tbuckley/cabot-search huggingface dataset:
Microcontainer Delivery of Antibiotic Improves Treatment of <i>Pseudomonas aeruginosa</i> Biofilms
Authors: Stine Egebro Birk, Janus Anders Juul Haagensen, Helle Krogh Johansen, Søren Molin, Line Hagner Nielsen, Anja Boisen
Journal: Advanced Healthcare Materials (2020)

Abstract Biofilm‐associated infections are difficult to treat effectively with antibiotics despite repeated treatments. Polymeric microdevices (microcontainers) have previously been shown to engulf in mucus layers and to provide tunable release. Such devices may overcome the challenge of delivering antibiotics into the biofilm, increasing the local drug concentration and hence improve local bacterial killing. In this work, microcontainers are loaded with the antibiotic, ciprofloxacin hydrochloride, and functionalized with polymeric lids of polyethylene glycol (PEG), chitosan, or Eudragit S100. The PEG lid gives rise to a drug release comparable to uncoated microcontainers showing complete release after 8 h, whereas chitosan and Eudragit S100 lids result in continuous release during the course of 24 h. All antibiotic‐containing microcontainers inhibit planktonic growth of Pseudomonas aeruginosa (PAO1) cells, but the degree of inhibition depends on the coating. Microcontainers with ciprofloxacin hydrochloride kill about three times more biofilm‐associated PAO1 cells compared with a single standard bolus. Moreover, the use of microcontainers in biofilm result in bacterial killing equal to a constant flow of a three times higher concentration of solubilized antibiotics. These studies suggest that microcontainers can be useful for antibiotic delivery in treatment of biofilm‐associated infections, resulting in more effective treatment and reduced use of antibiotics.
Effects of 20-year infancy-onset dietary counselling on cardiometabolic risk factors in the Special Turku Coronary Risk Factor Intervention Project (STRIP): 6-year post-intervention follow-up
Authors: Katja Pahkala, Tomi T Laitinen, Harri Niinikoski, Noora Kartiosuo, Suvi P Rovio, Hanna Lagström, Britt-Marie Loo, Pia Salo, Eero Jokinen, Costan G Magnussen, Markus Juonala, Olli Simell, Antti Jula, Tapani Rönnemaa, Jorma Viikari, Olli T Raitakari
Journal: The Lancet Child & Adolescent Health (2020)
Cost and Cost-effectiveness of Large-scale Screening for Type 1 Diabetes in Colorado
Authors: R. Brett McQueen, Cristy Geno Rasmussen, Kathleen Waugh, Brigitte I. Frohnert, Andrea K. Steck, Liping Yu, Judith Baxter, Marian Rewers
Journal: Diabetes Care (2020)

To assess the costs and project the potential lifetime cost-effectiveness of the ongoing Autoimmunity Screening for Kids (ASK) program, a large-scale, presymptomatic type 1 diabetes screening program for children and adolescents in the metropolitan Denver region.We report the resource utilization, costs, and effectiveness measures from the ongoing ASK program compared with usual care (i.e., no screening). Additionally, we report a practical screening scenario by including utilization and costs relevant to routine screening in clinical practice. Finally, we project the potential cost-effectiveness of ASK and routine screening by identifying clinical benchmarks (i.e., diabetic ketoacidosis [DKA] events avoided, HbA1c improvements vs. no screening) needed to meet value thresholds of $50,000-$150,000 per quality-adjusted life-year (QALY) gained over a lifetime horizon.Cost per case detected was $4,700 for ASK screening and $14,000 for routine screening. To achieve value thresholds of $50,000-$150,000 per QALY gained, screening costs would need to be offset by cost savings through 20% reductions in DKA events at diagnosis in addition to 0.1% (1.1 mmol/mol) improvements in HbA1c over a lifetime compared with no screening for patients who develop type 1 diabetes. Value thresholds were not met from avoiding DKA events alone in either scenario.Presymptomatic type 1 diabetes screening may be cost-effective in areas with a high prevalence of DKA and an infrastructure facilitating screening and monitoring if the benefits of avoiding DKA events and improved HbA1c persist over long-run time horizons. As more data are collected from ASK, the model will be updated with direct evidence on screening effects.
Robotically handled whole-tissue culture system for the screening of oral drug formulations
Authors: Thomas von Erlach, Sarah Saxton, Yunhua Shi, Daniel Minahan, Daniel Reker, Farhad Javid, Young-Ah Lucy Lee, Carl Schoellhammer, Tina Esfandiary, Cody Cleveland, Lucas Booth, Jiaqi Lin, Hannah Levy, Sophie Blackburn, Alison Hayward, Robert Langer, Giovanni Traverso
Journal: Nature Biomedical Engineering (2020)
Biodegradable nanoparticles decorated with different carbohydrates for efficient macrophage-targeted gene therapy
Authors: Qijing Chen, Mingzhu Gao, Zhongyu Li, Yue Xiao, Xin Bai, Kofi Oti Boakye-Yiadom, Xiaoyang Xu, Xue-Qing Zhang
Journal: Journal of Controlled Release (2020)
COVID-19 and Risks Posed to Personnel During Endotracheal Intubation
Authors: David N. Weissman, Marie A. de Perio, Lewis J. Radonovich
Journal: JAMA (2020)

