bluuebunny/crossref_metadata_2025 huggingface dataset:
Präzisionstherapie beim kolorektalen Karzinom
Authors: Stintzing Sebastian
Published: October 2017

Colorectal carcinoma (CRC) is a major cause for cancer related death in Western countries. Particularly in the metastatic stage (mCRC) 5-year survival rate remains low at around 15 %. Treatment decisions are influenced by tumor stage, location of the primary, and extend of metastases. The multidisciplinary tumor board with an experienced hepato-biliary surgeon, an interventional radiologist, the medical oncologist, the molecular pathologist and the radiation oncologist will gain further importance in the quest for the optimal treatment for each patient. In the adjuvant setting, next to the established clinical risk factors, individualization especially for UICC-stage II patients can be done according to the CDX2-expression, the MSI-status, and perhaps the PIK3-status. In the metastatic stage, RAS and BRAF mutational analyses are pivotal to choose the best treatment for our patients. Primary tumor location in RAS-wild-type patients is further helping the clinician to tailor first-line treatment. Ongoing phase-III-trials will further help the clinician to come to a personalized decision.
Zielgerichtete Therapie des Mammakarzinoms
Authors: Seiffert Katharina , Schmalfeldt Barbara , Müller Volkmar
Published: October 2017

Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research.
Slow-growing amelanotic malignant melanoma of the esophagus with long survival: a case report and review of the literature
Authors: Hirayama Yutaka , Masahiro Tajika , Tanaka Tsutomu , Ishihara Makoto , Ohnishi Sachiyo , Hara Kazuo , Mizuno Nobumasa , Hijioka Susumu , Okuno Nozomi , Abe Tetsuya , Uemura Norihisa , Kawakami Jiro , Kurahashi Shintarou , Shimizu Yasuhiro , Yatabe Yasushi , Niwa Yasumasa
Published: October 2017

Background and study aims We report a case of amelanotic malignant melanoma of the esophagus (AMME), an exceedingly rare disease. A 77-year-old Japanese woman presented to our hospital with features suggestive of a middle esophageal submucosal tumor, which was diagnosed pathologically as AMME. The patient underwent thoracoscopic resection of the esophagus and laparoscopic gastric tube reconstruction. Three years after surgery, computed tomography showed no recurrence. Generally, the prognosis of malignant melanoma of the esophagus is very poor. However, our patient had no recurrence, and is alive 3 years after surgery and 5 years after the tumor was first detected.
Evaluation of a novel, hybrid model (Mumbai EUS II) for stepwise teaching and training in EUS-guided biliary drainage and rendezvous procedures
Authors: Dhir Vinay , Itoi Takao , Pausawasdi Nonthalee , Khashab Mouen , Perez-Miranda Manuel , Sun Siyu , Park Do , Iwashita Takuji , Teoh Anthony , Maydeo Amit , Ho Khek
Published: October 2017

Background and aims EUS-guided biliary drainage (EUS-BD) and rendezvous (EUS-RV) are acceptable rescue options for patients with failed endoscopic retrograde cholangiopancreatography (ERCP). However, there are limited training opportunities at most centers owing to low case volumes. The existing models do not replicate the difficulties encountered during EUS-BD. We aimed to develop and validate a model for stepwise learning of EUS-BD and EUS-RV, which replicates the actual EUS-BD procedures.

Methods A hybrid model was created utilizing pig esophagus and stomach, with a synthetic duodenum and biliary system. The model was objectively assessed on a grade of 1 – 4 by two experts. Twenty-eight trainees were given initial training with didactic lectures and live procedures. This was followed by hands-on training in EUS-BD and EUS-RV on the hybrid model. Trainees were assessed for objective criteria of technical difficulties.

Results Both the experts graded the model as very good or above for all parameters. All trainees could complete the requisite steps of EUS-BD and EUS-RV in a mean time of 11 minutes (8 – 18 minutes). Thirty-six technical difficulties were noted during the training (wrong scope position, 13; incorrect duct puncture, 12; guidewire related problems, 11). Technical difficulties peaked for EUS-RV, followed by hepaticogastrostomy (HGS) and choledochoduodenostomy (CDS) (20, 9, and 7, P = 0.001). At 10 days follow-up, nine of 28 trainees had successfully performed three EUS-RV and seven EUS-BD procedures independently.

Conclusions The Mumbai EUS II hybrid model replicates situations encountered during EUS-RV and EUS-BD. Stepwise mentoring improves the chances of success in EUS-RV and EUS-BD procedures.
Positionspapier zur Detektion von Vorhofflimmern nach ischämischem Schlaganfall
Authors: Häusler Karl , Gröschel Klaus , Köhrmann Martin , Schnabel Renate , Anker Stefan , Brachmann Johannes , Böhm Michael , Diener Hans-Christoph , Doehner Wolfram , Endres Matthias , Gerloff Christian , Huttner Hagen , Kaps Manfred , Kirchhof Paulus , Nabavi Darius , Nolte Christian , Pfeilschifter Waltraud , Pieske Burkert , Poli Sven , Schäbitz Wolf , Thomalla Götz , Veltkamp Roland , Steiner Thorsten , Laufs Ulrich , Röther Joachim , Wachter Rolf
Published: October 2017

Das vorliegende Positionspapier zur Detektion von Vorhofflimmern nach ischämischem Schlaganfall beinhaltet eine Stellungnahme der Arbeitsgemeinschaft „Herz und Hirn“ der Deutschen Gesellschaft für Kardiologie – Herz- und Kreislaufforschung e. V. (DGK) und der Deutschen Schlaganfallgesellschaft e. V. (DSG), die in Zusammenarbeit mit der Stroke Unit-Kommission der DSG und dem Kompetenznetz Vorhofflimmern (AFNET) e. V. erstellt wurde.

