tbuckley/cabot-search huggingface dataset:
Neuropathology of patients with COVID-19 in Germany: a post-mortem case series
Authors: Jakob Matschke, Marc Lütgehetmann, Christian Hagel, Jan P Sperhake, Ann Sophie Schröder, Carolin Edler, Herbert Mushumba, Antonia Fitzek, Lena Allweiss, Maura Dandri, Matthias Dottermusch, Axel Heinemann, Susanne Pfefferle, Marius Schwabenland, Daniel Sumner Magruder, Stefan Bonn, Marco Prinz, Christian Gerloff, Klaus Püschel, Susanne Krasemann, Martin Aepfelbacher, Markus Glatzel
Journal: The Lancet Neurology (2020)

Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS.In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions.43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70-86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes.In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included.German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).
頭頸部の再発性もしくは転移性扁平上皮癌におけるスニチニブの第2相試験: GORTEC 2006-01 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: H Machiels Jean-Pascal, Henry Stephanie, Zanetta Sylvie, Kaminsky Marie-Christine, Michoux Nicolas, Rommel Denis, Schmitz Sandra, Bompas Emmanuelle, Dillies Anne-Francoise, Faivre Sandrine, Moxhon Anne, Duprez Thierry, Guigay Joel
Journal: Journal of Clinical Oncology (2010)
Continuous versus intermittent BRAF and MEK inhibition in patients with BRAF-mutated melanoma: a randomized phase 2 trial
Authors: Alain P. Algazi, Megan Othus, Adil I. Daud, Roger S. Lo, Janice M. Mehnert, Thach-Giao Truong, Robert Conry, Kari Kendra, Gary C. Doolittle, Joseph I. Clark, Michael J. Messino, Dennis F. Moore, Christopher Lao, Bryan A. Faller, Rangaswamy Govindarajan, Amy Harker-Murray, Luke Dreisbach, James Moon, Kenneth F. Grossmann, Antoni Ribas
Journal: Nature Medicine (2020)
Clonal spread of macrolide-resistant Mycoplasma pneumoniae sequence type-3 and type-17 with recombination on non-P1 adhesin among children in Taiwan
Authors: Huei-Min Hung, Chih-Hsien Chuang, Yi-Yin Chen, Wei-Chao Liao, Shiao-Wen Li, Ian Yi-Feng Chang, Chih-Ho Chen, Ting-Hsuan Li, Ya-Yu Huang, Yi-Chuan Huang, Yi-Ching Chen, Kuo-Chien Tsao, Yhu-Chering Huang, Cheng-Hsun Chiu, Tzou-Yien Lin, Yu-Chia Hsieh
Journal: Clinical Microbiology and Infection (2020)

Mycoplasma pneumoniae is currently the most commonly detected bacterial cause of childhood community-acquired pneumonia in several countries. Of note, clonal expansion of macrolide-resistant ST3 occurred in Japan and South Korea. An alarming surge in macrolide resistance complicates the treatment of pneumonia. We aimed to evaluate the clinical manifestation and clonal relatedness of M. pneumoniae circulating among children in Taiwan.We prospectively enrolled 626 children with radiologically confirmed pneumonia between 2017 and 2019. An M. pneumoniae infection was suspected on clinical grounds, and tested by real-time PCR and oropharyngeal swab cultures. We used multilocus sequence typing and whole-genome sequencing to characterize the genetic features of M. pneumoniae.A total of 226 children with M. pneumoniae pneumonia were enrolled. Macrolide resistance was found in 77% (174/226) of patients. Multi-locus sequence typing revealed that ST3 (n = 93) and its single-locus variant ST17 (n = 84) were the predominant clones among macrolide-resistant strains. ST17 presented clinical characteristics comparable to its ancestor ST3. On multivariate analysis, macrolide resistance (OR 3.5; 95% CI 1.4-8.5; p 0.007) was independently associated with fever >72 hours after macrolide treatment. By whole-genome sequencing, prediction analysis of recombination sites revealed one recombination site in ST3 and ST17 compared with M29 (a macrolide-sensitive ST3 strain isolated from China in 2005) containing cytadhesin MgpC-like protein, RepMP4 and RepMP5. ST17 had another recombination site containing an adhesin and RepMP2/3.In addition to macrolide resistance, ST3 and its ST17 variant might evolve through recombination between repetitive sequences and non-P1 cytadhesins for persistent circulation in Taiwan.
Integrated Wound Recognition in Bandages for Intelligent Treatment
Authors: Xuecheng He, Shijie Yang, Conghui Liu, Tailin Xu, Xueji Zhang
Journal: Advanced Healthcare Materials (2020)

