tbuckley/cabot-search huggingface dataset:
Antibiotics for Childhood Pneumonia — Do We Really Know How Long to Treat?
Authors: Anne B. Chang, Keith Grimwood
Journal: New England Journal of Medicine (2020)

The World Health Organization (WHO) recommends 3 days of oral amoxicillin (80 mg per kilogram of body weight per day) in children younger than 5 years of age who have fast-breathing pneumonia (cough lasting <14 days or difficulty breathing, along with fast breathing for age) and are living in areas with a low prevalence of human immunodeficiency virus.1 If retractions of the chest wall are present, 5 days of amoxicillin are recommended. In children with severe clinical pneumonia and danger signs (e.g., dehydration or reduced level of consciousness), 5 days of intravenous antibiotic agents are recommended. In this issue of . . .
Empirical Treatment With Carbapenem vs Third-generation Cephalosporin for Treatment of Spontaneous Bacterial Peritonitis
Authors: Sun Woong Kim, Jun Sik Yoon, Junyong Park, Yong Jin Jung, Jae Seung Lee, Jisoo Song, Han Ah Lee, Yeon Seok Seo, Minjong Lee, Jin Myung Park, Dae Hee Choi, Moon Young Kim, Seong Hee Kang, Jin Mo Yang, Do Seon Song, Sung Won Chung, Minseok Albert Kim, Hee Joon Jang, Hyunwoo Oh, Cheol-Hyung Lee, Yun Bin Lee, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Jeong-Hoon Lee
Journal: Clinical Gastroenterology and Hepatology (2020)
Changes in the epidemiology of hepatitis B virus infection following the implementation of immunisation programmes in northeastern Greece
Authors: G Zacharakis, S Kotsiou, M Papoutselis, N Vafiadis, F Tzara, E Pouliou, E Maltezos, J Koskinas, K Papoutselis
Journal: Eurosurveillance (2009)

The objective of this study was to investigate changes in the epidemiology of hepatitis B virus infection in the general population and selected groups of immigrants in the region of northeastern Greece over the last decade in relation to the introduction of hepatitis B vaccination programmes. Two population-based seroprevalence surveys were carried out during the years 1992-1994 and 1998-2006. In total, 25,105 individuals were tested for the presence of hepatitis B virus markers: HBsAg, anti-HBs and anti-HBc. Childhood/adolescence immunisation programmes began early in 1994 in selected groups of immigrants and were complemented by the national vaccination programme in 1998. Between 1992-1994 and 1998-2006, the HBsAg carrier rate declined from 5.4% [95% CI: 4.5-5.9] in adults (20-60 years old) and 1.9% [95% CI: 1.6-2.4] in children/adolescents (5-19 years old) of indigenous residents to 3.4% [95% CI: 2.9-3.8] and 0.6% [95% CI: 0.2-1.4] respectively (p<0.05). In spite of a decrease compared with 1992-1994, the percentage of HBsAg carriers was still relatively high in 1998-2006 among the Muslim religious minority group (8.2% [95% CI: 8.0-8.7] in adults and 2% [95% CI: 1.7-2.4] in children/adolescents) and in immigrants from the former Soviet Union (4.3% [95% CI: 3.6-4.7] in adults and 1.1% [95% CI: 0.8-2.4] in children/adolescents) (p<0.05 for both selected groups versus general population). The decline of the prevalence of HBsAg in the general population and selected groups of immigrants in northeastern Greece over the last decade supports the effectiveness of the ongoing immunisation programme although the information on the actual number of cases of acute HBV infection is not available.
People with mental health problems are more likely to be referred to government’s counterterrorism programme
Authors: Aisha Majid
Journal: BMJ (2020)

People with mental health problems are more likely to be reported by the NHS to Prevent, the government’s counterterrorism strategy, a report has found.1

Research by health charity Medact found that a disproportionate number of referrals come from mental health trusts or departments, reiterating a 2016 finding published in The BMJ .2

Medact sent freedom of information requests to a sample of 77 NHS trusts in Prevent Priority areas, and received 49 responses with varying degrees of disclosure. The four specialist mental health trusts that responded made 89 referrals to Prevent in the two years to March 2019. Of the 18 non-specialist trusts that replied with a breaking down of their data, 40 referrals came from mental health departments and 45 came from other departments.

