tbuckley/cabot-search huggingface dataset:
Menopausal Hormone Therapy and Type 2 Diabetes Prevention: Evidence, Mechanisms, and Clinical Implications
Authors: Franck Mauvais-Jarvis, JoAnn E. Manson, John C. Stevenson, Vivian A. Fonseca
Journal: Endocrine Reviews (2017)

Type 2 diabetes has reached epidemic proportions in the United States. Large, randomized controlled trials suggest that menopausal hormone therapy (MHT) delays the onset of type 2 diabetes in women. However, the mechanisms and clinical implications of this association are still a matter of controversy. This review provides an up-to-date analysis and integration of epidemiological, clinical, and basic studies, and proposes a mechanistic explanation for the effect of menopause and MHT on type 2 diabetes development and prevention. We discuss the beneficial effects of endogenous estradiol with respect to insulin secretion, insulin sensitivity, and glucose effectiveness; we also discuss energy expenditure and adipose distribution, both of which are affected by menopause and improved by MHT, which thereby decreases the incidence of type 2 diabetes. We reconcile differences among studies that investigated the effect of menopause and MHT formulations on type 2 diabetes. We argue that discrepancies arise from physiological differences in methods used to assess glucose homeostasis, ranging from clinical indices of insulin sensitivity to steady-state methods to assess insulin action. We also discuss the influence of the route of estrogen administration and the addition of progestogens. We conclude that, although MHT is neither approved nor appropriate for the prevention of type 2 diabetes due to its complex balance of risks and benefits, it should not be withheld from women with increased risk of type 2 diabetes who seek treatment for menopausal symptoms.
Ethical Issues in Fecal Microbiota Transplantion: Taking Into Account Identity and Family Relations
Authors: Suzanne Metselaar, Guy Widdershoven
Journal: The American Journal of Bioethics (2017)

Ma and colleagues (2017) rightfully explain that fecal microbiota transplantation (FMT), that is, transplants that involve introducing the stool from a healthy donor into the gastrointestinal tract...
Extending magnifying NBI diagnosis of intestinal metaplasia in the stomach: the white opaque substance marker
Authors: Takao Kanemitsu, Kenshi Yao, Takashi Nagahama, Kentaro Imamura, Shoko Fujiwara, Toshiharu Ueki, Kenta Chuman, Hiroshi Tanabe, Ota Atsuko, Akinori Iwashita, Toshio Shimokawa, Kunihisa Uchita, Takashi Kanesaka
Journal: Endoscopy (2017)

Abstract Background and aims Intestinal metaplasia (IM) of the stomach is associated with an increased risk of differentiated gastric cancer. While it is important to diagnose IM endoscopically, it can be difficult to observe by white-light endoscopy. In magnifying endoscopy with narrow-band imaging (M-NBI) of the stomach, a light-blue crest (LBC) is widely known to be a useful marker in the endoscopic diagnosis of IM. However, IM that exhibits only white opaque substance (WOS) without an LBC can also occur. The aim of this study was to elucidate whether the presence of WOS on M-NBI of the stomach could serve as a marker of IM in the same way that an LBC does. Methods The subjects were 40 consecutive patients who underwent M-NBI between July and December 2014. The primary endpoint in this study was to evaluate the diagnostic performance of M-NBI for histologically observed IM in WOS- and LBC-positive mucosa. Results The sensitivity and specificity of WOS for histologically diagnosed IM were 50.0 % (95 % confidence interval [CI] 40.0 % – 50.0 %) and 100.0 % (95 %CI 85.0 % – 100.0 %), respectively. Meanwhile, the sensitivity and specificity of LBC were 62.5 % (95 %CI 51.1 % – 65.9 %) and 93.8 % (95 %CI 76.7 % – 98.9 %), respectively. The sensitivity and specificity of WOS and/or LBC (WOS positive and LBC positive, WOS positive and LBC negative, or WOS negative and LBC positive) for histologically diagnosed IM were 87.5 % (95 %CI 76.9 % – 90.9 %) and 93.8 % (95 %CI 77.9 % – 98.9 %), respectively. Conclusions LBC and WOS are both useful markers for endoscopic diagnosis of IM. Combining both markers improves the sensitivity. Clinical trial number: UMINCTR000014453.
Post-bevacizumab treatment and clinical outcomes in recurrent malignant glioma.
Authors: Yongjun Cha, Yu Jung Kim, Tae Min Kim, Seung Hong Choi, Se-Hoon Lee, Dong-Wan Kim, Chul-Kee Park, Il Han Kim, Jee Hyun Kim, Eunhee Kim, Byung Se Choi, Chae-yong Kim, In Ah Kim, Dae Seog Heo
Journal: Journal of Clinical Oncology (2013)