Vorhofflimmern ist in den Leitlinien der Europäischen Gesellschaft für Kardiologie als eine mindestens 30 Sekunden anhaltende Episode einer Vorhofarrhythmie mit fehlenden P-Wellen definiert. Die 30-Sekundengrenze ist arbiträr gewählt und es ist unbekannt, ob das Schlaganfallrisiko bei Episoden von länger als 30 Sekunden höher ist als bei kürzeren Episoden.

Bei Patienten, die einen Schlaganfall erlitten haben, sollte die Detektion von Vorhofflimmern üblicherweise zu einer Umstellung der medikamentösen Sekundärprävention führen, da eine orale Antikoagulation einer Thrombozytenaggregationshemmung überlegen ist. Die Detektion eines bis dato nicht diagnostizierten Vorhofflimmerns sollte daher bei Patienten mit ischämischem Schlaganfall verbessert werden, um die medikamentöse Sekundärprävention des Schlaganfalls zu optimieren.

In diesem Positionspapier werden interdisziplinär erarbeitete Standards für eine „strukturierte Rhythmusvisite“ auf der Stroke Unit und ein diagnostisches „Stufenschema“ zur Detektion von Vorhofflimmern vorgeschlagen. Das Positionspapier fasst zudem den gegenwärtigen Kenntnisstand zur Detektion von Vorhofflimmern nach ischämischem Schlaganfall zusammen. Das Positionspapier soll den in der Versorgung von Schlaganfallpatienten tätigen Ärzten eine Handhabe geben, auch wenn bisher nicht abschließend geklärt ist, wie lange und mit welcher EKG-Methode Schlaganfallpatienten ohne bisher bekannte Herzrhythmusstörung bestmöglich monitoriert werden sollten. Dem Charakter eines Positionspapiers angemessen, wurde auf die Kennzeichnung von Evidenzgraden verzichtet, da es sich überwiegend um die Meinung von Experten handelt, die auf berichteten Fallserien und klinischer Erfahrung beruht und somit nicht mit einer Leitlinie gleichzusetzen ist und so auch nicht verstanden werden will.
Vorstellung eines pragmatischen Konzeptes zur bedarfsadaptierten Ernährungstherapie des kritisch kranken Patienten
Authors: Reckefuß Norbert , Kampa Ulrich
Published: October 2017

Hintergrund Die korrekte Anpassung der Ernährungstherapie des kritisch kranken Patienten stellt eine Herausforderung für jeden Intensivmediziner dar. Vor allem eine Überernährung muss hierbei in den ersten Tagen der kritischen Erkrankung unbedingt vermieden werden. Bisher publizierte Arbeiten zu dieser Thematik sind oft komplex und teilweise widersprüchlich, was die praktische Umsetzung weiter erschwert. Unser Ziel ist daher die Vorstellung eines einfachen und praktikablen Ernährungskonzepts, welches neben pathophysiologischen Grundlagen auch die Implementierung der neueren wissenschaftlichen Literatur und der aktuellen Leitlinien beinhaltet.

Ergebnisse Unser Ernährungsalgorithmus beruht auf den Veränderungen des Metabolismus kritisch kranker Patienten und bezieht daher die endogene Substratproduktion mit ein. In der Akutphase führen die Ausschöpfung vorhandener Leberglykogenreserven sowie eine gesteigerte Glukoneogenese in Verbindung mit einer peripheren Insulinresistenz in der Regel zu einer ausgeprägten Hyperglykämie. Sofern keine Kontraindikationen vorliegen, wird die Ernährungstherapie frühzeitig mit zunächst nur geringer Zufuhr begonnen (10 – 20 ml/h). In den folgenden Stunden und Tagen wird die (par)enterale Zufuhr abhängig von der aktuellen individuellen metabolischen Toleranz – erkennbar anhand von Blutzuckerwerten sowie notwendiger Insulindosierung – schrittweise erhöht (oder reduziert), bis das angestrebte Ernährungsziel erreicht ist.

Zusammenfassung Unser Konzept erweitert bisher publizierte Ernährungsalgorithmen, indem es eine praktikable Handlungsanweisung unter Beachtung der endogenen Substratproduktion bietet. Durch Einbeziehung von einfachen, günstigen und ubiquitär verfügbaren Parametern ermöglicht es eine frühe, bedarfsadaptierte Ernährung, die das Risiko einer Überernährung minimiert.
Spontane IOL-Dislokation – was können wir tun zur Prävention?
Authors: Kuchenbecker Joern
Published: October 2017

