tbuckley/cabot-search huggingface dataset:
Interactions between the gut microbiome and host gene regulation in cystic fibrosis
Authors: Gargi Dayama, Sambhawa Priya, David E. Niccum, Alexander Khoruts, Ran Blekhman
Journal: Genome Medicine (2020)

Abstract Background Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasians. It is caused by mutations in the CFTR gene, leading to poor hydration of mucus and impairment of the respiratory, digestive, and reproductive organ functions. Advancements in medical care have led to markedly increased longevity of patients with cystic fibrosis, but new complications have emerged, such as early onset of colorectal cancer. Although the pathogenesis of colorectal cancer in cystic fibrosis remains unclear, altered host-microbe interactions might play a critical role. To investigate this, we characterized changes in the microbiome and host gene expression in the colonic mucosa of cystic fibrosis patients relative to healthy controls, and identified host gene-microbiome interactions in the colon of cystic fibrosis patients. Methods We performed RNA-seq on colonic mucosa samples from cystic fibrosis patients and healthy controls to determine differentially expressed host genes. We also performed 16S rRNA sequencing to characterize the colonic mucosal microbiome and identify gut microbes that are differentially abundant between patients and healthy controls. Lastly, we modeled associations between relative abundances of specific bacterial taxa in the gut mucosa and host gene expression. Results We find that 1543 genes, including CFTR , show differential expression in the colon of cystic fibrosis patients compared to healthy controls. These genes are enriched with functions related to gastrointestinal and colorectal cancer, such as metastasis of colorectal cancer, tumor suppression, p53, and mTOR signaling pathways. In addition, patients with cystic fibrosis show decreased gut microbial diversity, decreased abundance of butyrate producing bacteria, such as Ruminococcaceae and Butyricimonas , and increased abundance of other taxa, such as Actinobacteria and Clostridium . An integrative analysis identified colorectal cancer-related genes, including LCN2 and DUOX2 , for which gene expression is correlated with the abundance of colorectal cancer-associated bacteria, such as Ruminococcaceae and Veillonella . Conclusions In addition to characterizing host gene expression and mucosal microbiome in cystic fibrosis patients, our study explored the potential role of host-microbe interactions in the etiology of colorectal cancer in cystic fibrosis. Our results provide biomarkers that may potentially serve as targets for stratifying risk of colorectal cancer in patients with cystic fibrosis.
Urgent inquiry is ordered into trust that subjected doctors to “witch hunt” to identify whistleblower
Authors: Clare Dyer
Journal: BMJ (2020)

The government has ordered NHS England and NHS Improvement to commission an urgent inquiry into a hospital trust accused of subjecting staff to a “witch hunt” to try to identify a whistleblower.1

Edward Argar, minister of state at the Department of Health and Social Care, has told the two organisations to ask an independent expert to carry out a rapid and independent review into the way West Suffolk NHS Trust handled the whistleblower case.

Doctors accused the trust of conducting a witch hunt, after managers asked staff for fingerprints and analysed handwriting samples in an attempt to find out who had written …
Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients
Authors: A. Algazi, S. Bhatia, S. Agarwala, M. Molina, K. Lewis, M. Faries, L. Fong, L.P. Levine, M. Franco, A. Oglesby, C. Ballesteros-Merino, C.B. Bifulco, B.A. Fox, D. Bannavong, R. Talia, E. Browning, M.H. Le, R.H. Pierce, S. Gargosky, K.K. Tsai, C. Twitty, A.I. Daud
Journal: Annals of Oncology (2020)

