tbuckley/cabot-search huggingface dataset:
Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases
Authors: Chiara Martinelli, Carlotta Pucci, Matteo Battaglini, Attilio Marino, Gianni Ciofani
Journal: Advanced Healthcare Materials (2019)

Abstract Many central nervous system (CNS) diseases are still incurable and only symptomatic treatments are available. Oxidative stress is suggested to be a common hallmark, being able to cause and exacerbate the neuronal cell dysfunctions at the basis of these pathologies, such as mitochondrial impairments, accumulation of misfolded proteins, cell membrane damages, and apoptosis induction. Several antioxidant compounds are tested as potential countermeasures for CNS disorders, but their efficacy is often hindered by the loss of antioxidant properties due to enzymatic degradation, low bioavailability, poor water solubility, and insufficient blood–brain barrier crossing efficiency. To overcome the limitations of antioxidant molecules, exploitation of nanostructures, either for their delivery or with inherent antioxidant properties, is proposed. In this review, after a brief discussion concerning the role of the blood–brain barrier in the CNS and the involvement of oxidative stress in some neurodegenerative diseases, the most interesting research concerning the use of nano‐antioxidants is introduced and discussed, focusing on the synthesis procedures, functionalization strategies, in vitro and in vivo tests, and on recent clinical trials.
An Adapting Bone Marrow Niche Creates a Nurturing Environment for Hematopoiesis during Immune Thrombocytopenia Progression
Authors: Oliver Herd, Maria Abril Arredondo Garcia, James Hewitson, Karen Hogg, Saleni Pravin Kumar, Katiuska Pulgar Prieto, Andrew Stone, Paul Genever, Ian Hitchcock
Journal: Blood (2019)
2019 AATS/ACC/SCAI/STS Expert Consensus Systems of Care Document: Operator and Institutional Recommendations and Requirements for Transcatheter Mitral Valve Intervention
Authors: Robert O. Bonow, Patrick T. O’Gara, David H. Adams, Vinay Badhwar, Joseph E. Bavaria, Sammy Elmariah, Judy W. Hung, JoAnn Lindenfeld, Alanna Morris, Ruby Satpathy, Brian Whisenant, Y. Joseph Woo
Journal: Journal of the American College of Cardiology (2019)
Enshrining funding in law won’t bring down waiting times straight away, health leaders warn
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The five year funding settlement for the NHS in England will be enshrined in law by the new government, Boris Johnson has announced.

The move, which in reality merely adds legal formality to the government’s prior commitment to deliver an average annual real terms increase of 3.4% to NHS funding over the next five years, was announced in the Queen’s speech on 19 December.1 The speech, which set out the new Conservative government’s priorities for the next five years after its victory in the UK general election on 12 December, also outlined plans to support the NHS workforce after Brexit with a new fast track entry visa to the UK and to …
Impact of Breast Cancer Treatment on Employment: Results of a Multicenter Prospective Cohort Study (CANTO)
Authors: Agnes Dumas, Ines Vaz Luis, Thomas Bovagnet, Mayssam El Mouhebb, Antonio Di Meglio, Sandrine Pinto, Cecile Charles, Sarah Dauchy, Suzette Delaloge, Patrick Arveux, Charles Coutant, Paul Cottu, Anne Lesur, Florence Lerebours, Olivier Tredan, Laurence Vanlemmens, Christelle Levy, Jerome Lemonnier, Christelle Mesleard, Fabrice Andre, Gwenn Menvielle
Journal: Journal of Clinical Oncology (2019)