Die IOL-Dislokation stellt neben den Eintrübungen von IOLs (Intraokularlinsen) eine weitere Komplikation der modernen IOL-Implantation dar. Zurzeit ist eine Zunahme der IOL-Dislokationen zu beobachten, die verschiedene Ursachen hat. Durch Kapselsackschrumpfung, insbesondere bei Patienten mit Pseudoexfoliation (PEX) und anderen okulären Ursachen, kommt es zu einer weiteren Belastung der oft bereits geschwächten Zonula. Der Einsatz eines Kapselspannrings allein hat sich bisher als nicht ausreichend effektiv erwiesen. Die Schrumpfung des Kapselsacks und damit weitere Belastung der Zonula kann z. B. durch zusätzliche Vorderkapselinzisionen vermindert werden und die IOL bei Zonulaschwäche auch bei erhaltenem Kapselsack oder geringer intraoperativer Zonulolyse vorzugsweise retroiridal fixiert werden, um eine spätere Dislokation zu verhindern. Die Effektivität dieser Maßnahmen sollte zukünftig in größeren Studien untersucht werden.
Das Humboldt’sche Bildungsideal in der Plastischen Chirurgie – Studentenumfrage zur Lehre und Venia
Legendi
Authors: Alawi Seyed Arash , Busch Lukas , Limbourg Anne , Jokuszies Andreas , Ipaktchi Ramin , Vogt Peter
Published: October 2017

Hintergrund Universitätskliniken und Kliniken mit universitärer Anbindung haben neben der klinischen Patientenversorgung vor allem den
Auftrag der Lehre und Forschung. In der aktuellen Entwicklung zeigt sich verschärft eine finanzielle Orientierung der ärztlichen Tätigkeit
mit einer Reduktion von Kapazitäten für Lehre und Forschung. Auf Basis einer betriebswirtschaftlichen Orientierung erfolgt eine Verlagerung
von Prioritäten innerhalb chirurgischer Disziplinen.

Methoden Im Rahmen einer Online-Umfrage wurden Medizinstudenten hinsichtlich ihrer subjektiven Einschätzung der akademischen
Qualifikation von Habilitanden und über die Einschätzung der aktuellen Lehrqualität befragt. Hierbei evaluierten die Studenten sowohl die
aktuelle Qualität der Lehre als auch die Perspektive einer akademischen Laufbahn und machten Vorschläge zur Verbesserung.

Ergebnisse An der Studentenumfrage nahmen insgesamt 166 Studenten teil. Von 123 Studenten gaben 78 % an, dass das Ansehen mit der
Habilitation steige. 85 % der Studenten gaben an, dass sich mit der Habilitation aber auch die Erwartungshaltung im Hinblick auf die
fachliche Qualifikation erhöht. 43 % der Studenten gaben an, sich in Zukunft habilitieren zu wollen.

Diskussion Unter den Studenten ist weiterhin die wissenschaftliche Karriere attraktiv, daher muss durch die Anpassung und
Modernisierung bestehender Arbeitszeitmodelle eine Umstrukturierung zugunsten attraktiver Arbeitsplatzbedingungen stattfinden.
Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations
Authors: Valli Piero , Mertens Joachim , Kröger Arne , Gubler Christoph , Gutschow Christian , Schneider Paul , Bauerfeind Peter
Published: October 2017

Background and study aims Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS).

Patients and methods Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique.

Results Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred.

Conclusion SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results.
Identification of Potential Biomarkers from Aconitum carmichaelii, a Traditional Chinese Medicine, Using a Metabolomic Approach
Authors: Zhao Dake , Shi Yana , Zhu Xinyan , Liu Li , Ji Pengzhang , Long Chunlin , Shen Yong , Kennelly Edward
Published: October 2017

Despite their well-known toxicity, Aconitum species are important traditional medicines worldwide. Aconitum carmichaelii, known in Chinese as 附子 (fuzi), is an officially recognized traditional Chinese medicine with characteristic analgesic and anti-inflammatory activities, whose principal pharmacological ingredients are considered as aconitine-type diterpene alkaloids. Notwithstanding the long-recorded use of A. carmichaelii in traditional Chinese medicine, no single-entity aconitum alkaloid drug has been developed for clinical use. UPLC-Q-TOF-MS was used to investigate the marker compounds that can be used to differentiate A. carmichaelii from seven other Aconitum species collected in Yunnan Province. Nontargeted principle component analysis scores plots found that all the tested Aconitum species clustered into three distinct groups, and A. carmichaelii was significantly different chemically than the other seven species. Furthermore, the primary and lateral roots of A. carmichaelii also showed significant differences. Using orthogonal partial least squares discriminate analysis analysis, eight marker compounds were identified, including 14-acetylkarakoline, aconitine, carmichaeline, fuziline, hypaconitine, mesaconitine, neoline, and talatisamine. Four of these aconitum alkaloids, fuziline, hypaconitine, mesaconitine, and neoline, showed significant analgesic activity in a dose-dependent manner compared to the negative and positive controls. However, hypaconitine, mesaconitine, and neoline exhibited significant acute toxicity activity, while fuziline showed no acute toxicity in mice, suggesting the relative safety of this alkaloid. This study provides a good example of how to differentiate an authentic medicinal plant from common adulterants using a metabolomics approach, and to identify compounds that may be developed into new drugs.
First-principles investigation of oxygen-excess defects in amorphous silica
Authors: Chen Zehua , Wang Jian-wei , Song Yu , Zuo Xu
Published: October 2017