According to the report, the …
Flexible and Stretchable Temperature Sensors Fabricated Using Solution‐Processable Conductive Polymer Composites
Authors: Li Dan, Anastasia L. Elias
Journal: Advanced Healthcare Materials (2020)

Abstract Accurate monitoring of physiological temperatures is important for the diagnosis and tracking of various medical conditions. This work presents the design, fabrication, and characterization of temperature sensors using conductive polymer composites (CPCs) patterned on both flexible and stretchable substrates through both drop coating and direct ink writing (DIW). These composites were formed using a high melting point biopolymer polyhydroxybutyrate (PHB) as the matrix and the graphenic nanomaterial reduced graphene oxide (rGO) as the nanofiller (from 3 to 12 wt%), resulting in a material that exhibits a temperature‐dependent resistivity. At room temperature the composites exhibited electrical percolation behavior. Around the percolation threshold, both the carrier concentration and mobility were found to increase sharply. Sensors were fabricated by drop‐coating PHB‐rGO composites onto ink‐jet printed silver electrodes. The temperature coefficient of resistance was determined to be 0.018 /°C for pressed rGO powders and 0.008 /°C for the 3 wt% samples (the highest responsivity of all composites). Composites were found to have good selectivity to temperature with respect to pressure and moisture. Thermal mapping was demonstrated using 6 × 7 arrays of sensing elements. Stretchable devices with a meandering pattern were fabricated using DIW, demonstrating the potential for these materials in healthcare monitoring devices.
Twin epidemics of covid-19 and non-communicable disease
Authors: Trevor A Sheldon, John Wright
Journal: BMJ (2020)

<h3>Summary</h3> Apoptosis is an integral physiological cell death process that occurs frequently and generates a huge number of apoptotic extracellular vesicles (apoEVs). However, whether apoEVs are necessary for maintaining organ homeostasis remains unclear. Here, we show that circulatory apoEVs engraft in liver and undergo specialized internalization by hepatocytes (HCs) based on surface signature of galactose and <i>N</i>-acetylgalactosamine. Furthermore, apoEVs rescue liver injury in apoptotic-deficient <i>Fas</i> mutant and <i>Caspase-3</i> knockout mice, which is exerted by restoring the featured hepatic ploidy homeostasis. Surprisingly, apoEVs form a chimeric organelle complex with recipient Golgi apparatus <i>via</i> SNARE-mediated membrane interaction, which consequently facilitates microtubule organization and HC cytokinesis. Notably, through Golgi recovery and ploidy transition, apoEVs contribute to liver regeneration and protect against acute hepatic failure. Collectively, these results identify a previously unrecognized role for apoEVs and the specific mechanisms by which they safeguard liver homeostasis, and suggest the potential of apoEV-based therapy for liver disorders.
Pragmatic Trials and the Evolution of Serious Illness Research
Authors: Katherine R. Courtright, Scott D. Halpern
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
CXCR4 in Tumor Epithelial Cells Mediates Desmoplastic Reaction in Pancreatic Ductal Adenocarcinoma
Authors: Toshihiro Morita, Yuzo Kodama, Masahiro Shiokawa, Katsutoshi Kuriyama, Saiko Marui, Takeshi Kuwada, Yuko Sogabe, Tomoaki Matsumori, Nobuyuki Kakiuchi, Teruko Tomono, Atsushi Mima, Tatsuki Ueda, Motoyuki Tsuda, Yuki Yamauchi, Yoshihiro Nishikawa, Yojiro Sakuma, Yuji Ota, Takahisa Maruno, Norimitsu Uza, Takashi Nagasawa, Tsutomu Chiba, Hiroshi Seno
Journal: Cancer Research (2020)

