tbuckley/cabot-search huggingface dataset:
A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury
Authors: Chenggui Wang, Min Wang, Kaishun Xia, Jingkai Wang, Feng Cheng, Kesi Shi, Liwei Ying, Chao Yu, Haibin Xu, Shining Xiao, Chengzhen Liang, Fangcai Li, Bo Lei, Qixin Chen
Journal: Bioactive Materials (2021)

The repair and motor functional recovery after spinal cord injury (SCI) remains a worldwide challenge. The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI. Using mesenchymal stem cells (MSCs) derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation. However, the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied. Herein, we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel (FE) with sustainable and long term extracellular vesicle release ([email protected]) for improving motor functional recovery after SCI. The orthotopic injection of [email protected] hydrogel could encapsulate extracellular vesicles on the injured spinal cord, thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation, reducing inflammatory reaction, promoting remyelination and axonal regeneration. This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.
Selective treatment pressure in colon cancer drives the molecular profile of resistant circulating tumor cell clones
Authors: Laure Cayrefourcq, Frédéric Thomas, Thibault Mazard, Eric Assenat, Said Assou, Catherine Alix-Panabières
Journal: Molecular Cancer (2021)

Abstract The characterization of circulating tumor cells (CTCs) holds promises for precision medicine because these cells are an important clinical indicator of treatment efficacy. We established the first and still only nine permanent colon CTC lines from peripheral blood samples of a patient with metastatic colon cancer collected at different time points during treatment and cancer progression. The study objectives were ( i ) to compare the gene expression profiles of these CTC lines, and ( ii ) to determine the main features acquired during treatment. The number of upregulated genes was higher in the CTC lines obtained after treatment, indicating that they acquired properties to escape treatment pressure. Among these upregulated genes, some are involved in the mTOR and PI3K/AKT signaling pathways. Moreover, cytidine deaminase expression was significantly increased in the CTC lines obtained after failure of the first- and second-line 5-fluorouracile-based treatments, suggesting that these CTCs can eliminate this specific drug and resist to therapy. Several enzymes involved in xenobiotic metabolism also were upregulated after treatment, suggesting the activation of detoxification mechanisms in response to chemotherapy. Finally, the significant higher expression of aldolase B in four of the six CTC lines obtained after treatment withdrawal and cancer progression indicated that these clones originated from liver metastases. In conclusion, these CTC lines generated at different time points during treatment of metastatic colon cancer in a single patient are characterized by the deregulation of different genes that promote ( i ) drug resistance, ( ii ) xenobiotic and energy metabolism, and ( iii ) stem cell properties and plasticity.
Transplantation of engineered exosomes derived from bone marrow mesenchymal stromal cells ameliorate diabetic peripheral neuropathy under electrical stimulation
Authors: Anamika Singh, Alok Raghav, Parvaiz Ahmad Shiekh, Ashok Kumar
Journal: Bioactive Materials (2021)

Diabetic peripheral neuropathy (DPN) is a long-term complication associated with nerve dysfunction and uncontrolled hyperglycemia. In spite of new drug discoveries, development of effective therapy is much needed to cure DPN. Here, we have developed a combinatorial approach to provide biochemical and electrical cues, considered to be important for nerve regeneration. Exosomes derived from bone marrow mesenchymal stromal cells (BMSCs) were fused with polypyrrole nanoparticles (PpyNps) containing liposomes to deliver both the cues in a single delivery vehicle. We developed DPN rat model and injected intramuscularly the fused exosomal system to understand its long-term therapeutic effect. We found that the fused system along with electrical stimulation normalized the nerve conduction velocity (57.60 ± 0.45 m/s) and compound muscle action potential (16.96 ± 0.73 mV) similar to healthy control (58.53 ± 1.10 m/s; 18.19 ± 1.45 mV). Gastrocnemius muscle morphology, muscle mass, and integrity were recovered after treatment. Interestingly, we also observed paracrine effect of delivered exosomes in controlling hyperglycemia and loss in body weight and also showed attenuation of damage to the tissues such as the pancreas, kidney, and liver. This work provides a promising effective treatment and also contribute cutting edge therapeutic approach for the treatment of DPN.
CRISPR-Based COVID-19 Smartphone Test in Development
Authors: Jennifer Abbasi
Journal: JAMA (2021)

