tbuckley/cabot-search huggingface dataset:
Abstract IA02: Host microbiome interactions in health and disease
Authors: Eran Elinav
Journal: Cancer Research (2020)

Abstract The mammalian intestine contains trillions of microbes, a community that is dominated by members of the domain Bacteria but also includes members of Archaea, Eukarya, and viruses. The vast repertoire of this microbiome functions in ways that benefit the host. The mucosal immune system coevolves with the microbiota beginning at birth, acquiring the capacity to tolerate components of the community while maintaining the capacity to respond to invading pathogens. The gut microbiota is shaped and regulated by multiple factors including our genomic composition, the local intestinal niche, and multiple environmental factors including our nutritional repertoire and biogeographic location. Moreover, it has been recently highlighted that dysregulation of these genetic or environmental factors leads to aberrant host-microbiome interactions, ultimately predisposing to pathologies ranging from chronic inflammation, obesity, the metabolic syndrome, and even cancer. We have identified various possible mechanisms participating in the reciprocal regulation between the host and the intestinal microbial ecosystem and demonstrate that disruption of these factors, in mice and humans, lead to dysbiosis and susceptibility to common multifactorial disease. Understanding the molecular basis of host-microbiome interactions may lead to development of new microbiome-targeting treatments. Citation Format: Eran Elinav. Host microbiome interactions in health and disease [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr IA02.
Ensuring gender and social equity in health: an analysis of Nigeria's Social Health Insurance Scheme and Basic Health Care Provision Fund
Authors: Iboro Nelson
Journal: The Lancet Global Health (2020)

BackgroundIt is expected that a well-functioning, pre-paid health financing system that aims to move a country towards universal health coverage (UHC) will be equitable and gender-balanced. However, this feature is not automatic; much depends on the policy environment, including legal frameworks, implementation design, and management of the health financing scheme. To move towards UHC, Nigeria is implementing two key reforms: the Basic Health Care Provision Fund (BHCPF) and Social Health Insurance Scheme (SHIS). The BHCPF was created under the 2014 National Health Act to provide a basic package of health care to all Nigerians. Here, I report on a review of policy and legal frameworks at the policy formulation stage of the reforms, with a focus on gender and equity.MethodsI used findings from Abia state gender and equity analysis conducted to identify gender-related and equity-related barriers and opportunities in the design and implementation of the BHCPF and SHIS. I undertook project monitoring of the early-stage policy formulation phase of the reforms across functional areas of governance, revenue generation, risk pooling, enrolment strategies, and health benefit package.FindingsInitial assessment results showed several service delivery barriers to gender parity in staff (men in leadership and women in service delivery positions), low level of male engagement, lack of youth-friendly health services, unavailability of gender-based violence services, and low level of knowledge and understanding of gender and equity issues among key state-level implementing institutions. But early intervention results showed that progress has been made in the inclusion of men and women in the governance of the scheme, the establishment of an equity fund to subsidise those who are too poor to pay and progressive financial contributions into the scheme based on the ability to pay, and a central pooling of risk. Furthermore, a sustainable effort towards bridging the knowledge gap of key health-care professionals and policymakers in gender and equity issues in health has been instituted by national government implementing agencies with the mainstreaming of gender issues in the BHCPF manual and followed through with trainings of community representatives and health service providers.InterpretationUHC is hinged on gender and social equity in access to health-care services. Efforts to achieve this must begin at the policy formulation stage and carry through to policy implementation. However, UHC does involve political trade-offs and the degree to which implementation practice will conform to policy directions already set out is yet to be seen.FundingUSAID through Health Policy Plus (HP+) implemented by Palladium.
Post-Marketing Surveillance with a Biosimilar of Rituximab (Novex®) in Argentina
Authors: Gustavo Milone, Maria Penna, Francisco Fernández, Eduardo Spitzer, Susana Millan, Pablo De Caso, Luis Beligoy, Daniel Argentieri, Fernando Pagani, Martín Alonso, Guillermo Streich, Nicolas Matias Kurgansky, María del Carmen Ríos Part, Martin Ignacio Brandt, Susana Mari, Roberto Gomez
Journal: Blood (2017)
Abstract A37: Restoration of oral microbiota dysbiosis in head and neck squamous cell carcinoma after surgery
Authors: Jason Y.K. Chan, Bowie Wong, Eddy W.Y. Wong, Paul Chan, Zigui Chen
Journal: Cancer Research (2020)

