tbuckley/cabot-search huggingface dataset:
In vivo dissolution of poorly water-soluble drugs: Proof of concept based on fluorescence bioimaging
Authors: Yinqian Yang, Yongjiu Lv, Chengying Shen, Tingting Shi, Haisheng He, Jianping Qi, Xiaochun Dong, Weili Zhao, Yi Lu, Wei Wu
Journal: Acta Pharmaceutica Sinica B (2020)

In vitro‒in vivo correlation (IVIVC) of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients. Nevertheless, in vivo dissolution profiles have never been accurately portrayed. The current practice of IVIVC has to resort to in vivo absorption fractions (Fa). In this proof-of-concept study, in vivo dissolution of a model poorly water-soluble drug fenofibrate (FNB) was investigated by fluorescence bioimaging. FNB crystals were first labeled by near-infrared fluorophores with aggregation-caused quenching properties. The dyes illuminated FNB crystals but quenched immediately and absolutely once been released into aqueous media, enabling accurate monitoring of residual drug crystals. The linearity established between fluorescence and crystal concentration justified reliable quantification of FNB crystals. In vitro dissolution was first measured following pharmacopoeia monograph protocols with well-documented IVIVC. The synchronicity between fluorescence and in vitro dissolution of FNB supported using fluorescence as a measure for determination of dissolution. In vitro dissolution correlated well with in vivo dissolution, acquired by either live or ex vivo imaging. The newly established IVIVC was further validated by correlating both in vitro and in vivo dissolution with Fa obtained from pharmacokinetic data.
Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data
Authors: Jose Leal, Shelby D. Reed, Rishi Patel, Oliver Rivero-Arias, Yanhong Li, Kevin A. Schulman, Robert M. Califf, Rury R. Holman, Alastair M. Gray
Journal: Diabetes Care (2020)

OBJECTIVE To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study. RESEARCH DESIGN AND METHODS We simulated the impact of delaying diabetes onset by 1–9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs. RESULTS Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567–$2,680 and £201–£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years. CONCLUSIONS Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies.
Cell-Free DNA: Proceed, but with Caution
Authors: R. John Crew, Pascale Khairallah, S. Ali Husain
Journal: Journal of the American Society of Nephrology (2020)

As the interest in telehealth and remote monitoring increases,[1][1] many transplant practitioners have turned to donor-derived cell-free DNA (dd-cfDNA) to noninvasively monitor the immunologic status of allografts. As use of this testing grows, it is important to highlight limitations in its
Cost-effectiveness of Sacubitril-Valsartan in Hospitalized Patients Who Have Heart Failure With Reduced Ejection Fraction
Authors: Thomas A. Gaziano, Gregg C. Fonarow, Eric J. Velazquez, David A. Morrow, Eugene Braunwald, Scott D. Solomon
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Sacubitril-valsartan use reduces mortality and hospitalizations compared with enalapril among patients with chronic heart failure with reduced ejection fraction (HFrEF); however, the cost-effectiveness of these treatments when initiated during hospitalization for HF is unknown. <h3>Objective</h3> To estimate the cost-effectiveness of inpatient initiation of sacubitril-valsartan vs enalapril compared with no initiation or posthospitalization initiation of sacubitril-valsartan among stabilized patients with HFrEF. <h3>Design, Setting, and Participants</h3> This economic evaluation included data on US patients with HFrEF who were eligible for sacubitril-valsartan treatment from December 8, 2009, to May 15, 2018. <h3>Main Outcomes and Measures</h3> A 5-state Markov model with all-cause mortality, HF, and non-HF hospitalization probabilities was used. Quality of life was estimated using Euro-QoL EQ-5D scores. Hospitalization, long-term care, and medication costs for sacubitril-valsartan and enalapril were modeled with a discount rate of 3%. The base-case analysis included a lifetime horizon from a health care and societal perspective. <h3>Results</h3> Modeled patients were a mean (SD) age of 63.8 (11.5) years. Inpatient treatment with sacubitril-valsartan ($5628 per year) was associated with 62 fewer HF-related admissions per 1000 patients compared with outpatient initiation or 116 fewer HF-related admissions compared with continuation of enalapril treatment. From a health care system perspective, initiation of sacubitril-valsartan during hospitalization saved $452 per year compared with continuing enalapril and $811 per year compared with initiation at 2 months after hospitalization and was associated with an incremental cost-effectiveness ratio of $21 532 per quality-adjusted life-year compared with continued enalapril treatment over a lifetime. From a societal perspective, inpatient initiation was estimated to save $460 per year per patient compared with no initiation of sacubitril-valsartan and $813 per year per patient compared with initiation after hospitalization. In a budget analysis, inpatient initiation of sacubitril-valsartan was estimated to save up to $449 per person for 1 year or $2550 per person over 5 years compared with continuation of enalapril. <h3>Conclusions and Relevance</h3> The findings suggest that, for patients with HFrEF, initiation of sacubitril-valsartan during hospitalization may be associated with reduced hospitalizations, increased quality-adjusted life expectancy, and cost savings compared with no initiation or initiation after hospitalization.
Ferroptosis, necroptosis, and pyroptosis in anticancer immunity
Authors: Rong Tang, Jin Xu, Bo Zhang, Jiang Liu, Chen Liang, Jie Hua, Qingcai Meng, Xianjun Yu, Si Shi
Journal: Journal of Hematology & Oncology (2020)

