tbuckley/cabot-search huggingface dataset:
Precision targeting of bacterial pathogen via bi-functional nanozyme activated by biofilm microenvironment
Authors: Yue Huang, Yuan Liu, Shrey Shah, Dongyeop Kim, Aurea Simon-Soro, Tatsuro Ito, Maryam Hajfathalian, Yong Li, Jessica C. Hsu, Lenitza M. Nieves, Faizan Alawi, Pratap C. Naha, David P. Cormode, Hyun Koo
Journal: Biomaterials (2020)

Human dental caries is an intractable biofilm-associated disease caused by microbial interactions and dietary sugars on the host's teeth. Commensal bacteria help control opportunistic pathogens via bioactive products such as hydrogen peroxide (H2O2). However, high-sugar consumption disrupts homeostasis and promotes pathogen accumulation in acidic biofilms that cause tooth-decay. Here, we exploit the pathological (sugar-rich/acidic) conditions using a nanohybrid system to increase intrinsic H2O2 production and trigger pH-dependent reactive oxygen species (ROS) generation for efficient biofilm virulence targeting. The nanohybrid contains glucose-oxidase that catalyzes glucose present in biofilms to increase intrinsic H2O2, which is converted by iron oxide nanoparticles with peroxidase-like activity into ROS in acidic pH. Notably, it selectively kills Streptococcus mutans (pathogen) without affecting Streptococcus oralis (commensal) via preferential pathogen-binding and in situ ROS generation. Furthermore, nanohybrid treatments potently reduced dental caries in a rodent model. Compared to chlorhexidine (positive-control), which disrupted oral microbiota diversity, the nanohybrid had significant higher efficacy without affecting soft-tissues and the oral-gastrointestinal microbiomes, while modulating dental health-associated microbial activity in vivo. The data reveal therapeutic precision of a bi-functional hybrid nanozyme against a biofilm-related disease in a controlled-manner activated by pathological conditions.
The Case for Cautious Interpretation and Replication: Lead-Time Bias as a Potential Explanation for the Link Between Duration of Untreated Psychosis and Outcome
Authors: Srividya N. Iyer, Kelly K. Anderson, Ashok Malla, Jai Shah, Ross Norman
Journal: American Journal of Psychiatry (2020)

issue of the Journal, seeks to explain the important but poorly understood association between duration of untreated psychosis (DUP) and outcomes (1).We commend the authors for advancing the field by testing a novel theory using sophisticated analytic techniques.However, several issues warrant critical examination, lest the article's findings be construed as negating the need for reducing treatment delay.First, the DUPs in this study are extremely long (mean days, 726, SD=94.89;mean weeks, 103.7; median days, 346; median weeks, 49.43) and may surpass a threshold beyond which longer-term outcomes may be uniformly low.Although the observed values may be "shorter" than those noted in the United States, as the authors state, they stand well above many estimates
Deep Learning Predicts HPV Association in Oropharyngeal Squamous Cell Carcinomas and Identifies Patients with a Favorable Prognosis Using Regular H&amp;E Stains
Authors: Sebastian Klein, Alexander Quaas, Jennifer Quantius, Heike Löser, Jörn Meinel, Martin Peifer, Steffen Wagner, Stefan Gattenlöhner, Claus Wittekindt, Magnus von Knebel Doeberitz, Elena-Sophie Prigge, Christine Langer, Ka-Won Noh, Margaret Maltseva, Hans Christian Reinhardt, Reinhard Büttner, Jens Peter Klussmann, Nora Wuerdemann
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is tumorigenic and has been associated with a favorable prognosis compared with OPSCC caused by tobacco, alcohol, and other carcinogens. Meanwhile, machine learning has evolved as a powerful tool to predict molecular and cellular alterations of medical images of various sources. Experimental Design: We generated a deep learning–based HPV prediction score (HPV-ps) on regular hematoxylin and eosin (H&amp;E) stains and assessed its performance to predict HPV association using 273 patients from two different sites (OPSCC; Giessen, n = 163; Cologne, n = 110). Then, the prognostic relevance in a total of 594 patients (Giessen, Cologne, HNSCC TCGA) was evaluated. In addition, we investigated whether four board-certified pathologists could identify HPV association (n = 152) and compared the results to the classifier. Results: Although pathologists were able to diagnose HPV association from H&amp;E-stained slides (AUC = 0.74, median of four observers), the interrater reliability was minimal (Light Kappa = 0.37; P = 0.129), as compared with AUC = 0.8 using the HPV-ps within two independent cohorts (n = 273). The HPV-ps identified individuals with a favorable prognosis in a total of 594 patients from three cohorts (Giessen, OPSCC, HR = 0.55, P &amp;lt; 0.0001; Cologne, OPSCC, HR = 0.44, P = 0.0027; TCGA, non-OPSCC head and neck, HR = 0.69, P = 0.0073). Interestingly, the HPV-ps further stratified patients when combined with p16 status (Giessen, HR = 0.06, P &amp;lt; 0.0001; Cologne, HR = 0.3, P = 0.046). Conclusions: Detection of HPV association in OPSCC using deep learning with help of regular H&amp;E stains may either be used as a single biomarker, or in combination with p16 status, to identify patients with OPSCC with a favorable prognosis, potentially outperforming combined HPV-DNA/p16 status as a biomarker for patient stratification.
Mesenchymal Stem Cells Successfully Deliver Oncolytic Virotherapy to Diffuse Intrinsic Pontine Glioma
Authors: Michael I. Chastkofsky, Katarzyna C. Pituch, Hiroaki Katagi, Markella Zannikou, Liliana Ilut, Ting Xiao, Yu Han, Adam M. Sonabend, David T. Curiel, Erin R. Bonner, Javad Nazarian, Craig M. Horbinski, C. David James, Amanda M. Saratsis, Rintaro Hashizume, Maciej S. Lesniak, Irina V. Balyasnikova
Journal: Clinical Cancer Research (2020)