Abstract The mismatch between irregular wounds and fixed dressings is an important but long‐neglected problem in wound management, which may cause imprecise or incomplete care outcomes. Continuous advances in the internet, Internet of Things, and materials science put forward higher requirements in precise wound treatment. Herein, an integrated wound recognition strategy is demonstrated by extracting digital geometric information of specific irregular wounds. Such online wound image scanning and recognition integrated with offline intelligent material fabrication can greatly reduce incomplete wound closure or potential irritation toward normal tissue around the wound site. As a proof‐of‐concept, an active matrix of Ag‐modified gelatin on bandages demonstrates promising antibacterial properties for practical application. In vivo mouse experiment reveals that wound‐customized bands enable precisely fitting in the irregular wound bed, resulting in accelerating wound healing efficiency. Such wound recognitions in a bandage involve multidisciplinary technology including image identification, computer modeling nanomaterial fabrication and modification, presenting a broad potential of personalized wound healthcare for a wide variety of clinical applications.
Porphyromonas gingivalis disrupts vascular endothelial homeostasis in a TLR-NF-κB axis dependent manner
Authors: Mengru Xie, Qingming Tang, Shaoling Yu, Jiwei Sun, Feng Mei, Jiajia Zhao, Lili Chen
Journal: International Journal of Oral Science (2020)

Abstract Cardiovascular disease is still the leading cause of mortality worldwide. Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases. Many studies have indicated that periodontal pathogens, especially Porphyromonas gingivalis , are closely correlated with vascular endothelial homeostasis, but the function of P. gingivalis and the underlying mechanisms are still elusive. To illuminate the effects and elucidate the mechanisms of P. gingivalis on endothelial structural integrity, we developed P. gingivalis infection models in vivo and in vitro. Endothelial cell proliferation, differentiation and apoptosis were detected. Here, we showed that P. gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells, which reduce the cell levels and cause the endothelium to lose its ability to repair itself. A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P. gingivalis , suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P. gingivalis . These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease.
HIV Antivirals Affect Endothelial Activation and Endothelial-Platelet Crosstalk
Authors: Akif A. Khawaja, Kirk A. Taylor, Andrew O. Lovell, Mark Nelson, Brian Gazzard, Marta Boffito, Michael Emerson
Journal: Circulation Research (2020)

People living with HIV on effective antiretroviral therapy are at increased risk of cardiovascular complications, possibly due to off-target drug effects. Some studies have associated antiretroviral therapy with increased risk of myocardial infarction and endothelial dysfunction, but a link between endothelial function and antiretrovirals has not been established.To determine the effects of antiretrovirals in common clinical use upon in vitro endothelial function to better understand cardiovascular risk in people living with HIV.Human umbilical cord vein endothelial cells or human coronary artery endothelial cells were pretreated with the antiretrovirals abacavir sulphate (ABC), tenofovir disoproxil fumarate, or tenofovir alafenamide. Expression of adhesion molecules, ectonucleotidases (CD39 and CD73), tissue factor (TF), endothelial-derived microparticle (EMP) numbers and phenotype, and platelet activation were evaluated by flow cytometry. TF and ectonucleotidase activities were measured using colourimetric plate-based assays. ABC-treated endothelial cells had higher levels of ICAM (intercellular adhesion molecule)-1 and TF expression following TNF (tumor necrosis factor)-α stimulation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide treatment gave rise to greater populations of CD39+CD73+ cells. These cell surface differences were also observed within EMP repertoires. ABC-treated cells and EMP had greater TF activity, while tenofovir disoproxil fumarate- and tenofovir alafenamide-treated cells and EMP displayed higher ectonucleotidase activity. Finally, EMP isolated from ABC-treated cells enhanced collagen-evoked platelet integrin activation and α-granule release.We report differential effects of antiretrovirals used in the treatment of HIV upon endothelial function. ABC treatment led to an inflammatory, prothrombotic endothelial phenotype that promoted platelet activation. In contrast, tenofovir disoproxil fumarate and tenofovir alafenamide conferred potentially cardioprotective properties associated with ectonucleotidase activity. These observations establish a link between antiretrovirals and specific functional effects that provide insight into cardiovascular disease in people living with HIV.
Devi Sridhar: illuminating global health governance
Authors: Richard Lane
Journal: The Lancet (2020)