CRISPR-Based COVID-19 Smartphone Test in DevelopmentA simplified point-of-care assay that turns a smartphone into a fluorescence microscope could expand coronavirus disease 2019 (COVID-19) testing capability, researchers reported in a study in Cell.The assay, which uses clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology, emits a fluorescent signal in the presence of the novel coronavirus's RNA.A smartphone camera can detect this signal directly, without amplification of the viral genome used in most genetic tests.This means the test can quantify the amount of virus in the sample-the quicker the signal is picked up, the higher the viral load.In the study, the assay was able to detect RNA extracted from patients' nasal swabs within 5 minutes.Samples with less virus could be detected within 30 minutes."Monitoring viral loads quantitatively would allow estimation of infection stage and help predict infectivity, recovery, and return from quarantine in real time," the authors wrote."We plan on applying for [Emergency
Nicotinamide for the treatment of heart failure with preserved ejection fraction
Authors: Mahmoud Abdellatif, Viktoria Trummer-Herbst, Franziska Koser, Sylvère Durand, Rui Adão, Francisco Vasques-Nóvoa, Johanna K. Freundt, Julia Voglhuber, Maria-Rosaria Pricolo, Michael Kasa, Clara Türk, Fanny Aprahamian, Elías Herrero-Galán, Sebastian J. Hofer, Tobias Pendl, Lavinia Rech, Julia Kargl, Nathaly Anto-Michel, Senka Ljubojevic-Holzer, Julia Schipke, Christina Brandenberger, Martina Auer, Renate Schreiber, Chintan N. Koyani, Akos Heinemann, Andreas Zirlik, Albrecht Schmidt, Dirk von Lewinski, Daniel Scherr, Peter P. Rainer, Julia von Maltzahn, Christian Mühlfeld, Marcus Krüger, Saša Frank, Frank Madeo, Tobias Eisenberg, Andreas Prokesch, Adelino F. Leite-Moreira, André P. Lourenço, Jorge Alegre-Cebollada, Stefan Kiechl, Wolfgang A. Linke, Guido Kroemer, Simon Sedej
Journal: Science Translational Medicine (2021)

The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
Gating of hippocampal rhythms and memory by synaptic plasticity in inhibitory interneurons
Authors: Xingzhi He, Jiarui Li, Guangjun Zhou, Jing Yang, Sam McKenzie, Yanjun Li, Wenwen Li, Jun Yu, Yang Wang, Jing Qu, Zhiying Wu, Hailan Hu, Shumin Duan, Huan Ma
Journal: Neuron (2021)
Abstract 13844: Machine Learning Developed Algorithms to Identify Patients With Congenital Heart Disease From Large Claims Databases
Authors: Ariane Marelli, Chao Li, Aihua Liu, Liming Guo, James M Brophy, Yi Yang
Journal: Circulation (2019)

Introduction: Large claims databases are increasingly used in medical research. Correct identification of patients with the disease of interest is the first and essential step. For complex disease ...
The Emotional Impact of COID-19 on Residents and Fellows
Authors: Muhammad Awan, Kristina Antuna
Journal: Journal of Allergy and Clinical Immunology (2021)

To determine the levels of burnout and anxiety experienced by residents and fellows during COVID-19. Multicentric prospective study. Survey included validated tools to evaluate burnout, psychological distress, anxiety, and depression. Additionally, we assessed participants' perception and emotional impact of COVID-19. We analyzed the prevalence and correlation of the different variables. We evaluated 110 residents and fellows. Age range 25-39 years; 42.7% were females. The 90.9% and 83.6% of participants reported fear of losing a loved one and getting sick or dying related to COVID-19. Additionally, 88.2% felt uncertain about their future, while 91.8% and 89.1% revealed that COVID-19 is affecting their quality of life and emotional status. The prevalence of psychological distress and burnout was 31.8% and 9.1%. Additionally, 20% and 11.8% screened positive for anxiety and depression. Psychological distress, anxiety, and depression had a significant correlation with being afraid of losing a loved one, being afraid of getting sick or dying, uncertainty about the future, changes in emotional status and quality of life. Burnout had a strong correlation with emotional status, and a weak correlation with being afraid of getting sick or dying, and quality of life. Medical trainees are at risk of burnout during their training. COVID-19 has added a new component that affects their personal and professional lives. Residents and fellows' quality of life, emotional status and their perception of the future has been affected by COVID-19. The outcomes in this paper show us a direct impact in the trainees' psychological distress levels, depression, and burnout risks.
Richard H R White
Authors: David V Milford, Martin White
Journal: BMJ (2021)

Richard H R White (“Dick”) was born on 6 November 1926 in Newcastle-under-Lyme. He graduated after preclinical studies at Emmanuel College, Cambridge, and clinical practice at Guy’s Hospital, London and went on to become one of the first paediatricians in the UK to specialise in nephrology.