Abstract Introduction: Increasing reports have indicated the association between oral microbiota dysbiosis and HNSCC, while it is unclear how the oral microbiota responds to surgery. In this study, we longitudinally collected oral rinse samples from patients with HNSCC right before and after surgery at 1, 3, and 6 months, in order to elucidate the dynamic changes of oral microbiota upon treatment. Materials and Methods: A total of 91 HNSCC patients were recruited, with 20 having been collected for a longitudinal set of samples for 6 months. Meanwhile, 93 healthy subjects were selected as controls. The microbiota from oral rinses was classified by 16S rRNA gene V3-V4 amplicon sequencing and QIIME2 algorithm. Results: Although there was no obvious difference in the alpha- and beta-diversities of oral microbiota between HNSCC patients and healthy subjects, we observed a number of bacterial genera significantly discriminating cases from controls. Further analysis of oral microbiota in HNSCC between pre- and post-surgery found that the community diversity was dramatically depressed at 1 month after surgery (p=0.001), but this was able to restore to the normal level from 3 months with no significant difference between 3 months and preop (p&amp;gt;0.05). The relative abundance of the commensal bacteria, including Streptococcus, Rothia, Corynebacterium, and Granulicatella, consistently increased along 1-, 3-, and 6-month recovery, while the periodontal pathogens Fusobacterium and Peptostreptococcus decreased. Conclusions: The findings indicate that a taxonomically defined microbial consortium is associated with HNSCC and the oral microbiota is able to restore to the community, trending to healthy status after surgery. Citation Format: Jason Y.K. Chan, Bowie Wong, Eddy W.Y. Wong, Paul Chan, Zigui Chen. Restoration of oral microbiota dysbiosis in head and neck squamous cell carcinoma after surgery [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A37.
Macrophages use a bet-hedging strategy for antimicrobial activity in phagolysosomal acidification
Authors: Quigly Dragotakes, Kaitlin M. Stouffer, Man Shun Fu, Yehonatan Sella, Christine Youn, Olivia Insun Yoon, Carlos M. De Leon-Rodriguez, Joudeh B. Freij, Aviv Bergman, Arturo Casadevall
Journal: Journal of Clinical Investigation (2020)

Microbial ingestion by a macrophage results in the formation of an acidic phagolysosome but the host cell has no information on the pH susceptibility of the ingested organism. This poses a problem for the macrophage and raises the fundamental question of how the phagocytic cell optimizes the acidification process to prevail. We analyzed the dynamical distribution of phagolysosomal pH in murine and human macrophages that had ingested live or dead Cryptococcus neoformans cells, or inert beads. Phagolysosomal acidification produced a range of pH values that approximated normal distributions, but these differed from normality depending on ingested particle type. Analysis of the increments of pH reduction revealed no forbidden ordinal patterns, implying that the phagosomal acidification process was a stochastic dynamical system. Using simulation modeling, we determined that by stochastically acidifying a phagolysosome to a pH within the observed distribution, macrophages sacrificed a small amount of overall fitness to gain the benefit of reduced variation in fitness. Hence, chance in the final phagosomal pH introduces unpredictability to the outcome of the macrophage-microbe, which implies a bet-hedging strategy that benefits the macrophage. While bet hedging is common in biological systems at the organism level, our results show its use at the organelle and cellular level.
Improvement in sperm quality and spermatogenesis following faecal microbiota transplantation from alginate oligosaccharide dosed mice
Authors: Pengfei Zhang, Yanni Feng, Lan Li, Wei Ge, Shuai Yu, Yanan Hao, Wei Shen, Xiao Han, Dongxue Ma, Shen Yin, Yu Tian, Lingjiang Min, Zhongyi Sun, Qingyuan Sun, Hongfu Zhang, Yong Zhao
Journal: Gut (2020)

