yong Zhou
Journal: The Journal of Experimental Medicine (2021)

Aging is a strong risk factor and an independent prognostic factor for progressive human idiopathic pulmonary fibrosis (IPF). Aged mice develop nonresolving pulmonary fibrosis following lung injury. In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice. We identified MDM4 as a matrix stiffness–regulated endogenous inhibitor of p53. Reducing matrix stiffness down-regulates MDM4 expression, resulting in p53 activation in primary lung myofibroblasts isolated from IPF patients. Gain of p53 function activates a gene program that sensitizes lung myofibroblasts to apoptosis and promotes the clearance of apoptotic myofibroblasts by macrophages. Destiffening of the fibrotic lung matrix by targeting nonenzymatic cross-linking or genetic ablation of Mdm4 in lung (myo)fibroblasts activates the Mdm4–p53 pathway and promotes lung fibrosis resolution in aged mice. These findings suggest that mechanosensitive MDM4 is a molecular target with promising therapeutic potential against persistent lung fibrosis associated with aging.
Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation
Authors: Danniel Zamora, Elizabeth R. Duke, Hu Xie, Bradley C. Edmison, Brenda Akoto, Richard Kiener, Terry Stevens-Ayers, Ralf Wagner, Marco Mielcarek, Wendy M. Leisenring, Keith R. Jerome, Joshua T. Schiffer, Greg Finak, Stephen C. De Rosa, Michael Boeckh
Journal: Blood (2021)
COVID-19 and liver disease: mechanistic and clinical perspectives
Authors: Thomas Marjot, Gwilym J. Webb, Alfred S. Barritt, Andrew M. Moon, Zania Stamataki, Vincent W. Wong, Eleanor Barnes
Journal: Nature Reviews Gastroenterology & Hepatology (2021)

Our understanding of the hepatic consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resultant coronavirus disease 2019 (COVID-19) has evolved rapidly since the onset of the pandemic. In this Review, we discuss the hepatotropism of SARS-CoV-2, including the differential expression of viral receptors on liver cell types, and we describe the liver histology features present in patients with COVID-19. We also provide an overview of the pattern and relevance of abnormal liver biochemistry during COVID-19 and present the possible underlying direct and indirect mechanisms for liver injury. Furthermore, large international cohorts have been able to characterize the disease course of COVID-19 in patients with pre-existing chronic liver disease. Patients with cirrhosis have particularly high rates of hepatic decompensation and death following SARS-CoV-2 infection and we outline hypotheses to explain these findings, including the possible role of cirrhosis-associated immune dysfunction. This finding contrasts with outcome data in pharmacologically immunosuppressed patients after liver transplantation who seem to have comparatively better outcomes from COVID-19 than those with advanced liver disease. Finally, we discuss the approach to SARS-CoV-2 vaccination in patients with cirrhosis and after liver transplantation and predict how changes in social behaviours and clinical care pathways during the pandemic might lead to increased liver disease incidence and severity. This Review provides mechanistic and clinical insights into COVID-19 in the context of liver disease, discussing the potential underlying biology and clinical features of SARS-CoV-2 infection in patients with pre-existing liver conditions. The management of these patients is also discussed, including SARS-CoV-2 vaccination strategies.
Citizen science in the time of COVID-19
Authors: Linda J Birkin, Eleftheria Vasileiou, Helen Ruth Stagg
Journal: Thorax (2021)

The COVID-19 pandemic has been a masterclass in the need for accurate, population-wide, frequently updated and rapidly analysed digital data sources in global health.

This issue of Thorax presents two studies using data from the smartphone Zoe COVID Symptom Study app, which has been collecting voluntarily self-reported information from consenting participants ≥18 years on COVID in the UK since its launch in March 2020. As of 16 December 2020, 4 481 148 individuals had registered to use the app across the UK, USA and Sweden.1 While there are other citizen science studies running in the UK to track COVID symptoms (eg, FluSurvey/Influenzanet and TrackTogether), the Zoe COVID app is by far the most extensive of these in coverage and participation numbers, and has contributed, for example, to identification of anosmia as a key symptom of COVID-19 in general (in May 2020),2 and delirium as a key symptom in older people (October 2020).3 

In this issue, Hopkinson et al sought to examine the impact of current smoking on the development of COVID-19, using data from March to April 2020.4 Among individuals who did not think they had previously had COVID-19, self-declared current smokers reported slightly increased odds for presenting the classic triad (cough, fever and breathlessness) of symptoms than non-smokers (OR: 1.14 (95% CI: 1.10 to 1.18)), in results adjusted for age, sex and body mass index. This association did not hold when analyses were constricted to individuals tested for SARS-CoV-2 (OR: 0.73 (95% CI: 0.65 to 0.81)), including after adjustment for potential confounding due to being a healthcare worker …
Abiraterone acetate in patients with metastatic castration-resistant prostate cancer, chemo-naive, who received a prior diethylstilbestrol therapy.
Authors: Diogo Assed Bastos, Giovani Thomaz Pioner, Renato Panhoca, Marjo Deninson Cardenuto Perez, Ronaldo Damião, Gustavo Werutsky, Estela Vacari Vacari, Amanda Yaeza Ferreira, Vanessa Carvalho Fabricio, Rosemarie Gidekel
Journal: Journal of Clinical Oncology (2021)

