bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition
Authors: Harding James J. , Lowery Maeve A. , Shih Alan H. , Schvartzman Juan M. , Hou Shengqi , Famulare Christopher , Patel Minal , Roshal Mikhail , Do Richard K. , Zehir Ahmet , You Daoqi , Selcuklu S. Duygu , Viale Agnes , Tallman Martin S. , Hyman David M. , Reznik Ed , Finley Lydia W.S. , Papaemmanuil Elli , Tosolini Alessandra , Frattini Mark G. , MacBeth Kyle J. , Liu Guowen , Fan Bin , Choe Sung , Wu Bin , Janjigian Yelena Y. , Mellinghoff Ingo K. , Diaz Luis A. , Levine Ross L. , Abou-Alfa Ghassan K. , Stein Eytan M. , Intlekofer Andrew M. 
Published: October 2018

Abstract

Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 or IDH2, respectively) contribute to oncogenesis via production of the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG production and induce clinical responses in patients with IDH1- and IDH2-mutant malignancies. Despite the promising activity of IDH inhibitors, the mechanisms that mediate resistance to IDH inhibition are poorly understood. Here, we describe four clinical cases that identify mutant IDH isoform switching, either from mutant IDH1 to mutant IDH2 or vice versa, as a mechanism of acquired clinical resistance to IDH inhibition in solid and liquid tumors.

Significance:
IDH-mutant cancers can develop resistance to isoform-selective IDH inhibition by “isoform switching” from mutant IDH1 to mutant IDH2 or vice versa, thereby restoring 2HG production by the tumor. These findings underscore a role for continued 2HG production in tumor progression and suggest therapeutic strategies to prevent or overcome resistance.
This article is highlighted in the In This Issue feature, p. 1494
How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors – is an algorithm the answer?
Authors: Trenk Dietmar , Schrör Karsten , Gawaz Meinrad , Kristensen Steen D. , Storey Robert F. , Huber Kurt , Siller-Matula Jolanta M. ,   for the European Platelet Academy
Published: October 2018

SummaryWithin the past decade, high on-treatment platelet reactivity (HTPR) on clopidogrel and its clinical implications have been frequently discussed. Although it has been previously assumed that HTPR is a phenomenon occurring only in patients treated with clopidogrel, recent data show that HTPR might also occur during treatment with prasugrel or ticagrelor in the acute phase of ST-elevation myocardial infarction. Moreover, it has been postulated that there is a therapeutic window for P2Y12 receptor blockers, thus indicating that HTPR is associated with thrombotic events whereas low on-treatment platelet reactivity (LTPR) is associated with bleeding events. The current paper focuses on tools to identify risk factors for HTPR (pharmacogenomic testing, clinical scoring and drug-drug interactions) and on the use of platelet function testing in order to identify patients who might not respond adequately to clopidogrel. The majority of recent clinical randomised trials have not supported the hypothesis that platelet function testing and tailored antiplatelet therapy are providing a favourable clinical outcome. These trials, mainly performed in low-to-moderate risk patients, will be reviewed and discussed. Finally, an algorithm based on current knowledge is suggested, which might be of use for design of clinical trials.
Acute Pulmonary Embolism in a National Danish Cohort: Increasing Incidence and Decreasing Mortality
Authors: Lehnert Per , Lange Theis , Møller Christian , Olsen Peter , Carlsen Jørn 
Published: October 2018

AbstractThis study reports the incidence, clinical profile and mortality for acute pulmonary embolism (PE) patients in the Danish population in four eras from 2004 to 2014. Patients admitted with first-time acute PE from 2004 through 2014 were identified from national patient registries classified according to the International Classification of Diseases, 10th edition, World Health Organization. A total of 30,275 patients from a population of 4,301,673 adult residents aged 18 years or older were diagnosed with first-time acute PE, corresponding to an incidence of 64 (95% confidence interval: 61–66) per 100,000 adult residents per year. Throughout the study period, PE incidence increased from 45 to 83 per 100,000 adult residents. Age at disease onset also increased during the study period, rising from 67.1 to 68.0 (p = 0.002). Cancer was the most frequent concomitant diagnosis, with an incidence of 15.9%. Thoracic computed tomography and referral to specialized cardiac centres increased significantly throughout the study period. The 30- and 90-day mortality rates decreased between 2004 and 2014 from 17 to 11% and from 23 to 18% (p < 0.00), respectively. The 5-year mortality risk was reduced when comparing Era IV (2012–2014) with Era I (2004–2005), with a hazard ratio of 0.93 (p = 0.01). In Denmark, the annual incidence of acute PE has increased during the past decade from 45 to 83 per 100,000 adults with a significant decrease in both short- and long-term mortalities. In recent years, patients were more likely to be investigated with modern diagnostics and referred to cardiac centres for specialized treatment.
Inhibition of Platelets by Clopidogrel Suppressed Ang II‐Induced Vascular Inflammation, Oxidative Stress, and Remodeling
Authors: An Xiangbo , Jiang Guinan , Cheng Cheng , Lv Zhengshuai , Liu Yang , Wang Feng 
Published: October 2018