2098 Background: Bevacizumab (Bev) and irinotecan combination therapy is effective against recurrent malignant glioma. However, post-Bev treatment and its clinical outcomes are not well investigated. Methods: We identified 103 consecutive recurrent malignant glioma patients who received Bev plus irinotecan at our institutions.Clinical records and magnetic resonance images were reviewed. Response and progression were assessed by RANO criteria. Results: Bev and irinotecan treatment produced response rate of 37.9% (95% CI, 29.1-47.5%). At a median follow-up time of 41 weeks, the median progression-free survival (PFS) was 17.1 weeks (95% CI, 14.3-20.0), and 6-month PFS (6M-PFS) was 27.8% (95% CI, 18.4-37.2). The median overall survival (OS) was 33.4 weeks (95% CI, 27.8-39.1). Response predicted for superior PFS (25.0 weeks vs. 11.0 weeks, p &lt; .001) and OS (45.9 weeks vs. 26.7 weeks, p &lt; .001). A total of 93 patients discontinued Bev treatment and the reasons for discontinuation were: disease progression in 59 (63.4%), toxicities in 4 (4.3%), physician’s decision in 5 (5.4%), patient’s refusal to further treatment in 25 (26.9%). The median OS was 26.7 weeks in 59 patients who discontinued Bev due to disease progression, and 45.7 weeks in 34 patients who discontinued Bev for reasons other than disease progression (p &lt; .001). Among 85 patients who progressed after Bev, 42 (49.4%) received further therapy: chemotherapy in 32 (37.6%), radiotherapy in 9 (10.6%), and surgery in 1 (1.2%). Further chemotherapy regimens included temozolomide (31.2%), ACNU/CDDP (25.0%), Bev reintroduction (18.8%), erlotinib (12.5%), PCV (9.4%), and intrathecal methotrexate (3.1%). The median survival time after Bev failure was 15.6 weeks (95% CI, 13.3-17.8). Patients who received further therapy showed longer median OS (18.6 weeks vs. 12.9 weeks, p &lt; .001). In patients who received chemotherapy, the median PFS and OS was 6.6 weeks and 20.6 weeks, respectively. Conclusions: Prognosis after Bev failure was poor. Proper selection of patients who may benefit from further treatment is warranted.
“Salvage treatment” for infections by extensively- and pan-drug-resistant pathogens is common and often sub-optimal
Authors: Garyfallia Poulakou, Dimitrios K Matthaiou, Matteo Bassetti, Hakan Erdem, George Dimopoulos, Daniel J Curcio, Jean Carlet, Jeffrey Lipman, Jean-François Timsit, Helen Giamarellou, Angelos Arfaras-Melainis, Jordi Rello
Journal: Intensive Care Medicine (2017)
CD133-negative glioma cells form tumours, while the onset of CD133 expression coincides with angiogenesis and shortened survival
Authors: Jian Wang, Per Sakariassen, Oleg Tsinkalovsky, Heike Immervoll, Stig Boe, Lars Prestegarden, Gro Rosland, Anders Molven, Rolf Bjerkvig, Per Enger
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