Abstract In recent years, cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has achieved considerable success in the clinic. However, ICIs are significantly limited by the fact that only one third of patients with most types of cancer respond to these agents. The induction of cell death mechanisms other than apoptosis has gradually emerged as a new cancer treatment strategy because most tumors harbor innate resistance to apoptosis. However, to date, the possibility of combining these two modalities has not been discussed systematically. Recently, a few studies revealed crosstalk between distinct cell death mechanisms and antitumor immunity. The induction of pyroptosis, ferroptosis, and necroptosis combined with ICIs showed synergistically enhanced antitumor activity, even in ICI-resistant tumors. Immunotherapy-activated CD8+ T cells are traditionally believed to induce tumor cell death via the following two main pathways: (i) perforin-granzyme and (ii) Fas-FasL. However, recent studies identified a new mechanism by which CD8+ T cells suppress tumor growth by inducing ferroptosis and pyroptosis, which provoked a review of the relationship between tumor cell death mechanisms and immune system activation. Hence, in this review, we summarize knowledge of the reciprocal interaction between antitumor immunity and distinct cell death mechanisms, particularly necroptosis, ferroptosis, and pyroptosis, which are the three potentially novel mechanisms of immunogenic cell death. Because most evidence is derived from studies using animal and cell models, we also reviewed related bioinformatics data available for human tissues in public databases, which partially confirmed the presence of interactions between tumor cell death and the activation of antitumor immunity.
Coming together to improve access to medicines: The genesis of the East African Community’s Medicines Regulatory Harmonization initiative
Authors: Hiiti Sillo, Aggrey Ambali, Samvel Azatyan, Chimwemwe Chamdimba, Eliangiringa Kaale, Joseph Kabatende, Murray Lumpkin, Jane H. Mashingia, David Mukanga, Bonaventure Nyabenda, Gordon Sematiko, Margareth Sigonda, Burhani Simai, Fred Siyoi, Stanley Sonoiya, Mike Ward, Vincent Ahonkhai
Journal: PLoS Medicine (2020)