Devi Sridhar has travelled far in her fairly short career. She was the youngest Rhodes Scholar, aged just 18 years, and became Professor of Global Public Health at the University of Edinburgh, UK, when she was 30. But milestones are of little interest to her, especially as her role as a leader in global health governance has been accelerated by the impacts of the COVID-19 pandemic. "This is the time for the global public health community to step up", she comments. "We have never before been required to work so intensively and as rapidly as in today's environment, where effective public health responses and global health governance are having an impact on the entire world's population.
Bicyclic azetidines kill the diarrheal pathogen <i>Cryptosporidium</i> in mice by inhibiting parasite phenylalanyl-tRNA synthetase
Authors: Sumiti Vinayak, Rajiv S. Jumani, Peter Miller, Muhammad M. Hasan, Briana I. McLeod, Jayesh Tandel, Erin E. Stebbins, Jose E. Teixeira, Julien Borrel, Arthur Gonse, Mingliang Zhang, Xianshui Yu, Amy Wernimont, Chris Walpole, Sean Eckley, Melissa S. Love, Case W. McNamara, Manmohan Sharma, Amit Sharma, Christina A. Scherer, Nobutaka Kato, Stuart L. Schreiber, Bruno Melillo, Boris Striepen, Christopher D. Huston, Eamon Comer
Journal: Science Translational Medicine (2020)

Bicyclic azetidines potently inhibit Cryptosporidium in vivo by targeting phenylalanyl-tRNA synthetase.
Identification of Pru du 6 as a potential marker allergen for almond allergy
Authors: Stefan Kabasser, Christine Hafner, Sharon Chinthrajah, Sayantani B. Sindher, Divya Kumar, Laurie E. Kost, Andrew J. Long, Kari C. Nadeau, Heimo Breiteneder, Merima Bublin
Journal: Allergy (2020)

Abstract Background Oral food challenges have demonstrated that diagnosis of almond allergy based on extract‐sIgE tests displays low specificity. Molecular allergy diagnosis is expected to improve accuracy, but its value in diagnosing almond allergy remains unknown. The aim of this study was to identify relevant almond allergens and examine their ability to improve almond allergy diagnosis. Methods IgE‐reactive proteins were purified from almond kernels. IgE binding to almond extract and the allergens was analyzed by quantitative ELISA using sera from 18 subjects with a proven almond allergy. The control group consisted of sera from 18 subjects allergic to peanut and/or tree nuts but tolerant to almond. Results Three IgE‐binding proteins were identified: legumin (Pru du 6), alpha‐hairpinin (Pru du 8), and mandelonitrile lyase (Pru du 10). Positive IgE (≥0.35 kU/L) to almond extract showed 94% sensitivity but only 33% specificity. IgE to Pru du 6 maintained high sensitivity (83%) and provided superior specificity (78%). Sera from almond‐allergic subjects had significantly higher IgE levels to almond extract ( P &lt; .0001) and Pru du 6 ( P &lt; .0001) than sera from tolerant donors. Sensitization to Pru du 6 was highly specific for almond allergy, while frequencies of sensitization to legumins from peanut, walnut, hazelnut, and cashew were similar in both groups. IgE to Pru du 8 and Pru du 10 was less sensitive (41% and 67%), but showed specificities of 100% and 61%. Conclusion The use of almond allergens markedly increases the diagnostic specificity compared to the extract. Pru du 6 is a potential new molecular marker for almond allergy.
Skin‐Interfaced Microfluidic Systems that Combine Hard and Soft Materials for Demanding Applications in Sweat Capture and Analysis
Authors: Jungil Choi, Shulin Chen, Yujun Deng, Yeguang Xue, Jonathan T. Reeder, Daniel Franklin, Yong Suk Oh, Jeffrey B. Model, Alexander J. Aranyosi, Stephen P. Lee, Roozbeh Ghaffari, Yonggang Huang, John A. Rogers
Journal: Advanced Healthcare Materials (2020)