LB-91 

ABSTRACT 

Recent work has identified CD133 as a marker of brain tumor-initiating cells. In this study, human glioblastoma biopsies were xenografted intracerebrally into nude rat brains. The resulting tumors expressed little or no CD133, and showed no contrast enhancement suggesting a normal vasculature with an intact blood-brain barrier. During serial passaging in vivo , the tumors gradually displayed more contrast enhancement. Real-time qPCR and immunoblots showed that this change was accompanied by increased angiogenesis, increased CD133 expression and a shorter survival. Biopsies were then dissociated and sorted by flow cytometry into CD133-negative and CD133-positive cell populations. Both populations incorporated BrdU in cell culture, expressed neural precursor markers, and were equally tumorigenic when implanted into the brains of immuno-deficient rats. Moreover, the implanted CD133-negative cells gave rise to tumors that contained CD133-positive cells. CD133 expression was also characterized in 6 tumorgenic glioma cell lines. Even though all the cell lines were tumorigenic, immunocytochemistry, flowcytometry qRT-PCR and immunoblotting showed no expression of CD133 on the tumor cells.    >In conclusion, the work demonstrates that also CD133-negative tumour cells can initiate brain tumour formation with similar take rates as their CD133-positive counterparts. Moreover, CD133 expression coincides with the onset of angiogenesis and a shorter survival suggesting a role for CD133-positive cells in tumour angiogenesis.
Abstract 198: Stim/orai Channel Complex In Normal And Hypertrophied Adult Cardiac Myocytes
Authors: Jean-sebastien Hulot, Youakim Saliba, Jeremy Fauconnier, Mathilde Keck, Ludovic Bénard, Alexandre Marchand, Nassim Farès, Anne-Marie Lompré
Journal: Circulation Research (2013)

Cardiac myocytes use Ca2+ not only in excitation-contraction coupling but also as a signaling molecule for cardiac growth. It is however unclear how Ca2+ triggers signaling in cardiac myocytes in the presence of the rapid and large Ca2+ fluctuations that occur during excitation-contraction coupling. We have recently reported that stromal interaction molecule 1 (STIM1), a calcium sensor in the sarcoplasmic reticulum, is a critical element in promoting cardiomyocyte growth through the control of a previously unrecognized sarcolemmal voltage-independent current. Our goal was to characterize the plasma membrane partners that contribute to STIM1-dependent currents in normal and hypertrophied adult cardiac myocytes. We firstly characterized the expression profile of TRPCs and ORAIs proteins in both normal and hypertrophied ventricular myocytes from abdominal aortic banded rats. The expression of TRPC1, 3, 4, 5 and 6 and of ORAI1 - 3 was identified with an up-regulation of TRPC1 in hypertrophied cells. We then used a non-viral method to deliver cy3-tagged siRNAs to ventricular myocytes to knock-down the candidate channels. The cardiac myocytes were isolated and whole cell patch-clamp technique as well as Fura-2 imaging were performed to measure the currents in cy3-labelled and in control cardiac myocytes. Our data demonstrated that the drug-inducible STIM1-dependent store-operated calcium entry was marginal in normal myocytes but was enhanced in hypertrophied myocytes. In addition, a basal inwardly rectifying current was observed in hypertrophied but not in control myocytes. This spontaneous current was recorded in the absence of calcium store depletion, required STIM1 expression and meets the characteristics of Arachidonate-Regulated Calcium selective (ARC) channels. ORAI silencing completely inhibited both store-dependent and store-independent currents suggesting the critical implication of ORAIs whereas TRPCs were only marginally involved. In conclusion, ORAI channels are involved in STIM1-dependent currents observed in hypertrophied adult cardiac myocytes. In addition to store-operated calcium entry, the STIM1/ORAI complex provides an alternative, store-independent pathway for agonist-activated Ca2+ entry.
The MicroRNA-199a/214 Cluster Targets E-Cadherin and Claudin-2 and Promotes High Glucose-Induced Peritoneal Fibrosis
Authors: Mingwen Che, Tiantian Shi, Shidong Feng, Huan Li, Xiaomin Zhang, Ning Feng, Weijuan Lou, Jianhua Dou, Guangbo Tang, Chen Huang, Guoshuang Xu, Qi Qian, Shiren Sun, Lijie He, Hanmin Wang
Journal: Journal of the American Society of Nephrology (2017)