Independent, science-based regulation of medical products is a critical part of ensuring quality healthcare.When conducted in a transparent, science-based, efficient, accountable, and predictable manner, it can help ensure access to quality products that patients need.• Several factors determine access to medicines, including treatment policy, pricing, and procurement, along with regulatory activities.Delays in regulatory filing and registration contribute to delays or lack of access to essential medicines in many African countries.• We describe the solution to this problem developed by the East African Community (EAC) and launched in 2012: the EAC Medicines Regulatory Harmonization (MRH) initiative.• Through the MRH initiative, the EAC hoped to increase the number of quality medicines that it registered by simplifying the application process for manufacturers.It also aimed to increase the speed at which it reviewed applications without decreasing rigor, by modernizing assessment processes and procedures.• The EAC MRH initiative is innovative in many ways, particularly in its decentralized structure, emphasis on work-sharing, and regulation through reliance driven by trust and goodwill.
Supporting the weight of the elephant in the room: Technical intelligence propped up by social cognition and language
Authors: Alex Thornton, Francesca Happé, Christine A. Caldwell
Journal: Behavioral and Brain Sciences (2020)

Abstract We consider the evolutionary plausibility of Osiurak and Reynaud's (O&amp;R) arguments. We argue that technical reasoning is not quite the magic bullet that O&amp;R assume, and instead propose a co-evolutionary account of the interplay between technical reasoning and social learning, with language emerging as a vital issue neglected in O&amp;R's account.
Abstract IA06: The Long-Term Ovarian Cancer Survivor Project: A Department of Defense initiative
Authors: Michael J. Birrer, Lari Wenzel, Austin Miller, Heather Lankes, Nilsa Ramirez, Giovanni Parmigiani, Samuel Mok, Kenneth Nephew, Thomas Conrads, George Coukos, George L. Maxwell, Giulia Fulci, Mary Scroggins
Journal: Clinical Cancer Research (2020)

Abstract In 2019 there will be 22,500 new cases of ovarian cancer, resulting in approximately 14,000 deaths. Ovarian cancer remains the highest case fatality rate of any gynecologic cancer. Despite significant improvement in the surgical and chemotherapeutic managements of ovarian cancer patients, the overall survival has not changed in 30 years. However, these new therapies have resulted in a significant improvement in median survival, resulting in increasing numbers of patients surviving greater than 10 years with disease. The clinical and molecular features of these unique patients remain uncharacterized. The Department of Defense Ovarian Cancer Research Program (DOD OCRP) funded the creation of our interdisciplinary Long-term Survivor Consortium (LTSC), composed of 6 research sites including MDACC, UAB, IU, UCI, Ludwig Cancer Research, and University Hospitals of Canton Vaud (CHUV) and INOVA, a bioinformatic center at DFCI, and administrative centers at UCI and UAB. The purpose of the consortium is to identify characteristics and predictors of long-term survival in advanced ovarian cancer patients. The consortium is overseen by both a scientific and advocacy advisory board to guide direction and efforts. 285 specimens of advanced-stage high-grade serous ovarian cancers with full clinical annotation including greater than 12 years of follow-up were analyzed for this project. In addition, 340 early-stage high-grade ovarian cancers were available for one of the AIMs of the project. These latter samples were obtained through the creation of an international consortium funded by the DOD OCRP. All specimens were first reviewed for tumor context by H&amp;E staining to determine percentage of tumor. The scientific platforms include whole transcriptome, microRNAs, global proteomics, immune profiling, and methylation. All specimens were analyzed on each individual platform and the results will be integrated in a global process. In parallel with these efforts, a systematic analysis of quality of life of patients at the time of diagnosis and later during the course of their disease based upon patient-reported outcome surveys has been undertaken. These data will also be integrated with genomic results to produce signatures that can further characterize long-term survivors of ovarian cancer. Citation Format: Michael J. Birrer, Lari Wenzel, Austin Miller, Heather Lankes, Nilsa Ramirez, Giovanni Parmigiani, Samuel Mok, Kenneth Nephew, Thomas Conrads, George Coukos, George L. Maxwell, Giulia Fulci, Mary Scroggins. The Long-Term Ovarian Cancer Survivor Project: A Department of Defense initiative [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA06.
Hyperglycemia at Hospital Admission Is Associated With Severity of the Prognosis in Patients Hospitalized for COVID-19: The Pisa COVID-19 Study
Authors: Alberto Coppelli, Rosa Giannarelli, Michele Aragona, Giuseppe Penno, Marco Falcone, Giusy Tiseo, Lorenzo Ghiadoni, Greta Barbieri, Fabio Monzani, Agostino Virdis, Francesco Menichetti, Stefano Del Prato, Agostini o Degl’Innocenti Sabrina, Antognoli Rachele, Baldassarri Rubia, Bertini Pietro, Biancalana Martina, Borselli Matteo, Brizzi Giulia, Calsolario Valeria, Carrozzi Laura, Celi Alessandro, Cinotti Francesco, Cipriano Alessandro, Corradi Francesco, De Marco Salvatore, Della Rocca Alessandra, Forfori Francesco, Forotti Giovanna, Galfo Valentina, Guarracino Fabio, Malacarne Paolo, Masi Stefano, Mengozzi Alessandro, Monfroni Marco, Morea Alessandra, Nencini Elia, Park Naria, Paterni Simone, Piagnani Chiara, Ruberti Francesca, Santini Massimo, Sciuto Maria, Spinelli Stefano
Journal: Diabetes Care (2020)

