bluuebunny/crossref_metadata_2025_split huggingface dataset:
Green epithelium revealed by narrow-band imaging (NBI): a feature for practical assessment of extent of gastric cancer after H. pylori eradication
Authors: Yagi Kazuyoshi , Nagayama Itsuo , Hoshi Takahiro , Abe Satoshi , Morita Shin-ichi , Suda Takeshi , Hasegawa Go , Sato Yu-ichi , Terai Shuji 
Published: November 2018

Abstract
Background and study aims Assessment of the extent of gastric cancer detected by endoscopy after successful eradication of H. pylori is often difficult even with narrow-band imaging (NBI)-magnifying endoscopy. Using the latter modality, it has often been noted that the cancerous area has a brownish color surrounded by green epithelium (GE). If the histological origin of this GE could be clarified, it could be of practical use for endoscopic assessment of the extent of cancer.
Materials and methods The endoscopic appearance of gastric cancer after eradication therapy was classified into four types: (A) cancer brownish, surrounding mucosa green; (B) cancer brownish, surrounding mucosa brownish; (C) cancer green, surrounding mucosa brownish; and (D) cancer green, surrounding mucosa green. A histological series of sections taken from tissues in each endoscopic view was stained with HE, and also for CDX2, MUC2, CD10 and MUC5AC. Staining intensity was evaluated by microscopy using a visual analog scale ranging from 0 to 3+: intensities of 0 and 1+ were rated as negative, and those of 2+ and 3+ as positive. Positive or negative immunostaining was examined for each type of endoscopic appearance A – D.
Results Among 42 lesions examined, 16 were type A, 18 type B, 6 type C and 2 type D. MUC2 was positive in the surrounding mucosa in 100 % of type A and D cases, but in only 28 % and 17 % of type B and C cases, respectively.
Conclusions GE observed by NBI-endoscopy corresponds to MUC2-positive mucosa and is thought to be a feature for practical assessment of the extent of cancer.
„Pathway protection“ – Verbesserte Motoneuron-Regeneration
durch additive End-zu-Seit-Koaptation sensorischer Axone
Authors: Györi Eva , Radtke Christine , Gordon Tessa , Borschel Gregory H. 
Published: November 2018

ZusammenfassungDie neuronale Regeneration nach proximaler Nervenverletzung und nach zeitlich
verzögerter Nervenrekonstruktion ist eingeschränkt, was klinisch eine große
Herausforderung darstellt. Experimentelle Studien haben gezeigt, dass die
periphere Nervenregeneration einerseits durch die „chronische Axotomie“ der
neuronalen Zellkörper und der proximalen Axone, welche von ihren Zielstrukturen
getrennt sind und andererseits durch die „chronische Denervation“ des distalen
Nervens beeinträchtigt wird. Der denervierte distale Nerv durchläuft
Veränderungen, die mit der Waller´schen Degeneration assoziiert sind. Es kommt
zu einer Aktivierung der Schwann-Zellen, die mit einwachsenden Axonen
interagieren und deren Regeneration fördern, sowie zu einer Erhöhung der
Konzentration von Wachstumsfaktoren. Diese Veränderungen führen zu der
Entwicklung eines regenerationsfördernden Milieus im distalen Nerven, welches
allerdings zeitlich begrenzt ist und bei lange andauernder Denervation abnimmt.
Dies führt zu einer deutlichen Reduktion der neuronalen Regeneration. In der
klinischen Situation führen proximale Nervenverletzungen, Rekonstruktionen mit
langen Regenerationsdistanzen und verzögerte Nervenrekonstruktionen zu
eingeschränkten funktionellen Ergebnissen. Um die neuronale Regeneration zu
verbessern, wurden verschiedene Techniken der „pathway protection“ entwickelt,
welche die chronische Denervation des distalen Nervens und der Zielorgane
reduzieren sollen. Der Großteil dieser „Babysitter-Techniken“ verwendet
motorische Spendernerven, die meist End-zu-Seit an den denervierten distalen
Nerven koaptiert werden. In experimentellen Studien wurde gezeigt, dass es durch
die einwachsenden Spenderaxone zu einer Erhöhung der Konzentration von
Wachstumsfaktoren kommt und dass die distalen Zielorgane früher reinnerviert
werden können. Durch motorische „Babysitter-Operationen“ wird allerdings ein
motorisches Spendernervdefizit geschaffen. Um dieses zu umgehen wurde in den
letzten Jahren die Möglichkeit der „pathway protection“ mit sensiblen
Spendernerven untersucht. In experimentellen Studien konnte die motorische
Regeneration durch End-zu-Seit-Koaptation sensibler Spendernerven an den
distalen denervierten Nerven, beziehungsweise an lange Nerventransplantate, die
Veränderungen der „chronischen Denervation“ durchlaufen, verbessert werden. Die
sensible „pathway protection“ wurde bereits klinisch eingesetzt, es liegen
allerdings noch keine funktionellen Langzeitergebnisse vor.
Inter-Rater Reliability of Pain Provocation Tests for Painful Lumbar Facet Joints. A Pilot Study
Authors: Thalhamer Christoph , Hahne Julia , Matthijs Omer , Machacek Peter 
Published: November 2018