Serum response factor (SRF) was found to be involved in the phenotypic transition and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs) that contain the SRF-binding consensus (CArG) element in the promoter region. Therefore, we investigated whether the miR-199a/214 gene cluster, which contains a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG) treatment significantly unregulated the expression of the miR-199a-5p/214–3p gene cluster in human peritoneal mesothelial cells (HPMCs). By chromatin immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a-5p/214–3p gene cluster promoter after HG stimulation. In vitro , in HPMCs, silencing of miR-199a-5p or miR-214–3p inhibited the HG-induced phenotypic transition and cell migration but enhanced cell adhesion, whereas ectopic expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p and miR-214–3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model, treatment with an SRF inhibitor silenced miR-199a-5p and miR-214–3p and alleviated HG-PD fluid–induced damage and fibrosis. Overall, this study reveals a novel SRF–miR-199a/miR-214–E-cadherin/claudin-2 axis that mediates damage and fibrosis in PD.
TCTAP C-254 Skin Ulcer Due to Hemodialysis Access-induced Distal Ischemia (HAIDI) in Patient with Giant Cell Arteritis Treated with Combination of Arteriovenous Fistula Banding and Endovascular Therapy
Authors: Susumu Odajima, Takumi Inoue, Masamichi Iwasaki, Takatoshi Hayashi
Journal: Journal of the American College of Cardiology (2017)
Resistance profile of drugs composing the “shorter” regimen for multidrug-resistant tuberculosis in Brazil, 2000–2015
Authors: Margareth Dalcolmo, Regina Gayoso, Giovanni Sotgiu, Lia D'Ambrosio, Jorge Luiz Rocha, Liamar Borga, Fatima Fandinho, Jose Ueleres Braga, Denise Arakaki Sanchez, Fernanda Dockhorn, Rosella Centis, Giovanni Battista Migliori
Journal: European Respiratory Journal (2017)

The difficulties in managing multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant (XDR) TB are well known. The regimens are very expensive, often toxic, and require up to 24 months to achieve an acceptable probability of success [1–3]. The first nationwide report on the drug resistance profile of the drugs composing the WHO "shorter" regimen in Brazil <http://ow.ly/XfJa3096FsT>
Microbiological screenings for infection control in unaccompanied minor refugees: the German Armed Forces Medical Service’s experience
Authors: Winfried Maaßen, Dorothea Wiemer, Claudia Frey, Christina Kreuzberg, Egbert Tannich, Rebecca Hinz, Andreas Wille, Andreas Fritsch, Ralf Matthias Hagen, Hagen Frickmann
Journal: Military Medical Research (2017)