OBJECTIVE To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels &amp;lt;7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38–6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67–12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18–10.47]). RESULTS Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27–3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92–3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P = 0.079) vs. Q1. CONCLUSIONS Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.
Osteogenesis, angiogenesis and immune response of Mg-Al layered double hydroxide coating on pure Mg
Authors: Shi Cheng, Dongdong Zhang, Mei Li, Xuanyong Liu, Yu Zhang, Shi Qian, Feng Peng
Journal: Bioactive Materials (2020)

Layered double hydroxides (LDHs) are widely studied to enhance corrosion resistance and biocompatibility of Mg alloys, which are promising bone implants. However, the influence of LDH coating on the osteointegration of Mg implants lacks of a systematic study. In this work, Mg-Al LDH coating was prepared on pure Mg via hydrothermal treatment. The as-prepared Mg-Al LDH coated Mg exhibited better
A theory limited in scope and evidence
Authors: Elena Miu, Robert Boyd, Peter J. Richerson, Thomas J. H. Morgan
Journal: Behavioral and Brain Sciences (2020)

Abstract What promised to be a refreshing addition to cumulative cultural evolution, by moving the focus from cultural transmission to technological innovation, falls flat through a lack of thoroughness, explanatory power, and data. A comprehensive theory of cumulative cultural change must carefully integrate all existing evidence in a cohesive multi-level account. We argue that the manuscript fails to do so convincingly.
A Cross-Sectional Analysis of Community Water Fluoridation and Prevalence of Pediatric Dental Surgery Among Medicaid Enrollees
Authors: Helen H. Lee, Luis Faundez, Anthony T. LoSasso
Journal: JAMA Network Open (2020)