Background

Platelets play a role in promoting inflammatory responses under several disease conditions. Platelets are activated in hypertensive patients. However, the mechanisms responsible for platelet‐mediating vascular inflammation are unknown. The present study investigated the role of platelets in promoting vascular inflammation following angiotensin II (Ang
II
) stimulation, and the efficacy of antiplatelet intervention.

Methods and Results

Within a mouse model of Ang
II
infusion (490 ng/kg per min), we measured the portion of P‐selectin–positive platelets and platelet‐monocyte (P‐M) binding in blood samples, and platelet accumulation and P‐M binding in vessels under Ang
II
stimulation at days 1, 3, and 7. We tested the efficacy of clopidogrel (15 mg/kg per day, followed by 5 mg/kg per day) on Ang
II
‐induced platelet activation, P‐M binding, vascular platelet accumulation, as well as vascular inflammation and remodeling at day 7 or 14. Clopidogrel reduced platelet vascular deposition (28.7±2.4% versus 18.3±2.9%), suppressed inflammatory cell infiltration (3.6±0.8×10
4
/vessel versus 2.3±1.2×10
4
/vessel) and oxidative stress, and attenuated vascular remodeling and dysfunction (55.0±5.5% versus 84.0±6.0%) following Ang
II
stimulation at day 7 or 14. Clopidogrel suppressed Ang
II
‐induced P‐M binding both at circulating (13.4±3.3% versus 5.9±2.7%) and regional (33.4±4.3% versus 11.9±2.7%) levels.

Conclusions

Platelets play a critical role in vascular inflammation under Ang
II
stimulation, with a marked promotion of P‐M binding as an important mechanism. Clopidogrel prevented vascular inflammation in Ang
II
‐infused mice.
Mechanisms underlying string-pulling behaviour in green-winged macaws
Authors: Gaycken Jana , Picken Drew J. , Pike Thomas W. , Burman Oliver H.P. , Wilkinson Anna 
Published: October 2018

Abstract
The string-pulling test is a classic test of physical cognition which is thought to examine an animal’s understanding of means-end comprehension, but may also result from trial and error learning. Here, we presented Green-winged macaws (Ara chloroptera) with a standard pull-up, and an alternative, pull-down, string pulling test to better understand the processes involved. Birds were divided into two groups: the experimental group were presented with the classic pull-up test and, upon completion, with the pull-down test, while the control group were only presented with the pull-down test. Six experimental birds solved the pull-up test, although none successfully completed the pull-down test; however, birds from the experimental group made significantly more pull-down actions than those from the control group. Together with previous findings on string-pulling behaviour in green-winged macaws, the results from the present study suggest that string-pulling behaviour in this species does not involve means-end understanding.
Spanish Fascist Women’s Transnational Relations during the Second World War: Between Ideology and Realpolitik
Authors: Morant i Ariño Toni 
Published: October 2018

Spanish fascist women played a very active role in the Falange’s cross-border relations with Nazi Germany and Fascist Italy during the Spanish Civil War and the Second World War. From the very beginning, fascist women took a preeminent place in these contacts and exchanges in order to see with their own eyes how both fascist models were at a practical level. These relationships between fascist women’s organizations were born out of deep ideological affinity and were especially fluid, firstly on a bilateral level and after 1940 on the ‘New Order’ Europe-wide multilateral, transnational collaboration. However, they lacked neither of political calculation nor could abstract from the wider frame of international politics in such an eminently war period. As this article will show, Falangist women used these fluid but less studied relationships to consolidate their own political position at home and explore other ways of political participation in a Nazi-Fascist New Europe, while at the same time trying to secure there a pre-eminent place for non-belligerent Spain. In the end, concerns about the own survival of the Franco dictatorship as the fate of war clearly changed in 1943, let ideological affinity succumb to the diplomatic conveniences they had once meant to overcome.
Australian pharmacy perspectives on increasing access to medicines through reclassification
Authors: Mey Amary , King Michelle , Kelly Fiona , Grant Gary , Townshend James , Baumann-Birkbeck Lyndsee , Woods Phillip , Hope Denise 
Published: October 2018

