tbuckley/cabot-search huggingface dataset:
Comparison of the effects of cisplatin and oxaliplatin on the gene expression profile of a human colorectal cancer cell line.
Authors: Delphine Meynard, Valerie Le Morvan, Antoine Vekris, Marie-Christine Haaz, Jacques Bonnet, Jacques Robert
Journal: Cancer Research (2004)

2250   Despite their chemical closeness and their similar putative mechanism of action, cisplatin and oxaliplatin have a very different spectrum of anticancer activity. This difference cannot be explained by simple pharmacokinetic considerations. We have explored their effects on the gene expression profile of a human colorectal cancer cell line of the NCI panel, HCT-15, using the Atlas Plastic Human 8K Microarray from Clontech, after 24 h exposures of exponentially growing cells to the IC 50  of each drug as determined by clonogenic assays (1.0 μM for cisplatin and 1.9 μM for oxaliplatin). A total of 994 genes out of 8126 were differentially expressed (expression ratio ≥2) upon cisplatin treatment (755 negatively and 239 positively) whereas only 368 genes out of 7622 were differentially expressed upon oxaliplatin treatment (128 negatively and 240 positively). For the identification of the functions of the genes affected by drug treatment, functional analysis was performed using the Gene Ontology Consortium database. The functions affected by cisplatin are: (1) DNA repair, with a positive regulation of replication repair (down-regulation of CDC7, up-regulation of CDC45), a negative regulation of recombination repair (down-regulation of RAD51, RAD9, RAD 52) and of bypass (down-regulation of DNA polymerase mu) and of NER (down-regulation of RAD23); (2) apoptosis execution (inhibition of caspases 1 and 7); (3) detoxification pathways (positive regulation of chloride channel 5 and 3 and glutathione peroxidase 5); (4) protein synthesis (negative regulation of ribosomal proteins and of initiation and elongation factors); and (5) transcriptional activity (down-regulation of several transcription factors). The major functions affected by oxaliplatin are different from those affected by cisplatin excepted for protein synthesis, but in this case with opposite alterations. The functions affected by oxaliplatin are: (1) protein synthesis (positive regulation of ribosomal proteins and of initiation factors, negative regulation of elongation factors); (2) cell adhesion (up-regulation of metalloproteinases and disintegrins 8, 15 and 17, up-regulation of lamin receptor 1); (3) oxidative stress (down-regulation of NADH dehydrogenase, up-regulation of mitochondrial ATP synthase, up-regulation of microsomal glutathione S-transferase 1, up-regulation of isocitrate dehydrogenase). No alteration of DNA repair pathways and of apoptosis signalling was induced by oxaliplatin. As a conclusion, it appears that the effects of these two platinum compounds at the gene expression level are quite different and may explain their different antitumor profiles. Real-time quantitative PCR control of these alterations is being performed as well as functional validation of the pathways identified.
Droplet Microarray Based on Patterned Superhydrophobic Surfaces Prevents Stem Cell Differentiation and Enables High‐Throughput Stem Cell Screening
Authors: Tina Tronser, Anna A. Popova, Mona Jaggy, Martin Bastmeyer, Pavel A. Levkin
Journal: Advanced Healthcare Materials (2017)

Over the past decades, stem cells have attracted growing interest in fundamental biological and biomedical research as well as in regenerative medicine, due to their unique ability to self-renew and differentiate into various cell types. Long-term maintenance of the self-renewal ability and inhibition of spontaneous differentiation, however, still remain challenging and are not fully understood. Uncontrolled spontaneous differentiation of stem cells makes high-throughput screening of stem cells also difficult. This further hinders investigation of the underlying mechanisms of stem cell differentiation and the factors that might affect it. In this work, a dual functionality of nanoporous superhydrophobic-hydrophilic micropatterns is demonstrated in their ability to inhibit differentiation of mouse embryonic stem cells (mESCs) and at the same time enable formation of arrays of microdroplets (droplet microarray) via the effect of discontinuous dewetting. Such combination makes high-throughput screening of undifferentiated mouse embryonic stem cells possible. The droplet microarray is used to investigate the development, differentiation, and maintenance of stemness of mESC, revealing the dependence of stem cell behavior on droplet volume in nano- and microliter scale. The inhibition of spontaneous differentiation of mESCs cultured on the droplet microarray for up to 72 h is observed. In addition, up to fourfold increased cell growth rate of mESCs cultured on our platform has been observed. The difference in the behavior of mESCs is attributed to the porosity and roughness of the polymer surface. This work demonstrates that the droplet microarray possesses the potential for the screening of mESCs under conditions of prolonged inhibition of stem cells' spontaneous differentiation. Such a platform can be useful for applications in the field of stem cell research, pharmacological testing of drug efficacy and toxicity, biomedical research as well as in the field of regenerative medicine and tissue engineering.
Diagnosis and management of postpartum haemorrhage
Authors: Edwin Chandraharan, Archana Krishna
Journal: BMJ (2017)