Very recent publications in Gut and elsewhere1 2 suggest that gut microbiota affects fertility. The application of faecal microbiota transplantation (FMT) to modify fertility is an emerging novel area of interest.3 FMT from women with polycystic ovary syndrome (PCOS) leads to the disruption of ovarian function and a decrease in fertility which indicates that modification of gut microbiota may be a valuable approach in the management of PCOS.2 FMT of gut microbes, that developed under a high-fat diet, into mice on a normal diet leads to the disruption of spermatogenesis and a reduction of sperm motility,1 which highlights that restoring gut microbiota may be a means of improving disturbed male infertility caused by environmental factors.1 However, to date, there are no reports that address improvements of fertility following FMT. In a recent study,4 we found that busulfan damages spermatogenesis and sperm quality, and disturbs gut microbiota as found in many other studies.5 6 Alginate oligosaccharides (AOS), a natural product with many benefits, rescues busulfan disrupted spermatogenesis by supporting gut microbiota through an increase in ‘beneficial’ bacteria4 such as Bacteroidales and Lactobacillaceae and a decrease in ‘harmful’ bacteria, such as Desulfovibrionaceae .7 Gut microbiota from AOS dosed animals may improve spermatogenesis through benefit to the recipients gut microbes.

To test this hypothesis, we set out to explore the beneficial improvement of sperm quality and …
Effect of antithrombotic prophylaxis (AP) on thrombosis-related complications and mortality in cancer patiets (pts) carrying a central venous devices (CVD)
Authors: C. Cimminiello, L. Isa, C. Vergani, L. Catena, M. Tomirotti, M. Visini, A. Alatri, A. De Paoli, G. Aondio, M. Verga
Journal: Journal of Clinical Oncology (2006)

8596 Background: Recent guidelines do recommend against antithrombotic prophylaxis in cancer pts having placed a central line to prevent catheter-related thrombosis. Methods: The present study, which was an observational and prospective one, involved 18 centres in Lombardia (Italy) to assess the management of CVD in pts affected by solid or haematological tumors to evaluate in the current practice the attitude to employ the AP and the clinical evolution as regard to the occurrence of catheter-related and systemic venous thromboses and survival. Results: 1,418 pts entered the study and were followed-up during a median period of 6 months for a total of 24,182 patients-months. Subjects receiving a continuous AP, mainly with mini-warfarin according to Levine, were 439 (31.6%): they were significantly older, with a more frequent history of Venous Thromboembolism (VTE), and with a cancer in a more advanced stage. A trend in favour of those not treated with AP was noticed as regard to catheter-related thrombosis, 3.2 % vs 1.5%, (p=0.058). The median time to the first catheter-related complication was 120 days. The frequency of systemic VTE including deep and superficial vein thromboses in sites other than the venous axis where the CVD had been placed and pulmonary embolism was significantly lower in patients not receiving AP: 1.8% vs 12.4%; OR 0.12 (95% CI: 0.07–0.22; p=.001). Mortality of pts avoiding AP was also significantly lower (23.7% vs 38%), OR 0.5 (95% CI: 0.4–0.6; p=.0001) In the multiple logistic regression analysis only advanced cancer and to be given AP were significantly associated with mortality. No major bleeding was recorded among pts assigned to receive continuous AP. Conclusions: The results of the present study do confirm the current drugs and schedules for AP are unable to prevent not only catheter-related thrombosis but also systemic VTE. Mortality does appear lower in those not treated with AP and the difference still exists after adjustment for age, history of previous VTE and to be given chemotherapy. The attitude to give a continuous AP to pts with central lines presenting with more severe disease or at increased thromboembolic risk seems to be ineffective if not dangerous. No significant financial relationships to disclose.
Value of CMR and PET in Predicting Ventricular Arrhythmias in Ischemic Cardiomyopathy Patients Eligible for ICD
Authors: Mischa T. Rijnierse, Anne-Lotte C.J. van der Lingen, Stefan de Haan, Marthe A.J. Becker, Hendrik J. Harms, Marc C. Huisman, Adriaan A. Lammertsma, Peter M. van de Ven, Albert C. van Rossum, Paul Knaapen, Cornelis P. Allaart
Journal: JACC. Cardiovascular imaging (2020)
Covid-19: doctors are warned not to go public about PPE shortages
Authors: Clare Dyer
Journal: BMJ (2020)

As hospitals run out of personal protective equipment (PPE) for frontline healthcare staff fighting the covid-19 pandemic, doctors report that trusts and NHS England are clamping down on their attempts to go public about the situation in mainstream news outlets or on social media.

After some trusts warned that they might have no fluid repellent gowns left, NHS England said staff might need to use alternatives, such as plastic aprons with coveralls.1

More than 50 healthcare workers have died from covid-19 and the lobbying group Doctors’ Association UK (DAUK) has set up an app, www.nhsppe.com, for doctors anonymously to report their concerns about shortages of gowns and masks to protect them from infection.