Interleukin 12 (IL-12) is a pivotal regulator of innate and adaptive immunity. We conducted a prospective open-label, phase II clinical trial of electroporated plasmid IL-12 in advanced melanoma patients (NCT01502293).Patients with stage III/IV melanoma were treated intratumorally with plasmid encoding IL-12 (tavokinogene telseplasmid; tavo), 0.5 mg/ml followed by electroporation (six pulses, 1500 V/cm) on days 1, 5, and 8 every 90 days in the main study and additional patients were treated in two alternative schedule exploration cohorts. Correlative analyses for programmed death-ligand 1 (PD-L1), flow cytometry to assess changes in immune cell subsets, and analysis of immune-related gene expression were carried out on pre- and post-treatment samples from study patients, as well as from additional patients treated during exploration of additional dosing schedules beyond the pre-specified protocol dosing schedule. Response was measured by study-specific criteria to maximize detection of latent and potentially transient immune responses in patients with multiple skin lesions and toxicities were graded by the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).The objective overall response rate was 35.7% in the main study (29.8% in all cohorts), with a complete response rate of 17.9% (10.6% in all cohorts). The median progression-free survival in the main study was 3.7 months while the median overall survival was not reached at a median follow up of 29.7 months. A total of 46% of patients in all cohorts with uninjected lesions experienced regression of at least one of these lesions and 25% had a net regression of all untreated lesions. Transcriptomic and immunohistochemistry analysis showed that immune activation and co-stimulatory transcripts were up-regulated but there was also increased adaptive immune resistance.Intratumoral Tavo was well tolerated and led to systemic immune responses in advanced melanoma patients. While tumor regression and increased immune infiltration were observed in treated as well as untreated/distal lesions, adaptive immune resistance limited the response.
Next of Kin
Authors: Anthony Khoo
Journal: Annals of Internal Medicine (2020)

Ad Libitum4 February 2020Next of KinAnthony Khoo, MBBS, SpecCertCR(Neuro)Anthony Khoo, MBBS, SpecCertCR(Neuro)Royal Adelaide Hospital, Adelaide, South Australia, Australia (A.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-2094 Audio Reading - “Next of Kin” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Next of Kin” by Anthony Khoo, MBBS, SpecCertCR(Neuro) Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail They ask me what you'd have wantedAs if we spent time talking of dyingRather than reveling in life's joy-filled rideCrafting constellations in the sky.It never occurredThat one day you'd complain ofSoapy eyes and joke of a hangoverGotten without trying,And the next be lying there bereft—Eyes unseeing, heartbeat replacedBy the metronome murmur ofLife distilled.Whispers of guilt and selfishQuestions of how, why, when:I should know your wishes but don't—We had always countedOn having a lifetimeTo understand each other. Author, Article, and Disclosure InformationAffiliations: Royal Adelaide Hospital, Adelaide, South Australia, Australia (A.K.)Current Author Address: Anthony Khoo, MBBS, SpecCertCR(Neuro) National Hospital for Neurology & Neurosurgery, Queen Square, London, United Kingdom; e-mail, anthony.[email protected]gov.au. PreviousarticleNextarticle Advertisement Audio Reading - “Next of Kin” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Next of Kin” by Anthony Khoo, MBBS, SpecCertCR(Neuro) Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 4 February 2020Volume 172, Issue 3Page: 219KeywordsDeceptionNeurologyNeurosurgery ePublished: 4 February 2020 Issue Published: 4 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Comprehensive characterization of the phosphoproteome of gastric cancer from endoscopic biopsy specimens
Authors: Yuichi Abe, Hidekazu Hirano, Hirokazu Shoji, Asa Tada, Junko Isoyama, Akemi Kakudo, Daigo Gunji, Kazufumi Honda, Narikazu Boku, Jun Adachi, Takeshi Tomonaga
Journal: Theranostics (2020)