130 Background: The use of diethylstilbestrol (DES) for the treatment of metastatic castration resistant prostate cancer (mCRPC) is very common in developing countries. Retrospective data suggests that abiraterone acetate (AA) is active in patients that progressed to DES. This phase II study evaluated the efficacy and safety of abiraterone acetate in chemotherapy-naïve patients with metastatic CRPC who have progressed to DES. Methods: Patients with DES−refractory metastatic CRPC with ongoing ADT, serum testosterone level &lt; 50 ng/dL and ECOG of 0-2 were included. All patients received AA 1,000 mg with prednisone 5 mg once daily in a 28 days cycles. The primary endpoint was the time to PSA progression (PSAP) by PCWG2 and was previously reported. We present here secondary endpoints: overall survival, PSA response, maximum PSA change from baseline and safety. Results: A total of 46 patients were enrolled, median age was 69.8 years, 76% had gleason &gt; = 7 at diagnosis, median time from metastatic disease to DES discontinuation was 25.9 months, and a median duration of prior DES of 7.2 months. AA treatment resulted in median time to PSA progression of 7.3 months. PSA response rate (³ 50%) was 47.5% (95% CI: 36,1% to 68,5%) at 12 weeks and 57.5% (95% CI: 27.0% to 59.1%) at any time. 93.4% received chemotherapy after progression to AA. The median overall survival was 29.6 months. Substantial declines in serum androgens from baseline to week 12 occurred and in this group a higher proportion of PSA responses occurred. The incidence of adverse events (AEs) related to AA was 74% and prednisone 59%. Hypertension (21.7%), fatigue (19.6%) and oedema peripheral (13.0%) were the most frequent AA related AEs. The most frequent prednisone related AEs were hyperglycaemia (15.2%) hypertension (10.9%). Serious AEs occurred in 23.9% of subjects and 3 subjects (6.5%) died of AEs not related to study drugs. Conclusions: AA is well tolerated and demonstrated activity in mCRPC patients previously treated with DES, therefore it should be considered an option in chemo-naïve patients. Serum androgens levels tend to decrease with AA treatment and are associated with PSA responses. Clinical trial information: NCT02217566.
Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor
Authors: Choon Boon Sim, Belinda Phipson, Mark Ziemann, Haloom Rafehi, Richard J. Mills, Kevin I. Watt, Kwaku D. Abu-Bonsrah, Ravi K.R. Kalathur, Holly K. Voges, Doan T. Dinh, Menno ter Huurne, Celine J. Vivien, Antony Kaspi, Harikrishnan Kaipananickal, Alejandro Hidalgo, Leanne M.D. Delbridge, Rebecca L. Robker, Paul Gregorevic, Cristobal G. dos Remedios, Sean Lal, Adam T. Piers, Igor E. Konstantinov, David A. Elliott, Assam El-Osta, Alicia Oshlack, James E. Hudson, Enzo R. Porrello
Journal: Circulation (2021)

