tbuckley/cabot-search huggingface dataset:
Upregulation of neuronal PGC-1α ameliorates cognitive impairment induced by chronic cerebral hypoperfusion
Authors: Bin Han, Wei Jiang, Haijie Liu, Junjie Wang, Kai Zheng, Pan Cui, Yan Feng, Chun Dang, Yali Bu, Qing Mei Wang, Zhenyu Ju, Junwei Hao
Journal: Theranostics (2020)

Rationale: Mitochondrial dysfunction and oxidative stress occur in vascular dementia (VaD), but the specific molecular mechanism regulating these events remains unclear.Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a master regulator for mitochondrial function.This study aims to investigate whether PGC-1α is involved in the pathophysiology of VaD.Methods: We firstly generated PGC-1α f/f Eno2-Cre mice to induce neuron-specific overexpression of PGC-1α by crossbreeding PGC-1α f/f mice with Eno2-cre mice.Then, the mice were subjected to bilateral common carotid artery stenosis to induce chronic cerebral hypoperfusion.Neurological function and hippocampal PGC-1α expression was evaluated.Next, RNA-Seq analysis and Seahorse assay were performed on the hippocampal neurons.In addition, mitochondrial antioxidants, uncoupling proteins, ROS production and the activation of glial cells were also measured.Results: Our results showed that hippocampal PGC-1α expression is down-regulated in the mouse VaD model induced by chronic cerebral hypoperfusion.In contrast, neuronal PGC-1α overexpression significantly ameliorated cognitive deficits.RNA-Seq analysis indicated that PGC-1α improved energy metabolism of neurons under hypoxic condition, and Seahorse assay confirmed that PGC-1α increases the metabolic activity of neurons.Further study demonstrated that PGC-1α boosted the expressions of mitochondrial antioxidants and uncoupling proteins (UCPs), including SOD2, Prx3, GPx1, UCP2, UCP4 and UCP5, which in turn reduced reactive oxygen species (ROS) production.Moreover, the activation of microglia and astrocytes was also found to decrease in the hippocampus.All of these changes greatly contributed to protect hippocampal neurons against ischemic insults.Conclusions: PGC-1α could suppress the excessive ROS and neuroinflammation in the hippocampus, opening up a potential therapeutic target for cognitive impairment.
PRP-chitosan thermoresponsive hydrogel combined with black phosphorus nanosheets as injectable biomaterial for biotherapy and phototherapy treatment of rheumatoid arthritis
Authors: Wenzhen Pan, Chengbai Dai, Yang Li, Yiming Yin, Ling Gong, Jeremiah Ong'achwa Machuki, Yun Yang, Shang Qiu, Kaijin Guo, Fenglei Gao
Journal: Biomaterials (2020)
Prolonged outbreak of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019
Authors: Lara Tavoschi, Silvia Forni, Andrea Porretta, Lorenzo Righi, Filippo Pieralli, Francesco Menichetti, Marco Falcone, Giulia Gemignani, Spartaco Sani, Paola Vivani, Tommaso Bellandi, Danilo Tacconi, Lucia Turini, Giulio Toccafondi, Gaetano Privitera, Pierluigi Lopalco, Angelo Baggiani, Fabrizio Gemmi, Grazia Luchini, Maurizio Petrillo, Lorenzo Roti, Patrizio Pezzotti, Annalisa Pantosti, Stefania Iannazzo, Maria Teresa Mechi, Gian Maria Rossolini
Journal: Eurosurveillance (2020)

In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) have increased since November 2018. Between November 2018 and October 2019, 1,645 samples were NDM-CRE-positive: 1,270 (77.2%) cases of intestinal carriage, 129 (7.8%) bloodstream infections and 246 (14.9%) infections/colonisations at other sites. Klebsiella pneumoniae were prevalent (1,495; 90.9%), with ST147/NDM-1 the dominant clone. Delayed outbreak identification and response resulted in sustained NDM-CRE transmission in the North-West area of Tuscany, but successfully contained spread within the region.
Helen Salisbury: Risk taking and decision making
Authors: Helen Salisbury
Journal: BMJ (2020)