Using ab initio calculations, we investigate the interactions among neutral excess oxygen atoms and amorphous silica (a-SiO2), along with hole trapping on neutral excess-oxygen defects. The calculations demonstrate that the interaction of excess oxygen with the a-SiO2 network results in two distinct defect structures referred to as the oxygen bridge-bonded (OBB) and peroxy linkage configurations. The OBB configuration may relax to a lower-energy structure after trapping a hole, representing a potential relaxation channel to the peroxy radical (POR) defect. The calculated hyperfine parameters are in excellent agreement with POR defect experiments and show that the oxygen atoms trapping the unpaired spin are bound to only one silicon atom. This implies that the OBB configuration is the major precursor of POR defects.
Design considerations for open-well microfluidic platforms for hypoxic cell studies
Authors: Byrne Matthew B. , Leslie Matthew T. , Patel Heeral S. , Gaskins H. Rex , Kenis Paul J. A.
Published: October 2017

Regions of hypoxia are common in solid tumors and are associated with enhanced malignancy, metastasis, and chemo/radio resistance. Real-time hypoxic cellular experimentation is challenging due to the constant need for oxygen control. Most microfluidic platforms developed thus far for hypoxic cell studies are burdened by complex design parameters and are difficult to use for uninitiated investigators. However, open-well microfluidic platforms enable short and long term hypoxic cell studies with an ease of use workflow. Specifically, open-well platforms enable manipulation and addition of cells, media, and reagents using a micropipette for hypoxic cell studies in tunable dissolved oxygen concentrations as low 0.3 mg/l. We analyzed design considerations for open-well microfluidic platforms such as media height, membrane thickness, and impermeable barriers to determine their effects on the amount of dissolved oxygen within the platform. The oxygen concentration was determined by experimental measurements and computational simulations. To examine cell behavior under controlled oxygen conditions, hypoxia-induced changes to hypoxia inducible factor activity and the mitochondrial redox environment were studied. A fluorescent reporter construct was used to monitor the stabilization of hypoxia inducible factors 1α and 2α throughout chronic hypoxia. Reporter construct fluorescence intensity inversely correlated with dissolved oxygen in the medium, as expected. Additionally, the glutathione redox poise of the mitochondrial matrix in living cancer cells was monitored throughout acute hypoxia with a genetically encoded redox probe and was observed to undergo a reductive response to hypoxia. Overall, these studies validate an easy to use open-well platform suitable for studying complex cell behaviors in hypoxia.
Poloidal rotation driven by electron cyclotron resonance wave in tokamak plasmas
Authors: Zhou Qing , Xu Xinliang , Wen Jie , Nie Lin , Tang Changjian , Gong Yubin
Published: October 2017

The poloidal electric filed, which is the drive field of poloidal rotation, has been observed and increases obviously after the injection of electron cyclotron resonance wave in HL-2A experiment, and the amplitude of the poloidal electric field is in the order of 103 V/m. Through theoretical analysis using Stringer rotation model, the observed poloidal electric field is of the same order as the theoretical calculation value. In addition, the magnetic pump damping which would damp the poloidal rotation is calculated numerically and the calculation results show that the closer to the core plasmas, the stronger the magnetic pump damping will be. Meanwhile, according to the value of the calculated magnetic pump damping, the threshold of the poloidal electric field which could overcome magnetic pump damping and drive poloidal rotation in tokamak plasmas is given out. Finally, the poloidal rotation velocity over time at different minor radius is studied theoretically.
Effect of synthesis methods and a comparative study of structural and magnetic properties of zinc ferrite
Authors: Hossain Md. Sazzad , Hoque S. Manjura , Liba S. I. , Choudhury Shamima
Published: October 2017

Zinc ferrite samples were prepared by two different routes which are chemical co-precipitation and standard solid state double sintering method. Structural properties of ZnFe2O4 were determined, and initial particle size was found as 5 nm in the samples prepared by chemical co-precipitation technique. The XRD patterns showed the single phase of ZnFe2O4 spinel structure and confirmed by the lattice parameter and the unmixed hkl values for both the synthesis techniques. M-H curves at room temperature showed superparamagnetic nature of the samples sintered from 200°C to 600°C, synthesized by chemical co-precipitation technique. The Mössbauer analysis at room temperature showed a doublet which is the signature of superparamagnetic nature, and it is in agreement with the acquired M-H curves. The magnetization of ZnFe2O4 synthesized by chemical co-precipitation method was found higher than the magnetization of ZnFe2O4 synthesized by the solid-state double sintering method in the sintering temperature from 1100°C to 1300°C.
Traditional manual tillage significantly affects soil redistribution and CO2 emission in agricultural plots on the Loess Plateau
Authors: Geng Yan , Yu Hanqing , Li Yong , Tarafder Mahbubul , Tian Guanglong , Chappell Adrian
Published: October 2017

Traditional manual tillage using hand tools is widely used by local farmers in hilly and mountainous regions in China and many South-east Asian countries. Manual tillage could result in severe soil erosion, redistributing slopes from upslope areas (erosion) to lower slopes (deposition). This soil redistribution process may potentially affect the soil carbon cycle, but few studies have quantified soil CO2 emission under different manual tillage practices. In the present study we evaluated the soil redistribution and its effects on in situ CO2 emission as affected by manual tillage of different intensities on three short slopes representing typical cultivated landscapes on the Loess Plateau. Soils were removed at 2, 6 and 10 cm depths by three types of hand tools, namely a hoe, mattock and spade respectively, from the upslope and subsequently accumulated at the downslope to simulate soil erosion and deposition processes by traditional manual tillage. Across the tilled hillslopes, soil CO2 emission was reduced at sites of erosion but enhanced at sites of deposition. Tillage with greater intensity (i.e. hoeing < mattocking < spading) resulted in greater change in CO2 emission. This change in soil CO2 emission was largely associated with the depletion of soil organic carbon (SOC) stocks at erosion sites and the increments of SOC available for decomposition at deposition sites. Moreover, with increasing tillage intensity, soil redistribution by manual tillage shifted the hillslope from a C sink to C neutral or even a C source. Furthermore, manual tillage resulted in substantial changes in soil CO2 emission and redistributed soil in amounts that dwarf animal-powered tillage. The results of the present study imply that manual tillage-induced soil redistribution could have a large effect on the C balance across the local landscape and therefore may have considerable implications for estimates of regional and global C budgets.
Assessing fish welfare.
Authors: Braithwaite V. A.
Published: October 2017