Objectives Availability of medicines without prescription can increase consumers’ timely access to treatment and promote self-management of minor ailments and adherence to long-term medications. Globally, access to relevant medicines has improved through increased reclassification of medicines from prescription to non-prescription availability. However, Australian reclassification lags behind countries with comparable health systems, and the factors influencing this are poorly understood. Methods Semi-structured interviews were conducted during May 2015 to explore the perspectives of Australian pharmacists and support staff on future reclassification. Interview responses were transcribed verbatim, and the data were analysed thematically, primarily informed by the general inductive approach. Results Participants identified a broad range of medicines as candidates for future reclassification by applying risk versus benefit judgements, assessing any medicines with potential for misuse and hazardous medicines as unsuitable. Key drivers for change in classification were underpinned by participants’ desire to support consumers’ management of minor ailments and adherence for those on long-term therapy. Barriers to reclassification were identified by pharmacy staff as internal, negatively impacting pharmacists’ readiness for reclassification and external, negatively impacting the overall progress of change. Conclusions While the research provided valuable insights to inform the ongoing discussion on future reclassification, a larger, more representative sample is needed to confirm these findings.
Ideal telestroke time targets: Telestroke-based treatment times in the United States stroke belt
Authors: Nalleballe Krishna , Sharma Rohan , Brown Aliza , Joiner Renee , Kapoor Nidhi , Morgan Tiffany , Benton Tina , Williamson Conelia , Culp William , Lowery Curtis , Onteddu Sanjeeva 
Published: October 2018

Background Studying critical time interval requirements can enhance thrombolytic treatment for stroke patients in telestroke networks. We retrospectively examined 12 concurrent months of targeted time interval information in the South Central US telemedicine programme, Arkansas Stroke Assistance through Virtual Emergency Support (AR SAVES). Hypothesis: We hypothesised that consult data analysis would highlight areas for improvement to shorten overall door to Intra venous (IV) tissue plasminogen activator (tPA) administration time. Methods We analysed critical time targets for 238 consecutive telestroke neurology consults obtained over 12 months from AR SAVES spoke sites when tPA was administered. The following time intervals were analysed: emergency department (ED) door to Computed Tomography (D-CT); ED door to call centre (D-CC) for initiation of consult; ED door to neurology call (D-NC); neurology call to camera (NC-Cam); tele consult time (Con); ED door to tissue plasminogen activator (tPA)/needle (DTN). Results The median times of D-CT (13 min, inter quartile range (IQR) 6–22 min), D-CC (34 min, IQR 20–45 min), D-NC (40 min, IQR 21–71 min), NC-Cam (4 min, IQR 2–8 min), and Con (25 min, IQR 17–37 min) all contributed to a DTN median time of 71 min (IQR 50–104 min). A total of 238 patients received tPA with a 29.4% treatment rate and a DTN time of ≤60 min was achieved in 25.2% of patients. Conclusions Focusing on reducing D-CC and Con times may help to achieve the DTN time of < 60 min for the majority of patients. Having ideal time targets for telestroke patients akin to traditional patients will help identify and improve the overall goal of a DTN time < 60 min.
Stereotactic Body Radiotherapy for Spinal Metastases: Clinical Experience in 134 Cases From a Single Japanese Institution
Authors: Ito Kei , Ogawa Hiroaki , Shimizuguchi Takuya , Nihei Keiji , Furuya Tomohisa , Tanaka Hiroshi , Karasawa Katsuyuki 
Published: October 2018