Diffuse intrinsic pontine glioma (DIPG) is among the deadliest of pediatric brain tumors. Radiotherapy is the standard-of-care treatment for DIPG, but offers only transient relief of symptoms for patients with DIPG without providing significant survival benefit. Oncolytic virotherapy is an anticancer treatment that has been investigated for treating various types of brain tumors.Here, we have explored the use of mesenchymal stem cells (MSC) for oncolytic virus (OV) delivery and evaluated treatment efficacy using preclinical models of DIPG. The survivin promoter drives the conditional replication of OV used in our studies. The efficiency of OV entry into the cells is mediated by fiber modification with seven lysine residues (CRAd.S.pK7). Patients' samples and cell lines were analyzed for the expression of viral entry proteins and survivin. The ability of MSCs to deliver OV to DIPG was studied in the context of a low dose of irradiation.Our results show that DIPG cells and tumors exhibit robust expression of cell surface proteins and survivin that enable efficient OV entry and replication in DIPG cells. MSCs loaded with OV disseminate within a tumor and release OV throughout the DIPG brainstem xenografts in mice. Administration of OV-loaded MSCs with radiotherapy to mice bearing brainstem DIPG xenografts results in more prolonged survival relative to that conferred by either therapy alone (P < 0.01).Our study supports OV, CRAd.S.pK7, encapsulated within MSCs as a therapeutic strategy that merits further investigation and potential translation for DIPG treatment.
Association of Physical Activity Intensity With Mortality
Authors: Yafeng Wang, Jing Nie, Gerson Ferrari, Juan Pablo Rey-Lopez, Leandro F. M. Rezende
Journal: JAMA Internal Medicine (2020)

