tbuckley/cabot-search huggingface dataset:
Injectable thermoresponsive hydrogels as drug delivery system for the treatment of central nervous system disorders: A review
Authors: Elena Bellotti, Andrea L. Schilling, Steven R. Little, Paolo Decuzzi
Journal: Journal of Controlled Release (2020)

The central nervous system (CNS), consisting of the brain, spinal cord, and retina, superintends to the acquisition, integration and processing of peripheral information to properly coordinate the activities of the whole body. Neurodegenerative and neurodevelopmental disorders, trauma, stroke, and brain tumors can dramatically affect CNS functions resulting in serious and life-long disabilities. Globally, the societal and economic burden associated with CNS disorders continues to grow with the ageing of the population thus demanding for more effective and definitive treatments. Despite the variety of clinically available therapeutic molecules, medical interventions on CNS disorders are mostly limited to treat symptoms rather than halting or reversing disease progression. This is attributed to the complexity of the underlying disease mechanisms as well as to the unique biological microenvironment. Given its central importance, multiple barriers, including the blood brain barrier and the blood cerebrospinal fluid barrier, protect the CNS from external agents. This limits the access of drug molecules to the CNS thus contributing to the modest therapeutic successes. Loco-regional therapies based on the deposition of thermoresponsive hydrogels loaded with therapeutic agents and cells are receiving much attention as an alternative and potentially more effective approach to manage CNS disorders. In this work, the current understanding and challenges in the design of thermoresponsive hydrogels for CNS therapy are reviewed. First, the biological barriers that hinder mass and drug transport to the CNS are described, highlighting the distinct features of each barrier. Then, the realization, characterization and biomedical application of natural and synthetic thermoresponsive hydrogels are critically presented. Advantages and limitations of each design and application are discussed with the objective of identifying general rules that could enhance the effective translation of thermoresponsive hydrogel-based therapies for the treatment of CNS disorders.
Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA
Authors: Jonathan C. Dudley, Maximilian Diehn
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

Because cancer is caused by an accumulation of genetic mutations, mutant DNA released by tumors can be used as a highly specific biomarker for cancer. Although this principle was described decades ago, the advent and falling costs of next-generation sequencing have made the use of tumor DNA as a biomarker increasingly practical. This review surveys the use of cellular and cell-free DNA for the detection of cancer, with a focus on recent technological developments and applications to solid tumors. It covers (a) key principles and technology enabling the highly sensitive detection of tumor DNA; (b) assessment of tumor DNA in plasma, including for genotyping, minimal residual disease detection, and early detection of localized cancer; (c) detection of tumor DNA in body cavity fluids, such as urine or cerebrospinal fluid; and (d) challenges posed to the use of tumor DNA as a biomarker by the phenomenon of benign clonal expansions.
Abstract P125: Multiple Measures of Energy Expenditure and Substrate Oxidation in Non-obese White and African American Young Adults
Authors: Peter T Katzmarzyk, Eric Ravussin
Journal: Circulation (2018)