Adverse effects of breast cancer treatment can negatively affect survivors' work ability. Previous reports lacked detailed clinical data or health-related patient-reported outcomes (PROs) and did not prospectively assess the combined impact of treatment and related sequelae on employment.We used a French prospective clinical cohort of patients with stage I-III breast cancer including 1,874 women who were working and ≥ 5 years younger than legal retirement age (≤ 57 years) at breast cancer diagnosis. Our outcome was nonreturn to work (non-RTW) 2 years after diagnosis. Independent variables included treatment characteristics as well as toxicities (Common Toxicity Criteria Adverse Events [CTCAE] v4) and PROs (European Organization for Research and Treatment of Cancer [EORTC] Quality of life Questionnaires, Breast cancer module [QLQ-BR23] and Fatigue module [QLQ-FA12], Hospital Anxiety and Depression Scale) collected 1 year after diagnosis. Logistic regression models assessed correlates of non-RTW, adjusting for age, stage, comorbidities, and socioeconomic covariates.Two years after diagnosis, 21% of patients had not returned to work. Odds of non-RTW were significantly increased among patients treated with combinations of chemotherapy and trastuzumab (odds ratio [OR] v chemotherapy-hormonotherapy: for chemotherapy-trastuzumab, 2.01; 95% CI, 1.18 to 3.44; for chemotherapy-trastuzumab-hormonotherapy, 1.62; 95% CI, 1.10 to 2.41). Other significant associations with non-RTW included grade ≥ 3 CTCAE toxicities (OR v no, 1.59; 95% CI, 1.15 to 2.18), arm morbidity (OR v no, 1.59; 95% CI, 1.19 to 2.13), anxiety (OR v no, 1.47; 95% CI, 1.02 to 2.11), and depression (OR v no, 2.29; 95% CI, 1.34 to 3.91).Receipt of systemic therapy combinations including trastuzumab was associated with increased odds of non-RTW. Likelihood of unemployment was also higher among patients who reported severe physical and psychological symptoms. This comprehensive study identifies potentially vulnerable patients and warrants supportive interventional strategies to facilitate their RTW.
Engineering Naturally Occurring CD7 Negative Cells for the Immunotherapy of CD7 Positive Leukemia
Authors: Abdullah Freiwan, Abishek Vaidya, Caitlin Zebley, Yiping Fan, Deanna Langfitt, Benjamin Youngblood, Maksim Mamonkin, Stephen Gottschalk, Mireya Paulina Velasquez
Journal: Blood (2019)
Association of insulin resistance and β-cell dysfunction with incident diabetes among adults in China: a nationwide, population-based, prospective cohort study
Authors: Tiange Wang, Jieli Lu, Lixin Shi, Gang Chen, Min Xu, Yu Xu, Qing Su, Yiming Mu, Lulu Chen, Ruying Hu, Xulei Tang, Xuefeng Yu, Mian Li, Zhiyun Zhao, Yuhong Chen, Li Yan, Guijun Qin, Qin Wan, Meng Dai, Di Zhang, Zhengnan Gao, Guixia Wang, Feixia Shen, Zuojie Luo, Yingfen Qin, Li Chen, Yanan Huo, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Shenghan Lai, Yufang Bi, Ralph A DeFronzo, Weiqing Wang, Guang Ning
Journal: The Lancet Diabetes & Endocrinology (2019)
Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis
Authors: Maria Beatrice Musumeci, Francesco Cappelli, Domitilla Russo, Giacomo Tini, Marco Canepa, Agnese Milandri, Rachele Bonfiglioli, Gianluca Di Bella, Filomena My, Marco Luigetti, Marina Grandis, Camillo Autore, Stefano Perlini, Federico Perfetto, Claudio Rapezzi
Journal: JACC. Cardiovascular imaging (2019)
In vivo confocal microscopy of dermoscopic suspicious lesions in patients with xeroderma pigmentosum: A cross-sectional study
Authors: Lílian Rocha, Paula Silva Ferreira, João Avancini, Silvia Lourenço, Caroline de Freitas Barbosa, Caroline Colacique, Cyro Festa-Neto
Journal: Journal of the American Academy of Dermatology (2019)
Comparative Effectiveness of Sacubitril-Valsartan Versus ACE/ARB Therapy in Heart Failure With Reduced Ejection Fraction
Authors: Nicholas Y. Tan, Lindsey R. Sangaralingham, S. Jeson Sangaralingham, Xiaoxi Yao, Nilay D. Shah, Shannon M. Dunlay
Journal: JACC Heart Failure (2019)
Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials
Authors: Robert C Doebele, Alexander Drilon, Luis Paz-Ares, Salvatore Siena, Alice T Shaw, Anna F Farago, Collin M Blakely, Takashi Seto, Byung Chul Cho, Diego Tosi, Benjamin Besse, Sant P Chawla, Lyudmila Bazhenova, John C Krauss, Young Kwang Chae, Minal Barve, Ignacio Garrido-Laguna, Stephen V Liu, Paul Conkling, Thomas John, Marwan Fakih, Darren Sigal, Herbert H Loong, Gary L Buchschacher, Pilar Garrido, Jorge Nieva, Conor Steuer, Tobias R Overbeck, Daniel W Bowles, Elizabeth Fox, Todd Riehl, Edna Chow-Maneval, Brian Simmons, Na Cui, Ann Johnson, Susan Eng, Timothy R Wilson, George D Demetri
Journal: The Lancet Oncology (2019)
Replicative potency of oncolytic VSV-GP differentially shapes the immune signature in three distinct syngeneic tumour models
Authors: G. Wollmann, B. Spiesschaert, K. Das, L.-M. Schreiber, P. Erlmann, B. Stierstorfer, D. von Laer, P. Mueller, C. Urbiola
Journal: Annals of Oncology (2019)
Nonhuman sequence learning findings argue against Hoerl and McCormack's two systems of temporal cognition
Authors: Benjamin J De Corte, Edward A Wasserman
Journal: Behavioral and Brain Sciences (2019)