Health care personnel who care for critically ill patients with suspected or confirmed novel coronavirus disease 2019 (COVID-19) routinely participate in procedures, such as endotracheal intubation, that may create infectious aerosols.Among persons infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, approximately 8% will require endotracheal intubation and mechanical ventilation. 1 Aerosol-generating procedures have been described as "…procedures performed on patients [that] are more likely to generate higher concentrations of infectious respiratory aerosols than coughing, sneezing, talking, or breathing." 2 Health Protection Scotland defines aerosol-generating procedures "as medical and patient care procedures that result in the production of airborne particles (aerosols) that create the potential for airborne transmission of infections that may otherwise only be transmissible by the droplet route." 3 Although there is no generally accepted and comprehensive list of aerosol-generating procedures performed during clinical care, examples include open suctioning of airways, sputum induction, manual ventilation, endotracheal intubation and extubation, noninvasive ventilation, bronchoscopy, and tracheotomy. 4There is great interest in understanding the hazards posed by the range of potentially hazardous aerosol-generating procedures for the transmission of COVID-19 and other infectious diseases.Among the aerosol-generating procedures, performing endotracheal intubation is especially hazardous.The proceduralist performing endotracheal intubation is close to the patient's airway before, during, and after the procedure.The proceduralist is also likely to be present for the associated interventions that create respiratory aerosols, such as manual (bag) ventilation.A systematic literature review and meta-analysis that evaluated transmission of SARS coronavirus 1 (SARS-CoV-1) to health care personnel in association with exposure to aerosolgenerating procedures found a significantly increased odds ratio of 6.6. 5This review also found an absolute risk increase of between 10% (cohort studies) and 15% (case-control studies) for transmission of SARS-CoV-1-associated infection to health care personnel performing intubation. 5In addition, several other types of aerosol-generating procedures were also associated with increased risk for SARS-CoV-1, including tracheotomy, noninvasive ventilation, and manual ventilation prior to intubation. 5 However, tracheal intubation was the procedure most consistently associated with transmission across the studies reviewed.Given that high viral loads of SARS-CoV-2 are found in sputum and upper respiratory secretions of patients with COVID-19, endotracheal intubation should also be viewed as a highrisk procedure for exposure to and transmission of SARS-CoV-2.
Letter to the editor: Anti-RAS drugs and SARS-CoV-2 infection
Authors: Jingwei Bian, Rongsheng Zhao, Suodi Zhai, Zijian Li
Journal: Acta Pharmaceutica Sinica B (2020)

â¢There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation.â¢The level of ACE2 expression is not completely related with the risk of COVID-19 infection.â¢There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials.â¢It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.
Pharmacokinetics, safety, and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial
Authors: Catherine Hanna, Kathreena M Kurian, Karin Williams, Colin Watts, Alan Jackson, Ross Carruthers, Karen Strathdee, Garth Cruickshank, Laurence Dunn, Sara Erridge, Lisa Godfrey, Sarah Jefferies, Catherine McBain, Rebecca Sleigh, Alex McCormick, Marc Pittman, Sarah Halford, Anthony J Chalmers
Journal: Neuro-Oncology (2020)