The German Military Medical Service contributed to the medical screening of unaccompanied minor refugees (UMRs) coming to Germany in 2014 and 2015. In this study, a broad range of diagnostic procedures was applied to identify microorganisms with clinical or public health significance. Previously, those tests had only been used to screen soldiers returning from tropical deployments. This instance is the first time the approach has been studied in a humanitarian context. The offered screenings included blood cell counts, hepatitis B serology and microscopy of the stool to look for protozoa and worm eggs as well as PCR from stool samples targeting pathogenic bacteria, protozoa and helminths. If individuals refused certain assessments, their decision to do so was accepted. A total of 219 apparently healthy male UMRs coming from Afghanistan, Egypt, Somalia, Eritrea, Syria, Ghana, Guinea, Iran, Algeria, Iraq, Benin, Gambia, Libya, Morocco, Pakistan, and Palestine were assessed. All UMRs who were examined at the study department were included in the assessment. We detected decreasing frequencies of pathogens that included diarrhoea-associated bacteria [Campylobacter (C.) jejuni, enteropathogenic Escherichia (E.) coli (EPEC), enterotoxic E. coli (ETEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC)/Shigella spp.), Giardia (G.) duodenalis, helminths (comprising Schistosoma spp., Hymenolepis (H.) nana, Strongyloides (S.) stercoralis] as well as hepatitis B virus. Pathogenic microorganisms dominated the samples by far. While G. duodenalis was detected in 11.4% of the assessed UMRs, the incidence of newly identified cases in the German population was 4.5 cases per 100,000 inhabitants. We conclude that the applied in-house PCR screening systems, which have proven to be useful for screening military returnees from tropical deployments, can also be used for health assessment of immigrants from the respective sites. Apparently healthy UMRs may be enterically colonized with a broad variety of pathogenic and apathogenic microorganisms. Increased colonization rates, as shown for G. duodenalis, can pose a hygiene problem in centralized homes for asylum seekers.
Selective Inhibition of HDAC6 with a New Prototype Inhibitor (ACY-1215) Overcomes Bortezomib Resistance In Multiple Myeloma (MM)
Authors: Loredana Santo, Teru Hideshima, Andrew L. Kung, Matthew Jarpe, Diana Cirstea, Kishan Patel, Samantha Pozzi, Jen C. Tseng, Scott J Rodig, James Bradner, Kenneth C. Anderson, Simon Jones, Noopur Raje
Journal: Blood (2010)
A new fate mapping system reveals context-dependent random or clonal expansion of microglia
Authors: Tuan Leng Tay, Dominic Mai, Jana Dautzenberg, Francisco Fernández-Klett, Gen Lin, None Sagar, Moumita Datta, Anne Drougard, Thomas Stempfl, Alberto Ardura-Fabregat, Ori Staszewski, Anca Margineanu, Anje Sporbert, Lars M Steinmetz, J Andrew Pospisilik, Steffen Jung, Josef Priller, Dominic Grün, Olaf Ronneberger, Marco Prinz
Journal: Nature Neuroscience (2017)
Monokine Induced by Interferon-γ (MIG) Serum Levels Are a Marker of Disease Load and Correlate with Prognosis in Multiple Myeloma.
Authors: Martin Schreder, Gudrun Koch, Daniel Heintel, Kathrin Strasser-Weippl, Katrin Frischmuth, Ulrich Jaeger, Heinz Ludwig, Niklas Zojer
Journal: Blood (2006)
Phase I/II, two-part, open-label, multiple-dose, dose-escalation study of siltuximab in patients with solid tumors.
Authors: Eric Angevin, Elena Elez, Steven J. Cohen, Jean-Luc Van Laethem, Christian Ottensmeier, Florence Joly, Isabelle Ray-Coquard, Jose A. Lopez-Martin, Luc Dirix, Jean-Pascal Machiels, Sally Clive, Neil Matthew Steven, Manjula Reddy, Brett Hall, Thomas Puchalski, Rajesh Bandekar, Helgi Van De Velde, Brenda J. Tromp, Jessica Vermeulen, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2012)