Abstract
Background With a life-time prevalence of 39%, low back pain (LBP) is one of the most common musculoskeletal disorders. Correct diagnosis of underlying causes is commonly seen as a prerequisite for successful therapy of LBP. Currently, there is no useful, non-invasive clinical test to diagnose painful lumbar zygapophyseal joints. Clinical tests with high diagnostic accuracy are therefore desirable. Inter-rater reliability is commonly seen as a prerequisite of test validity. The objective of this pilot study was thus to evaluate inter-rater reliability of new clinical pain provocation tests for diagnosing painful lumbar zygapophyseal joints. If a clinically significant level of inter-rater reliability were to be determined, this study could constitute a first step towards establishing the clinical utility of this new set of tests in the structural diagnosis of low back disorders.
Material and Methods Patients participating in this study were recruited in a specialist hospital throughout June 2015 until September 2016. Both female and male patients with current LBP, with or without buttock or lower extremity symptoms were screened for inclusion. Patients had preferably to be 50 years or older in order to be included in this study. The upper age limit was set at 90 years. They also had to be fluent in German to be able to follow verbal instructions. Exclusion criteria comprised the presence of red flags, surgical spinal fusion at any level of the lumbar spine, discectomy within the past 12 months, radiculopathy and/or radicular pain, interventional treatments for the IVD, SIJs or ZAJs within the past three months, psychiatric disorders, current litigation issues concerning back pain, and central nervous system diseases. Three certified manual therapy instructors tested patients independently. Fleissʼ kappa values and percent agreements were calculated.
Results Subjects included a sample of 48 patients (15 males and 33 females) with a mean age of 66.48 years (range 33 – 90) presenting at a specialist hospital with low back pain. The new pain provocation tests for lumbar zygapophyseal joints showed moderate reliability (Fleissʼ κ = 0.46) and an overall percent agreement of 68.8%. Separate tests for the zygapophyseal joints of L5–S1 showed fair reliability (Fleissʼ κ = 0.37) and an overall percent agreement of 64.6%. Unidimensional tests that were used in the study to exclude the intervertebral disc as a nociceptive generator showed fair reliability as well (average κ of 0.28 and 0.39, respectively). Neither drop outs nor adverse events occurred.
Conclusion The new pain provocation tests for lumbar zygapophyseal joints showed clinically significant levels of inter-rater reliability. Validation of these tests against fluoroscopy-guided medial branch blocks is warranted.
Percutaneous K-wires vs palmar locking plate fixation for
different types of distal radial fractures: a comparison of the outcomes of two
methods to controll our guidelines
Authors: Zyluk Andrzej , Janowski Piotr , Szlosser Zbigniew , Puchalski Piotr 
Published: November 2018

AbstractThe objective of the study was a comparison of the outcomes of K-wire vs plate
fixation for distal radial fractures used according to the proposed
institutional algorithm. Fracture configurations A2, A3, B1, B2, C1 and some C2
were operated on with K-wire pinning, whereas B3 and some B2, C3 and some C2
were with locking palmar-plate fixation.
Patients and Methods: Four hundred and sixty-seven patients were
non-randomly allocated for either K-wire (n = 363) or palmarplate (n = 104)
fixation. The results were assessed at 3 and 12 months by the same outcome
measures.
Results: At the 3-month assessment, statistically significant differences
in grip strength and the DASH scores were noted in favour of the plate-fixation
group. At the 12-month assessment, statistically significant differences were
observed in the wrist palmar and dorsal flexion, favouring the plate-fixation
group. Statistically significant differences were noted in radiological measures
of the palmar tilt and the ulnar variance, both favouring the plate-fixation
method. Meaningful secondary dislocations were noted in ten patients, all in the
K-wire-fixation group.
Conclusion: We conclude that palmar locking plate fixation in even more
severe fractures leads to better radiological and clinical outcomes than K-wire
fixation in less severe fractures.
Die Korrektur intraartikulärer Fehlstellungen am distalen
Radius auf der Basis computergestützter virtueller Planungen
Authors: Pillukat Thomas , Osorio Maria , Prommersberger Karl-Josef 
Published: November 2018