#### What you need to know

Postpartum haemorrhage is a major cause of death during pregnancy and early motherhood, accounting for 25% of maternal deaths worldwide,1 and is the second leading direct cause of maternal deaths in the UK.2 It is defined as blood loss of more than 500 mL from the female genital tract after delivery of the fetus (or >1000 mL after a caesarean section). Primary postpartum haemorrhage occurs within the first 24 hours of delivery, whereas secondary postpartum haemorrhage occurs between 24 hours and 12 weeks after delivery and is less common.1 For every maternal death due to postpartum haemorrhage, there are at least 10 “near-misses.” Serious maternal morbidities include multiorgan failure, multiple blood transfusion, and peripartum hysterectomy.1 There have been recent advances in the management of postpartum haemorrhage secondary to coagulopathy and abnormal invasion of the placenta.3

This review highlights the causes, diagnosis, and management of postpartum haemorrhage and is aimed at those involved in obstetric and postnatal care.

#### Sources and selection criteria

We searched PubMed using the key words “postpartum haemorrhage,” “balloon tamponade,” “uterine compression suture,” “embolization,” and “obstetric haemorrhage” from 1981 to 2016. We also considered review articles from 2001 to 2016 …
Tenofovir alafenamide as a rescue therapy in a patient with HBV-cirrhosis with a history of Fanconi syndrome and multidrug resistance
Authors: Glenda Grossi, Alessandro Loglio, Floriana Facchetti, Marta Borghi, Roberta Soffredini, Enrico Galmozzi, Giovanna Lunghi, Anuj Gaggar, Pietro Lampertico
Journal: Journal of Hepatology (2017)
Long-term Intra-articular Steroid Injections and Knee Cartilage—Reply
Authors: Timothy E. McAlindon, Michael P. LaValley
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Efficacy, safety, and biomarker results of trastuzumab emtansine (T-DM1) in patients (pts) with previously treated HER2-overexpressing locally advanced or metastatic non-small cell lung cancer (mNSCLC).
Authors: Tom Stinchcombe, Rolf A. Stahel, Lukas Bubendorf, Philip Bonomi, Augusto E. Villegas, Dariusz Kowalski, Christina S. Baik, Dolores Isla, Javier De Castro, Pilar Garrido Lopez, Achim Rittmeyer, Marcello Tiseo, Sven Franz Stanzel, Sanne de Haas, Lisa Lam, Michael Lu, Solange Peters
Journal: Journal of Clinical Oncology (2017)