It is unclear whether, for the same amount of total physical activity, a higher proportion of vigorous physical activity (VPA) to total physical activity is associated with a greater reduction in mortality.To examine the association of the proportion of VPA to total physical activity (defined as moderate to vigorous physical activity [MVPA]) with all-cause mortality, cardiovascular disease mortality, and cancer mortality.This cohort study included 403 681 adults from the National Health Interview Survey 1997-2013 who provided data on self-reported physical activity and were linked to the National Death Index records through December 31, 2015. Statistical analysis was performed from May 15, 2018, to August 15, 2020.Proportion of VPA to total physical activity among participants performing any MVPA.All-cause mortality, cardiovascular disease mortality, and cancer mortality. Cox proportional hazards regression models were performed to estimate hazard ratios (HRs) and 95% CIs, adjusted for sociodemographic characteristics, lifestyle risk factors, and total physical activity.Among the 403 681 individuals (225 569 women [51.7%]; mean [SD] age, 42.8 [16.3] years) in the study, during a median 10.1 years (interquartile range, 5.4-14.6 years) of follow-up (407.3 million person-years), 36 861 deaths occurred. Mutually adjusted models considering the recommendations of moderate physical activity (MPA; 150-299 vs 0 minutes per week) and VPA (≥75-149 vs 0 minutes per week) showed similar associations for all-cause mortality (MPA: HR, 0.83; 95% CI, 0.80-0.87; and VPA: HR, 0.80; 95% CI, 0.76-0.84) and cardiovascular disease mortality (MPA: HR, 0.75; 95% CI, 0.68-0.83; and VPA: HR, 0.79; 95% CI, 0.70-0.91). For the same contrasts, VPA (HR, 0.89; 95% CI, 0.80-0.99) showed a stronger inverse association with cancer mortality compared with MPA (HR, 0.94; 95% CI, 0.86-1.02). Among participants performing any MVPA, a higher proportion of VPA to total physical activity was associated with lower all-cause mortality but not with cardiovascular disease and cancer mortality. For instance, compared with participants with 0% of VPA (no vigorous activity), participants performing greater than 50% to 75% of VPA to total physical activity had a 17% lower all-cause mortality (hazard ratio, 0.83; 95% CI, 0.78-0.88), independent of total MVPA. The inverse association between proportion of VPA to total physical activity and all-cause mortality was consistent across sociodemographic characteristics, lifestyle risk factors, and chronic conditions at baseline.This study suggests that, for the same volume of MVPA, a higher proportion of VPA to total physical activity was associated with lower all-cause mortality. Clinicians and public health interventions should recommend 150 minutes or more per week of MVPA but also advise on the potential benefits associated with VPA to maximize population health.
Long-Term Outcome of Stem Cell Therapy for Acute Myocardial Infarction: Right Results, Wrong Reasons⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: James S. Forrester, Raj R. Makkar, Eduardo Marbán
Journal: Journal of the American College of Cardiology (2009)
Clinical spectrum of coronavirus disease 2019 in Iceland: population based cohort study
Authors: Elias Eythorsson, Dadi Helgason, Ragnar Freyr Ingvarsson, Helgi K Bjornsson, Lovisa Bjork Olafsdottir, Valgerdur Bjarnadottir, Hrafnhildur Linnet Runolfsdottir, Solveig Bjarnadottir, Arnar Snaer Agustsson, Kristin Oskarsdottir, Hrafn Hliddal Thorvaldsson, Gudrun Kristjansdottir, Brynja Armannsdottir, Agnar Bjarnason, Birgir Johannsson, Olafur Gudlaugsson, Magnus Gottfredsson, Martin I Sigurdsson, Olafur S Indridason, Runolfur Palsson
Journal: BMJ (2020)

Abstract Objective To characterise the symptoms of coronavirus disease 2019 (covid-19). Design Population based cohort study. Setting Iceland. Participants All individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcription polymerase chain reaction (RT-PCR) between 17 March and 30 April 2020. Cases were identified by three testing strategies: targeted testing guided by clinical suspicion, open invitation population screening based on self referral, and random population screening. All identified cases were enrolled in a telehealth monitoring service, and symptoms were systematically monitored from diagnosis to recovery. Main outcome measures Occurrence of one or more of 19 predefined symptoms during follow-up. Results Among 1564 people positive for SARS-CoV-2, the most common presenting symptoms were myalgia (55%), headache (51%), and non-productive cough (49%). At the time of diagnosis, 83 (5.3%) individuals reported no symptoms, of whom 49 (59%) remained asymptomatic during follow-up. At diagnosis, 216 (14%) and 349 (22%) people did not meet the case definition of the Centers for Disease Control and Prevention and the World Health Organization, respectively. Most (67%) of the SARS-CoV-2-positive patients had mild symptoms throughout the course of their disease. Conclusion In the setting of broad access to RT-PCR testing, most SARS-CoV-2-positive people were found to have mild symptoms. Fever and dyspnoea were less common than previously reported. A substantial proportion of SARS-CoV-2-positive people did not meet recommended case definitions at the time of diagnosis.
The Tetracentron genome provides insight into the early evolution of eudicots and the formation of vessel elements
Authors: Ping-Li Liu, Xi Zhang, Jian-Feng Mao, Yan-Ming Hong, Ren-Gang Zhang, Yilan E, Shuai Nie, Kaihua Jia, Chen-Kun Jiang, Jian He, Weiwei Shen, Qizouhong He, Wenqing Zheng, Samar Abbas, Pawan Kumar Jewaria, Xuechan Tian, Chang-jun Liu, Xiaomei Jiang, Yafang Yin, Bo Liu, Li Wang, Biao Jin, Yongpeng Ma, Zongbo Qiu, František Baluška, Jozef Šamaj, Xinqiang He, Shihui Niu, Jianbo Xie, Lei Xie, Huimin Xu, Hongzhi Kong, Song Ge, Richard A. Dixon, Yuannian Jiao, Jinxing Lin
Journal: Genome biology (2020)