Abstract Hoerl &amp; McCormack propose that animals learn sequences through an entrainment-like process, rather than tracking the temporal addresses of each event in a given sequence. However, past research suggests that animals form “temporal maps” of sequential events and also comprehend the concept of ordinal position. These findings suggest that a clarification or qualification of the authors’ hypothesis is needed.
Induction of apoptosis via bcl-2 dependent mitochondrial pathway in leukemia cells by treatment with a selective COX-2 inhibitor, etodolac
Authors: S. Nakamura, M. Kobayashi, N. Sahara, K. Shigeno, K. Takeshita, K. Naito, A. Takeshita, K. Ohnishi
Journal: Blood (2003)
Don’t scrap the sugar tax, doctors tell Johnson
Authors: Abi Rimmer
Journal: BMJ (2019)

Doctors have called on the UK prime minister, Boris Johnson, to retain the soft drink industry levy amid concerns that he may abandon so called “sin taxes.”

The Royal College of Physicians of Edinburgh also called for the levy to be extended to other products such as caffeinated drinks, milkshakes, and fruit smoothies.

In April 2018 the UK’s soft drink industry levy came into effect, with an 18p/L tax on drinks containing ≥5 g/mL of sugar and 24p/L on those with ≥8 g/mL. …
Plasmacytoid dendritic cell deficiency in neonates enhances allergic airway inflammation via reduced production of IFN-α
Authors: Min Wu, Liuchuang Gao, Miao He, Hangyu Liu, Han Jiang, Ketai Shi, Runshi Shang, Bing Liu, Shan Gao, Hebin Chen, Feili Gong, Erwin W. Gelfand, Yafei Huang, Junyan Han
Journal: Cellular and Molecular Immunology (2019)

Allergic asthma, a chronic inflammatory airway disease associated with type 2 cytokines, often originates in early life. Immune responses at an early age exhibit a Th2 cell bias, but the precise mechanisms remain elusive. Plasmacytoid dendritic cells (pDCs), which play a regulatory role in allergic asthma, were shown to be deficient in neonatal mice. We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model. Adoptive transfer of pDCs or administration of IFN-α to neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1-/- mice. Similarly, adult mice developed more severe allergic inflammation when pDCs were depleted. The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20, GM-CSF, and IL-33, which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway. In asthmatic patients, the percentage of pDCs and the level of IFN-α were lower in children than in adults. These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergen-induced allergic airway inflammation.
Thinking about thinking about time
Authors: Jonathan Redshaw, Adam Bulley, Thomas Suddendorf
Journal: Behavioral and Brain Sciences (2019)

Abstract Hoerl &amp; McCormack (H&amp;M) discuss the possible function of meta-representations in temporal cognition but ultimately take an agnostic stance. Here we outline the fundamental role that we believe meta-representations play. Because humans know that their representations of future events are just representations, they are in a position to compensate for the shortcomings of their own foresight and to prepare for multiple contingencies.
Esophageal muscle layer tear during endoscopic submucosal dissection treated by polyglycolic acid sheets and fibrin glue
Authors: Hiroki Yukimoto, Kyosuke Tanaka, Yuhei Umeda, Junya Tsuboi, Aiji Hattori, Reiko Yamada, Yasuhiko Hamada
Journal: Endoscopy (2019)