2583 Background: Siltuximab (S) is a chimeric mAb with high affinity for soluble IL-6. This Ph 1/2 study evaluated safety, efficacy and PK of escalating, multiple IV doses of S from a new cell line in patients (pts) with advanced refractory solid tumors. Methods: In Ph 1, S was given to 20 pts with advanced solid tumors at escalating dose levels (2.8 or 5.5 mg/kg q2w or 11 or 15 mg/kg q3w) and to 24 pts with taxane and platinum resistant ovarian cancer (OVC) or KRAS mutant (KRASmt) tumors at 15 mg/kg q3w. In Ph 2, 17 OVC pts and 23 KRASmt pts received the Ph 1 selected dose of 15 mg/kg q3w. The Ph 2 primary efficacy endpoint was clinical benefit rate (CBR: CR + PR + SD of &gt; 6 wk). Results: In Ph 1-2, 84 pts (35 colorectal, 29 OVC, 9 pancreatic, 11 other) pretreated with a median of 4 prior tx regimens received a median of 3 (range 1, 45) cycles. 1 DLT occurred at 5.5 mg/kg; MTD was not reached. 62% pts had AEs gr ≥ 3 in Ph 1-2, most common were hepatic function abnormalities (15%), PS deterioration (12%), fatigue (11%). 10% pts had possibly S-related AEs gr ≥ 3; only neutropenia (4%) was reported in &gt;1 pt. 42% pts had SAEs, most were related to underlying disease, 2% were possibly S-related. 18 deaths occurred on study, 17 due to PD, 1 due to AE. No pt had antibodies to S. The PK profile was bi-exponential with a t1/2 ranging 15 − 20 d. PK profile of S from the new Chinese hamster ovary cell line appears similar to the previous murine Sp2/0 myeloma cell line. CBR in Ph 2 was 5%. ORR by RECIST was 26% SD in Ph 1, 9% SD in Ph 2. 1 OVC pt had CA 125 response. In Ph 2 the median PFS was ~ 2 mo in both cohorts; the median OS was 4.2 mo in KRAMSmt and 11 mo in OVC. Hb increased by a max of ≥10 g/L in 73% pts given 15 mg/kg in Ph 2, with 94% showing a median decrease of 68% at d 8 after dose 1 in hepcidin, a regulator of iron homeostasis. CRP was suppressed in all pts during tx, with median decrease 93% at 11 mg/kg and 88 − 93% at 15 mg/kg as early as d 8 after dose 1. Other biomarkers will be presented. Conclusions: S appears to be well tolerated; doses of 11 − 15 mg/kg q3-4w can be used in future studies. No CR/PR was observed, although some pts with advanced solid tumors had durable SD and CRP suppression. Improvement in Hb was observed in a large proportion of pts, indicating a role of IL-6 in anemia that needs to be further explored.
Longitudinal Microbiome Profile in Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Study in 100 Patients
Authors: Raffaella Greco, Nicasio Mancini, Renée Pasciuta, Maria Chiara Barbanti, Mara Morelli, Luca Vago, Fabio Giglio, Maria Teresa Lupo Stanghellini, Alessandra Forcina, Laura Infurnari, Sarah Marktel, Andrea Angelo Assanelli, Matteo Giovanni Carrabba, Massimo Bernardi, Consuelo Corti, Jacopo Peccatori, Massimo Clementi, Fabio Ciceri
Journal: Blood (2016)
TCTAP C-160 Mechanical Rotation less Thrombectomy in Chronic Total Occlusion Lesion Complicated with Spiral Dissection: Whether We Are in Hurry or Not
Authors: Johan Senihardja, Rizki Francis Pandelaki, Benny Mulyanto Setiadi, Monique Priscilla Fransiska Rotty, Bambang Budiono, Janry Anton Pangemanan, Agnes Lucia Panda
Journal: Journal of the American College of Cardiology (2017)
Prognostic Value of Chromosomal Abnormalities for Follicular Lymphoma in the Rituximab-Era
Authors: Takeki Mitsui, Akihiko Yokohama, Hiromi Koiso, Akio Saito, Kohtaro Toyama, Hiroaki Shimizu, Takuma Ishizaki, Hiroyuki Irisawa, Takayuki Saito, Kayoko Murayama, Morio Matsumoto, Hiroshi Handa, Hirokazu Murakami, Norifumi Tsukamoto
Journal: Blood (2016)
Focus on the person, not the problem
Authors: Sophie Cook
Journal: BMJ (2017)

The NHS is strapped for cash, and doctors must be part of any solution. But how should we respond to demands for ever greater productivity and efficiency? We are encouraged to practise evidence based medicine in a cost effective way. But it’s not always clear when to intervene and when to watch and wait. Evidence to guide decisions often conflicts or is absent; the needs and preferences of our patients differ. There are more grey …
Lack of decline in hepatitis C virus incidence among HIV-positive men who have sex with men during 1990–2014
Authors: Daniela Katinka van Santen, Jannie Johanna van der Helm, Julia Del Amo, Laurence Meyer, Antonella D'Arminio Monforte, Matt Price, Charles Antoine Béguelin, Robert Zangerle, Mette Sannes, Kholoud Porter, Ronald Bertus Geskus, Maria Prins
Journal: Journal of Hepatology (2017)