My patient was coughing but is better now.Meanwhile, blood tests reveal although there are no signs of infection, she's mildly anaemic.Should I repeat the test?Add some other blood tests to look for a cause?Check for blood in the stool?What I decide to do, and how soon, will be a matter of judgment, taking into account exact numbers, deviation from previous results, her other health problems, and what she herself thinks.We may also consider how easy it is for her to come to the surgery for further tests.
Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma: results from two phase 3, randomised, double-blind, placebo-controlled trials
Authors: Jonathan A Bernstein, J Christian Virchow, Kevin Murphy, Jorge Fernando Maspero, Joshua Jacobs, Yochai Adir, Marc Humbert, Mario Castro, Douglas A Marsteller, Jennifer McElhattan, Lisa Hickey, Margaret Garin, Rebecca Vanlandingham, Guy Brusselle
Journal: The Lancet Respiratory Medicine (2020)
Abstract P1-01-05: Intraoperative three-dimensions MiniiSCAN<i>R</i> for determine adequate margin in breast cancer specimens before histopathological examination
Authors: Suphawat Laohawiriyakamol, Piyanun Wangkulankul, Piyanoot Woodtichartpreecha, Puttisak Puttawibul
Journal: Cancer Research (2020)

Abstract Background: 20-30% of breast conserving surgery patients undergo a second re-excision procedure due to tumor-positive margins at final histopathology. Various modalities are used to assess the adequacy of surgical resection to minimize positive margin and reoperation rates. MiniiSCAN™ is a method of intraoperative specimen radiography that allows for margin evaluation following excisional breast lesion either BI-RADS 4 and 5. The mechanism of MiniiSCAN™ is similar to computer tomography but specimen is rotated on the plate instead circular rotating frame with an x-ray tube mounted on 1 side and a detector on the opposite side in conventional computerized tomography scan. It is easily and short time to reconstructed into 3 dimensions. This machine was developed by Songklanagarind hospital and National Science and Technology Development Agency, Thailand. Objective: To evaluate the efficacy of MiniiSCAN™ as a surgical margin guidance tool compared with pathological margin in breast cancer specimens. Materials &amp; Methods: A retrospective review was designed, 62 consecutive cases of abnormal mammogram (BI-RADS 4,5) with or without wire localization from 1 June 2016 to 30 June 2019 were identified from the electronic medical records at Prince of Songkla University. Results: Of the 62 specimens imaged, 17 had invasive cancer and ten had in-situ pathological diagnoses. Of these, 10 patients had a positive tumor margin and 17 a negative tumor margin at final histopathology. Margin status evaluation by MiniiSCAN™ reconstruction were calculated in 4 minutes (acquisition and reconstruction time). Of the 27 specimens readings, the margin status in 24 patients was correctly predicted by MiniiSCAN™. There were two false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of MiniiSCAN™ in margin status prediction were 88.89%, 80%, 94.11%, 88.89% and 88.89%, respectively. Conclusion: MiniiSCAN™ could be integrated into routine care, enabling the surgical team to perform and interpret specimen radiographs rapidly and make immediate surgical decisions. Keywords: Abnormal mammography, Breast cancer, CT scan, Specimen radiography Citation Format: Suphawat Laohawiriyakamol, Piyanun Wangkulankul, Piyanoot Woodtichartpreecha, Puttisak Puttawibul. Intraoperative three-dimensions MiniiSCANR for determine adequate margin in breast cancer specimens before histopathological examination [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-05.
Tandem Autologous Hematopoietic Stem Cell Transplantation Treatment for Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China
Authors: Yao Liu, Jun Rao, Jiali Li, Qin Wen, Shifeng Lou, Yi Su, Tonghua Yang, Sanbin Wang, Gao Lei, Cheng Zhang, Kong Peiyan, Li Gao, Wang Mai-Hong, Lidan Zhu, Xixi Xiang, Sha Zhou, Xiangui Peng, Jiangfan Zhong, Defu Zeng, Xi Zhang
Journal: Blood (2018)
Effective monotherapy despite intratumor heterogeneity: Clonal convergence within the PI3K pathway and sensitivity to mTOR inhibitors in patients with advanced renal cell carcinoma (RCC).
Authors: Martin Henner Voss, A. Ari Hakimi, Yingbei Chen, Can G. Pham, Angela Rose Brannon, Sasinya N. Scott, Shugaku Takeda, Han Liu, Robert John Motzer, Michael F. Berger, James Hsieh
Journal: Journal of Clinical Oncology (2013)