Abstract Background Tetracentron sinense is an endemic and endangered deciduous tree. It belongs to the Trochodendrales, one of four early diverging lineages of eudicots known for having vesselless secondary wood. Sequencing and resequencing of the T. sinense genome will help us understand eudicot evolution, the genetic basis of tracheary element development, and the genetic diversity of this relict species. Results Here, we report a chromosome-scale assembly of the T. sinense genome. We assemble the 1.07 Gb genome sequence into 24 chromosomes and annotate 32,690 protein-coding genes. Phylogenomic analyses verify that the Trochodendrales and core eudicots are sister lineages and showed that two whole-genome duplications occurred in the Trochodendrales approximately 82 and 59 million years ago. Synteny analyses suggest that the γ event, resulting in paleohexaploidy, may have only happened in core eudicots. Interestingly, we find that vessel elements are present in T. sinense , which has two orthologs of AtVND7 , the master regulator of vessel formation. T. sinense also has several key genes regulated by or regulating TsVND7.2 and their regulatory relationship resembles that in Arabidopsis thaliana. Resequencing and population genomics reveals high levels of genetic diversity of T. sinense and identifies four refugia in China. Conclusions The T. sinense genome provides a unique reference for inferring the early evolution of eudicots and the mechanisms underlying vessel element formation. Population genomics analysis of T. sinense reveals its genetic diversity and geographic structure with implications for conservation.
17502 Melanomas of the scalp: Is hair coverage preventing early diagnosis?
Authors: Amanda Regio Pereira, Helena Collgros, Sérgio Henrique Hirata, Elisa Benati, Caterina Longo, Giuseppe Argenziano, Emi Dika, Martina Lambertini, Scott Menzies, Angela Lobato Williams, Pascale Guitera
Journal: Journal of the American Academy of Dermatology (2020)
PH-responsive strontium nanoparticles for targeted gene therapy against mammary carcinoma cells
Authors: Athirah Bakhtiar, Ezharul Hoque Chowdhury
Journal: Asian Journal of Pharmaceutical Sciences (2020)

Genetic intervention via the delivery of functional genes such as plasmid DNA (pDNA) and short-interfering RNA (siRNA) offers a great way to treat many single or multiple genetic defects effectively, including mammary carcinoma. Delivery of naked therapeutic genes or siRNAs is, however, short-lived due to biological clearance by scavenging nucleases and circulating monocytes. Low cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing activity. Development of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid delivery. Inorganic nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation activity. Here we introduce strontium salt-based nanoparticles, namely, strontium sulfate, strontium sulfite and strontium fluoride as new inorganic nanocarriers. Generated strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and siRNA. Degradation of the particles was seen with a drop in pH, suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic materials. While the particles are relatively nontoxic towards the cells, siRNA-loaded SrF2 and SrSO3 particles exerted superior transgene expression and knockdown activity of MAPK and AKT, leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 cells. Strontium salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.
Correspondence on ‘EULAR recommendations for a core data set for pregnancy registries in rheumatology’
Authors: Diederik De Cock, Isaline Soenen, Delphine Bertrand, Sofia Pazmino, Veerle Stouten, Rene Westhovens, Patrick Verschueren
Journal: Annals of the Rheumatic Diseases (2020)

Although recommendations to manage women with rheumatoid arthritis (RA) during the reproductive phase have been established, there is further need for evidence-based information on drug treatment and safety during pregnancy.1 Registries are excellent data sources to address remaining questions. Therefore, a minimal core data set for registers studying pregnancy in rheumatology has been developed recently by an EULAR task force.2 We evaluated the feasibility of data collection according to this minimal core data set in the daily clinical management of pregnant women with RA within the rheumatology department of the University Hospital of Leuven (UHL).

We performed a retrospective patient chart study in a population of 1072 patients (360 men and 712 women) with RA with a planned rheumatology outpatient visit at UHL between November 2019 and November 2020. Women were included if they were diagnosed with RA before getting pregnant, had a recorded pregnancy during the past 5 years and …
Percutaneous Transluminal Coronary Angioplasty Versus Medical Therapy for Stable Angina Pectoris: Outcomes for Patients With Double-Vessel Versus Single-Vessel Coronary Artery Disease in a Veterans Affairs Cooperative Randomized Trial fn1fn1This study was supported by the Cooperative Studies Program (study no. 267) of the U.S. Department of Veterans Affairs, Washington, D.C.
Authors: Edward D. Folland, Pamela M. Hartigan, Alfred F. Parisi
Journal: Journal of the American College of Cardiology (1997)
68Ga–Prostate-Specific Membrane Antigen PET/CT Uptake in Intraventricular Meningioma in the Choroid Plexus
Authors: Matheus Zanelatto Junqueira, Nelisa Helena Rocha, Marcelo Tatit Sapienza
Journal: Clinical Nuclear Medicine (2020)