The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide (TMZ) chemotherapy in preclinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side effects of TMZ. The OPARATIC trial was conducted to measure penetration of recurrent glioblastoma by olaparib and assess the safety and tolerability of its combination with TMZ.
Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy
Authors: Ying Hao, YuWen Chen, XinLong He, Fan Yang, RuXia Han, ChengLi Yang, Wei Li, ZhiYong Qian
Journal: Bioactive Materials (2020)

The prevalence of skin cancer is rising along with the rapid population aging in recent years. Traditional therapies, such as surgical treatment, radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, may accompany serious side effects, limiting their clinical benefits. According to the biological characteristics of skin cancer, we have already established two kinds of synergetic systems of photothermal therapy (microneedle) and chemotherapy, containing gold nanorods (GNR). Although the microneedle system exhibited great potential for skin cancer treatment, the system could be still improved further. So, we designed a near-infrared light-responsive 5-fluorouracil (5-Fu) and indocyanine green (ICG) loaded monomethoxy-poly (ethylene glycol)-polycaprolactone (MPEG-PCL) nanoparticle (5-Fu-ICG-MPEG-PCL), and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system (HA MN) to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers, including human epidermoid cancer and melanoma. In this system, hyaluronic acid, the microneedle carrier, possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant; 5-Fu is recommended by FDA for skin cancer treatment; ICG, a photothermal agent, possesses a strong photothermal ability and is approved by FDA for its use in the human body. We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin, and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer, improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.
Abstract 13233: Impact of Thyroid Function on Patients Admitted for Acute Decompensated Heart Failure
Authors: Carola Zambrano, Pablo Klin, Juan A Moukarzel, Juan P Ochoa, Luis Varela, Federico Zeppa, Andres Bilbao, Francisco Klein
Journal: Circulation (2013)

Although it is recommended to assess thyroid function as part of the evaluation of patients (pts) with heart failure, this recommendation is based on consensus agreement rather than on evidence fro...
Correction to: Does the preoperative platelet-tolymphocyte ratio and neutrophil-tolymphocyte ratio predict morbidity after gastrectomy for gastric cancer?
Authors: İbrahim Mungan, Çilem Bayındır Dicle, Şerife Bektaş, Sema Sarı, Serdar Yamanyar, Mine Çavuş, Sema Turan, Erdal Birol Bostancı
Journal: Military Medical Research (2020)

In the original publication of this article [1] there are two garbled codes in the second sentence, the fourth paragraph of the Background section. The correct sentence should be: Tumor growth leads to the increased production of inflammatory cytokines and growth factors (mainly IL-1, IL-3, IL-6, IL-11, IL-23, and TNF-), and this perpetual process ensures immortality. These promoting factors are also important for angiogenesis and hematopoiesis, which explains the increase in blood cell types in cancerous diseases. The original publication has been corrected.
Low lymph flow decreases with age and correlates with non-sentinel node metastases and poor survival in stage III melanoma
Authors: Mark B. Faries, Richard Essner, Leland J. Foshag, Anton J. Bilchik, Theresa Zogakis, Donald L. Morton
Journal: Cancer Research (2006)