4573 Background: Rapalogs, inhibitors of mTOR, are approved for treatment of advanced RCC. Recent reports of clonal heterogeneity challenge the concept of targeted monotherapy and the development of genomic biomarkers. Still, a subset of patients (pts) derives extended benefit from single agent rapalogs. This study analyzed such outliers so as to explore the genomic background of rapalog sensitivity in the setting of clonal heterogeneity. Methods: Cases were chosen based on time to treatment failure &gt; 20 mos and tissue availability. DNA was extracted from spatially separate areas in primary tumors, metastases and the germline. Custom target capture and ultra-deep sequencing identified small indels, single base pair substitutions and copy number changes across all exons of 230 target genes. Results: 4 pts contributed 13 specimens (11 primary tumor samples, 2 metastases); mean exon coverage was 443X. Genomic alterations with activating effect on PI3K pathway signaling were seen in 11 of 13 specimens (Table). Clonal heterogeneity was present in all pts. For 2 pts, different mechanisms activated the pathway in separate sites, in 1 pt through separate genes. Conclusions: Pathway-activating genomic events across all sites explain rapalog benefit in 3 of 4 pts. Different disease sites in the same pt can harbor separate mechanisms activating the targeted pathway. This suggests that clonal convergence within the PI3K pathway can create an oncogenomic landscape sensitive to rapalogs despite branching clonal evolution. It supports the notion of sampling &gt;1 disease site during future biomarker development. [Table: see text]
Abstract GS3-02: Durvalumab compared to maintenance chemotherapy in patients with metastatic breast cancer: Results from phase II randomized trial SAFIR02-IMMUNO
Authors: Florence Dalenc, Ingrid Garberis, Thomas Filleron, Amélie Lusque, Thomas Bachelot, Monica Arnedos, Mario Campone, Marie-Paule Sablin, Hervé Bonnefoi, Marta Jimenez, Jacquet Alexandra, Fabrice Andre
Journal: Cancer Research (2020)

Abstract Background : While treatment with anti-PDL1 improves outcome in combination with chemotherapy in patients with metastatic triple negative breast cancer, its efficacy is not explored yet in the context of maintenance therapy after chemotherapy, in a population of Her2-negative metastatic breast cancer. Methods : In SAFIR02 trial (NCT : 02299999), patients are selected to present a Her2-negative metastatic breast cancer eligible to 1st or 2nd line chemotherapy. All patients underwent a biopsy of metastatic disease, followed by targeted sequencing and Oncoscan when &amp;gt;30% cancer cells are present on HES slides. After 6 to 8 cycles of induction chemotherapy, patients who present an actionable genomic alteration are randomized between targeted therapies and continuation of maintenance chemotherapy, and patients without actionable alterations are randomized between durvalumab (dose, schedule) for 2 years and maintenance chemotherapy. As a substudy of the SAFIR02-breast trial, the SAFIR02-IMMUNO trial has its primary endpoint, the PFS, hierarchized as the primary end-point of the core of the study. The plan was to include 190 patients in order to have 80% power using a two-sided logrank test at the 5 % level of significance to detect an improvement from 3 months to 4.76 months corresponding to an HR of 0.63. Results : 191 patients have been randomized between durvalumab and maintenance chemotherapy (190 women) until now, 45.5% TNBC and 53.4% RH+. The median age was 55 years. . 91.6% (175/191) patients were randomized on their first line of chemotherapy in metastatic setting. Median number of metastatic sites at the beginning of the chemotherapy line was 2. PDL1 staining was performed on 89 available tumor FFPE blocks using SP142 antibody. 30% (n=27/89) patients presented a PDL1 positive tumor. PFS and OS will be presented at the conference.Conclusion : This is the first randomized trial comparing aPDL1 inhibitor to chemotherapy in the maintenance setting and to address the question of the efficacy of aPDL1i in HR+/Her2- and triple negative breast cancers. Citation Format: Florence Dalenc, Ingrid Garberis, Thomas Filleron, Amélie Lusque, Thomas Bachelot, Monica Arnedos, Mario Campone, Marie-Paule Sablin, Hervé Bonnefoi, Marta Jimenez, Jacquet Alexandra, Fabrice Andre. Durvalumab compared to maintenance chemotherapy in patients with metastatic breast cancer: Results from phase II randomized trial SAFIR02-IMMUNO [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS3-02.
Abstract P1-15-09: What are the outcomes of importance for patient education in breast cancer?
Authors: Ghazaleh Kazemi, Mark Levine, Harold Reiter, Christina Sinding
Journal: Cancer Research (2020)