8509 Background: T-DM1 is an antibody-drug conjugate approved for HER2-positive metastatic breast cancer. We report primary results from a fully enrolled, ongoing phase 2 study (NCT02289833) of pts with previously treated HER2-overexpressing mNSCLC who received single-agent T-DM1. Methods: Eligible pts had HER2-overexpressing mNSCLC and were previously treated with platinum-based therapy. Pts received T-DM1 3.6 mg/kg every 3 weeks and were analyzed in 2 cohorts based on centrally determined HER2 status (immunohistochemistry [IHC]2+ vs IHC3+ [≥10% cells stained with 2+ or 3+ intensity, respectively]). HER2 amplification was assessed via ISH (HER2 gene ratio ≥2.0). The primary endpoint is objective response rate (ORR; proportion of pts with confirmed [≥4 weeks] complete or partial response per RECIST v1.1). Results: The clinical cutoff date for this analysis was Oct 26, 2016.Of 393 screened pts, 102 (27%) were IHC2+ and 29 (7%) were IHC3+. In total, 49 pts (IHC2+, n = 29; IHC3+, n = 20) received T-DM1. At cutoff, median follow-up was 16.3 (range 0.9*–22.4; * = censored observation) months. No IHC2+ pt had a response (0%, 95% CI 0–11.9); 4 IHC3+ pts had partial responses (20%, 95% CI 5.7–43.7) with a median duration of response of 7.3 (range 2.9–8.3) months. Median progression-free survival (PFS) in IHC2+ and IHC3+ pts was 2.6 (95% CI 1.4–2.8) and 2.7 (95% CI 1.4–8.3) months, respectively. At 6 months after start of study treatment, 9 pts (IHC2+, n = 4; IHC3+, n = 5) were still at risk for a PFS event. Median overall survival was 12.2 (95% CI 3.8–not estimable [NE]) months in IHC2+ pts and 12.1 (95% CI 9.3–NE) months in IHC3+ pts. Of 16 pts with HER2 amplification (IHC2+, n = 5; IHC3+, n = 11), 3 responded, all in the IHC3+ cohort (27.3%, 95% CI 6.0–61.0). Eleven pts (22%) experienced a grade 3–4 adverse event, with fatigue and dyspnea being the only events reported in &gt; 1 pt (n = 2 each). Conclusions: This is the first study to report on the clinical activity of T-DM1 in HER2-overexpressing mNSCLC. Objective responses were observed in IHC3+ pts. Additional molecular analyses are underway to refine markers for optimal pt selection. Clinical trial information: NCT02289833.
A novel mechanism of lncRNA and miRNA interaction: CCAT2 regulates miR-145 expression by suppressing its maturation process in colon cancer cells
Authors: Yingjie Yu, Pratima Nangia-Makker, Lulu Farhana, Adhip P. N. Majumdar
Journal: Molecular Cancer (2017)

Although both long and micro RNAs are emerging as important functional components in colorectal cancer (CRC) progression and metastasis, the mechanism of their interaction remains poorly understood. CCAT2 (Colon cancer-associated transcript-2), a long noncoding RNA (lncRNA), has been reported to be over-expressed in CRC and is found to promote tumor growth. miRNAs, a class of naturally occurring short RNAs negatively control the expression of target genes by cleaving mRNA or through translation repression. Recently, we reported that miR-145 and miR-21 cooperate to regulate colon cancer stem cell (CSC) proliferation and differentiation. Considering that CCAT2 is mainly located in the nucleus and miRNA maturation process begins in the nucleus, we hypothesize that CCAT2 selectively blocks miR-145 maturation process, resulting in decreased mature miR-145 affecting colon CSC proliferation and differentiation.The levels of CCAT2 were manipulated by transfection of CCAT2 expression plasmid or knockdown by siRNA or by CRISPR/Cas9. Quantitative RT-PCR was performed to examine the expression of CCAT2 and pri-, pre- and mature miR-145/21. Fluorescence in situ hybridization (FISH) was used to visualize CCAT2 in the cells. In vitro processing of pri-miRNA-145 was performed using T7 RNA polymerase and recombinant human Dicer.We have observed that modulated expression of CCAT2 regulates the expression of miR-145 in colon cancer HCT-116 and HT-29 cells. Knockout of CCAT2 increases miR-145 and negatively regulates miR-21 in HCT-116 cells, impairs proliferation and differentiation. In contrast, stable up-regulation of CCAT2 decreases mature miR-145 and increases the expression of several CSC markers in colon cancer cells. We have also observed that CCAT2 is enriched in the nucleus and correlates with the expression of pre-miR-145 but not pre-miR-21 in HCT-116 cells. These results indicate CCAT2 selectively blocks miR-145 maturation by inhibiting pre-miR-145 export to cytoplasm. Further, we revealed that CCAT2 blocks cleavage of pre-miR-145 by Dicer in vitro.Our results identify CCAT2 as a negative regulator of miRNA-145 biogenesis, and expose a novel mechanism of lncRNA-miRNA crosstalk.
International development and validation of a classification system for the identification of Barrett’s neoplasia using acetic acid chromoendoscopy: the Portsmouth acetic acid classification (PREDICT)
Authors: Kesavan Kandiah, Fergus J Q Chedgy, Sharmila Subramaniam, Gaius Longcroft-Wheaton, Paul Bassett, Alessandro Repici, Prateek Sharma, Oliver Pech, Pradeep Bhandari
Journal: Gut (2017)