An 88-year-old woman was referred to our hospital because of esophageal squamous cell carcinoma that had been detected by esophagogastroduodenoscopy. Computed tomography (CT) showed no abnormalities. Endoscopy revealed a half-circumferential, subtle, reddish lesion on the left side of the middle esophagus ([Video 1]). Chromoendoscopy with iodine dye made the lesion clear as an unstained area ([Fig. 1]). Endoscopic submucosal dissection (ESD) with carbon dioxide insufflation was performed. During the ESD procedure, massive gas insufflations were repeated many times because of poor endoscopic view. When en bloc resection was completed, endoscopy revealed a proper muscle layer tear on the anterior side of the ESD ulcer, and the epicardium was seen through the muscle layer tear ([Fig. 2], arrows). Massive gas insufflation may cause blunt injury to muscle tissue. By using a grasping forceps, a total of ten 1 cm × 1 cm polyglycolic acid (PGA) sheets were delivered to the site and attached by fibrin glue ([Fig. 3] and [Fig. 4]). In addition, CT showed free air and fluid collection in the mediastinum. Therefore, we administered antibiotics as well as continuous esophageal suction by a nasogastric tube for 1 week. The lesion had been resected completely, and histological examination revealed squamous cell carcinoma confined to the lamina propria mucosae. Periodic endoscopic examinations showed the healing course of the post-ESD ulcer. The ulcer healed completely without signs of cancer recurrence at 10 weeks post-ESD ([Fig. 5]).
Reactive Oxygen Species Drive Proliferation in Acute Myeloid Leukemia via the Glycolytic Regulator PFKFB3
Authors: Andrew J. Robinson, Goitseone L. Hopkins, Namrata Rastogi, Marie Hodges, Michelle Doyle, Sara Davies, Paul S. Hole, Nader Omidvar, Richard L. Darley, Alex Tonks
Journal: Cancer Research (2019)

Abstract Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a poor clinical outcome. Previously, we showed that overproduction of reactive oxygen species (ROS), arising from constitutive activation of NOX2 oxidase, occurs in &amp;gt;60% of patients with AML and that ROS production promotes proliferation of AML cells. We show here that the process most significantly affected by ROS overproduction is glycolysis. Whole metabolome analysis of 20 human primary AML showed that blasts generating high levels of ROS have increased glucose uptake and correspondingly increased glucose metabolism. In support of this, exogenous ROS increased glucose consumption while inhibition of NOX2 oxidase decreased glucose consumption. Mechanistically, ROS promoted uncoupling protein 2 (UCP2) protein expression and phosphorylation of AMPK, upregulating the expression of a key regulatory glycolytic enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Overexpression of PFKFB3 promoted glucose uptake and cell proliferation, whereas downregulation of PFKFB3 strongly suppressed leukemia growth both in vitro and in vivo in the NSG model. These experiments provide direct evidence that oxidase-derived ROS promotes the growth of leukemia cells via the glycolytic regulator PFKFB3. Targeting PFKFB3 may therefore present a new mode of therapy for this disease with a poor outcome. Significance: These findings show that ROS generated by NOX2 in AML cells promotes glycolysis by activating PFKFB3 and suggest PFKFB3 as a novel therapeutic target in AML.
Reactive Oxygen Species‐Scavenging Scaffold with Rapamycin for Treatment of Intervertebral Disk Degeneration
Authors: Jinyu Bai, Yingzi Zhang, Qin Fan, Jialu Xu, Huajian Shan, Xiang Gao, Qingle Ma, Lei Sheng, Xin Zheng, Weinan Cheng, Dazhuang Li, Mingchao Zhang, Yu Hao, Liangzhu Feng, Qian Chen, Xiaozhong Zhou, Chao Wang
Journal: Advanced Healthcare Materials (2019)

Abstract The chronic inflammatory microenvironment is characterized by the elevated level of reactive oxygen species (ROS). Here, it is hypothesized that developing an ROS‐scavenging scaffold loaded with rapamycin (Rapa@Gel) may offer a new strategy for modulating the local inflammatory microenvironment to improve intervertebral disk tissue regeneration. The therapeutic scaffold consisting of ROS‐degradable hydrogel can be injected into the injured degeneration site of intervertebral disk (IVD) and can release therapeutics in a programmed manner. The ROS scavenged by scaffold reduces the inflammatory responses. It is found that when rats are treated with Rapa@Gel, this results in an increase in the percentage of M2‐like macrophages and a decrease in M1‐like macrophages in the inflammatory environment, respectively. Regeneration of IVD is achieved by Rapa@Gel local treatment, due to the increased M2 macrophages and reduced inflammation. This strategy may be extended to the treatment of many other inflammatory diseases.
A Successful Trial for Lupus — How Good Is Good Enough?
Authors: Jane E. Salmon, Timothy B. Niewold
Journal: New England Journal of Medicine (2019)