Rationale: Cancer phosphoproteomics can provide insights regarding kinases that can be targeted for therapeutic applications.Monitoring the phosphoproteomics in cancer is expected to play a key role in optimizing treatments with kinase inhibitors.Clinical phosphoproteomics in surgical tissues and patient-derived models has been studied intensively.However, the reported data may not accurately reflect the phosphosignaling status in patients due to the effect of ischemia occurring during surgery or changes in the characteristics of cancer cells when establishing the models.In contrast, endoscopic biopsies have an advantage for clinical phosphoproteomics because they can be rapidly cryo-preserved.We aimed to develop a highly sensitive method for phosphoproteomics in endoscopic biopsies of gastric cancer.Methods: Three tumor biopsies and three normal gastric biopsies were obtained by endoscopy at one time, and subjected to our optimized phosphoproteomics.Phosphopeptides were enriched with an immobilized metal affinity chromatography, and labeled with Tandem Mass Tag reagent.Quantified phosphosites were compared between the pairs of tumor/normal biopsies within same patient.Cancer-specific activated pathways and kinases were identified by pathway enrichment analysis and kinase-substrate enrichment analysis.Results: Our protocol enabled the identification of more than 10,000 class 1 phosphosites from endoscopic biopsies.A comparison between samples from cancer tissue and normal mucosa demonstrated differences in the phosphosignaling, including biomarkers of response to DNA damage.Finally, cancer-specific activation of DNA damage response signaling was validated by additional phosphoproteomics of other patients and western blotting of gastric cancer/normal cells.Conclusion: In summary, our pioneering approach will facilitate more accurate clinical phosphoproteomics in endoscopic biopsies, which can be applied to monitor the activities of therapeutic kinases and, ultimately, can be a useful tool to precision medicine.
Safety and Efficacy of Ledipasvir/Sofosbuvir without on-Treatment Laboratory Monitoring in HCV-Infected Rwandans: The Shared 2 Study
Authors: P Grant, J Kabahizi, A Mbituyumuremyi, J I Van Nuil, C Mukabatsinda, M J Damascene, F Shumbusho, C Ntirenganya, S Nsanzimana, N Gupta
Journal: Hepatology (2018)
Treatment of Severe Malaria in the United States
Authors: Chandy C. John
Journal: Annals of Internal Medicine (2020)

Letters4 February 2020Treatment of Severe Malaria in the United StatesChandy C. John, MD, MSChandy C. John, MD, MSAmerican Society of Tropical Medicine and Hygiene, Washington, DC (C.C.J.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0674 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The American Society of Tropical Medicine and Hygiene (ASTMH) shares Krey and Travassos' (1) concerns about treatment of severe malaria in the United States. Since Eli Lilly and Company announced that they would discontinue production of quinidine, the ASTMH has been discussing with the Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration (FDA) how together we can best ensure that patients with severe malaria in the United States have rapid access to highly effective treatment. The CDC and FDA have been working together to address this issue and facilitate the availability of ...References1. Krey RA, Travassos MA. Severe malaria treatment in the United States at the precipice. Ann Intern Med. 2019;171:362-3. [PMID: 31426092]. doi:10.7326/M19-1144 LinkGoogle Scholar2. La Jolla Pharmaceutical. Research pipeline: LJPC-0118. 2018. Accessed at http://lajollapharmaceutical.com/2019/07/la-jolla-pharmaceutical-company-receives-orphan-designation-from-fda-for-ljpc-0118-artesunate-for-the-treatment-of-malaria on 19 December 2019. Google Scholar3. Centers for Disease Control and Prevention. Intravenous artesunate for treatment of severe malaria in the United States. Updated 11 December 2019. Accessed at www.cdc.gov/malaria/diagnosis_treatment/artesunate.html on 19 December 2019. Google Scholar Author, Article, and Disclosure InformationAffiliations: American Society of Tropical Medicine and Hygiene, Washington, DC (C.C.J.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0674. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSevere Malaria Treatment in the United States at the Precipice Rebecca A. Krey and Mark A. Travassos Treatment of Severe Malaria in the United States Emilia M. Sordillo , Melissa Gitman , Michael D. Nowak , and Alberto E. Paniz Mondolfi Metrics 4 February 2020Volume 172, Issue 3Page: 224-225KeywordsArtesunateConflicts of interestDisclosureDrugsFood and Drug AdministrationHygieneMalariaNew drug applicationsQuinineTreatment guidelines ePublished: 4 February 2020 Issue Published: 4 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
開放型洗浄用カテーテルを適用した部位の新規な組織学的情報-60の焼灼部位における組織学的検討 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Igawa Osamu, Adachi Masamitsu, Yano Akio, Miake Junichiro, Inoue Yoshiaki, Ogura Kazuyoshi, Katoh Mamoru, Iitsuka Kazuhiko, Kondo Takehito, Hisatome Ichiro
Journal: Circulation (2010)
A Phase II Study (PERSEUS) of Two Doses of EMD 525797 (DI17E6) in Patients (PTS) with Asymptomatic or Mildly Symptomatic Metastatic Castrate-Resistant Prostate Cancer (MCRPC)
Authors: K. Miller, M. Hussain, G. Mordenti, H. Lannert
Journal: Annals of Oncology (2012)
Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map
Authors: Jianhong Zhu, Xiaoxia Yu, Yayuan Zheng, Jianfang Li, Yong Wang, Yin Lin, Zhichao He, Wenxia Zhao, Chuxiong Chen, Kaifeng Qiu, Junyan Wu
Journal: The Lancet Diabetes & Endocrinology (2020)
胃腸内悪性腫瘍のその場手術,実時間識別のための新法としての急速蒸発イオン化質量分析(REIMS)
Authors: Sasi Szabo L, Balog J, Szaniszlo T, Szalay D, Godorhazy L, Toth M, Damjanovich L, Takacs Z
Journal: Annals of Oncology (2010)
Predicting Response to IDH1/IDH2 Inhibitors Beyond IDH Mutations Using a Computational Model and Its Validation: A Beat AML Project Study
Authors: Leylah M. Drusbosky, Robinson Vidva, Saji Gera, Arko Das, Krishna K Tiwari, Vishwas Joseph, Subrat Mohapatra, Neelesh Lunkad, Taher Abbasi, Shireen Vali, Cristina E. Tognon, Stephen E Kurtz, Jeffrey W. Tyner, Brian J. Druker, Christopher R. Cogle
Journal: Blood (2017)
Mitochondrial Protein UQCRC1 is Oncogenic and a Potential Therapeutic Target for Pancreatic Cancer
Authors: Qing Wang, Mengge Li, Yu Gan, Shuheng Jiang, Jie Qiao, Wei Zhang, Yingchao Fan, Yuling Shen, Yanfang Song, Zihong Meng, Ming Yao, Jianren Gu, Zhigang Zhang, Hong Tu
Journal: Theranostics (2020)