There is a growing need to understand how our current interactions and practices influence fish welfare and wellbeing. Particularly given the increasing use of fish both as model organisms in research, for example zebrafish used in biomedical experiments, and also in terms of food production in aquaculture, where we now rear and harvest several different species of fish on farms. Determining which factors matter from a fish welfare perspective and finding appropriate ways to assay fish welfare have been the focus of several research projects over the last decade. These have led to a much better appreciation of what kinds of situation result in poor fish welfare, and what can be done to promote positive welfare through best practice. Assays of fish welfare depend on the species of concern, the environment in which the fish are housed, how the fish are handled, the routine husbandry practices that they are exposed to, and how they are killed. Approaches that address welfare span from regular, repeated behavioural observations, to the use of multiple traits to create a welfare index, through to the use of molecular tools to act as an early warning system by detecting early changes in stress physiology gene expression. The field of fish welfare is still at a relatively early stage of development, but a growing interest in this topic has promoted innovative new tools and techniques that are delivering better welfare assays for the fish we maintain in captivity.
Rajini’s Finger, Indexicality, and the Metapragmatics of Presence
Authors: Nakassis Constantine V.
Published: October 2017

This article explores the ways in which Tamil film stars, so-called mass heroes such as the “Superstar” Rajinikanth, are presenced in theatrical events of their onscreen revelation and apperception. Drawing on film analysis, ethnographic accounts of theatrical reception, and metadiscourse by filmgoers and industry personnel, I focus on Rajini’s onscreen pointing gestures in highly charged moments of presencing. As I argue, these data provoke reflection on indexicality—defined by Charles Sanders Peirce as a semiotic ground based on “real connection” or “existential relation,” such as copresence, contiguity, or causality—for at issue with Rajini’s fingers is precisely the question of his auratic being and presence. Instead of analyzing performative acts of presencing through appeal to the analytic of indexicality, then, what if we interrogate those ethnographic particularities of existence and presence that constitute the ground for indexical relations and effects as such? Such an inquiry would refuse to leave indexicality as a self-evident, pregiven analytic, but instead pose it as an open ethnographic question. Opening up the question of existence and presence, as I show, allows us to unearth other semiotic “grounds” of indexicality and representation beyond those that we all too often take for granted.
The Tuhao and the Bureaucrat: The Qualia of “Quality” in Rural China
Authors: Ingebretson Britta
Published: October 2017

For the past thirty years, the Chinese state has focused on raising the quality (suzhi) of rural Chinese, who are seen as particularly lacking. This article shows how local bureaucrats undertake this project through distinguishing the stereotyped figure of the tuhao “rural rich,” who represents the façade of modernity without its substance, from the truly modern high-quality citizen. These oppositional figures are defined and identified through a dialectic process of rhematization and dicentization, which ties together and locates the qualities of coarseness, carelessness, and ruralness in the tuhao, and qualities of fineness, meticulousness, and carefulness in the high-quality bureaucrat. These qualia, which organize preexisting cultural logics of difference, are thereby subsumed to the state project of quality-raising. Through this process of identification, local bureaucrats commensurate local forms of valorization with those of the Chinese state and devalue nongovernmental local elites as tuhao.
From the Page to the Floor: Baroque Dance Notation and Kellom Tomlinson’s The Art of Dancing Explained
Authors: Karl-Johnson Gabriella
Published: October 2017

The late seventeenth century gave rise to a powerful innovation in Western European social and theatrical dance, the art of dance notation. The new representational technology of dance notation provided a means to broadcast fashionable dances emerging from the French court as well as new compositions from dancing masters operating in London and elsewhere. In the first three decades of the eighteenth century, dance notation quickly reached faddish heights, with published dance manuals in high demand among upper levels of English society. One publication from the era, Kellom Tomlinson’s The Art of Dancing Explained by Reading and Figures, provides a window onto the descriptive tool of dance notation, its function in society, and its eventual decline. While providing a previously unimagined communicational technology, the completeness and specificity of the dominant form of dance notation ultimately spelled its demise.
Quantifying biological samples using Linear Poisson Independent Component Analysis for MALDI-ToF mass spectra
Authors: Deepaisarn S , Tar P D , Thacker N A , Seepujak A , McMahon A W
Published: October 2017

Motivation

Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI) facilitates the analysis of large organic molecules. However, the complexity of biological samples and MALDI data acquisition leads to high levels of variation, making reliable quantification of samples difficult. We present a new analysis approach that we believe is well-suited to the properties of MALDI mass spectra, based upon an Independent Component Analysis derived for Poisson sampled data. Simple analyses have been limited to studying small numbers of mass peaks, via peak ratios, which is known to be inefficient. Conventional PCA and ICA methods have also been applied, which extract correlations between any number of peaks, but we argue makes inappropriate assumptions regarding data noise, i.e. uniform and Gaussian.