Abstract Background: Patient education is an important component of quality cancer care. However, there remains much debate about its effects, merits and limitations. There is a lack of consensus on the intended effects of educational interventions and a lack of standardized outcome measures to assess quality. As a result, multiple outcomes measures are used without consistency and in differing combinations in the literature making it difficult to compare relative efficacy of interventions. The primary objective of this study was to identify outcomes of importance for patient education interventions in breast cancer. Methods: A generic qualitative study using interpretive description was conducted to discover what key stakeholders in the process of patient education in breast cancer (patients, physicians and nurses) would identify as outcomes of importance. The study population included breast cancer patients, physicians and nurses caring for breast cancer patients at the Juravinski Hospital and Cancer Centre in Hamilton, Ontario. Four focus groups and one semi-structured interview was conducted using purposeful sampling and an iterative design. Results: Eight patients, five nurses and four physicians participated in this study. Five common themes to all groups with respect to outcomes of importance in patient education were discovered: improving knowledge, improving coping ability, providing an orientation to the cancer system, enabling shared decision making and impacting behaviour during cancer treatment. Conclusion: Despite the surprising variability and inconsistency of outcomes discovered in the patient education literature, this qualitative study demonstrated that patients, physicians and nurses generally agree on what constitute important outcomes and serves as a first step in the process of developing validated outcomes for patient education interventions in cancer. Citation Format: Ghazaleh Kazemi, Mark Levine, Harold Reiter, Christina Sinding. What are the outcomes of importance for patient education in breast cancer? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-15-09.
Liver tissue microbiome in NAFLD: next step in understanding the gut–liver axis?
Authors: Herbert Tilg, Remy Burcelin, Valentina Tremaroli
Journal: Gut (2020)

The pathogenesis of non-alcoholic fatty liver disease (NAFLD), the most common global liver disease, is complex as multiple parallel hits drive this disorder. Whereas lipotoxicity, insulin resistance, inflammatory processes, oxidative stress and others reflect key components, studies from the past years have clearly shown that the gut microbiome might also substantially contribute to the evolution of NAFLD including its inflammatory component, that is, non-alcoholic steatohepatitis (NASH). Several studies from the last years have revealed alterations in the gut microbiome in people with NAFLD compared with healthy controls. NAFLD subjects accompanied by advanced fibrosis exhibit a gut microbiome signature with increased concentrations of Proteobacteria and Escherichia coli .1 Gut bacteria-derived metabolites such as phenylacetic acid and endotoxin are associated with degree of steatosis in female NAFLD patients and this metabolite, and the microbiota from NAFLD patients, induced hepatic lipid accumulation when given to mice.2 Therefore, evidence is increasing that the intestinal microbiota and its metabolites might play a crucial role in the pathogenesis of liver diseases including NAFLD.3 

The liver is the key gatekeeper of blood flow from the portal vein draining the intestine and is constantly challenged by intestine-derived bacteria and bacterial components, such as endotoxin and other soluble molecules. Importantly, an intact intestinal epithelial barrier might protect the liver from bacterial …
B-Symptoms, Performance Status and Response to First Therapy As Survival Predictive Factors for Peripheral T-Cell Lymphoma at Progression/Relapse: A Single Institute Analysis
Authors: Yuko Shirouchi, Takanori Fukuta, Anna Nishihara, Norihito Inoue, Hideki Uryu, Yoshiharu Kusano, Noriko Nishimura, Yuko Mishima, Masahiro Yokoyama, Naoko Tsuyama, Kengo Takeuchi, Yasuhito Terui
Journal: Blood (2018)
Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17–22)
Authors: Kathryn E Stephenson, Frank Wegmann, Frank Tomaka, Stephen R Walsh, C Sabrina Tan, Ludo Lavreys, Jessica L Ansel, Diane G Kanjilal, Kate Jaegle, Joseph P Nkolola, Lauren Peter, Rachel Fogel, Connor Bradshaw, Anna Tyler, Tatenda Makoni, Lisa Howe, Darla Quijada, Abishek Chandrashekar, Esther A Bondzie, Erica N Borducchi, Katherine E Yanosick, Jenny Hendriks, Steven Nijs, Carla Truyers, Jeroen Tolboom, Roland C Zahn, Michael S Seaman, Galit Alter, Daniel J Stieh, Maria Grazia Pau, Hanneke Schuitemaker, Dan H Barouch
Journal: The Lancet HIV (2020)
Xpert MTB/RIF Ultra and Xpert MTB/RIF for diagnosis of tuberculosis in an HIV-endemic setting with a high burden of previous tuberculosis: a two-cohort diagnostic accuracy study
Authors: Hridesh Mishra, Byron W P Reeve, Zaida Palmer, Judy Caldwell, Tania Dolby, Charissa C Naidoo, Jennifer G Jackson, Samuel G Schumacher, Claudia M Denkinger, Andreas H Diacon, Paul D van Helden, Florian M Marx, Robin M Warren, Grant Theron
Journal: The Lancet Respiratory Medicine (2020)
Small intestinal bacterial overgrowth (SIBO) as a potential cause of impaired spermatogenesis
Authors: Kelton Tremellen, Karma Pearce
Journal: Gut (2020)