4766  Introduction: Sentinel lymphadenectomy, now a standard procedure in melanoma, uses a radiocolloid injected at the primary tumor site and detected in sentinel lymph nodes (SLN) after transit via lymphatics. Older patients are known to have lower rates of SLN metastasis, but worse prognosis in melanoma, suggesting that a diminution of lymphatic flow with age correlates with a worse prognosis. We hypothesized that decreased lymph flow, as detected during lymphatic mapping correlates with poor outcomes. Methods: We examined lymph flow by comparing radioactivity in SLNs to radioactivity at the injection site. Three count values were prospectively recorded for each site and averaged. The pathologic status of the SLN and non-SLN was recorded. Survival was estimated by the Kaplan-Meier method and compared using the logrank test. Results: Between March 2000 and June 2005, 196 patients were found to have positive SLN. Mean relative radioactivity was 18.1% of the primary site (median 12.1%). Older patients (>50yrs) had lower counts within their hottest SLN than younger patients (p = 0.043). With fairly short follow up, there was a trend toward worse overall survival in patients with less than the median relative counts, which verged on significance in patients with the lowest flow (lowest third) (p=0.055, figure). In addition, patients with non-SLN metastases had significantly lower SLN counts than those whose non-SLN were clear (p=0.023) and patients with low flow had greater mean total positive lymph nodes (2.1 vs 1.3, p=0.01). Because of the confounding relationship of age and lymph flow, we compared survival of patients >50 years old with cold versus warm nodes. Three-year survival estimates were 74% for warm and 47% for cold, a difference that did not achieve statistical significance (p=0.29) at this sample size. Conclusion: Lymphatic flow decreases with advancing age and appears to be a prognostic factor in melanoma. These data suggest that decreased lymphatic function as measured by lymph flow, portents a worse outcome in melanoma. They also suggest that immune surveillance by the lymphatic system serves an important protective function in melanoma.
Coronavirus disease 19 (Covid-19) and non-steroidal anti-inflammatory drugs (NSAID)
Authors: Alessandro Giollo, Giovanni Adami, Davide Gatti, Luca Idolazzi, Maurizio Rossini
Journal: Annals of the Rheumatic Diseases (2020)

We have read with interest the report by Monti et al 1 concerning the clinical course of coronavirus disease (Covid-19) in patients with chronic inflammatory arthritis. However, we could not find data about the use of non-steroidal anti-inflammatory drugs (NSAID) among their patients.

Whether concomitant NSAID treatment may be harmful or safe in patients with Covid-19 is unknown. However, anti-inflammatory therapies might prevent fatal cytokine storm of Covid-19. Ibuprofen, a commonly prescribed NSAID, was found to reduce interleukin-6 (IL-6) in human tissues,2 and in sputum. …
CCMetagen: comprehensive and accurate identification of eukaryotes and prokaryotes in metagenomic data
Authors: Vanessa R. Marcelino, Philip T. L. C. Clausen, Jan P. Buchmann, Michelle Wille, Jonathan R. Iredell, Wieland Meyer, Ole Lund, Tania C. Sorrell, Edward C. Holmes
Journal: Genome biology (2020)

Abstract There is an increasing demand for accurate and fast metagenome classifiers that can not only identify bacteria, but all members of a microbial community. We used a recently developed concept in read mapping to develop a highly accurate metagenomic classification pipeline named CCMetagen. The pipeline substantially outperforms other commonly used software in identifying bacteria and fungi and can efficiently use the entire NCBI nucleotide collection as a reference to detect species with incomplete genome data from all biological kingdoms. CCMetagen is user-friendly, and the results can be easily integrated into microbial community analysis software for streamlined and automated microbiome studies.
Sex-specific differences in age-related aortic valve calcium load: A systematic review and meta-analysis
Authors: Veronika A. Myasoedova, Alessandro Di Minno, Paola Songia, Ilaria Massaiu, Valentina Alfieri, Vincenza Valerio, Donato Moschetta, Daniele Andreini, Francesco Alamanni, Mauro Pepi, Daniela Trabattoni, Paolo Poggio
Journal: Ageing Research Reviews (2020)
Evolution of Human Brain Size-Associated NOTCH2NL Genes Proceeds toward Reduced Protein Levels
Authors: Gerrald A Lodewijk, Diana P Fernandes, Iraklis Vretzakis, Jeanne E Savage, Frank M J Jacobs
Journal: Molecular Biology and Evolution (2020)

