tbuckley/cabot-search huggingface dataset:
China coronavirus: mild but infectious cases may make it hard to control outbreak, report warns
Authors: Elisabeth Mahase
Journal: BMJ (2020)

<h3>Background</h3> The training and match injury-incidence in professional men9s football remains high and current preventive strategies only seem partially effective, allowing players to present with intrinsic weaknesses each consecutive season. Professional football is a balance-reliant, open skill performed in an environment rich in visual, vestibular and proprioceptive input. Pre-season balance ability - a significant independent intrinsic predictor of injuries and a long-term persisting between-individual difference in injury susceptibility – depends on this input. Measurements of postural control while in a unilateral stance have been shown to predict football injury-susceptibility. Therefore, effective prevention of injury may start with the measurement of postural control followed by interventions targeted at internal risk factor(s). Stomatognathic conditions/malocclusion may have a strong negative impact on the athletes proprioceptive abilities. Therefore, the primary question in this study was: do cranial osteopathic interventions that reduce malocclusion to the better improve balance control in male elite football players? <h3>Aim</h3> This study aimed at investigating dental/occlusal factors and unilateral balance as non-contact injury risk factors in professional football players and the contribution of osteopathic techniques to decrease these risks. <h3>Method</h3> Sixty three injury-free male professional football players with malocclusion were recruited amongst three Belgian Premier League teams and were tested individually. Balance was measured using COF area recordings during a validated unipodal force plate balance test. Four balance test conditions (dominant/non-dominant leg×eyes open/closed) were used to evaluate the short-term effects of three standardized cranial osteopathic techniques. <h3>Results</h3> All the post-treatment measures show smaller mean COF values (balance improvement) when compared to pre-treatment base-line recordings, with the strongest improvement for the conditions with eyes closed (paired t-test, p&lt;0.0005). Indicators of stomatognathic conditions showed significant correlations with base-line COF and balance improvement. <h3>Conclusions</h3> This study indicates that cranial osteopathic interventions with professional football players result in substantial improvement of balance in challenging test conditions (i.e. standing on one leg with eyes closed), and especially if one or more specific stomatognathic conditions are present. Improvement of balance as a non-specific indicator of injury susceptibility and of soccer performance is a dynamic process that involves many features, that could be included in future prospective studies. The results are suggestive for implementation of this approach in football, but at the same time point at the need for follow-up studies with a larger sample size and long-term evaluation.
Towards extracellular matrix normalization for improved treatment of solid tumors
Authors: Hoda Soleymani Abyaneh, Maximilian Regenold, Trevor D. McKee, Christine Allen, Marc A. Gauthier
Journal: Theranostics (2020)