We commend Ding and colleagues for their innovative work investigating how high-fat diet-induced changes to the gut microbiome can alter spermatogenesis.1 This link between the gut microbiome and testicular function had earlier been suggested by studies that reported the consumption of probiotic bacteria could improve spermatogenesis and testosterone production in both mice and men.2 3 Furthermore, we had earlier published the Gut Endotoxin Leading to a Decline IN Gonadal function (GELDING) theory that outlined the scientific evidence behind why obesity related change in the gut microbiome, and the associated increase in intestinal permeability with passage of gut bacterial endotoxin (metabolic endotoxaemia, ME) into the systemic circulation, may impair testicular function.4 Since that publication we have gone on to show that obesity related ME is associated with low-grade systemic inflammation, reduction in testosterone production and impaired sperm quality5 6—all consistent with the probiotic studies2 3 and the experimental findings of Ding …
What Is the Real Impact of Estrogen Receptor Status on the Prognosis and Treatment of HER2-Positive Early Breast Cancer?
Authors: Mariana Brandão, Rafael Caparica, Luca Malorni, Aleix Prat, Lisa A. Carey, Martine Piccart
Journal: Clinical Cancer Research (2020)

HER2+ early breast cancer is a heterogeneous disease, comprising all the intrinsic breast cancer subtypes. The only biomarker available nowadays for anti-HER2 treatment selection is HER2 status itself, but estrogen receptor (ER) status is emerging as a robust predictive marker within HER2+ disease. In this Perspective, we discuss the biological and clinical differences between patients with HER2+/ER-positive (ER+) disease versus those with HER2+/ER-negative (ER-neg) tumors, namely, short-term and long-term (>5 years after diagnosis) prognosis, response to neoadjuvant treatment and benefit from adjuvant anti-HER2-targeted therapies. We also address other possible biomarkers to be used for patient selection in future clinical trials, such as gene signatures, PAM50 subtypes, tumor-infiltrating lymphocytes, PIK3CA mutations, and changes in Ki67 score during treatment and discuss their limitations. Finally, we suggest new clinical trial designs that can have an impact on clinical practice, aiming to test treatment deescalation separately for patients with HER2+/ER+ and HER2+/ER-neg tumors. We also propose an integrated classification of HER2+ disease, comprising DNA, RNA, protein expression, and microenvironment characteristics, in order to identify those tumors that are truly "HER2-addicted" and may benefit the most from anti-HER2 treatment.
Unvaccinated “Wakefield cohorts” blamed for 5000 cases of mumps in England last year
Authors: Zosia Kmietowicz
Journal: BMJ (2020)

Students and young people who may have missed out on their measles, mumps, and rubella (MMR) vaccinations are being encouraged to get immunised as figures show there were 5042 laboratory confirmed cases of mumps in England in 2019, the highest number of cases since 2009. This compared with 1066 cases in 2018, according to …
18F-FDOPA PET/CT Findings in a Patient With Primary Cerebral Amyloidoma
Authors: Laura Rozenblum, Marc Bertaux, Franck Bielle, Morgan Ollivier, Sylvain Choquet, Ytel Garcilazo, Karima Mokhtari, Aurélie Kas
Journal: Clinical Nuclear Medicine (2020)

Abstract Amino acid PET, including 18 F-FDOPA, is recommended for initial characterization, delineation of tumor extent, and follow-up of gliomas because of its high diagnostic performances. 18 F-FDOPA accumulates inside tumor cells via the l -type amino acid transporter 1 (LAT1) whose expression is increased in gliomas. We report here a case of a histopathologically proven brain amyloidoma that was first addressed for a suspected glioma. Congo red staining showed scattered extracellular deposits of amyloid and immunohistochemistry-highlighted LAT1 expression, explaining the high 18 F-FDOPA uptake found in this lesion. This case indicates that differential diagnosis of the 18 F-FDOPA uptake in brain lesions should include amyloidoma.