Object: This study aimed to clarify the outcomes of stereotactic body radiotherapy for spinal metastases with a uniform dose fractionation schedule in our institution. Materials and Methods: Patients treated with spine stereotactic body radiotherapy were retrospectively reviewed. The prescribed dose was 24 Gy in 2 fractions. End points were local control, pain control, and adverse events. Local control was defined as elimination, shrinkage, or stable disease in the tumor on imaging evaluations. Pain status was measured on a scale of 0 to 10 by patients’ self-reports, and pain response was defined as the time at which pain scale score decreased by 2 or more from the baseline score without increase in analgesics. In addition, various treatment- and tumor-specific factors were evaluated to determine predictive values for local and pain control. Results: This study included 134 lesions in 131 patients, with: lesion histopathology, lung/colorectal/thyroid/renal/breast/prostate/sarcoma/other cancer, 24/22/18/14/12/10/6/25; reirradiation stereotactic body radiotherapy, 82 (61.2%) cases; and postoperative stereotactic body radiotherapy for epidural spinal cord compression, 45 (33.6%) cases. Median follow-up after stereotactic body radiotherapy was 9 months. The 1-year local control rate was 72.3%. Seventy (79.5%) of the 88 cases with pain from spinal metastases achieved pain response. The 1-year pain progression-free rate was 61.7%. Regarding metastases from colorectal cancer, local and pain control rates at 1 year were significantly lower compared with other cancer types (local control rate, 34.1% vs 81.8%; P < .01; pain progression-free rate, 36.9% vs 69.9%; P = .02). On multivariate analysis, colorectal cancer metastases and radiation history were identified as independent predictors of lower local and pain control rates. Radiation-induced myelopathy, radiculopathy, and vertebral compression fractures were observed in 0, 2 (1.5%), and 16 (11.9%) cases, respectively. Conclusions: This study showed that spine stereotactic body radiotherapy achieved good local and pain control, with a clinically acceptable safety profile. However, stereotactic body radiotherapy may be less effective against spinal metastases from colorectal cancer.
Does the innate relative size of the humeral head and glenoid affect the risk of anterior shoulder instability?
Authors: Willigenburg NW , Bouma RA , Scholtes VAB , van der Hulst VPM , van Deurzen DFP , van den Bekerom MPJ 
Published: October 2018

Background Bony lesions after shoulder dislocation reduce the joint contact area and increase the risk of recurrent instability. It is unknown whether the innate relative sizes of the humeral head and glenoid may predispose patients to shoulder instability. This study evaluated whether anterior shoulder instability is associated with a larger innate humeral head/glenoid ratio (IHGR). Methods We evaluated CT scans of 40 shoulders with anterior shoulder instability and 48 controls. We measured axial humeral head diameter and glenoid diameter following native contours, discarding any bony lesions, and calculated IHGR by dividing both diameters. Multivariate logistic regression determined whether the IHGR, corrected for age and gender as potential confounders, was associated with anterior shoulder instability. Results Mean IHGR was 1.48 ± 0.23 in the group with anterior shoulder instability and 1.42 ± 0.20 in the group without anterior shoulder instability. Measurements for axial humeral head and axial glenoid diameters demonstrated excellent intra-rater reliability (ICC range: 0.94–0.95). IHGR was not significantly associated with anterior shoulder instability (OR = 1.105, 95%CI = 0.118–10.339, p = 0.930). Discussion The innate ratio of humeral head and glenoid diameters was not significantly associated with anterior shoulder instability in this retrospective sample of 88 shoulder CT scans.
The efficiency of the posterior-only approach using shaped titanium mesh cage for the surgical treatment of spine tuberculosis in children: A preliminary study
Authors: Zhang Hongqi , Guo Qiang , Wang Yunjia , Guo Chaofeng , Tang Mingxing 
Published: October 2018

Purpose: The study aimed to evaluate the efficiency of the posterior-only approach using shaped titanium mesh cage for surgical treatment of spinal tuberculosis (TB) in children. Methods: Between January 2011 and July 2013, 22 children with a single motion spinal segment involved, including 10 with thoracic, 4 with thoracolumbar, and 8 with lumbar, were enrolled in the study. The patients were treated by the posterior-only approach using the shaped titanium mesh cages. Their medical records and radiographs were retrospectively analyzed. Results: The mean operating time was 163 min (ranging from 120 min to 200 min). Blood loss was 210–550 ml with an average of 300 ml. The mean follow-up period was 41.1 months. At the final follow-up, all patients showed a solid bony fusion without the infection recurrence. The average bone fusion time was 6.2 months. The average correction of the local segment kyphosis angle was 6.9° (from 9.2° preoperative to 2.3° postoperative). Minimal loss in correction angle was noted in these patients at the final follow-up (only 1.5°). Changes in erythrocyte sedimentation rate, local segment kyphosis angle, and neurological status demonstrated a significant clinical improvement in all children at their last follow-up. Conclusion: Children with spinal TB of a single motion spinal segment involved can be successfully treated by the posterior-only approach using shaped titanium mesh cage. It is a minimally invasive, safe, and effective surgical procedure.
Prophylaxis of complications in venous surgery
Authors: Leo M. , Di Mitri R. , Romano R. 
Published: October 2018