It is currently challenging to eradicate cancer.In the case of solid tumors, the dense and aberrant extracellular matrix (ECM) is a major contributor to the heterogeneous distribution of small molecule drugs and nano-formulations, which makes certain areas of the tumor difficult to treat.As such, much research is devoted to characterizing this matrix and devising strategies to modify its properties as a means to facilitate the improved penetration of drugs and their nano-formulations.This contribution presents the current state of knowledge on the composition of normal ECM and changes to ECM that occur during the pathological progression of cancer.It also includes discussion of strategies designed to modify the composition/properties of the ECM as a means to enhance the penetration and transport of drugs and nano-formulations within solid tumors.Moreover, a discussion of approaches to image the ECM, as well as ways to monitor changes in the ECM as a function of time are presented, as these are important for the implementation of ECM-modifying strategies within therapeutic interventions.Overall, considering the complexity of the ECM, its variability within different tissues, and the multiple pathways by which homeostasis is maintained (both in normal and malignant tissues), the available literature -while promising -suggests that improved monitoring of ECM remodeling in vivo is needed to harness the described strategies to their full potential, and match them with an appropriate chemotherapy regimen.
The Impact of Abiraterone Acetate (AA) Therapy on Patient-Reported Pain and Functional Status in Chemotherapy-Naive Patients with Progressive, Metastatic Castration-Resistant Prostate Cancer (MCRPC)
Authors: E. Basch, C.J. Ryan, T. Kheoh, K. Fizazi, C.J. Logothetis, D.E. Rathkopf, M.R. Smith, P.N. Mainwaring, Y. Hao, T. Griffin, S. Li, M. Meyers, A. Molina, C. Cleeland
Journal: Annals of Oncology (2012)
集学的なアプローチにより原発性糸球体腎症を評価するネフローゼ症候群研究ネットワーク(NEPTUNE)の設計
Authors: A Gadegbeku Crystal, S Gipson Debbie, B Holzman Lawrence, O Ojo Akinlolu, X K Song Peter, Barisoni Laura, G Sampson Matthew, B Kopp Jeffrey, V Lemley Kevin, J Nelson Peter, C Lienczewski Chrysta, G Adler Sharon, B Appel Gerald, C Cattran Daniel, J Choi Michael, Contreras Gabriel, M Dell Katherine, C Fervenza Fernando, L Gibson Keisha, A Greenbaum Larry, D Hernandez Joel, M Hewitt Stephen, R Hingorani Sangeeta, Hladunewich Michelle, C Hogan Marie, L Hogan Susan, J Kaskel Frederick, C Lieske John, E C Meyers Kevin, H Nachman Patrick, C Nast Cynthia, M Neu Alicia, N Reich Heather, R Sedor John, B Sethna Christine, Trachtman Howard, R Tuttle Katherine, Zhdanova Olga, E Zilleruelo Gaston, Kretzler Matthias
Journal: Kidney International (2013)
Mechanisms of Metabolic Acidosis–Induced Kidney Injury in Chronic Kidney Disease
Authors: Donald E. Wesson, Jerry M. Buysse, David A. Bushinsky
Journal: Journal of the American Society of Nephrology (2020)

Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis. Chronic metabolic acidosis also stimulates ammoniagenesis that increases acid excretion but also leads to ammonia-induced complement activation and deposition of C3 and C5b-9 that can cause tubule-interstitial damage, further worsening disease progression. These effects, along with acid accumulation in kidney tissue, combine to accelerate progression of kidney disease. Treatment of chronic metabolic acidosis attenuates these adaptive responses; reduces levels of angiotensin II, aldosterone, and ET-1; reduces ammoniagenesis; and diminishes inflammation and fibrosis that may lead to slowing of CKD progression.
Molecular crosstalk between Y5 receptor and neuropeptide Y drives liver cancer
Authors: Peter Dietrich, Laura Wormser, Valerie Fritz, Tatjana Seitz, Monica De Maria, Alexandra Schambony, Andreas E. Kremer, Claudia Günther, Timo Itzel, Wolfgang E. Thasler, Andreas Teufel, Jonel Trebicka, Arndt Hartmann, Markus F. Neurath, Stephan von Hörsten, Anja K. Bosserhoff, Claus Hellerbrand
Journal: Journal of Clinical Investigation (2020)

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.
PEGylated Bilirubin-coated Iron Oxide Nanoparticles as a Biosensor for Magnetic Relaxation Switching-based ROS Detection in Whole Blood
Authors: Dong Yun Lee, Sukmo Kang, Yonghyun Lee, Jin Yong Kim, Dohyun Yoo, Wonsik Jung, Soyoung Lee, Yong Yeon Jeong, Kwangyeol Lee, Sangyong Jon
Journal: Theranostics (2020)