His first paediatric post was in Bath, and he subsequently worked at the Hospital for Sick Children, Great Ormond Street, London, and the Evelina Hospital, London. It was at Great Ormond Street Hospital that Richard began his interest in histology, first undertaking liver biopsies and then, after having observed Hugh de Wardener perform renal biopsies in adults, pioneered renal biopsies in children, initially under general anaesthetic using a needle modified to his own design. From July 1960 to September 1962, Richard was a paediatrician at Mulago Hospital, Kampala, where he continued with his renal interest and further developed the technique of renal biopsy. He subsequently promoted renal biopsy under sedation and local anaesthetic and published his experience in the Lancet , Archives of Disease in Childhood , and Paediatric Nephrology . On his return to the Evelina Hospital in 1962 he participated in a study of nephrotic syndrome in the South Thames area that required him to travel to district general hospitals to …
Prevalence and risk factors for cisplatin-induced hearing loss in children, adolescents, and young adults: a multi-institutional North American cohort study
Authors: Diana J Moke, Chunqiao Luo, Joshua Millstein, Kristin R Knight, Shahrad R Rassekh, Beth Brooks, Colin J D Ross, Michael Wright, Victoria Mena, Teresa Rushing, Adam J Esbenshade, Bruce C Carleton, Etan Orgel
Journal: The Lancet Child & Adolescent Health (2021)
Abstract 15317: Reclassifying Hypertrophic Cardiomyopathy Variants of Unknown Significance Based on Structural Determinants Improves Risk Stratification
Authors: Amanda C Garfinkel, Allison L Cirino, Sharlene M Day, Euan A Ashley, Michelle Michels, Steven D Colan, Daniel Jacoby, Iacopo Olivotto, Christopher N Toepfer, Alexandre C Pereira, Jonathan G Seidman, Carolyn Y Ho, Christine E Seidman
Journal: Circulation (2018)

Background: Data from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) shows that genotype predicts clinical outcomes in hypertrophic cardiomyopathy (HCM). Patients with pathogenic sarcomere mu...
Respiratory syncytial virus in young children: community cohort study integrating serological surveys, questionnaire and electronic health records, Born in Bradford cohort, England, 2008 to 2013
Authors: Ania Zylbersztejn, Lucy Pembrey, Harvey Goldstein, Guy Berbers, Rutger Schepp, Fiona van der Klis, Charles Sande, Dan Mason, John Wright, Rosalind Smyth, Pia Hardelid
Journal: Eurosurveillance (2021)

Background Bronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants. Aim To describe RSV epidemiology in children in the community in a high-income setting. Methods We used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records. We used finite mixture models to classify children as RSV infected/not infected according to their antibody concentrations at age 1 and 2 years. We assessed risk factors for primary RSV infection at each age using Poisson regression models. Results The study cohort included 700 children with cord blood samples; 490 had additional blood samples taken at both ages 1 and 2 years old. Of these 490 children, 258 (53%; 95% confidence interval (CI): 48–57%) were first infected with RSV at age 1, 99 of whom (38%; 95% CI: 33–43%) had been in contact with healthcare during peak RSV season (November–January). Having older siblings, birth in October–June and attending formal childcare were associated with risk of RSV infection in infancy. By age 2, a further 164 of 490 children (33%; 95% CI: 29–38%) had been infected. Conclusion Over half of children experienced RSV infection in infancy, a further one third had evidence of primary RSV infection by age 2, and one in seven remained seronegative by their second birthday. These findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes in high-income settings.
Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss
Authors: Florian Seyfried, Jutarop Phetcharaburanin, Maria Glymenaki, Arno Nordbeck, Mohammed Hankir, Jeremy K Nicholson, Elaine Holmes, Julian R. Marchesi, Jia V. Li
Journal: Gut Microbes (2021)

Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease.
BCL-2 Inhibition with ABT-199 Shows Efficacy in AML Cell Lines with Synergistic Effects upon Addition of the MEK Inhibitor GDC-0973 and Prolongs Survival in an NAS/BCL-2-Mediated Mouse Model of AML Post-MDS
Authors: Rose Ann Padua, Mathieu Chiquet, Qi Zhang, Claire Kappel, Patricia Krief, Niclas Setterblad, Omidvar, Marina Konopleva, Michael Andreeff, Marika Pla, Lionel Ades, Pierre Fenaux, Christine Chomienne
Journal: Blood (2017)
Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model
Authors: Jan Heyckendorf, Sebastian Marwitz, Maja Reimann, Korkut Avsar, Andrew R. DiNardo, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H.E. Kaufmann, Irina Kontsevaya, Frank van Leth, Anna M. Mandalakas, Florian P. Maurer, Marius Müller, Dörte Nitschkowski, Ioana D. Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Jan Rybniker, Helmut J.F. Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Isabelle Suárez, Elena Terhalle, Markus Unnewehr, January Weiner, Torsten Goldmann, Christoph Lange
Journal: European Respiratory Journal (2021)