Abstract Ever since the availability of genomes from Neanderthals, Denisovans, and ancient humans, the field of evolutionary genomics has been searching for protein-coding variants that may hold clues to how our species evolved over the last ∼600,000 years. In this study, we identify such variants in the human-specific NOTCH2NL gene family, which were recently identified as possible contributors to the evolutionary expansion of the human brain. We find evidence for the existence of unique protein-coding NOTCH2NL variants in Neanderthals and Denisovans which could affect their ability to activate Notch signaling. Furthermore, in the Neanderthal and Denisovan genomes, we find unusual NOTCH2NL configurations, not found in any of the modern human genomes analyzed. Finally, genetic analysis of archaic and modern humans reveals ongoing adaptive evolution of modern human NOTCH2NL genes, identifying three structural variants acting complementary to drive our genome to produce a lower dosage of NOTCH2NL protein. Because copy-number variations of the 1q21.1 locus, encompassing NOTCH2NL genes, are associated with severe neurological disorders, this seemingly contradicting drive toward low levels of NOTCH2NL protein indicates that the optimal dosage of NOTCH2NL may have not yet been settled in the human population.
Tubuloreticular inclusions in COVID-19–related collapsing glomerulopathy
Authors: François Gaillard, Sophie Ismael, Aurélie Sannier, Hassan Tarhini, Thomas Volpe, Clarisse Greze, Marie Christine Verpont, Ilyass Zouhry, Christophe Rioux, François-Xavier Lescure, David Buob, Eric Daugas
Journal: Kidney International (2020)
Covid-19: benefit for death in service may not go far enough, warns BMA
Authors: Abi Rimmer
Journal: BMJ (2020)

Families of NHS workers who die from coronavirus in the course of their work will receive a £60 000 (€69 000; $75 000) payment, the government has announced.

The BMA has warned, however, that while the sum may provide some immediate financial relief it could leave families bereft of longer term financial security.

The association said that this was particularly the case for staff who were not current members of the NHS pension scheme or who had only recently joined the scheme.

Before the announcement, only members of the NHS pension scheme were eligible for death in service benefits. The BMA also warned that locum doctors would not be eligible for benefits if they died on a day that they are not scheduled to …
Evidence for B cell maturation but not trained immunity in uninfected infants exposed to hepatitis C virus
Authors: Anton Lutckii, Benedikt Strunz, Anton Zhirkov, Olga Filipovich, Elena Rukoiatkina, Denis Gusev, Yuriy Lobzin, Björn Fischler, Soo Aleman, Matti Sällberg, Niklas K Björkström
Journal: Gut (2020)

Objectives Vertical transmission of hepatitis C virus (HCV) is rare compared with other chronic viral infections, despite that newborns have an immature, and possibly more susceptible, immune system. It further remains unclear to what extent prenatal and perinatal exposure to HCV affects immune system development in neonates. Design To address this, we studied B cells, innate immune cells and soluble factors in a cohort of 62 children that were either unexposed, exposed uninfected or infected with HCV. Forty of these infants were followed longitudinally from birth up until 18 months of age. Results As expected, evidence for B cell maturation was observed with increased age in children, whereas few age-related changes were noticed among innate immune cells. HCV-infected children had a high frequency of HCV-specific IgG-secreting B cells. Such a response was also detected in some exposed but uninfected children but not in uninfected controls. Consistent with this, both HCV-exposed uninfected and HCV-infected infants had evidence of early B cell immune maturation with an increased proportion of IgA-positive plasma cells and upregulated CD40 expression. In contrast, actual HCV viraemia, but not mere exposure, led to alterations within myeloid immune cell populations, natural killer (NK) cells and a distinct soluble factor profile with increased levels of inflammatory cytokines and chemokines. Conclusion Our data reveal that exposure to, and infection with, HCV causes disparate effects on adaptive B cells and innate immune cell such as myeloid cells and NK cells in infants.
Palliative Care Benefits Patients With Parkinson Disease
Authors: Anita Slomski
Journal: JAMA (2020)

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Abstract 12935: Associations of Maternal Cardiovascular Health in Pregnancy With Offspring Cardiovascular Health in Childhood: The Hyperglycemia and Adverse Pregnancy Outcome Follow up Study
Authors: Amanda M Perak, Nicola Lancki, Alan Kuang, Darwin R Labarthe, Svati H Shah, Lynn P Lowe, Denise M Scholtens, William L Lowe, Donald M Lloyd-jones
Journal: Circulation (2019)

Introduction: Pregnancy may be a key window to optimize cardiovascular health (CVH) for the mother and program lifelong CVH for her child. However, no study has examined CVH (as defined by the AHA)...