Results

We provide evidence that the Gaussian assumption is incorrect, motivating the need for our Poisson approach. The method is demonstrated by making proportion measurements from lipid-rich binary mixtures of lamb brain and liver, and also goat and cow milk. These allow our measurements and error predictions to be compared to ground truth.

Availability and implementation

Software is available via the open source image analysis system TINA Vision, www.tina-vision.net.

Supplementary information

Supplementary data are available at Bioinformatics online.
MetaCherchant: analyzing genomic context of antibiotic resistance genes in gut microbiota
Authors: Olekhnovich Evgenii I , Vasilyev Artem T , Ulyantsev Vladimir I , Kostryukova Elena S , Tyakht Alexander V
Published: October 2017

Motivation

Antibiotic resistance is an important global public health problem. Human gut microbiota is an accumulator of resistance genes potentially providing them to pathogens. It is important to develop tools for identifying the mechanisms of how resistance is transmitted between gut microbial species and pathogens.

Results

We developed MetaCherchant—an algorithm for extracting the genomic environment of antibiotic resistance genes from metagenomic data in the form of a graph. The algorithm was validated on a number of simulated and published datasets, as well as applied to new ‘shotgun’ metagenomes of gut microbiota from patients with Helicobacter pylori who underwent antibiotic therapy. Genomic context was reconstructed for several major resistance genes. Taxonomic annotation of the context suggests that within a single metagenome, the resistance genes can be contained in genomes of multiple species. MetaCherchant allows reconstruction of mobile elements with resistance genes within the genomes of bacteria using metagenomic data. Application of MetaCherchant in differential mode produced specific graph structures suggesting the evidence of possible resistance gene transmission within a mobile element that occurred as a result of the antibiotic therapy. MetaCherchant is a promising tool giving researchers an opportunity to get an insight into dynamics of resistance transmission in vivo basing on metagenomic data.

Availability and implementation

Source code and binaries are freely available for download at https://github.com/ctlab/metacherchant. The code is written in Java and is platform-independent.

Supplementary information

Supplementary data are available at Bioinformatics online.
Machine learning annotation of human branchpoints
Authors: Signal Bethany , Gloss Brian S , Dinger Marcel E , Mercer Tim R
Published: October 2017

Motivation

The branchpoint element is required for the first lariat-forming reaction in splicing. However current catalogues of human branchpoints remain incomplete due to the difficulty in experimentally identifying these splicing elements. To address this limitation, we have developed a machine-learning algorithm—branchpointer—to identify branchpoint elements solely from gene annotations and genomic sequence.

Results

Using branchpointer, we annotate branchpoint elements in 85% of human gene introns with sensitivity (61.8%) and specificity (97.8%). In addition to annotation, branchpointer can evaluate the impact of SNPs on branchpoint architecture to inform functional interpretation of genetic variants. Branchpointer identifies all published deleterious branchpoint mutations annotated in clinical variant databases, and finds thousands of additional clinical and common genetic variants with similar predicted effects. This genome-wide annotation of branchpoints provides a reference for the genetic analysis of splicing, and the interpretation of noncoding variation.

Availability and implementation

Branchpointer is written and implemented in the statistical programming language R and is freely available under a BSD license as a package through Bioconductor.

Supplementary information

Supplementary data are available at Bioinformatics online.
Simulating the dynamics of targeted capture sequencing with CapSim
Authors: Cao Minh Duc , Ganesamoorthy Devika , Zhou Chenxi , Coin Lachlan J M
Published: October 2017

Motivation

Targeted sequencing using capture probes has become increasingly popular in clinical applications due to its scalability and cost-effectiveness. The approach also allows for higher sequencing coverage of the targeted regions resulting in better analysis statistical power. However, because of the dynamics of the hybridization process, it is difficult to evaluate the efficiency of the probe design prior to the experiments which are time consuming and costly.

Results

We developed CapSim, a software package for simulation of targeted sequencing. Given a genome sequence and a set of probes, CapSim simulates the fragmentation, the dynamics of probe hybridization and the sequencing of the captured fragments on Illumina and PacBio sequencing platforms. The simulated data can be used for evaluating the performance of the analysis pipeline, as well as the efficiency of the probe design. Parameters of the various stages in the sequencing process can also be evaluated in order to optimize the experiments.

Availability and implementation

CapSim is publicly available under BSD license at https://github.com/Devika1/capsim.

Supplementary information

Supplementary data are available at Bioinformatics online.
pStab: prediction of stable mutants, unfolding curves, stability maps and protein electrostatic frustration
Authors: Gopi Soundhararajan , Devanshu Devanshu , Krishna Praveen , Naganathan Athi N
Published: October 2017

We present a web-server for rapid prediction of changes in protein stabilities over a range of temperatures and experimental conditions upon single- or multiple-point substitutions of charged residues. Potential mutants are identified by a charge-shuffling procedure while the stability changes (i.e. an unfolding curve) are predicted employing an ensemble-based statistical-mechanical model. We expect this server to be a simple yet detailed tool for engineering stabilities, identifying electrostatically frustrated residues, generating local stability maps and in constructing fitness landscapes.

Availability and implementation

The web-server is freely available at http://pbl.biotech.iitm.ac.in/pStab and supports recent versions of all major browsers.