Introduction: African Americans (AA) experience higher rates of obesity and related disorders than the general U.S. population. It has been hypothesized that the increased risk of obesity among AA may be explained, in part, by lower levels of energy expenditure (EE) and lower levels of fat oxidation. However, many different measures of EE and substrate oxidation have been employed across previous studies. Objective: The objective of this study was to compare multiple measures of EE and substrate oxidation among White (W) and AA adults. We hypothesize that AA will have lower EE and lower fat oxidation rates than W. Methods: A sample of 12 young (ages 22 to 35 y), non-obese AA adults was recruited from the local community and pair-matched by age, sex and body mass index (BMI) to a sample of 12 W adults. Height and weight were measured and BMI was calculated (kg/m 2 ). Total fat mass (FM) and fat free mass (FFM) were measured using dual energy x-ray absorptiometry. Resting EE (REE) and respiratory quotient (RQ) were measured in a fasting state using a metabolic cart; 24-hour EE, 24-h RQ, sleep EE and sleep RQ were measured in a whole room calorimeter; and free-living total daily EE (TDEE) was measured over two weeks using doubly labelled water. Physical activity level (PAL) was computed as TDEE/REE. Differences between W and AA were determined using general linear models, adjusting for FFM. Results: The analytic sample had a mean age of 27.0 y (SD 4.3 y) and mean BMI of 22.9 kg/m 2 (SD 2.9 kg/m 2 ). There were no significant differences in age, BMI, FM or FFM between W and AA (all p&gt;0.05). However, W had significantly higher REE (1459 vs 1305 kcal/day; p=0.001), 24-h EE (1826 versus 1737 kcal/day; p=0.02), sleep EE (1509 vs 1405 kcal/day; p=0.005); but not TDEE (2452 vs 2313 kcal/day; p=0.30) compared to AA. There were no race differences in RQ (0.83 vs 0.83; p=0.93), 24-h RQ (0.86 vs 0.88; p=0.24) or sleep RQ (0.86 vs 0.87; p=0.44). On the other hand, AA had higher PAL (1.34 vs 1.26; p=0.04) compared to W. Conclusions: Non-obese W adults demonstrated higher REE, 24-h EE, and sleep EE compared to AA, but had similar levels of free-living TDEE. It appears as though some AA adults may compensate for lower REE by increased physical activity, which may be an effective strategy to prevent weight gain and obesity.
Defining the Balance between the Expression of Procoagulant, Anticoagulant and Angiogenic Molecules in Myeloma Plasma Cells
Authors: Loula Papageorgiou, Sandrine Thouronde, Patrick Van Dreden, Stella Salta, Laurent Garderet, Christelle Mazurier, Ismail Elalamy, Grigorios T. Gerotziafas
Journal: Blood (2017)
The PRICES statement: an ESICM expert consensus on methodology for conducting and reporting critical care echocardiography research studies
Authors: Filippo Sanfilippo, Stephen Huang, Antoine Herpain, Martin Balik, Michelle S. Chew, Fernando Clau-Terré, Carlos Corredor, Daniel De Backer, Nick Fletcher, Guillaume Geri, Armand Mekontso-Dessap, Anthony McLean, Andrea Morelli, Sam Orde, Tatjana Petrinic, Michel Slama, Iwan C. C. van der Horst, Philippe Vignon, Paul Mayo, Antoine Vieillard-Baron
Journal: Intensive Care Medicine (2020)
15021 The family impact of atopic dermatitis in children aged 6-11 years: A cross-sectional study in the United States, Canada, Europe, and Japan
Authors: Sebastien Barbarot, Jonathan I. Silverberg, Abhijit Gadkari, Eric L. Simpson, Paola Mina-Osorio, Tarek Mnif, Isabelle Guillemin, Miriam C. Fenton, Laurent Eckert
Journal: Journal of the American Academy of Dermatology (2020)
Skeletal Muscle Perfusion in Peripheral Arterial Disease: A Novel End Point for Cardiovascular Imaging⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Christopher M. Kramer
Journal: JACC. Cardiovascular imaging (2008)
Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR‐Preserved trial
Authors: Stefan D. Anker, Javed Butler, Gerasimos Filippatos, Muhammad Shahzeb Khan, João Pedro Ferreira, Edimar Bocchi, Michael Böhm, Hans Pieter Brunner‐La Rocca, Dong‐Ju Choi, Vijay Chopra, Eduardo Chuquiure, Nadia Giannetti, Juan Esteban Gomez‐Mesa, Stefan Janssens, James L. Januzzi, Jose R. Gonzalez‐Juanatey, Bela Merkely, Stephen J. Nicholls, Sergio V. Perrone, Ileana L. Piña, Piotr Ponikowski, Michele Senni, Marie‐France Seronde, David Sim, Jindrich Spinar, Iain Squire, Stefano Taddei, Hiroyuki Tsutsui, Subodh Verma, Dragos Vinereanu, Jian Zhang, Waheed Jamal, Sven Schnaidt, Janet M. Schnee, Martina Brueckmann, Stuart J. Pocock, Faiez Zannad, Milton Packer
Journal: European Journal of Heart Failure (2020)

EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares them with patients enrolled in prior HFpEF trials. EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients [left ventricular ejection fraction (LVEF) >40%] with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of heart failure hospitalization. Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72 ± 9 years, 45% were women. Almost all patients had New York Heart Association class II or III symptoms (99.6%), and 23% had prior heart failure hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54 ± 9%) was slightly lower while the median NT-proBNP [974 (499-1731) pg/mL] was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of comorbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.
15491 Systematic literature review examining efficacy of abobotulinumtoxinA for esthetic indications
Authors: Joel Cohen, Mark Nestor, Alessio Redaelli, Marina Landau, Said Hilton, Andreas Nikolis, Syed Haq, Inna Prygova, Maurizio Viel, Alessandra Nogueira
Journal: Journal of the American Academy of Dermatology (2020)
16437 Effects of cleansing on skin barrier function in atopic dermatitis and healthy skin: A pilot study
Authors: Aleksi J. Hendricks, Bryan W. Kromenacker, Alyssa Thompson, Elizabeth I. Mata, Catherine M. Ludwig, Jody F. Platto, Khiem A. Tran, Vivian Shi
Journal: Journal of the American Academy of Dermatology (2020)
Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Toward a Unified Theory⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Michael Silberbach
Journal: Journal of the American College of Cardiology (2009)
Abortion Surveillance — United States, 2018
Authors: Katherine Kortsmit, Tara C. Jatlaoui, Michele G. Mandel, Jennifer A. Reeves, Titilope Oduyebo, Emily Petersen, Maura K. Whiteman
Journal: MMWR Surveillance Summaries (2020)

CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States.
Development and validation of a deep learning algorithm detecting 10 common abnormalities on chest radiographs
Authors: Ju Gang Nam, Minchul Kim, Jongchan Park, Eui Jin Hwang, Jong Hyuk Lee, Jung Hee Hong, Jin Mo Goo, Chang Min Park
Journal: European Respiratory Journal (2020)

We aimed to develop a deep learning algorithm detecting 10 common abnormalities (DLAD-10) on chest radiographs, and to evaluate its impact in diagnostic accuracy, timeliness of reporting and workflow efficacy.DLAD-10 was trained with 146 717 radiographs from 108 053 patients using a ResNet34-based neural network with lesion-specific channels for 10 common radiological abnormalities (pneumothorax, mediastinal widening, pneumoperitoneum, nodule/mass, consolidation, pleural effusion, linear atelectasis, fibrosis, calcification and cardiomegaly). For external validation, the performance of DLAD-10 on a same-day computed tomography (CT)-confirmed dataset (normal:abnormal 53:147) and an open-source dataset (PadChest; normal:abnormal 339:334) was compared with that of three radiologists. Separate simulated reading tests were conducted on another dataset adjusted to real-world disease prevalence in the emergency department, consisting of four critical, 52 urgent and 146 nonurgent cases. Six radiologists participated in the simulated reading sessions with and without DLAD-10.DLAD-10 exhibited area under the receiver operating characteristic curve values of 0.895-1.00 in the CT-confirmed dataset and 0.913-0.997 in the PadChest dataset. DLAD-10 correctly classified significantly more critical abnormalities (95.0% (57/60)) than pooled radiologists (84.4% (152/180); p=0.01). In simulated reading tests for emergency department patients, pooled readers detected significantly more critical (70.8% (17/24) versus 29.2% (7/24); p=0.006) and urgent (82.7% (258/312) versus 78.2% (244/312); p=0.04) abnormalities when aided by DLAD-10. DLAD-10 assistance shortened the mean±sd time-to-report critical and urgent radiographs (640.5±466.3 versus 3371.0±1352.5 s and 1840.3±1141.1 versus 2127.1±1468.2 s, respectively; all p<0.01) and reduced the mean±sd interpretation time (20.5±22.8 versus 23.5±23.7 s; p<0.001).DLAD-10 showed excellent performance, improving radiologists' performance and shortening the reporting time for critical and urgent cases.
Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in Patients With New-Onset T2DM: 3-Year Follow-up of EDICT
Authors: Muhammad Abdul-Ghani, Curtiss Puckett, John Adams, Ahmad Khattab, Gozde Baskoy, Eugenio Cersosimo, Curtis Triplitt, Ralph A. DeFronzo
Journal: Diabetes Care (2020)