Only one drug for patients with systemic lupus erythematosus (SLE), belimumab, has been approved on the basis of support from a randomized, placebo-controlled trial, and numerous development programs of immunomodulatory treatments have failed to show benefits with respect to primary end points in phase 3 trials. Patients continue to be burdened with complications from uncontrolled disease and from adverse effects and risks associated with glucocorticoids and immunosuppressive drugs that are used to treat lupus. Morand et al. now report in the Journal a successful phase 3 trial, TULIP-2 (Treatment of Uncontrolled Lupus via the Interferon Pathway–2),1 in which the active . . .
A Historical Examination of Military Records of US Army Suicide, 1819 to 2017
Authors: Jeffrey Allen Smith, Michael Doidge, Ryan Hanoa, B. Christopher Frueh
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Suicide rates among active-duty personnel in the US military have increased substantially since 2004, and numerous studies have attempted to contextualize and better understand this phenomenon. Placing contemporary examinations of suicides among active-duty personnel in the US Army in historical context provides opportunities for joint historical and epidemiological research to inform health care professionals and policy makers. <h3>Objectives</h3> To consolidate data on suicide rates among active-duty personnel in the US Army as far back as historical records allow and to identify historical trends to separate them from more acute causal factors. <h3>Design, Setting, and Participants</h3> This cross-sectional study included all active-duty service members in the US Army from 1819 to 2017 as identified and detailed in US government publications, studies, and journal articles. Empirical data were extracted from US government publications and journal articles published from 1819 to 2017. Data collection and analysis were completed between July and August of 2019. <h3>Exposure</h3> Suicide. <h3>Main Outcomes and Measures</h3> Suicide rates per 100 000 individuals. <h3>Results</h3> Starting in 1843, the overall trend in annual suicide rates among active-duty service members in the US Army increased, with a peak rate of 118.3 per 100 000 in 1883. From that historical high point, the rate decreased in 3 successive waves, each corresponding to the end of the following wars: the Spanish-American War (1898), World War I (1914-1918), and World War II (1939-1945). The latter had the historically lowest rate of 5 per 100 000 in 1944 to 1945. During the Cold War (approximately 1945-1991), the rate generally stabilized in the low teens to midteens (ie, 10-15 per 100 000). The rate increased again during the Afghanistan and Iraq Wars, increasing to 29.7 per 100 000 in 2012. From 2008 to present, the annual rate has remained within the range of 20.2 to 29.7 per 100 000. <h3>Conclusions and Relevance</h3> This study represents the most extensive historical examination of suicides in the US Army to date. By taking a long-term historical approach to suicide among active-duty personnel in the US Army, this study affords future researchers a new analytical tool and an additional perspective from which to better differentiate long-term and historical trends from more short-term and temporary causal factors.
Solute carrier transporters: the metabolic gatekeepers of immune cells
Authors: Wenxin Song, Danyuan Li, Lei Tao, Qi Luo, Ligong Chen
Journal: Acta Pharmaceutica Sinica B (2019)

Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.
<i>Diabetes Care</i> in 2020: Following and Leading the Stories of Diabetes
Authors: Matthew C. Riddle
Journal: Diabetes Care (2019)

With the simple turning of a calendar page, 2020 is upon us, as is the time for the annual New Year message from the editorial committee of Diabetes Care . Each year we highlight the past year’s activities and offer a preview of what lies ahead. An important event in 2019 was the announcement of impact factors for scientific journals. The yearly statement of current impact factors revealed another clear increase for Diabetes Care , from 13.4 to 15.3, placing us among the elite journals in any specialty. We are proud of this ranking and hope for a further increase next year.

Last year’s editorial outlined some goals, policies, and procedures that contribute to the journal’s character (1). Today we offer a wider perspective. Diabetes Care is the translational journal of the American Diabetes Association (ADA), linking basic science to clinical science and care. Providing a broad range of expertise, the editorial committee is composed of scientists, clinicians, epidemiologists, and experts in writing, editing, and medical publication. While we all started with deep experience in one or more of these fields, together we are called upon to extend our roles to become journalists. This means more than picking the best scientific studies as they are submitted. It involves actively soliciting, improving, and discussing articles that, collectively, form the stories that matter most to our community. …