Supplementary information

Supplementary data are available at Bioinformatics online.
Predicting protein–DNA binding free energy change upon missense mutations using modified MM/PBSA approach: SAMPDI webserver
Authors: Peng Yunhui , Sun Lexuan , Jia Zhe , Li Lin , Alexov Emil
Published: October 2017

Motivation

Protein–DNA interactions are essential for regulating many cellular processes, such as transcription, replication, recombination and translation. Amino acid mutations occurring in DNA-binding proteins have profound effects on protein–DNA binding and are linked with many diseases. Hence, accurate and fast predictions of the effects of mutations on protein–DNA binding affinity are essential for understanding disease-causing mechanisms and guiding plausible treatments.

Results

Here we report a new method Single Amino acid Mutation binding free energy change of Protein–DNA Interaction (SAMPDI). The method utilizes modified Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) approach along with an additional set of knowledge-based terms delivered from investigations of the physicochemical properties of protein–DNA complexes. The method is benchmarked against experimentally determined binding free energy changes caused by 105 mutations in 13 proteins (compiled ProNIT database and data from recent references), and results in correlation coefficient of 0.72.

Availability and implementation

http://compbio.clemson.edu/SAMPDI

Supplementary information

Supplementary data are available at Bioinformatics online.
Composite Knots Obtained by Twisting Torus Knots
Authors: Lee Sangyop
Published: October 2017

A twisted torus knot is obtained from a torus knot by performing full twists on some adjacent strands of the torus knot. Morimoto constructed infinitely many twisted torus knots which are composite knots and he conjectured that his knots are all of composite twisted torus knots. We show that his conjecture is almost true by giving a complete list of such twisted torus knots.
The Prevalence of Burnout Among US Neurosurgery Residents
Authors: Shakir Hakeem J , McPheeters Matthew J , Shallwani Hussain , Pittari Joseph E , Reynolds Renée M
Published: October 2017

BACKGROUND

Burnout is a syndrome of emotional exhaustion, depersonalization, and reduced personal accomplishment. Its prevalence among US physicians exceeds 50% and is higher among residents/fellows. This is important to the practice of neurosurgery, as burnout is associated with adverse physical health, increased risk of substance abuse, and increased medical errors. To date, no study has specifically addressed the prevalence of burnout among neurosurgery residents.

OBJECTIVE

To determine and compare the prevalence of burnout among US neurosurgery residents with published rates for residents/fellows and practicing physicians from other specialties.

METHODS

We surveyed 106 US neurosurgery residency training programs to perform a descriptive analysis of the prevalence of burnout among residents. Data on burnout among control groups were used to perform a cross-sectional analysis. Nonparametric tests assessed differences in burnout scores among neurosurgery residents, and the 2-tailed Fisher's exact test assessed burnout between neurosurgery residents and control populations.

RESULTS

Of approximately 1200 US neurosurgery residents, 255 (21.3%) responded. The prevalence of burnout was 36.5% (95% confidence interval: 30.6%-42.7%). There was no significant difference in median burnout scores between gender (P = .836), age (P = .183), or postgraduate year (P = .963) among neurosurgery residents. Neurosurgery residents had a significantly lower prevalence of burnout (36.5%) than other residents/fellows (60.0%; P < .001), early career physicians (51.3%; P < .001), and practicing physicians (53.5%; P < .001).

CONCLUSION

Neurosurgery residents have a significantly lower prevalence of burnout than other residents/fellows and practicing physicians. The underlying causes for these findings were not assessed and are likely multifactorial. Future studies should address possible causes of these findings.
Diagnosis and Outcome of Biopsies of Indeterminate Lesions of the Cavernous Sinus and Meckel's Cave: A Retrospective Case Series in 85 Patients
Authors: Hughes Joshua D , Kapurch Joseph , Van Gompel Jamie J , Meyer Fredric B , Pollock Bruce E , Atkinson John , Link Michael J
Published: October 2017

BACKGROUND

When clinical presentation, laboratory studies, or imaging cannot diagnose cavernous sinus (CS) and/or Meckel's cave (MC) lesions, biopsy may be necessary.

OBJECTIVE

To review our institutional series of biopsies of indeterminate CS and MC lesions.

METHODS

Records from January 1994 to June 2016 were searched for biopsied indeterminate CS and MC lesions. We defined indeterminate as having an atypical imaging appearance or a broad differential and the need for tissue for definitive diagnosis. We defined primary tumors as originating from cells inherent or near the CS and MC.

RESULTS

Eighty-five patients were included (median age 59 [2-85] yr); 22 (28%) had a cancer history. Approaches included frontotemporal craniotomy (n = 48, 56%), endoscopic endonasal (n = 20, 24%), percutaneous transforamen ovale (n = 12, 14%), or retrosigmoid craniotomy (n = 5, 6%). Final diagnosis was metastatic in 27 (32%), primary in 21 (25%), inflammatory in 13 (15%), hematologic in 11 (13%), fungal in 5 (5%), and nondefinitive or nondiagnostic in 8 (10%) patients. Thirteen (59%) patients with a cancer history (n = 22) had a diagnosis consistent with their prior cancer; the remaining had a second pathology (n = 6, 27%) or nondiagnostic biopsy (n = 3, 14%). Two patients had surgical complications resulting in death.