Despite in-depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals governing postnatal maturation of the human heart.Single-nucleus RNA sequencing of 54 140 nuclei from 9 human donors was used to profile transcriptional changes in diverse cardiac cell types during maturation from fetal stages to adulthood. Bulk RNA sequencing and the Assay for Transposase-Accessible Chromatin using sequencing were used to further validate transcriptional changes and to profile alterations in the chromatin accessibility landscape in purified cardiomyocyte nuclei from 21 human donors. Functional validation studies of sex steroids implicated in cardiac maturation were performed in human pluripotent stem cell-derived cardiac organoids and mice.Our data identify the progesterone receptor as a key mediator of sex-dependent transcriptional programs during cardiomyocyte maturation. Functional validation studies in human cardiac organoids and mice demonstrate that the progesterone receptor drives sex-specific metabolic programs and maturation of cardiac contractile properties.These data provide a blueprint for understanding human heart maturation in both sexes and reveal an important role for the progesterone receptor in human heart development.
Kidney Function after Treatment for Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study
Authors: Daniel M. Green, Mingjuan Wang, Matthew Krasin, DeoKumar Srivastava, Songul Onder, Dennis W. Jay, Kirsten K. Ness, William Greene, Jennifer Q. Lanctot, Kyla C. Shelton, Liang Zhu, Daniel A. Mulrooney, Matthew J. Ehrhardt, Andrew M. Davidoff, Leslie L. Robison, Melissa M. Hudson
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Although associations of treatment for childhood cancer with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust. The authors evaluated the prevalence of and factors associated with increased odds for kidney impairment in a large cohort of adult survivors of childhood cancer diagnosed ≥10 years earlier. About 2.1% had stages 3–5 CKD. Factors associated with stages 3–5 CKD included treatment ever with a calcineurin inhibitor, increasing cumulative dose of certain chemotherapy agents, increasing volume of kidney irradiated to ≥5 or ≥10 Gy, nephrectomy (in patients who received radiation to the kidney) in models for higher–radiation therapy dose-volume exposures, and others. These findings may inform surveillance guidelines for survivors of childhood cancer and the design of future treatment regimens. Background Survivors of childhood cancer may be at increased risk for treatment-related kidney dysfunction. Although associations with acute kidney toxicity are well described, evidence informing late kidney sequelae is less robust. Methods To define the prevalence of and risk factors for impaired kidney function among adult survivors of childhood cancer who had been diagnosed ≥10 years earlier, we evaluated kidney function (eGFR and proteinuria). We abstracted information from medical records about exposure to chemotherapeutic agents, surgery, and radiation treatment and evaluated the latter as the percentage of the total kidney volume treated with ≥5 Gy (V5), ≥10 Gy (V10), ≥15 Gy (V15), and ≥20 Gy (V20). We also used multivariable logistic regression models to assess demographic and clinical factors associated with impaired kidney function and Elastic Net to perform model selection for outcomes of kidney function. Results Of the 2753 survivors, 51.3% were men, and 82.5% were non-Hispanic White. Median age at diagnosis was 7.3 years (interquartile range [IQR], 3.3–13.2), and mean age was 31.4 years (IQR, 25.8–37.8) at evaluation. Time from diagnosis was 23.2 years (IQR, 17.6–29.7). Approximately 2.1% had stages 3–5 CKD. Older age at evaluation; grade ≥2 hypertension; increasing cumulative dose of ifosfamide, cisplatin, or carboplatin; treatment ever with a calcineurin inhibitor; and volume of kidney irradiated to ≥5 or ≥10 Gy increased the odds for stages 3–5 CKD. Nephrectomy was significantly associated with stages 3–5 CKD in models for V15 or V20. Conclusions We found that 2.1% of our cohort of childhood cancer survivors had stages 3–5 CKD. These data may inform screening guidelines and new protocol development.
Secukinumab: A Review in Psoriatic Arthritis
Authors: Hannah A. Blair
Journal: Drugs (2021)

Secukinumab (Cosentyx®) is a fully human monoclonal antibody that selectively targets interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriatic arthritis (PsA). Administered subcutaneously, the first-in-class anti-IL-17 agent is approved in numerous countries worldwide for the treatment of adults with active PsA. In the phase III FUTURE trials, secukinumab 150 or 300 mg improved the clinical signs and symptoms of PsA versus placebo in patients with active disease despite previous treatment with NSAIDs, biological disease-modifying anti-rheumatic drugs (bDMARDs) and/or tumour necrosis factor inhibitors (TNFi). The benefits of secukinumab were seen regardless of whether or not patients had received previous TNFi therapy, and were maintained during longer term (up to 5 years) treatment. In FUTURE 1 and 5, secukinumab inhibited structural joint damage and was associated with sustained low rates of radiographic progression through 1–3 years of treatment. Treatment with secukinumab improved physical function and health-related quality of life (HR-QOL) and was generally well tolerated, both in the short- and longer-term. In the head-to-head EXCEED trial, secukinumab did not quite attain statistical significance for superiority versus adalimumab in the joint domain. In conclusion, secukinumab is effective across all key PsA domains and is generally well tolerated, and thus represents a useful treatment alternative to TNFi and other bDMARDs in adult patients with active PsA.
Racial and ethnic health disparities in healthcare settings
Authors: Tom Gardiner, Sonya Abraham, Olivia Clymer, Mala Rao, Shamini Gnani
Journal: BMJ (2021)

The precise combination of factors responsible for the disproportionate effect of covid-19 on ethnic minority groups is likely to be complex.However, a clear message from the 4000 stakeholders taking part in Public Health England's review into such ethnic disparities was the need actively to involve diverse and under-represented communities in the process of tackling disparities in health settings. 1 Our health services can adapt quickly to unprecedented circumstances.Secondary and tertiary care sector providers have built diagnostic, treatment, and protective pathways to accommodate varying levels of covid-19 risk.Primary and outpatient care have adopted an entirely new way of working, with a telephone first and remote consultation model.The research community has also mobilised in a completely new way, with the UK initiating and leading some of the world's major covid-19 vaccine and therapeutic trials.