To compare the long-term efficacy of initiating therapy with metformin/pioglitazone/exenatide in patients with new-onset type 2 diabetes mellitus (T2DM) versus sequential addition of metformin followed by glipizide and insulin.Drug-naive patients (N = 318) with new-onset T2DM were randomly assigned to receive for 3 years either 1) combination therapy with metformin, pioglitazone, and exenatide (triple therapy) or 2) sequential addition of metformin followed by glipizide and insulin (conventional therapy) to maintain HbA1c at <6.5% (48 mmol/mol). Insulin sensitivity and β-cell function were measured at baseline and 3 years. The primary outcome was the difference in HbA1c between the groups at 3 years.Baseline HbA1c ± SEM values were 9.0% ± 0.2% and 8.9% ± 0.2% in the triple therapy and conventional therapy groups, respectively. The decrease in HbA1c resulting from triple therapy was greater at 6 months than that produced by conventional therapy (0.30% [95% CI 0.21-0.39]; P = 0.001), and the HbA1c reduction was maintained at 3 years in patients receiving triple therapy compared with conventional therapy (6.4% ± 0.1% and 6.9% ± 0.1%, respectively), despite intensification of antihyperglycemic therapy in the latter. Thus, the difference in HbA1c between the two treatment groups at 3 years was 0.50% (95% CI 0.39-0.61; P < 0.0001). Triple therapy produced a threefold increase in insulin sensitivity and 30-fold increase in β-cell function. In conventional therapy, insulin sensitivity did not change and β-cell function increased by only 34% (both P < 0.0001 vs. triple therapy).Triple therapy with agents that improve insulin sensitivity and β-cell function in patients with new-onset T2DM produces greater, more durable HbA1c reduction than agents that lower glucose levels without correcting the underlying metabolic defects.
Lefamulin: A Novel Oral and Intravenous Pleuromutilin for the Treatment of Community-Acquired Bacterial Pneumonia
Authors: George G. Zhanel, Christina Deng, Sheryl Zelenitsky, Courtney K. Lawrence, Heather J. Adam, Alyssa Golden, Liam Berry, Frank Schweizer, Michael A. Zhanel, Neal Irfan, Denice Bay, Philippe Lagacé-Wiens, Andrew Walkty, Lionel Mandell, Joseph P. Lynch, James A. Karlowsky
Journal: Drugs (2020)
Reversibility of Intrathoracic Lipotoxicity in Obesity After Bariatric Surgery: Use of Magnetic Resonance Imaging⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Albert de Roos
Journal: Journal of the American College of Cardiology (2012)
Nottingham trust must urgently improve “unsafe” maternity services, says CQC
Authors: Clare Dyer
Journal: BMJ (2020)

The Care Quality Commission (CQC) has taken urgent action to prevent mothers and babies from being exposed to the risk of harm at a major teaching trust.

Maternity services run by Nottingham University Hospitals NHS Trust were downgraded to “inadequate” after an unannounced inspection.12 The regulator attached conditions to the registration of these services at Nottingham City Hospital and Queen’s Medical Centre, issuing a formal warning notice requiring improvements within three months.

The CQC’s inspections in October followed a coroner’s inquest into the death of baby Wynter Andrews, who was found to have died as a result of neglect, as well as 24 inspections by the Health Safety Inspection Branch (HSIB). The HSIB concluded in some cases that a …
Trade-offs between cost and accuracy in active case finding for tuberculosis: A dynamic modelling analysis
Authors: Lucia Cilloni, Katharina Kranzer, Helen R. Stagg, Nimalan Arinaminpathy
Journal: PLoS Medicine (2020)