Pancreatic ductal adenocarcinoma (PDAC) features abundant stromal cells with an excessive extracellular matrix (ECM), termed the desmoplastic reaction. CXCR4 is a cytokine receptor for stromal cell-derived factor-1 (CXCL12) expressed in PDAC, but its roles in PDAC and the characteristic desmoplastic reaction remain unclear. Here, we generated a mouse model of PDAC with conditional knockout of Cxcr4 (KPC-Cxcr4-KO) by crossing Cxcr4 flox mice with Pdx1-Cre;KrasLSL-G12D/+;Trp53LSL-R172H/+ (KPC-Cxcr4-WT) mice to assess the development of pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancers. Tumor cell characteristics of those two types were analyzed in vitro. In addition, CXCR4 expression in human pancreatic cancer specimens was evaluated by IHC staining. In KPC-Cxcr4-KO mice, the number and pathologic grade of PanIN lesions were reduced, but the frequency of pancreatic cancers did not differ from that in KPC-Cxcr4-WT mice. The pancreatic tumor phenotype in KPC-Cxcr4-KO mice was significantly larger and undifferentiated, characterized by abundant vimentin-expressing cancer cells, significantly fewer fibroblasts, and markedly less deposition of ECM. In vitro, KPC-Cxcr4-KO tumor cells exhibited higher proliferative and migratory activity than KPC-Cxcr4-WT tumor cells. Myofibroblasts induced invasion activity in KPC-Cxcr4-WT tumor cells, showing an epithelial-mesenchymal interaction, whereas KPC-Cxcr4-KO tumor cells were unaffected by myofibroblasts, suggesting their unique nature. In human pancreatic cancer, undifferentiated carcinoma did not express CXCR4 and exhibited histologic and IHC features similar to those in KPC-Cxcr4-KO mice. In summary, the CXCL12/CXCR4 axis may play an important role in the desmoplastic reaction in PDAC, and loss of CXCR4 induces phenotype changes in undifferentiated carcinoma without a desmoplastic reaction. SIGNIFICANCE: The current study uncovers CXCR4 as a key regulator of desmoplastic reaction in PDAC and opens the way for new therapeutic approaches to overcome the chemoresistance in patients with PDAC.
Longitudinal anti-SARS-CoV-2 antibody profile and neutralization activity of a COVID-19 patient
Authors: Shengxia Yin, Xin Tong, Aijun Huang, Han Shen, Yang Li, Yong Liu, Chao Wu, Rui Huang, Yuxin Chen
Journal: Journal of Infection (2020)

We followed–up a mild COVID-19 patient for 91 days and serially monitored his serum antibodies to four SARS-CoV-2 related antigens (NP, RBD, S1 and ECD) and neutralization activities. Our data revealed a profile of serial antibody responses during the progress and a quick decline of neutralization activities after discharge.
Accelerating Development of SARS-CoV-2 Vaccines — The Role for Controlled Human Infection Models
Authors: Meagan E Deming, Nelson L Michael, Merlin Robb, Myron S Cohen, Kathleen M Neuzil
Journal: New England Journal of Medicine (2020)

Accelerating Development of SARS-CoV-2 Vaccines Controlled human infection models have been proposed as a strategy for accelerating SARS-CoV-2 vaccine development. But scientific and technical fact...
Abstract A80: Targeting ovarian cancer stem cell by Dot1L inhibition
Authors: Yaqi Zhang, Yinu Wang, Guangyuan Zhao, Daniela Matei
Journal: Clinical Cancer Research (2020)

Abstract Cancer stem cells (CSCs) are a specific population of cancer cells that are responsible for tumor initiation, chemoresistance, and metastasis. Previously, our lab has demonstrated ovarian cancer cells with high aldehyde dehydrogenase (ALDH) activities have multiple stem cell-like characteristics, including self-renewal, high clonogenicity, and chemoresistance. Here we identify that H3K79 methyltransferase DOT1L (disruptor of telomeric silencing-1-like) is a critical factor in self-renewal and tumor initiation capabilities of ovarian cancer stem cells (OCSCs). Firstly, we found that DOT1L have higher expression in ALDH(+)/CD133(+) OCSCs compared to double negative cells. Ovarian cancer cells with DOT1L-knockdown have reduced CSC fractions in flow cytometry analysis. Besides, knockdown of DOT1L expression impairs clonogenicity characteristics of CSCs, according to in vitro colony-forming assay and spheroid formation assay results. In order to effectively inhibit the enzymatic activity of DOT1L, we applied specific DOT1L inhibitor (DOT1Li) EPZ5676 to specifically target OCSCs and confirmed that the treatment of DOT1Li was able to block H3K79 methylation in ovarian cancer cells, and effectively represses the expression of stemness-associated transcriptional factors. Results from RNA-seq analysis and gene set enrichment assay have indicated that multiple stem-related pathways are repressed in DOT1Li-treated OCSCs. Furthermore, DOT1Li treatment not only shows inhibitory effects on colony forming in vitro but also delays tumor initiation in vivo compared to control treatment, which validates the effects of DOT1Li on CSCs inhibition. Based on our result, we infer that DOT1L is critical for self-renewal and tumor initiation abilities in ovarian cancer stem cells, and DOT1L inhibition by specific inhibitor provides a potential therapeutic strategy to target CSCs in ovarian cancer treatment. Citation Format: Yaqi Zhang, Yinu Wang, Guangyuan Zhao, Daniela Matei. Targeting ovarian cancer stem cell by Dot1L inhibition [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A80.
The Meaning of Care and Ethics to Mitigate the Harshness of Triage in Second-Wave Scenario Planning During the COVID-19 Pandemic
Authors: Mathias Wirth, Laurèl Rauschenbach, Brian Hurwitz, Heinz-Peter Schmiedebach, Jennifer A. Herdt
Journal: The American Journal of Bioethics (2020)