Background Barrett’s oesophagus is an established risk factor for developing oesophageal adenocarcinoma. However, Barrett’s neoplasia can be subtle and difficult to identify. Acetic acid chromoendoscopy (AAC) is a simple technique that has been demonstrated to highlight neoplastic areas but lesion recognition with AAC remains a challenge, thereby hampering its widespread use. Objective To develop and validate a simple classification system to identify Barrett’s neoplasia using AAC. Design The study was conducted in four phases: phase 1—development of component descriptive criteria; phase 2—development of a classification system; phase 3—validation of the classification system by endoscopists; and phase 4—validation of the classification system by non-endoscopists. Results Phases 1 and 2 led to the development of a simplified AAC classification system based on two criteria: focal loss of acetowhitening and surface patterns of Barrett’s mucosa. In phase 3, the application of PREDICT (Portsmouth acetic acid classification) by endoscopists improved the sensitivity and negative predictive value (NPV) from 79.3% and 80.2% to 98.1% and 97.4%, respectively (p&lt;0.001). In phase 4, the application of PREDICT by non-endoscopists improved the sensitivity and NPV from 69.6% and 75.5% to 95.9% and 96.0%, respectively (p&lt;0.001). Conclusion We developed and validated a classification system known as PREDICT for the diagnosis of Barrett’s neoplasia using AAC. The improvement seen in the sensitivity and NPV for detection of Barrett’s neoplasia in phase 3 demonstrates the clinical value of PREDICT and the similar improvement seen among non-endoscopists demonstrates the potential for generalisation of PREDICT once proven in real time.
Tailoring diagnostic studies in hand, foot and mouth disease: polymerase chain reaction testing of lesional skin
Authors: K.M. MacArthur, B.A. Cohen
Journal: British Journal of Dermatology (2017)

Hand, Foot, Mouth Disease (HFMD) is a highly contagious enteroviral infection with the potential for significant morbidity. In recent years, there has been an increase in atypical cutaneous manifestations of HFMD. We present a pilot case series utilizing Polymerase Chain Reaction (PCR) testing of lesional skin to render a diagnosis of HFMD. These preliminary results suggest that lesional skin PCR testing could be an effective and minimally-invasive test for diagnosing HFMD.

This article is protected by copyright. All rights reserved.
Abstract 14125: Prognostic Impact of and Risk Score for the Onset of Atrial Fibrillation in Patients at High Risk for Heart Failure -A Report From the CHART-2 Study
Authors: Takeshi Yamauchi, Yasuhiko Sakata, Masanobu Miura, Takeo Onose, Kanako Tsuji, Ruri Abe, Takuya Oikawa, Shintaro Kasahara, Kotaro Nochioka, Jun Takahashi, Takashi Shiroto, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2016)

Background:  The prognostic impact of atrial fibrillation (AF) in patients in Stage A/B, who are at high-risk for heart failure (HF), is unclear. Furthermore, there is no risk estimation model for AF onset in those patients.   Methods:  We examined clinical background, treatments, and long-term prognosis of 5,382 consecutive patients with Stage A/B enrolled in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). We aimed to develop a new risk score to predict AF onset using the CHART-2 database.   Results:  At enrollment, 1,217 (22.6%) had AF. They were characterized, as compared with those without AF, by higher age (70.5 vs. 66.8 yrs.), lower estimated glomerular filtration rate (64.0 vs. 68.3 ml/min/1.73m 2 ), higher brain natriuretic peptide levels (106 vs. 37.0 pg/ml) and lower LV ejection fraction (63.6 vs. 65.2 %) (all P Figure ). Average annual incidence of new AF (/1000 patients) was 10, 53, and 177 with the risk score 0-3, 4-8, and 9-12, respectively (P   Conclusions:  AF is associated with worse prognosis in patients at high-risk for HF, where the new risk score may be useful to stratify the risk of new AF in those patients.
Image Gallery: Cutaneous presentation of disseminated cryptococcosis in a patient with undiagnosed <scp>HIV</scp> infection
Authors: H. Qu, Z. Zhao, J. Yu
Journal: British Journal of Dermatology (2017)