Zusammenfassung
Hintergrund Die computerassistierte virtuelle 3D-Planung von
extraartikulären Korrekturen am distalen Radius und die Übertragung der
virtuellen Planung auf den Radius in vivo wurde bereits kürzlich beschrieben. Im
Gegensatz dazu fehlen bisher ähnliche Studien zu intraartikulären Korrekturen.
Unter Berücksichtigung der technischen Schwierigkeiten und potentiellen Risiken
wäre eine Methode, die die Probleme des begrenzten Zuganges und der
Schwierigkeiten von Reposition und Fixation überwindet, wertvoll. Die
vorliegende Studie präsentiert eine Technik für intraartikuläre Korrekturen am
distalen Radius, basierend auf einer computergestützten 3D-virtuellen Planung
und individuell gefertigten patientenspezifischen Instrumenten.
Patienten und Methoden Zwischen 2013 und 2016 unterzogen sich 6 Patienten
(1 weiblich, 5 männlich) einer intraartikulären Korrekturosteotomie am distalen
Radius. Das Durchschnittsalter betrug 48 (38–60) Jahre, das Intervall zwischen
Unfall und Korrektur betrug 10 (4–13) Monate. Alle Patienten waren vorhergehend
auswärts operiert worden. Die computerassistierte Planung wurde in
Zusammenarbeit mit einem industriellen Partner (Materialise NV, 15
Technologielaan, 3001 Leuven, Belgium) durchgeführt. Dazu wurden im eigenen Haus
CT-Schnitte beider Handgelenke und Unterarme anhand eines speziellen Protokolls
angefertigt, aus denen beide distalen Radii virtuell rekonstruiert wurden. Das
Spiegelbild der 3D-Rekonstruktion des unverletzten Radius wurde dem 3-D-Bild des
fehlverheilten Radius überlagert, sodass die Fehlstellung exakt erkennbar war.
Die Korrektur wurde Schritt für Schritt virtuell im Rahmen einer
Online-Konferenz geplant. Die Stabilisierung der Fragmente wurde durch das
Einfügen von Platten und Schrauben in die 3D-Darstellung simuliert. Basierend
auf dieser Planung wurden für jeden Schritt patientenspezifische Bohr- und
Sägeschablonen angefertigt (Fa. Materialise) und an die eigene Einrichtung
ausgeliefert. Das operative Vorgehen und die Technik werden anhand eines
typischen Beispiels dargestellt und variierten mit den individuellen
Gegebenheiten.
Ergebnisse Es traten keine Komplikationen auf. Alle Patienten zeigten eine
knöcherne Heilung. Zusätzliche Eingriffe waren nicht erforderlich. Postoperative
Computertomographien zeigten, dass Stufenbildungen in der Regel gut korrigiert
wurden, hingegen Spaltbildungen oft fortbestanden.
Syntheses of Cyclomarins – Interesting Marine Natural Products with Distinct Mode of Action towards Malaria and Tuberculosis
Authors: Kiefer Alexander , Kazmaier Uli 
Published: November 2018

The cyclomarins are cyclic heptapeptides from marine streptomycetes containing four rather unusual amino acids. Interestingly, the cyclomarins address two completely different targets: ClpC1, a subunit of the caseinolytic protease of Mycobacterium tuberculosis (MTB), as well as PfAp3Aase of Plasmodium falciparum. Therefore, the cyclomarins are interesting lead structures for the development of drugs targeting tuberculosis and malaria. As a result, several synthetic protocols towards the synthesis of these unusual building blocks as well as the natural products themselves have been developed, which will be discussed in this review.1	Introduction2	Synthesis of the Building Blocks3	Total Synthesis of Cyclomarin C by Yao and Co-workers4	Total Synthesis of Cyclomarin A and C by Barbie and Kazmaier5	Conclusion
‘Heteroaromatic Rings of the Future’: Exploration of Unconquered Chemical Space
Authors: Thorimbert Serge , Botuha Candice , Passador Kevin 
Published: November 2018