Eccrine sweat contains a rich blend of electrolytes, metabolites, proteins, metal ions, and other biomarkers. Changes in the concentrations of these chemical species can indicate alterations in hydration status and they can also reflect health conditions such as cystic fibrosis, schizophrenia, and depression. Recent advances in soft, skin-interfaced microfluidic systems enable real-time measurement of local sweat loss and sweat biomarker concentrations, with a wide range of applications in healthcare. Uses in certain contexts involve, however, physical impacts on the body that can dynamically deform these platforms, with adverse effects on measurement reliability. The work presented here overcomes this limitation through the use of microfluidic structures constructed in relatively high modulus polymers, and designed in geometries that offer soft, system level mechanics when embedded low modulus elastomers. Analytical models and finite element analysis quantitatively define the relevant mechanics of these systems, and serve as the basis for layouts optimized to allow robust operation in demanding, rugged scenarios such as those encountered in football, while preserving mechanical stretchability for comfortable, water-tight bonding to the skin. Benchtop testing and on-body field studies of measurements of sweat loss and chloride concentration under imposed mechanical stresses and impacts demonstrate the key features of these platforms.
“One stop shop” diagnostic services in the community are needed to clear backlog
Authors: Emma Wilkinson
Journal: BMJ (2020)

A radical overhaul of diagnostic services is needed in England to provide quick access to scans and tests during and after the covid-19 pandemic, report commissioned by the NHS has concluded.

Community diagnostic hubs for cancer, cardiac, respiratory, and other conditions should be set up as “one stop shops” away from acute hospitals and kept as clear of covid-19 as possible, said Mike Richards, the NHS’s first cancer tsar and the former Care Quality Commission chief inspector of hospitals.

Emergency and elective testing should also be kept separate to prevent hold-ups for patients, he said in a review of diagnostic services as part of the NHS plan …
Do sex differences in thermoregulation pose a concern for female athletes preparing for the Tokyo Olympics?
Authors: Sean R Notley, Sebastien Racinais, Glen P Kenny
Journal: British Journal of Sports Medicine (2020)

The hot-humid environmental conditions (27°C–31°C, 60%–80% relative humidity) expected for the 2021 Tokyo Olympics will pose a considerable thermoregulatory challenge for athletes, which will impair performance and potentially compromise safety. Perhaps due to the conventional belief that women are at a thermoregulatory disadvantage compared with men, many coaches have questioned whether training and competing in such conditions will be particularly challenging for female athletes. As an extension of this editorial series,1 we therefore provide a physiologist’s perspective on three of the common questions raised.

Numerous investigators have documented sex differences in exercise thermoregulation; however, until recently, it remained uncertain whether those differences were related to sex per se or simply due to secondary differences in body size and aerobic fitness between the men and women studied. Such secondary differences influence exercise thermoregulation primarily by modulating metabolic heat production and the heat loss required to prevent continued rises in core temperature. For example, due to their smaller size, heat production per unit body mass or surface area and the resultant rise in core temperature would be greater in women during weight-supported exercise at a fixed work rate (eg, cycling at 200 W). While determining the potential, magnitude of these effects during training or competition is complex, they pose no more of a …
T-cell responses to MERS coronavirus infection in people with occupational exposure to dromedary camels in Nigeria: an observational cohort study
Authors: Chris Ka Pun Mok, Airu Zhu, Jingxian Zhao, Eric H Y Lau, Junxiang Wang, Zhao Chen, Zhen Zhuang, Yanqun Wang, Abeer N Alshukairi, Salim A Baharoon, Wenling Wang, Wenjie Tan, Weiwen Liang, Jamiu O Oladipo, Ranawaka A P M Perera, Sulyman A Kuranga, Malik Peiris, Jincun Zhao
Journal: The Lancet Infectious Diseases (2020)
Cardiomyocyte Induction and Regeneration for Myocardial Infarction Treatment: Cell Sources and Administration Strategies
Authors: Lihong He, Xiongbiao Chen
Journal: Advanced Healthcare Materials (2020)