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a malignant disease with a poor prognosis. One prominent aspect of PDAC that contributes to its aggressive behavior is its altered cellular metabolism. The aim of this study was to characterize the oncogenic effects of ubiquinol-cytochrome c reductase core protein I (UQCRC1), a key component of mitochondrial complex III, in PDAC development and to assess its potential as a therapeutic target for PDAC. Experimental Design: The expression of UQCRC1 in human PDAC tissues and p48-Cre/p53Flox/WT/LSL-KrasG12D (KPC) mouse pancreatic intraepithelial neoplasias (PanINs) was determined by immunohistochemistry. The role of UQCRC1 in promoting PDAC growth was evaluated in vitro in PANC-1 and CFPAC-1 cells and in vivo in transplanted mouse models of PDAC. Extracellular flux and RNA-Seq analyses were applied to investigate the mechanism of UQCRC1 in the regulation of mitochondrial metabolism and PDAC cell growth. The therapeutic potential of UQCRC1 in PDAC was assessed by knockdown of UQCRC1 using an RNA interference approach. Results: UQCRC1 expression showed a gradual increase during the progression from PanIN stages to PDAC in KPC mice. Elevated expression of UQCRC1 was observed in 72.3% of PDAC cases and was correlated with poor prognosis of the disease. UQCRC1 promoted PDAC cell growth in both in vitro experiments and in vivo subcutaneous and orthotopic mouse models. UQCRC1 overexpression resulted in increased mitochondrial oxidative phosphorylation (OXPHOS) and ATP production. The overproduced ATP was released into the extracellular space via the pannexin 1 channel and then functioned as an autocrine or paracrine agent to promote cell proliferation through the ATP/P2Y2-RTK/AKT axis. UQCRC1 knockdown or ATP release blockage could effectively inhibit PDAC growth. Conclusion: UQCRC1 has a protumor function and may serve as a potential prognostic marker and therapeutic target for PDAC.
Repair of Retinal Degeneration following Ex Vivo Minicircle DNA Gene Therapy and Transplantation of Corrected Photoreceptor Progenitors
Authors: Alona O. Barnea-Cramer, Mandeep Singh, Dominik Fischer, Samantha De Silva, Michelle E. McClements, Alun R. Barnard, Robert E. MacLaren
Journal: Molecular Therapy (2020)
Nanococktail Based on AIEgens and Semiconducting Polymers: A Single Laser Excited Image-Guided Dual Photothermal Therapy
Authors: Zi Long, Jun Dai, Qinyu Hu, Quan Wang, Shijie Zhen, Zujin Zhao, Zitong Liu, Jing-Jing Hu, Xiaoding Lou, Fan Xia
Journal: Theranostics (2020)