William Pitt and co-workers have created a virtual exploratory heterocyclic library ‘VEHICLe’ containing over 200 unconquered bicyclic heteroaromatic rings, synthetically feasible with potential medicinal interest. Since the publication of the 22 ‘heteroaromatic rings of the future’ by Pitt in 2009, 15 of them have been successfully synthesized as bicyclic or polycyclic forms and evaluated for applications in both biology and material science. This short review presents the critical synthesis associated with innovative synthetic methodologies of the synthetically conquered ring scaffolds from the list of 22 with a spotlight on the scientific contribution of this fascinating article for the expansion of the chemical diversity.1	Introduction2	Heteroaromatic Rings of the Future: The Synthetic challenge?2.1	4-Pyrido[1,3]oxazin-4-one-P1
2.2	Pyrrolo[2,1-b][1,3]oxazin-4-one-P4
2.3	Furo[2,1-e]pyridazin-4(1H)-one-P5
2.4	Isoxazolo[3,4-c]pyridin-7-one-P6
2.5	5H,6H-[1,2]Thiazolo[5,4-c]pyridin-5-one-P7
2.6	4H,5H-Furo[3,2-b]pyridin-5-one-P8
2.7	1H,5H,6H-Pyrazolo[3,4-c]pyridin-5-one-P9
2.8	Thieno[3,4-c]pyridazine-P10
2.9	Pyrrolo[1,2-c][1,2,3]triazine-P11
2.10	Thieno[3,4-a]oxazole-P12
2.11	2,4-Dihydropyrrolo[3,2-c]pyrazole-P13
2.12	Pyrazolo[1,5-b]isoxazole-P14
2.13	Imidazo[1,5-c]pyrimidin-3(2H)-one-P16
2.14	Cyclopenta[b][1,4]oxazin-5(4H)-one-P17
2.15	2,3-Dihydro-2,6-naphthyridin-3-one-P18
3	Conclusion
Alveolar Hemorrhage in Vasculitis (Primary and Secondary)
Authors: Nasser Mouhamad , Cottin Vincent 
Published: November 2018

AbstractDefined by the accumulation of red blood cells into the alveolar space, diffuse alveolar hemorrhage (DAH) is a severe and potentially fatal medical condition requiring careful attention. In contrast to simple extravasation of erythrocytes facilitated by impaired hemostasis or hemodynamic causes, DAH in vasculitis is due to capillaritis, that is, inflammation of capillaries. Dyspnea, hemoptysis, chest infiltrates, and abrupt fall of blood hemoglobin level represent the cardinal features of DAH; yet, hemoptysis is lacking in one-third of cases. Bronchoalveolar lavage, retrieving bright red fluid, is the best diagnostic clue, also excluding infection and other causes of hemoptysis. Although not recommended, lung biopsy is the gold standard for the diagnosis of DAH and pulmonary capillaritis. Pulmonary capillaritis may be primary as in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis or secondary to drugs (especially antithyroid drugs such as propylthiouracil), infections, connective tissue diseases especially systemic lupus erythematosus, or other small vessel vasculitides. Newer toxic causes of drugs of abuse may be difficult to diagnose. Granulomatosis with polyangiitis and microscopic polyangiitis are the most common causes of capillaritis and DAH, whereas DAH is extremely rare in eosinophilic granulomatosis with polyangiitis. When pulmonary capillaritis is not secondary to underlying systemic vasculitis, idiopathic pauci-immune pulmonary capillaritis may be considered, with or without ANCA. Supportive treatment strategy is mandatory in all cases of DAH. Mechanical ventilation and extracorporeal membrane oxygenation may be used in severe cases. Early identification and removal of the putative drug is crucial in drug-induced vasculitis/DAH and may obviate the need for immunosuppressive therapy. High-dose corticosteroids, intravenous cyclophosphamide, and recently rituximab are the mainstay of treatment in vasculitis. Plasma exchange is recommended in anti–glomerular basement membrane disease and in severe DAH associated with systemic lupus erythematosus and is used in selected cases in ANCA-associated vasculitis.
Musculoskeletal Radiology in the Middle East: Training Programs, Current Practice, and Future Directions
Authors: Ashkanani Ali , Alkhayat Abdullah 
Published: November 2018

AbstractThis article outlines the development of radiology training in the Middle East. It discusses the history of radiology in the region and current available pathways to subspecialize in musculoskeletal (MSK) radiology. Owing to the rapidly changing demographics and health indicators in the region, a major shift has occurred in the government's focus in directing more resources to advance the health care system. This in addition to intraregional initiatives, such as the establishment of many radiologic societies, has provided strong incentives toward developing radiology training programs in the region. There are profound differences in the region regarding the development of radiology, with only few countries offering structured radiology training programs and MSK radiology fellowships. To keep up with the explosion of information in imaging technology and hold clinical ground, current and future MSK radiologists must overcome certain challenges and change their approach to stay clinically relevant.
Apnea Threshold in Pediatric Brain Death: A Case with Variable Results Across Serial Examinations
Authors: Sosa Tina , Berrens Zachary , Conway Susan , Stalets Erika 
Published: November 2018