Dental surgery under general anesthesia (DGA) is an ineffective, costly treatment for caries. Interventions to reduce the need for DGA are challenging because children's parents may not seek care until surgery is required. Community water fluoridation (CWF) effectively prevents early childhood caries, but its effectiveness in reducing severe early childhood caries is unknown.To determine whether access to CWF is associated with the prevalence of DGA.This is a cross-sectional analysis of Medicaid claims data from 2011 to 2012. Deidentified data were derived from Medicaid claims and enrollee files for Massachusetts, Texas, Connecticut, Illinois, and Florida for children aged 9 years and younger enrolled in either a fee-for-service or managed care plan through their state's Medicaid program. Linear regression models tested for associations between CWF and covariates. Multivariable linear regression models tested for associations between CWF and outcomes. Regression models included clustered SEs at the county level. Data analysis was performed from December 2018 to March 2020.Access to CWF was determined by estimating the proportion of a county's total population that had access to a fluoridated public water system.The main outcome was county-level DGA prevalence. Other outcomes were caries-related visit prevalence and patient quality indicators (asthma and diabetes). Covariates included county-level demographic, socioeconomic, and dental practitioner variables.A total of 436 counties within 5 states per year (872 county-year observations), were included in the analysis. Adjusted analysis revealed that a 10% increase in the proportion of county's population access to CWF was associated with lower caries-related visit prevalence (-0.45 percentage points; 95% CI, -0.59 to -0.31 percentage points; P < .001). Increasing CWF access in 10% increments was associated with decreased DGA prevalence in unadjusted analysis (-0.39 percentage points; 95% CI, -0.67 to -0.12 percentage points; P = .006) but not in adjusted analysis (-0.23 percentage points; 95% CI, -0.49 to 0.02 percentage points; P = .07). Increasing the proportion of county's access to CWF by 10% was not associated with the prevalence of asthma-related exacerbations (-0.02 percentage points; 95% CI, -0.10 to 0.05 percentage points; P = .53) or diabetes-related exacerbations (-0.0003 percentage points; 95% CI, -0.0014 to 0.0009 percentage points; P = .66).This study extends our understanding of CWF's benefits for children's oral health. Specifically, these findings suggest that increasing a population's access to CWF's is associated with decreased caries-related visits and may also be associated with use of dental surgical services within high-risk populations.
Prevalence of Fatty Liver Disease and Fibrosis Detected by Transient Elastography in Adults in the United States, 2017-2018
Authors: Donghee Kim, George Cholankeril, Rohit Loomba, Aijaz Ahmed
Journal: Clinical Gastroenterology and Hepatology (2020)

Fatty liver disease is a clinicopathologic spectrum that encompasses simple steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Transient elastography has evolved as an accurate technique and noninvasive tool for assessing hepatic fibrosis in clinical practice.1 The controlled attenuation parameter (CAP) score has been added to elastography, which computes ultrasound attenuation related to hepatic steatosis and improves the measurement of hepatic steatosis.1,2 Given the unmet need to reckon the current burden of disease, it is essential to estimate the recent prevalence of fatty liver disease and fibrosis assessed by transient elastography in the United States. We investigated the sex-, race/ethnicity-, and body mass index-based prevalence of fatty liver disease and hepatic fibrosis by CAP-enhanced transient elastography in the United States.
Clinically Applicable Deep Learning Framework for Measurement of the Extent of Hair Loss in Patients With Alopecia Areata
Authors: Solam Lee, Jong Won Lee, Sung Jay Choe, Sejung Yang, Sang Baek Koh, Yeon Soon Ahn, Won-Soo Lee
Journal: JAMA Dermatology (2020)

This study aims to develop a deep learning framework to determine the Severity of Alopecia Tool (SALT) score for measurement of hair loss in patients with alopecia areata.
Exquisite design of injectable Hydrogels in Cartilage Repair
Authors: Jiawei Wu, Qi Chen, Chao Deng, Baoping Xu, Zeiyan Zhang, Yang Yang, Tingli Lu
Journal: Theranostics (2020)

Cartilage damage is still a threat to human beings, yet there is currently no treatment available to fully restore the function of cartilage. Recently, due to their unique structures and properties, injectable hydrogels have been widely studied and have exhibited high potential for applications in therapeutic areas, especially in cartilage repair. In this review, we briefly introduce the properties of cartilage, some articular cartilage injuries, and now available treatment strategies. Afterwards, we propose the functional and fundamental requirements of injectable hydrogels in cartilage tissue engineering, as well as the main advantages of injectable hydrogels as a therapy for cartilage damage, including strong plasticity and excellent biocompatibility. Moreover, we comprehensively summarize the polymers, cells, and bioactive molecules regularly used in the fabrication of injectable hydrogels, with two kinds of gelation, i.e., physical and chemical crosslinking, which ensure the excellent design of injectable hydrogels for cartilage repair. We also include novel hybrid injectable hydrogels combined with nanoparticles. Finally, we conclude with the advances of this clinical application and the challenges of injectable hydrogels used in cartilage repair.