Rationale: Magnetic relaxation switching (MRSw) induced by target-triggered aggregation or dissociation of superparamagnetic iron oxide nanoparticles (SPIONs) have been utilized for detection of diverse biomarkers.However, an MRSw-based biosensor for reactive oxygen species (ROS) has never been documented.Methods: To this end, we constructed a biosensor for ROS detection based on PEGylated bilirubin (PEG-BR)-coated SPIONs (PEG-BR@SPIONs) that were prepared by simple sonication via ligand exchange.In addition, near infra-red (NIR) fluorescent dye was loaded onto PEG-BR@SPIONs as a secondary option for fluorescence-based ROS detection.Results: PEG-BR@SPIONs showed high colloidal stability under physiological conditions, but upon exposure to the model ROS, NaOCl, in vitro, they aggregated, causing a decrease in signal intensity in T2-weighted MR images.Furthermore, ROS-responsive PEG-BR@SPIONs were taken up by lipopolysaccharide (LPS)-activated macrophages to a much greater extent than ROS-unresponsive control nanoparticles (PEG-DSPE@SPIONs).In a sepsis-mimetic clinical setting, PEG-BR@SPIONs were able to directly detect the concentrations of ROS in whole blood samples through a clear change in T2 MR signals and a 'turn-on' signal of fluorescence.Conclusions: These findings suggest that PEG-BR@SPIONs have the potential as a new type of dual mode (MRSw-based and fluorescence-based) biosensors for ROS detection and could be used to diagnose many diseases associated with ROS overproduction.
Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes
Authors: Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison, Charles R Mackay
Journal: Nature Immunology (2017)
Inhibition of N-type calcium channels in cardiac sympathetic neurons attenuates ventricular arrhythmogenesis in heart failure
Authors: Dongze Zhang, Huiyin Tu, Chaojun Wang, Liang Cao, Wenfeng Hu, Bryan T Hackfort, Robert L Muelleman, Michael C Wadman, Yu-Long Li
Journal: Cardiovascular Research (2020)

Cardiac sympathetic overactivation is an important trigger of ventricular arrhythmias in patients with chronic heart failure (CHF). Our previous study demonstrated that N-type calcium (Cav2.2) currents in cardiac sympathetic post-ganglionic (CSP) neurons were increased in CHF. This study investigated the contribution of Cav2.2 channels in cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF.
Adrenomedullin: A Double-edged Sword in Septic Shock and Heart Failure Therapeutics?
Authors: Muddassir Mehmood
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

We agree that fluid administered during initial sepsis resuscitation, before ICU admission, is a crucial consideration for randomized trials of fluid management in critical illness.A strength of the current analysis is that, for patients presenting to the emergency department or operating room, choice of crystalloid was controlled from initial presentation through ICU discharge-a key difference from other randomized trials studying crystalloid composition in critically ill patients (5).Further research is needed to specifically evaluate the relative effects of crystalloid composition during initial resuscitation in the emergency department compared with fluid administration after ICU admission.We also thank Dr. Hammond and colleagues for their metaanalysis combining the results of our SMART sepsis subgroup analysis with results from prior studies comparing balanced crystalloids to saline among patients with sepsis.In their metaanalysis, the point estimate favored balanced crystalloids over saline for all outcomes, and 95% confidence intervals demonstrated a statistically significant difference (major adverse kidney events and acute kidney injury) or approached a statistically significant difference (receipt of renal replacement therapy and death).We agree that, while awaiting additional data, using of balanced crystalloids rather than saline for adults with sepsis is reasonable.
Abstract 10711: Upregulation Cardiac Beta3-Adrenergic Receptor-Activated Inducible Nitric Oxide Synthase Uncoupling Promotes Cardiac Aging
Authors: Che Ping Cheng, Peng Zhou, Zhe Chen, Xiaowei Zhang, Xiaoqiang Sun, Dalane Kitzman, Michael Callahan, Heng-Jie Cheng
Journal: Circulation (2019)

Background: There is substantial evidence supporting oxidative stress as an important mechanism to age-related cardiac dysfunction and altered β3-adrenergic receptor (AR)-activated nitric oxide syn...
Lindsay Symon: neurosurgery professor and distinguished surgeon whose research into the ischaemic penumbra improved stroke treatment
Authors: Penny Warren
Journal: BMJ (2020)

One evening in the mid-1970s, neurosurgeon Lindsay Symon was walking to dinner at Queen Square in London with his colleague Anthony Strong. They were discussing Symon’s neuroscience experiments, and how an area of tissue death in the brain could have a rim around it where there was no evoked response but what Symon described as the “lethal phenomenon of cell membrane failure” had not yet occurred. Raising blood pressure in the brain could successfully restore life to the area, but the window of opportunity was small—no more than a few hours.