Abstract Occlusion of coronary artery and subsequent damage or death of myocardium can lead to myocardial infarction (MI) and even heart failure—one of the leading causes of deaths world wide. Notably, myocardium has extremely limited regeneration potential due to the loss or death of cardiomyocytes (i.e., the cells of which the myocardium is comprised) upon MI. A variety of stem cells and stem cell‐derived cardiovascular cells, in situ cardiac fibroblasts and endogenous proliferative epicardium, have been exploited to provide renewable cellular sources to treat injured myocardium. Also, different strategies, including direct injection of cell suspensions, bioactive molecules, or cell‐incorporated biomaterials, and implantation of artificial cardiac scaffolds (e.g., cell sheets and cardiac patches), have been developed to deliver renewable cells and/or bioactive molecules to the MI site for the myocardium regeneration. This article briefly surveys cell sources and delivery strategies, along with biomaterials and their processing techniques, developed for MI treatment. Key issues and challenges, as well as recommendations for future research, are also discussed.
1733P Real-world data: Cancer and SARS-CoV-2 infection
Authors: B. Nunez Garcia, M. Blanco Clemente, A. Morito Aguilar, M. Martinez Cutillas, C. Traseira, Y. Garitaonaindia, R. Aguado Noya, C. Alfaro Autor, G. Visedo, F. franco, V. calvo de juan, M. Provencio Pulla
Journal: Annals of Oncology (2020)
Enhanced Detection of Treatment Effects on Metastatic Colorectal Cancer with Volumetric CT Measurements for Tumor Burden Growth Rate Evaluation
Authors: Michael L. Maitland, Julia Wilkerson, Sanja Karovic, Binsheng Zhao, Jessica Flynn, Mengxi Zhou, Patrick Hilden, Firas S. Ahmed, Laurent Dercle, Chaya S. Moskowitz, Ying Tang, Dana E. Connors, Stacey J. Adam, Gary Kelloff, Mithat Gonen, Tito Fojo, Lawrence H. Schwartz, Geoffrey R. Oxnard
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Mathematical models combined with new imaging technologies could improve clinical oncology studies. To improve detection of therapeutic effect in patients with cancer, we assessed volumetric measurement of target lesions to estimate the rates of exponential tumor growth and regression as treatment is administered. Experimental Design: Two completed phase III trials were studied (988 patients) of aflibercept or panitumumab added to standard chemotherapy for advanced colorectal cancer. Retrospectively, radiologists performed semiautomated measurements of all metastatic lesions on CT images. Using exponential growth modeling, tumor regression (d) and growth (g) rates were estimated for each patient's unidimensional and volumetric measurements. Results: Exponential growth modeling of volumetric measurements detected different empiric mechanisms of effect for each drug: panitumumab marginally augmented the decay rate [tumor half-life; d [IQR]: 36.5 days (56.3, 29.0)] of chemotherapy [d: 44.5 days (67.2, 32.1), two-sided Wilcoxon P = 0.016], whereas aflibercept more significantly slowed the growth rate [doubling time; g = 300.8 days (154.0, 572.3)] compared with chemotherapy alone [g = 155.9 days (82.2, 347.0), P ≤ 0.0001]. An association of g with overall survival (OS) was observed. Simulating clinical trials using volumetric or unidimensional tumor measurements, fewer patients were required to detect a treatment effect using a volumetric measurement-based strategy (32–60 patients) than for unidimensional measurement-based strategies (124–184 patients). Conclusions: Combined tumor volume measurement and estimation of tumor regression and growth rate has potential to enhance assessment of treatment effects in clinical studies of colorectal cancer that would not be achieved with conventional, RECIST-based unidimensional measurements.