Background Active case finding (ACF) may be valuable in tuberculosis (TB) control, but questions remain about its optimum implementation in different settings. For example, smear microscopy misses up to half of TB cases, yet is cheap and detects the most infectious TB cases. What, then, is the incremental value of using more sensitive and specific, yet more costly, tests such as Xpert MTB/RIF in ACF in a high-burden setting? Methods and findings We constructed a dynamic transmission model of TB, calibrated to be consistent with an urban slum population in India. We applied this model to compare the potential cost and impact of 2 hypothetical approaches following initial symptom screening: (i) ‘moderate accuracy’ testing employing a microscopy-like test (i.e., lower cost but also lower accuracy) for bacteriological confirmation and (ii) ‘high accuracy’ testing employing an Xpert-like test (higher cost but also higher accuracy, while also detecting rifampicin resistance). Results suggest that ACF using a moderate-accuracy test could in fact cost more overall than using a high-accuracy test. Under an illustrative budget of US$20 million in a slum population of 2 million, high-accuracy testing would avert 1.14 (95% credible interval 0.75–1.99, with p = 0.28) cases relative to each case averted by moderate-accuracy testing. Test specificity is a key driver: High-accuracy testing would be significantly more impactful at the 5% significance level, as long as the high-accuracy test has specificity at least 3 percentage points greater than the moderate-accuracy test. Additional factors promoting the impact of high-accuracy testing are that (i) its ability to detect rifampicin resistance can lead to long-term cost savings in second-line treatment and (ii) its higher sensitivity contributes to the overall cases averted by ACF. Amongst the limitations of this study, our cost model has a narrow focus on the commodity costs of testing and treatment; our estimates should not be taken as indicative of the overall cost of ACF. There remains uncertainty about the true specificity of tests such as smear and Xpert-like tests in ACF, relating to the accuracy of the reference standard under such conditions. Conclusions Our results suggest that cheaper diagnostics do not necessarily translate to less costly ACF, as any savings from the test cost can be strongly outweighed by factors including false-positive TB treatment, reduced sensitivity, and foregone savings in second-line treatment. In resource-limited settings, it is therefore important to take all of these factors into account when designing cost-effective strategies for ACF.
31P The prognostic value of pre-treatment peripheral neutrophil-lymphocyte-ratio (NLR) and its correlation with mutant p53 expression in Indonesian triple negative breast cancer patients
Authors: R.Y. Purwanto, A.D. Satiti, B. Leo, I. Widodo, S.H. Hutajulu, M.S. Hardiyanti, J. Kurnianda, K.W. Taroeno-Hariadi, T. Aryandono, S.M. Haryana, I. Purwanto
Journal: Annals of Oncology (2020)
Preclinical platform for long-term evaluation of immuno-oncology drugs using hCD34+ humanized mouse model
Authors: Nahee Park, Kamal Pandey, Sei Kyung Chang, Ah-Young Kwon, Young Bin Cho, Jin Hur, Nar Bahadur Katwal, Seung Ki Kim, Seung Ah Lee, Gun Woo Son, Jong Min Jo, Hee Jung Ahn, Yong Wha Moon
Journal: Journal for ImmunoTherapy of Cancer (2020)

Well-characterized preclinical models are essential for immune-oncology research. We investigated the feasibility of our humanized mouse model for evaluating the long-term efficacy of immunotherapy and biomarkers. Humanized mice were generated by injecting human fetal cord blood-derived CD34+ hematopoietic stem cells to NOD-scid IL2rγnull (NSG) mice myeloablated with irradiation or busulfan. The humanization success was defined as a 25% or higher ratio of human CD45+ cells to mice peripheral blood mononuclear cells. Busulfan was ultimately selected as the appropriate myeloablative method because it provided a higher success rate of humanization (approximately 80%) and longer survival time (45 weeks). We proved the development of functional T cells by demonstrating the anticancer effect of the programmed cell death-1 (PD-1) inhibitor in our humanized mice but not in non-humanized NSG mice. After confirming the long-lasting humanization state (45 weeks), we further investigated the response durability of the PD-1 inhibitor and biomarkers in our humanized mice. Early increase in serum tumor necrosis factor α levels, late increase in serum interleukin 6 levels and increase in tumor-infiltrating CD8+ T lymphocytes correlated more with a durable response over 60 days than with a non-durable response. Our CD34+ humanized mouse model is the first in vivo platform for testing the long-term efficacy of anticancer immunotherapies and biomarkers, given that none of the preclinical models has ever been evaluated for such a long duration.