Symon said the area reminded him of a candle flame, where around the bright centre there is a shaded zone known as the penumbra. And so, the concepts of “ischaemic penumbra” and “thresholds of ischaemia” came into being. Symon and his colleagues first published papers on the subject in 1977. This crucial insight into cerebrovascular physiology was essential to recovery after brain surgery and, among other things, led to the modern treatment of stroke with swift administration of clot busting drugs.

In 1990, the Observer magazine, as part …
The 1995 Albert Lasker Medical Research Award. The war against disease and disability
Authors: M O Hatfield
Journal: JAMA (1995)

AS THE chairman of the US Senate Appropriations Committee, I know all too well the difficulties we as a nation face in dividing increasingly strained financial resources among our domestic priorities. We must cut federal spending. We must reduce the deficit. But certain programs will continue to receive federal support and the new Congress has been actively involved in setting priorities. In my view, the decision whether to continue funding an agency or program is based on three factors. First, is the program vital to the wellbeing of Americans and to our national security? Second, is the activity one that the federal government is best suited to conduct, or would a state or local government deliver the service more efficiently? Third, does the program contribute to our nation's future? Few programs fit these criteria better than medical research. Medical research offers a tremendous economic return on every dollar spent, and
Evolving Magnetically Levitated Plasma Proteins Detects Opioid Use Disorder as a Model Disease
Authors: Ali Akbar Ashkarran, Tina Olfatbakhsh, Milad Ramezankhani, Richard C. Crist, Wade H. Berrettini, Abbas S. Milani, Sepideh Pakpour, Morteza Mahmoudi
Journal: Advanced Healthcare Materials (2020)

Abstract There are several methods (e.g., enzyme‐linked immunosorbent assay and liquid chromatography mass spectroscopy) that already use human plasma to detect a variety of possible diseases. However, this paper introduces the capabilities of magnetic levitation (Maglev) to detect disease (Opioid Use Disorder, used here as a model disease) by using levitation of human plasma proteins. The presented proof‐of‐concept findings revealed that the optical images of magnetically levitated plasma proteins carry important information about the health spectrum of plasma donors. In addition, the liquid chromatography mass spectroscopy analysis of the magnetically levitated plasma proteins demonstrated remarkable differences between the plasma of healthy individuals and patients with opioid use disorders. Overall, the presented method provides diagnostic value for disease detection using optical images of evolving magnetically levitated plasma proteins and/or proteomic information.
Cost-Effectiveness of Transitional Care Services After Hospitalization With Heart Failure
Authors: Manuel R. Blum, Henning Øien, Harris L. Carmichael, Paul Heidenreich, Douglas K. Owens, Jeremy D. Goldhaber-Fiebert
Journal: Annals of Internal Medicine (2020)