AbstractConsensus guidelines currently exist for the evaluation of pediatric patients with suspected brain death. The guidelines include the requirement for two consistent examinations separated by an observation period and a threshold of 60 mm Hg for PaCO2 during apnea testing. We present a patient who met all prerequisites to perform brain death examination but had variability in examinations during apnea testing. We discuss our strategy in managing these unexpected findings, including the importance of open and ongoing communication with the family, and the implications for current guidelines for the determination of brain death in pediatric patients.
NOXA genetic amplification or pharmacologic induction primes lymphoma cells to BCL2 inhibitor-induced cell death
Authors: Liu Yuxuan , Mondello Patrizia , Erazo Tatiana , Tannan Neeta Bala , Asgari Zahra , de Stanchina Elisa , Nanjangud Gouri , Seshan Venkatraman E. , Wang Shenqiu , Wendel Hans-Guido , Younes Anas 
Published: November 2018

Significance
BCL2 selective inhibitors are promising agents currently under clinical investigation for treatment of BCL2-dependent cancers. However, the clinical activity of BCL2 inhibitors in patients with diffuse large B cell lymphoma (DLBCL) has been disappointing. In this study, we identified PMAIP1/NOXA gene amplification as a marker of sensitivity to BCL2 inhibitors in DLBCL. Cells lacking NOXA amplification were less sensitive to BCL2 inhibitors due to codependency on MCL1 and BCL2 proteins. We show that pharmacologic induction of NOXA by the HDAC inhibitor panobinostat primes DLBCL to BCL2 inhibitor-induced cell death by disrupting the codependency on BCL2 and MCL1, mimicking the biologic effects of NOXA genetic amplification. Our data provide a mechanistic rationale for combining HDAC inhibitors with BCL2 inhibitors in DLBCL.
Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists
Authors: Liu Hongtao , Hofmann Josefa , Fish Inbar , Schaake Benjamin , Eitel Katrin , Bartuschat Amelie , Kaindl Jonas , Rampp Hannelore , Banerjee Ashutosh , Hübner Harald , Clark Mary J. , Vincent Sandra G. , Fisher John T. , Heinrich Markus R. , Hirata Kunio , Liu Xiangyu , Sunahara Roger K. , Shoichet Brian K. , Kobilka Brian K. , Gmeiner Peter 
Published: November 2018

Significance
The development of selective antagonists for muscarinic acetylcholine receptors is challenging due to high homology in orthosteric binding sites among subtypes. Starting from a single amino acid difference in the orthosteric pockets in M2 muscarinic acetylcholine receptor (M2R) and M3R, we developed an M3R-selective antagonist using molecular docking and structure-based design. The resulting M3R antagonist showed up to 100-fold selectivity over the M2R in affinity and 1,000-fold selectivity in vivo. The docking-predicted geometry was further confirmed by a 3.1 Å crystal structure of M3R in complex with the selective antagonist. The potential of structure-based design to develop selective drugs with reduced off-target effects is supported by this study.
Evolution of weak cooperative interactions for biological specificity
Authors: Gao Ang , Shrinivas Krishna , Lepeudry Paul , Suzuki Hiroshi I. , Sharp Phillip A. , Chakraborty Arup K. 
Published: November 2018

Significance
Functional specificity in biology is mediated by two classes of mechanisms, “lock–key” interactions and multivalent weak cooperative interactions (WCI). Despite growing evidence that WCI are widely prevalent in higher organisms, little is known about the selection forces that drove its evolution and repeated positive selection for mediating biological specificity in metazoa. We report that multivalent WCI for mediating biological specificity evolved as the number of tasks that organisms had to perform with functional specificity became large (e.g., multicellular organisms). We find that the evolution of multivalent WCI confer enhanced and robust evolvability to organisms, and thus it has been repeatedly positively selected. Thus, we provide insights on the evolution of WCI and, more broadly, on the evolution of evolvability.
Comparing introductory sections in city audio guides in Italian and English
Authors: Fina Maria Elisa 
Published: November 2018

Abstract
The aim of this paper is to analyse introductory sections in Italian, British/Irish and American city audio guides
from a contrastive perspective, in order to identify possible differences in the type and distribution of content. Three main
content types and their corresponding subtypes were identified in the introductions of fifty professional city audio guides and
were both quantitatively and qualitatively compared across the three groups. Differences between audio guides in Italian and in
English are identified and discussed in reference to Hall’s ‘contexting’ theory (1983,
1990), and the findings are then compared to existing guidelines for audio guides
production provided by scholars and professionals in the field. Finally, on the basis of the results, translation issues are
addressed by providing a list of aspects that could be taken into account when producing English versions of Italian audio
guides.