The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB.Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points.50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001).Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB.
Uptake Rates of Novel Therapies and Survival Among Privately Insured Versus Publicly Insured Patients With Colorectal Cancer in Germany
Authors: Lina Jansen, Daniel Boakye, Elizabeth Alwers, Prudence R. Carr, Christoph Reissfelder, Martin Schneider, Uwe M. Martens, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner
Journal: Journal of the National Comprehensive Cancer Network (2021)

In the era of personalized medicine, cancer care is subject to major changes and innovations. It is unclear, however, to what extent implementation of such innovations and their impact on patient outcomes differ by health insurance type. This study compared provision of treatment and survival outcomes among patients with colorectal cancer (CRC) who had statutory health insurance (SHI) versus private health insurance (PHI) in Germany.We analyzed patterns of CRC treatment (surgery, chemotherapy/radiotherapy, and targeted therapy) and survival in a large cohort of patients who were diagnosed with CRC in 2003 through 2014 and were observed for an average of 6 years. Associations of type of health insurance with treatment administration and with overall, CRC-specific, and recurrence-free survival were investigated using multivariable logistic and Cox proportional hazards models, respectively.Of 3,977 patients with CRC, 427 (11%) had PHI. Although type of health insurance was not associated with treatment administration in patients with stage I-III disease, those with stage IV disease with PHI more often received targeted therapy (65% vs 40%; odds ratio, 2.43; 95% CI, 1.20-4.91), with differences decreasing over time because of catch-up of uptake rates in patients with SHI. Median overall survival was longer in patients with PHI than in those with SHI (137.0 vs 114.9 months; P=.010), but survival advantages were explained to a large extent by differences in sociodemographic factors. In patients with stage IV disease, survival advantages of PHI were nonsignificant and were restricted to the early years after diagnosis.We observed major differences in uptake of targeted therapy between patients with PHI and those with SHI but no differences in patient survival after adjusting for relevant sociodemographic, clinical, and tumor characteristics. Further studies are needed on factors associated with the uptake of therapeutic innovations and their impact on patient survival by health insurance type.
Association Between DPP-4 Inhibitors and COVID-19–Related Outcomes Among Patients With Type 2 Diabetes
Authors: Yunha Noh, In-Sun Oh, Han Eol Jeong, Kristian B. Filion, Oriana Hoi Yun Yu, Ju-Young Shin
Journal: Diabetes Care (2021)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), uses angiotensin-converting enzyme 2 to invade human cells. However, recent evidence suggested that dipeptidyl peptidase 4 (DPP-4) may be used as a coreceptor when SARS-CoV-2 enters the target cells (1). Interestingly, upregulation of DPP-4 is associated with older age, respiratory or cardiovascular disease, and diabetes (2), all of which were reported to exacerbate COVID-19. Given the pathophysiological evidence, DPP-4 inhibitors were suggested to have beneficial effects on COVID-19. Given the high fatality rate of COVID-19 among patients with diabetes, there is an urgent need to understand the effect DPP-4 inhibitors may have on COVID-19. Therefore, we aimed to determine whether use of DPP-4 inhibitors reduces the risk of adverse COVID-19–related outcomes among patients with type 2 diabetes (T2D).

We conducted a nationwide cohort study using the Health Insurance Review and Assessment Service database linked with the Korea Disease Control and Prevention Agency database, which covers the entire South Korean population of ≥50 million, from 1 January 2017 to 15 May 2020. We included patients who had a positive test result for COVID-19 as of 15 May 2020, had been diagnosed with T2D within the preceding 3 years before COVID-19 diagnosis (cohort entry), and had ≥1 antidiabetic prescription within the 180 days before cohort entry. We excluded patients aged <18 years; those prescribed metformin monotherapy only, to restrict inclusion to patients who were on second- or third-line therapy for T2D; those prescribed insulin monotherapy as they are likely to be patients with type 1 diabetes; those prescribed only insulin and metformin as they do not belong to …