But many are also reporting attempts to stop them speaking to the media about their fears. One consultant wrote of “a general email from the trust, then personal advice, that social media is being monitored and to be careful.”

A junior doctor mentioned “an email saying we should not be posting ‘inappropriate’ social media comments or posts regarding the state of PPE.” Another wrote, “We are emailed daily to avoid speaking to anyone in the press or social …
Bosutinib in Newly Diagnosed Chronic Myeloid Leukemia (CML): Gastrointestinal (GI), Liver, and Hematological Safety Characterization in the BFORE Trial
Authors: Michael J. Mauro, Carlo Gambacorti-Passerini, Michael W. Deininger, Charles Chuah, Dong-Wook Kim, Iryna Dyagil, Natalia Glushko, Dragana Milojkovic, Philipp D. le Coutre, Valentín García Gutiérrez, Laurence Reilly, Allison Jeynes-Ellis, Rocco J. Crescenzo, Roberto Uehara, Eric Leip, Liza DeAnnuntis, Nathalie Bardy-Bouxin, Andreas Hochhaus, Timothy H. Brümmendorf, Jorge E. Cortes
Journal: Blood (2017)
Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics
Authors: Teresa G Krieger, Stephan M Tirier, Jeongbin Park, Katharina Jechow, Tanja Eisemann, Heike Peterziel, Peter Angel, Roland Eils, Christian Conrad
Journal: Neuro-Oncology (2020)

Abstract Background Glioblastoma (GBM) consists of devastating neoplasms with high invasive capacity, which have been difficult to study in vitro in a human-derived model system. Therapeutic progress is also limited by cellular heterogeneity within and between tumors, among other factors such as therapy resistance. To address these challenges, we present an experimental model using human cerebral organoids as a scaffold for patient-derived GBM cell invasion. Methods This study combined tissue clearing and confocal microscopy with single-cell RNA sequencing of GBM cells before and after co-culture with organoid cells. Results We show that tumor cells within organoids extend a network of long microtubes, recapitulating the in vivo behavior of GBM. Transcriptional changes implicated in the invasion process are coherent across patient samples, indicating that GBM cells reactively upregulate genes required for their dispersion. Potential interactions between GBM and organoid cells identified by an in silico receptor–ligand pairing screen suggest functional therapeutic targets. Conclusions Taken together, our model has proven useful for studying GBM invasion and transcriptional heterogeneity in vitro, with applications for both pharmacological screens and patient-specific treatment selection on a time scale amenable to clinical practice.
Symptomatic COVID-19 in Eye Professionals in Wuhan, China
Authors: Chunyan Qiao, Hui Zhang, Mingguang He, Guishuang Ying, Changzheng Chen, Yanping Song, Julius Oatts, Zhonghua Liu, Yiqiao Xing, Zefeng Xiao, Min Ke, Ya Ye, Xiaoniao Chen, Jihong Luo, Ying Han, Ningli Wang
Journal: Ophthalmology (2020)
A combined approach of convection-enhanced delivery of peptide nanofiber reservoir to prolong local DM1 retention for diffuse intrinsic pontine glioma treatment
Authors: Vanessa Bellat, Yago Alcaina, Ching-Hsuan Tung, Richard Ting, Adam O Michel, Mark Souweidane, Benedict Law
Journal: Neuro-Oncology (2020)