Although the number of severely ill people is declining in some epicenters, there is a risk of a second wave of COVID-19 infection (Shungquin and Yuanyuan 2020) with a large number of patients who ...
Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2
Authors: James Brett Case, Paul W. Rothlauf, Rita E. Chen, Zhuoming Liu, Haiyan Zhao, Arthur S. Kim, Louis-Marie Bloyet, Qiru Zeng, Stephen Tahan, Lindsay Droit, Ma. Xenia G. Ilagan, Michael A. Tartell, Gaya Amarasinghe, Jeffrey P. Henderson, Shane Miersch, Mart Ustav, Sachdev Sidhu, Herbert W. Virgin, David Wang, Siyuan Ding, Davide Corti, Elitza S. Theel, Daved H. Fremont, Michael S. Diamond, Sean P.J. Whelan
Journal: Cell Host & Microbe (2020)
Dysregulation of cancer genes by recurrent intergenic fusions
Authors: Jae Won Yun, Lixing Yang, Hye-Young Park, Chang-Woo Lee, Hongui Cha, Hyun-Tae Shin, Ka-Won Noh, Yoon-La Choi, Woong-Yang Park, Peter J. Park
Journal: Genome biology (2020)

Abstract Background Gene fusions have been studied extensively, as frequent drivers of tumorigenesis as well as potential therapeutic targets. In many well-known cases, breakpoints occur at two intragenic positions, leading to in-frame gene-gene fusions that generate chimeric mRNAs. However, fusions often occur with intergenic breakpoints, and the role of such fusions has not been carefully examined. Results We analyze whole-genome sequencing data from 268 patients to catalog gene-intergenic and intergenic-intergenic fusions and characterize their impact. First, we discover that, in contrast to the common assumption, chimeric oncogenic transcripts—such as those involving ETV4 , ERG , RSPO3 , and PIK3CA— can be generated by gene-intergenic fusions through splicing of the intervening region. Second, we find that over-expression of an upstream or downstream gene by a fusion-mediated repositioning of a regulatory sequence is much more common than previously suspected, with enhancers sometimes located megabases away. We detect a number of recurrent fusions, such as those involving ANO3 , RGS9 , FUT5 , CHI3L1 , OR1D4 , and LIPG in breast; IGF2 in colon; ETV1 in prostate; and IGF2BP3 and SIX2 in thyroid cancers. Conclusion Our findings elucidate the potential oncogenic function of intergenic fusions and highlight the wide-ranging consequences of structural rearrangements in cancer genomes.
Nutrient Control of mRNA Translation
Authors: Xin Erica Shu, Robert V. Swanda, Shu-Bing Qian
Journal: Annual Review of Nutrition (2020)

The emergence of genome-wide analyses to interrogate cellular DNA, RNA, and protein content has revolutionized the study of control networks that mediate cellular homeostasis. mRNA translation represents the last step of genetic flow and primarily defines the proteome. Translational regulation is thus critical for gene expression, in particular under nutrient excess or deficiency. Until recently, it was unclear how the global effects of translational control are orchestrated by nutrient signaling pathways. An emerging concept of translational reprogramming addresses how to maintain the expression of specific proteins during nutrient stress by translation of selective mRNAs. In this review, we describe recent advances in our understanding of translational control principles; nutrient-sensing mechanisms; and their dysregulation in human diseases such as diabetes, cancer, and aging. The mechanistic understanding of translational regulation in response to different nutrient conditions may help identify potential dietary and therapeutic targets to improve human health.
Re: Lan Zhu, Nianqiao Gong, Bin Liu, et al. Coronavirus Disease 2019 Pneumonia in Immunosuppressed Renal Transplant Recipients: A Summary of 10 Confirmed Cases in Wuhan, China. Eur Urol 2020;77:748–54
Authors: Amit Bansal, Anant Kumar
Journal: European Urology (2020)
JP1 suppresses proliferation and metastasis of melanoma through MEK1/2 mediated NEDD4L-SP1-Integrin αvβ3 signaling
Authors: Jiahua Cui, Chuanjun Shu, Jin Xu, Dongyin Chen, Jin Li, Kun Ding, Minjuan Chen, Aiping Li, Jingdong He, Yongqian Shu, Liuqing Yang, Ruiwen Zhang, Jianwei Zhou
Journal: Theranostics (2020)