CONCLUSION

In this patient cohort, metastatic tumors were the most likely pathology. The biopsy threshold should be lower in patients with a cancer history if clinical or radiographic diagnosis is uncertain as 27% had a second disease. However, we consider biopsy as a last resort because the risk of major morbidity/mortality, while low, is not zero.
Radiation-Induced Changes After Stereotactic Radiosurgery for Brain Arteriovenous Malformations: A Systematic Review and Meta-Analysis
Authors: Ilyas Adeel , Chen Ching-Jen , Ding Dale , Buell Thomas J , Raper Daniel M S , Lee Cheng-Chia , Xu Zhiyuan , Sheehan Jason P
Published: October 2017

BACKGROUND

Radiation-induced changes (RICs) are the most common complication of stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs), and they appear as perinidal T2-weighted hyperintensities on magnetic resonance imaging, with or without associated neurological symptoms.

OBJECTIVE

To determine the rates of RIC after AVM SRS and identify risk factors.

METHODS

A literature review was performed using PubMed and MEDLINE to identify studies reporting RIC in AVM patients treated with SRS. RICs were classified as radiologic (any neuroimaging evidence), symptomatic (any associated neurological deterioration, regardless of duration), and permanent (neurological decline without recovery). Baseline, treatment, and outcomes data were extracted for statistical analysis.

RESULTS

Based on pooled data from 51 studies, the overall rates of radiologic, symptomatic, and permanent RIC after AVM SRS were 35.5% (1143/3222 patients, 32 studies), 9.2% (499/5447 patients, 46 studies), and 3.8% (202/5272 patients, 39 studies), respectively. Radiologic RIC was significantly associated with lack of prior AVM rupture (odds ratio [OR] = 0.57; 95% confidence interval [CI]: 0.47-0.69; P < .001) and treatment with repeat SRS (OR = 6.19; 95% CI: 2.42-15.85; P < .001). Symptomatic RIC was significantly associated with deep AVM location (OR = 0.38; 95% CI: 0.21-0.67; P < .001).

CONCLUSION

Approximately 1 in 3 patients with AVMs treated with SRS develop radiologically evident RIC, and of those with radiologic RIC, 1 in 4 develop neurological symptoms. Lack of prior AVM hemorrhage and repeat SRS are risk factors for radiologic RIC, and deep nidus location is a risk factor for symptomatic RIC.
Deep Brain Stimulation-Related Infections: Analysis of Rates, Timing, and Seasonality
Authors: Hardaway Fran A , Raslan Ahmed M , Burchiel Kim J
Published: October 2017

BACKGROUND

Infection is one of the most common complications of deep brain stimulation (DBS). Long-term infection rates beyond the immediate postoperative period are rarely evaluated.

OBJECTIVE

To study short- and long-term DBS-related infection rates; to evaluate any potential seasonality associated with DBS-related infections.

METHODS

We retrospectively reviewed all DBS surgeries performed in a 5-yr period at 1 hospital by a single surgeon. Infection rates and clinical characteristics were analyzed. Postoperative “infections” were defined as occurring within 6 mo of implantation of DBS hardware, while “erosions” were defined as transcutaneous exposure of hardware at ≥6 mo after implantation. Based on the date of surgery preceding an infection, rates of infection were calculated on a monthly and seasonal basis and compared using Chi square and logistic regression analyses.

RESULTS

A total of 443 patients underwent 592 operations; 311 patients underwent primary DBS placement with 632 electrodes. Primary DBS placement infection incidence was 2.6%. DBS procedure infection and infection rate by electrode were 2.9% and 3.2%, respectively. Infectious complications presented later than 6 mo postoperatively in 38% of infected patients Summer (July-September) infection rate was significantly higher than other seasons (P = .002). The odds ratio of an infection related to a surgery performed in August was found to be 4.15 compared to other months (P = .021).

CONCLUSION

There is a persistent risk of DBS infection and erosion beyond the first year of DBS implantation. Start of the academic year was associated with increased infection rate at our institution.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on Pathological Methods and Prognostic Factors in Vestibular Schwannomas
Authors: Sughrue Michael E , Fung Kar-Ming , Van Gompel Jamie J , Peterson Jo Elle G , Olson Jeffrey J
Published: October 2017

TARGET POPULATION

Adults diagnosed with vestibular schwannomas.

QUESTION 1

What is the prognostic significance of Antoni A vs B histologic patterns in vestibular schwannomas?

RECOMMENDATION

No recommendations can be made due to a lack of adequate data.

QUESTION 2

What is the prognostic significance of mitotic figures seen in vestibular schwannoma specimens?

RECOMMENDATION

No recommendations can be made due to a lack of adequate data.

QUESTION 3

Are there other light microscopic features that predict clinical behavior of vestibular schwannomas?

RECOMMENDATION

No recommendations can be made due to a lack of adequate data.

QUESTION 4

Does the KI-67 labeling index predict clinical behavior of vestibular schwannomas?

RECOMMENDATION

No recommendations can be made due to a lack of adequate data.

QUESTION 5

Does the proliferating cell nuclear antigen labeling index predict clinical behavior of vestibular schwannomas?

RECOMMENDATION

No recommendations can be made due to a lack of adequate data.

QUESTION 6

Does degree of vascular endothelial growth factor expression predict clinical behavior of vestibular schwannomas?

RECOMMENDATION

No recommendations can be made due to a lack of adequate data.

 The full guideline can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_6.