Abstract Background Diffuse intrinsic pontine glioma (DIPG) is a highly lethal malignancy that occurs predominantly in children. DIPG is inoperable and post-diagnosis survival is less than 1 year, as conventional chemotherapy is ineffective. The intact blood–brain barrier (BBB) blocks drugs from entering the brain. Convection-enhanced delivery (CED) is a direct infusion technique delivering drugs to the brain, but it suffers from rapid drug clearance. Our goal is to overcome the delivery barrier via CED and maintain a therapeutic concentration at the glioma site with a payload-adjustable peptide nanofiber precursor (NFP) that displays a prolonged retention property as a drug carrier. Methods The post-CED retention of 89Zr-NFP was determined in real time using PET/CT imaging. Emtansine (DM1), a microtubule inhibitor, was conjugated to NFP. The cytotoxicity of the resulting DM1-NFP was tested against patient-derived DIPG cell lines. The therapeutic efficacy was evaluated in animals bearing orthotopic DIPG, according to glioma growth (measured using bioluminescence imaging) and the long-term survival. Results DM1-NFP demonstrated potency against multiple glioma cell lines. The half-maximal inhibitory concentration values were in the nanomolar range. NFP remained at the infusion site (pons) for weeks, with a clearance half-life of 60 days. DM1-NFP inhibited glioma progression in animals, and offered a survival benefit (median survival of 62 days) compared with the untreated controls (28 days) and DM1-treated animal group (26 days). Conclusions CED, in combination with DM1-NFP, complementarily functions to bypass the BBB, prolong drug retention at the fusion site, and maintain an effective therapeutic effect against DIPG to improve treatment outcome.
Inpatient Use of Ambulatory Telemetry Monitors for COVID-19 Patients Treated With Hydroxychloroquine and/or Azithromycin
Authors: David Chang, Moussa Saleh, James Gabriels, Haisam Ismail, Bruce Goldner, Jonathan Willner, Stuart Beldner, Raman Mitra, Roy John, Laurence M. Epstein
Journal: Journal of the American College of Cardiology (2020)
Universal weekly testing as the UK COVID-19 lockdown exit strategy
Authors: Julian Peto, Nisreen A Alwan, Keith M Godfrey, Rochelle A Burgess, David J Hunter, Elio Riboli, Paul Romer, Iain Buchan, Tim Colbourn, Céire Costelloe, George Davey Smith, Paul Elliott, Majid Ezzati, Ruth Gilbert, Mark S Gilthorpe, Robbie Foy, Richard Houlston, Hazel Inskip, Deborah A Lawlor, Adrian R Martineau, Nuala McGrath, David McCoy, Martin Mckee, Klim McPherson, Miriam Orcutt, Bharat Pankhania, Neil Pearce, Richard Peto, Andrew Phillips, Jugnoo Rahi, Paul Roderick, Sonia Saxena, Ann Wilson, Guiqing Lily Yao
Journal: The Lancet (2020)
Risk of target non-attainment in obese compared to non-obese patients in calculated linezolid therapy
Authors: L. Ehmann, P. Simon, D. Busse, D. Petroff, C. Dorn, W. Huisinga, A. Dietrich, M. Zeitlinger, H. Wrigge, C. Kloft
Journal: Clinical Microbiology and Infection (2020)
Abstract A38: RNA-seq analysis identified candidate pathogens for prostate cancer
Authors: Shingo Ashida, Chiaki Kawada, Masanori Daibata, Keiji Inoue, Hidewaki Nakagawa
Journal: Cancer Research (2020)

Abstract There is an abundance of evidence that chronic inflammation is linked to prostate cancer (PC), and pathogen infection is considered to be one of the possible causes for PC. Prostate infections by bacteria or viruses have been widely investigated. However, most of these studies have showed conflicting and controversial results. Most studies have focused on the PCR-based targeted detection of bacteria or viruses, and pathogen for PC remains to be found. To identify pathogen for PC, we investigated the transcriptomes of human prostate samples using whole-genome next-generation sequencing. The prostate specimens obtained by radical prostatectomy from 20 PC patients were sliced and divided into four sections. High-quality RNAs were extracted from the sections including PC. RNA-seq libraries were constructed according to the Illumina protocol and next-generation sequenced on a HiSeq 2000 instrument. To explore the potential of other pathogens being associated with PC, we performed de novo assembly of unmapped reads from the RNA-seq data from 20 PC samples. RNA-seq analysis identified four bacteria as candidate pathogens, which included Cutibacterium acnes, uncultured Chroococcidiopsis, Micrococcus luteus, and Moraxella osloensis. Among these candidate pathogens, Cutibacterium acnes was detected in 19 of 20 PC tissue samples by immunohistochemistry. We also performed PCR to detect other candidate pathogens (uncultured Chroococcidiopsis, Micrococcus luteus, and Moraxella osloensis) in PC samples for validation. Our findings provide further evidence of Cutibacterium acnes infections in human PCs as a promising pathogen for PC, and suggest that uncultured Chroococcidiopsis, Micrococcus luteus, and Moraxella osloensis could be novel candidate pathogens for PC. Further research is required and ongoing to clarify the molecular mechanisms underlying bacterial pathogenesis of PC. Citation Format: Shingo Ashida, Chiaki Kawada, Masanori Daibata, Keiji Inoue, Hidewaki Nakagawa. RNA-seq analysis identified candidate pathogens for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A38.