Background: Patients with heart failure (HF) discharged from the hospital are at high risk for death and rehospitalization. Transitional care service interventions attempt to mitigate these risks. Objective: To assess the cost-effectiveness of 3 types of postdischarge HF transitional care services and standard care. Design: Decision analytic microsimulation model. Data Sources: Randomized controlled trials, clinical registries, cohort studies, Centers for Disease Control and Prevention life tables, Centers for Medicare & Medicaid Services data, and National Inpatient Sample (Healthcare Cost and Utilization Project) data. Target Population: Patients with HF who were aged 75 years at hospital discharge. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Disease management clinics, nurse home visits (NHVs), and nurse case management. Outcome Measures: Quality-adjusted life-years (QALYs), costs, net monetary benefits, and incremental cost-effectiveness ratios (ICERs). Results of Base-Case Analysis: All 3 transitional care interventions examined were more costly and effective than standard care, with NHVs dominating the other 2 interventions. Compared with standard care, NHVs increased QALYs (2.49 vs. 2.25) and costs ($81 327 vs. $76 705), resulting in an ICER of $19 570 per QALY gained. Results of Sensitivity Analysis: Results were largely insensitive to variations in in-hospital mortality, age at baseline, or costs of rehospitalization. Probabilistic sensitivity analysis confirmed that transitional care services were preferred over standard care in nearly all 10 000 samples, at willingness-to-pay thresholds of $50 000 or more per QALY gained. Limitation: Transitional care service designs and implementations are heterogeneous, leading to uncertainty about intervention effectiveness and costs when applied in particular settings. Conclusion: In older patients with HF, transitional care services are economically attractive, with NHVs being the most cost-effective strategy in many situations. Transitional care services should become the standard of care for postdischarge management of patients with HF. Primary Funding Source: Swiss National Science Foundation, Research Council of Norway, and an Intermountain–Stanford collaboration.
In emergencies, health research must go beyond public engagement toward a true partnership with those affected
Authors: Katharine Wright, Michael Parker, Sanjoy Bhattacharya, Karl Blanchet, Simon Caney, Emily Ying Yang Chan, Beatriz da Costa Thomé, Philippe Guérin, Julian Hughes, Patricia Kingori, Heidi Larson, Soka Moses, Sharifah Sekalala, Julian Sheather, Paulina Tindana
Journal: Nature Medicine (2020)
Phase II Single-Arm Study of Preoperative Pemetrexed (P) Plus Cisplatin (C) in Non-Small Cell Lung Cancer (NSCLC) Patients
Authors: M. Chabowski, R. Ramlau, W. Dyszkiewicz, N. Chouaki, V. Soldatenkova, R. Varea, S. Barriga, C.M. Visseren-Grul, T. Orlowski
Journal: Annals of Oncology (2012)
Abstract 179: Effects of Necrosulfonamide on Post-Resuscitation Survival and Neurological Function in a Rat Model of Cardiac Arrest
Authors: Fenglian He, Guanghui Zheng, Juntao Hu, Weiwei Ge, Xianfei Ji, Jing Xu, Christine Moore, Jennifer Bradley, Mary Ann A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2019)

Introduction: Gasdermin D (GSDMD), a previously unknown protein, serves as a key effector in pyroptosis and its inhibition has protective effects during cerebral ischemia and reperfusion. Necrosulfonamide (NSA) specifically blocks the mixed lineage kinase domain-like pseudo kinase (MLKL), which directly binds to GSDMD preventing pyroptotic cell death and interleukin-1 (IL-1) release. In this study, we investigated the effects of NSA on survival and neurological function after cardiac arrest and resuscitation. Hypothesis: Administration of NSA following cardiopulmonary resuscitation (CPR) will improve survival and neurological function in a rat model of cardiac arrest. Methods: Twelve male Sprague-Dawley rats weighting between 450-550g were utilized. Ventricular fibrillation was induced and untreated for 6 min followed by defibrillation after 8 min of CPR. Animals were then randomized into two groups: NSA and control. NSA (10mg/kg) or vehicle was administered 5 minutes after restoration of spontaneous circulation (ROSC) by intraperitoneal injection. Duration of survival and neurological deficit scores were recorded at 24, 48, and 72 hours after ROSC. Results: All animals were resuscitated successfully. Duration of survival was significantly longer in the NSA group compared to control (p&lt;0.05, Figure 1). The severity of post-resuscitation cerebral dysfunction was significantly reduced in the NSA group compared to control (p&lt;0.05, Figure 2). Conclusion: Administration of NSA after ROSC improves post-resuscitation survival and neurological function in a rat model of cardiac arrest.
Multicenter prospective study on multivariant diagnostics of autoimmune bullous dermatoses using the BIOCHIP technology
Authors: Nina van Beek, Stine Krüger, Tarek Fuhrmann, Susanne Lemcke, Stephanie Goletz, Christian Probst, Lars Komorowski, Giovanni Di Zenzo, Marian Dmochowski, Kossara Drenovska, Michael Horn, Hana Jedlickova, Cezary Kowalewski, Ljiljana Medenica, Dedee Murrell, Aikaterini Patsatsi, Shamir Geller, Soner Uzun, Snejina Vassileva, Xuejun Zhu, Kai Fechner, Detlef Zillikens, Winfried Stöcker, Enno Schmidt, Kristin Rentzsch
Journal: Journal of the American Academy of Dermatology (2020)