SummaryAim: The purpose of this article is to underline complications in venous surgery during the past 30 years and new ones arising with the introduction of technologies. We also discuss the “natural reduction” of some of these and how to prevent complications.Methods: We have analysed different types of studies on different surgical procedures in the treatment of varicose veins and compared them with own outcomes.Results: Considering all techniques, we have wound infections in 2,3–4 % of cases, cellulitis in 2,6–16 %, lymphatic complications in 1,3–60 %, pain in 2–23 %, neurologic disease including nerve damages, bruising and numbness in 0–50 %, thrombophlebitis in 0,3–20 %, deep vein thrombosis with or without pulmonary embolism in 0–5,7 %, injury of major vessel in 0,17 %, haematoma in 1,3–31 %, oedema in <1–15 %, hyperpigmentation in 3–11 %, ecchymosis in 0,8–9 %, skin burns in 0,2–8 %, erythema in 2–33 % and endothermal heat-induced-thrombosis (HEIT) in 0–7,5 % of cases.Conclusion: Our outcomes confirmed literature results. We conclude that new technologies improve results and reduce complications, as do tumescent anaesthesia, medical stockings, early mobilization and low weight heparin prophylaxis (LMWH) in high risk patients.
Avoiding aesthetic complications after endovenous radiofrequency ablation
Authors: Stegher S. , Calliari F. M. , Viani M. P. , Bissacco D. 
Published: October 2018

SummaryRadiofrequency endovenous ablation treatment is a safe, effective and durable technique for the treatment of great saphenous vein truncal incompetence. However, it is associated with relatively rare complications, such as ecchymosis, paresthesia, hyperpigmentation, phlebitis, haematoma, deep vein thrombosis and pulmonary embolism. Among these, aesthetic complications are the most frequent minor complications occurred after the procedure. This brief review defines and describes aesthetic complications after endovenous radiofrequency ablation of great saphenous vein and provides useful tips to minimize their incidence. Aesthetic complications can be avoided with a careful and accurate preoperative patient and vein evaluation, proper operative indication, adherence to procedure and device instruction for use and best postoperative management.
Das subfasziale venöse Ödem im NMR
Authors: Stumptner T. 
Published: October 2018

ZusammenfassungDas venöse Blut der Beine wird über ein Venensystem zurück zum Herzen transportiert, wobei die subfaszialen Venen mit einem Anteil von ca. 80% die Hauptlast tragen. Eine Insuffizienz im System wird über die venöse Hypertonie somit vorwiegend den subfaszialen Raum betreffen. Dieses Drainagedefizit erklärt über die dabei vorliegende extravasale Volumenüberlastung und die daraus folgende vermehrte Faszienspannung die Beschwerden und die klinischen Befunde als Folge der Ödembildung. Das Ödem konnte im MRT dargestellt und seine therapeutische Beeinflussbarkeit mittels unelastischer Kompressionsverbände nach H. Fischer objektiviert werden.
Hautpflege bei chronisch venöser Insuffizienz
Authors: Erfurt-Berge C. , Mahler V. , Geier J. 
Published: October 2018

ZusammenfassungAn Hand von Daten des Informationsverbundes Dermatologischer Kliniken (IVDK) der Jahre 2012–2016 wird das Spektrum von Kontaktsensibilisierungen bei 2011 Patienten mit Ulcus cruris venosum, Stauungsekzem und/oder einem Kontaktekzem bei chronisch venöser Insuffizienz (CVI) beschrieben, und mit dem Sensibilisierungsspektrum einer Kontrollgruppe (n=30 924) im ähnlichen Alter, aber ohne diese Erkrankungen verglichen. Unverändert zu früheren IVDK-Auswertungen zeigten CVI Patienten gehäuft Sensibilisierungen gegen das folgende Allergenspektrum: Perubalsam, Bestandteile von Salbengrundlagen, insbesondere Wollwachsalkohole, Antioxidantien, insbesondere tert-Butylhydrochinon, Kolophonium, Duftstoffe und Parabene. Für die Hautpflege bei entsprechenden Patienten empfehlen sich daher duftstoff- und parabenfreie Produkte ohne Perubalsam (Myroxylon pereirae), Wollwachsalkohole (Lanolin alcohol) und tert-Butylhydrochinon (TBHQ). Dabei ist das sogenannte Parabenund Wollwachs-Paradox zu berücksichtigen: CVI Patienten können an ekzematös veränderter Haut am Unterschenkel auf Parabene oder Wollwachsalkohole reagieren, während diese Stoffe auf normaler Haut an anderen Körperregionen vertragen werden.