Semiconducting polymers (SPs)-based dual photothermal therapy (PTT) obtained better therapeutic effect than single PTT due to its higher photothermal conversion efficiency. However, most dual PTT need to use two lasers for heat generation, which brings about inconvenience and limitation to the experimental operations. Herein, we report the development of "nanococktail" nanomaterials (DTPR) with 808 nm-activated image-guided dual photothermal properties for optimized cancer therapy. Methods: In this work, we co-encapsulated AIEgens (TPA-BDTO, T) and SPs (PDPPP, P) by using maleimide terminated amphiphilic polymer (DSPE-PEG2000-Mal, D), then further conjugated the targeting ligands (RGD, R) through "click" reaction. Finally, such dual PTT nanococktail (termed as DTPR) was constructed. Results: Once DTPR upon irradiation with 808 nm laser, near-infrared fluorescence from T could be partially converted into thermal energy through fluorescence resonance energy transfer (FRET) between T and P, coupling with the original heat energy generated by the photothermal agent P itself, thus resulting in image-guided dual PTT. The photothermal conversion efficiency of DTPR reached 60.3% (dual PTT), much higher as compared to its inherent photothermal effect of only 31.5% (single PTT), which was further proved by the more severe photothermal ablation in vitro and in vivo upon 808 nm laser irradiation. Conclusion: Such smart "nanococktail" nanomaterials could be recognized as a promising photothermal nanotheranostics for image-guided cancer treatment.
Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells
Authors: Motoshi Suzuki, Ke Cao, Seiichi Kato, Yuji Komizu, Naoki Mizutani, Kouji Tanaka, Chinatsu Arima, Mei Chee Tai, Kiyoshi Yanagisawa, Norie Togawa, Takahiro Shiraishi, Noriyasu Usami, Tetsuo Taniguchi, Takayuki Fukui, Kohei Yokoi, Keiko Wakahara, Yoshinori Hasegawa, Yukiko Mizutani, Yasuyuki Igarashi, Jin-ichi Inokuchi, Soichiro Iwaki, Satoshi Fujii, Akira Satou, Yoko Matsumoto, Ryuichi Ueoka, Keiko Tamiya-Koizumi, Takashi Murate, Mitsuhiro Nakamura, Mamoru Kyogashima, Takashi Takahashi
Journal: Journal of Clinical Investigation (2019)

The corresponding author recently notified the JCI that the patient data presented in Figure 1B were not correct.Analysis of the correct patient data set does not show a significant difference in CERS6 expression in human lung adenocarcinomas with positive invasive growth (definite) compared with those with negligible invasive growth or without invasive growth (focal/none).The Editors have requested an institutional investigation into this matter, and we will inform our readers of the outcome when the investigation is complete.
Abstract 10675: Anticoagulation Choice After Cardiac Surgery: Are Novel Oral Anticoagulants Safe?
Authors: Robert Leatherby, Vincenzo Caruso, Marina Barron, Harvinder Bhamra, Arvind Singh
Journal: Circulation (2018)

Introduction: Novel oral anticoagulants (NOACs) have been increasingly used in place of warfarin, for non-valvular atrial fibrillation and venous thromboembolism. Their use for post cardiac surgery...
Liver transplantation for hepatitis C patients in the era of direct-acting antiviral treatment: A retrospective cohort study
Authors: Adeel S. Khan, Nathaniel Adams, Neeta Vachharajani, LeighAnne Dageforde, Jason Wellen, Surendra Shenoy, Jeffrey S. Crippin, Majella B. Doyle, William C. Chapman
Journal: International Journal of Surgery (2020)