DEAR EDITOR, A 52-year-old man developed a painless ulcer a few days after pigeon droppings fell on his intact forehead.He reported a history of multiple unprotected sexual encounters and was diagnosed, by skin biopsy (haematoxylin and eosin and periodic acid-Schiff staining), with cryptococcosis and HIV infection.Six weeks later the patient presented with fever and difficulty breathing; pulmonary computed tomography scan and cerebrospinal fluid culture confirmed systemic dissemination.The patient's cutaneous and general condition substantially improved after antiretroviral and antifungal treatment.The unusual story of pigeon droppings should prompt biopsy; the patient's personal history and cryptococcosis indicated potential immunodeficiency and the need for HIV testing.
Clinicopathological Factors Associated With Prognosis of Patients With Intrahepatic Cholangiocarcinoma After Hepatectomy—Reply
Authors: Mustafa Raoof, Gagandeep Singh
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Head and Neck Squamous Cell Carcinomas Are Characterized by a Stable Immune Signature Within the Primary Tumor Over Time and Space
Authors: Oliver Wood, James Clarke, Jeongmin Woo, Adal H. Mirza, Christopher H. Woelk, Gareth J. Thomas, Pandurangan Vijayanand, Emma King, Christian H. Ottensmeier
Journal: Clinical Cancer Research (2017)

Genetic and morphologic heterogeneity is well-documented in solid cancers. Immune cells are also variably distributed within the tumor; this heterogeneity is difficult to assess in small biopsies, and may confound our understanding of the determinants of successful immunotherapy. We examined the transcriptomic variability of the immunologic signature in head and neck squamous cell carcinoma (HNSCC) within individual tumors using transcriptomic and IHC assessments.
Mortality following new-onset Rheumatoid Arthritis: has modern Rheumatology had an impact?
Authors: Marie Holmqvist, Lotta Ljung, Johan Askling
Journal: Annals of the Rheumatic Diseases (2017)

To investigate if, and when, patients diagnosed with rheumatoid arthritis (RA) in recent years are at increased risk of death.Using an extensive register linkage, we designed a population-based nationwide cohort study in Sweden. Patients with new-onset RA from the Swedish Rheumatology Quality Register, and individually matched comparators from the general population were followed with respect to death, as captured by the total population register.17 512 patients with new-onset RA between 1 January 1997 and 31 December 2014, and 78 847 matched general population comparator subjects were followed from RA diagnosis until death, emigration or 31 December 2015. There was a steady decrease in absolute mortality rates over calendar time, both in the RA cohort and in the general population. Although the relative risk of death in the RA cohort was not increased (HR=1.01, 95% CI 0.96 to 1.06), an excess mortality in the RA cohort was present 5 years after RA diagnosis (HR after 10 years since RA diagnosis=1.43 (95% CI 1.28 to 1.59)), across all calendar periods of RA diagnosis. Taking RA disease duration into account, there was no clear trend towards lower excess mortality for patients diagnosed more recently.Despite decreasing mortality rates, RA continues to be linked to an increased risk of death. Thus, despite advancements in RA management during recent years, increased efforts to prevent disease progression and comorbidity, from disease onset, are needed.
Weak Regulation of Many Targets Is Cumulatively Powerful—An Evolutionary Perspective on microRNA Functionality
Authors: Yixin Zhao, Xu Shen, Tian Tang, Chung-I Wu
Journal: Molecular Biology and Evolution (2017)

Why do microRNAs (miRNAs) weakly repress so many targets such that most targets do not have phenotypic effects? An increasingly accepted view posits that weak targeting has no biological function and each miRNA effectively has only a few functional targets. Here, we review the evolutionary arguments for this postulate and find these arguments seriously flawed. In contrast, from the systems perspective, the power of broad and weak targeting may reside in the cumulative effects of all repressions, which collectively stabilize gene regulatory networks. This view predicts that miRNAs would show little tendency to downsize their target pools. A survey of "twin-miRs" production indeed validates this prediction.