Background: JWA gene is known to down-regulate SP1 and reduces the expression level of Integrin αvβ3. Here, we identified a functional polypeptide (JP1) based on the active fragment of the JWA protein to suppress melanoma growth and metastasis by inhibiting the Integrin αvβ3. Methods: We conducted a series of melanoma growth and metastasis mouse models to evaluate anti-melanoma effect of JP1 peptide. 18F-labeled JP1 (18F-NFP-JP1) was detected by Micro-PET assay to demonstrate drug biodistribution. Toxicity test in cynomolgus monkeys and pharmacokinetic studies in rats were done to assess the druggability. The expression of MEK1/2, NEDD4L, SP1 and Integrin αvβ3 were detected in vitro and vivo models. Results: The peptide JP1 with the best anticancer effect was obtained. Micro-PET assay showed that JP1 specifically targeting to melanoma cells in vivo. JP1 inhibited melanoma growth, metastasis, and prolonged the survival of mouse. JP1 reduced the dosage and toxicity in combination with DTIC in melanoma xenograft and allograft mouse models. Cynomolgus monkey toxicity test showed no observed adverse effect level (NOAEL) of JP1 was 150 mg/kg. Mechanistically, JP1 was shown to activate p-MEK1/2 and triggered SP1 ubiquitination in melanoma cells. NEDD4L, an E3 ubiquitin ligase, was activated by p-MEK1/2 and to ubiquitinate SP1 at K685 site, resulting in subsequent degradation. Conclusions: JP1 was developed as a novel peptide that indicated therapeutic roles on proliferation and metastasis of melanoma through the NEDD4L-SP1-Integrin αvβ3 signaling.
Focused Ultrasound Hyperthermia Augments Release of Glioma-derived Extracellular Vesicles with Differential Immunomodulatory Capacity
Authors: Natasha D. Sheybani, Alec J. Batts, Alexander S. Mathew, E. Andrew Thim, Richard J. Price
Journal: Theranostics (2020)

Background: Increasing evidence points to the critical role of extracellular vesicles (EVs) as molecular parcels that carry a diverse array of bioactive payloads for coordination of complex intracellular signaling.Focused ultrasound (FUS) hyperthermia is a technique for non-invasive, non-ionizing sublethal heating of cells in a near-instantaneous manner; while it has been shown to improve drug delivery and immunological recognition of tumors, its impact on EVs has not been explored to date.The goal of this study was to determine whether FUS impacts the release, proteomic profile, and immune-activating properties of tumor-derived EVs.Methods: Monolayered murine glioma cells were seeded within acoustically transparent cell culture chambers, and FUS hyperthermia was applied to achieve complete coverage of the chamber.Glioma-derived EVs (GEVs) were isolated for characterization by Nanoparticle Tracking Analysis, cryo-electron microscopy and mass spectrometry.An in vitro experimental setup was designed to further dissect the impact of GEVs on innate inflammation; immortalized murine dendritic cells (DCs) were pulsed with GEVs (either naïve or FUS hyperthermia-exposed) and assayed for production of IL-12p70, an important regulator of DC maturation and T helper cell polarization toward the interferon-γproducing type 1 phenotype.Results: We confirmed that FUS hyperthermia significantly augments GEV release (by ~46%) as well as shifts the proteomic profile of these GEVs.Such shifts included enrichment of common EV-associated markers, downregulation of markers associated with cancer progression and resistance and modulation of inflammation-associated markers.When DCs were pulsed with GEVs, we noted that naïve GEVs suppressed IL-12p70 production by DCs in a GEV dose-dependent manner.In contrast, GEVs from cells exposed to FUS hyperthermia promoted a significant upregulation in IL-12p70 production by DCs, consistent with a pro-inflammatory stimulus.Conclusion: FUS hyperthermia triggers release of proteomically distinct GEVs that are capable of facilitating an important component of innate immune activation, lending both to a potential mechanism by which FUS interfaces with the tumor-immune landscape and to a role for GEV-associated biomarkers in monitoring response to FUS.