A 68-year-old man in whom a prostate cancer biochemical recurrence was being investigated was referred for a full-body Ga-prostate-specific membrane antigen PET/CT. Focal uptake in a lesion on the choroid plexus projection was detected. Patient had no neurological complaints. A previous MRI performed 4 years ago showed the same lesion. According to the location and radiological and clinical characteristics, the diagnosis of meningioma was defined. The interpretation of prostate-specific membrane antigen PET/CT must take into account the low frequency of metastases in sites such as the central nervous system, and the possibility of intense uptake in lesions unrelated to prostate cancer.
Predictive performance of interferon-γ release assays and tuberculin skin tests – Authors' reply
Authors: Jiaru Yang, Zhenhua Ji, Yu Zhang, Peng Yue, Xin Xu, Wenjing Cao, Guozhong Zhou, Shiyuan Wen, Zhe Ding, Lianbao Li, Taigui Chen, Miaomiao Jian, Lisha Luo, Shiqi Luo, Jing Kong, Feng Wang, Fukai Bao, Aihua Liu
Journal: The Lancet Infectious Diseases (2020)
93P Assessment of nutritional status of colorectal cancer patients in a tertiary government hospital
Authors: R.N. Velasco, L.I. Catedral, R.E. King, K.A. Mondragon, F.I.L. Ting, A.V. Chua, L.M. Leones, A.R.B. Hernandez, J.M. Callueng, J. Yasay, M. Tampo, D. Sacdalan
Journal: Annals of Oncology (2020)
A Randomized Trial of Laryngeal Mask Airway in Neonatal Resuscitation
Authors: Nicolas J. Pejovic, Susanna Myrnerts Höök, Josaphat Byamugisha, Tobias Alfvén, Clare Lubulwa, Francesco Cavallin, Jolly Nankunda, Hege Ersdal, Mats Blennow, Daniele Trevisanuto, Thorkild Tylleskär
Journal: New England Journal of Medicine (2020)

Face-mask ventilation is the most common resuscitation method for birth asphyxia. Ventilation with a cuffless laryngeal mask airway (LMA) has potential advantages over face-mask ventilation during neonatal resuscitation in low-income countries, but whether the use of an LMA reduces mortality and morbidity among neonates with asphyxia is unknown.In this phase 3, open-label, superiority trial in Uganda, we randomly assigned neonates who required positive-pressure ventilation to be treated by a midwife with an LMA or with face-mask ventilation. All the neonates had an estimated gestational age of at least 34 weeks, an estimated birth weight of at least 2000 g, or both. The primary outcome was a composite of death within 7 days or admission to the neonatal intensive care unit (NICU) with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization.Complete follow-up data were available for 99.2% of the neonates. A primary outcome event occurred in 154 of 563 neonates (27.4%) in the LMA group and 144 of 591 (24.4%) in the face-mask group (adjusted relative risk, 1.16; 95% confidence interval [CI], 0.90 to 1.51; P = 0.26). Death within 7 days occurred in 21.7% of the neonates in the LMA group and 18.4% of those in the face-mask group (adjusted relative risk, 1.21; 95% CI, 0.90 to 1.63), and admission to the NICU with moderate-to-severe hypoxic-ischemic encephalopathy at day 1 to 5 during hospitalization occurred in 11.2% and 10.1%, respectively (adjusted relative risk, 1.27; 95% CI, 0.84 to 1.93). Findings were materially unchanged in a sensitivity analysis in which neonates with missing data were counted as having had a primary outcome event in the LMA group and as not having had such an event in the face-mask group. The frequency of predefined intervention-related adverse events was similar in the two groups.In neonates with asphyxia, the LMA was safe in the hands of midwives but was not superior to face-mask ventilation with respect to early neonatal death and moderate-to-severe hypoxic-ischemic encephalopathy. (Funded by the Research Council of Norway and the Center for Intervention Science in Maternal and Child Health; NeoSupra ClinicalTrials.gov number, NCT03133572.).
Beta-Blockers as First-Line Antihypertensive Therapy: The Crumbling Continues⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Carl J. Lavie, Franz H. Messerli, Richard V. Milani
Journal: Journal of the American College of Cardiology (2009)