bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate Granger causality unveils directed parietal to prefrontal cortex connectivity during task-free MRI
Authors: Duggento Andrea , Passamonti Luca , Valenza Gaetano , Barbieri Riccardo , Guerrisi Maria , Toschi Nicola 
Published: March 2018

AbstractWhile a large body of research has focused on the study of functional brain “connectivity”, few investigators have focused on directionality of brain-brain interactions which, in spite of the mostly bidirectional anatomical substrates, cannot be assumed to be symmetrical. We employ a multivariate Granger Causality-based approach to estimating directed in-network interactions and quantify its advantages using extensive realistic synthetic BOLD data simulations to match Human Connectome Project (HCP) data specification. We then apply our framework to resting state functional MRI (rs-fMRI) data provided by the HCP to estimate the directed connectome of the human brain. We show that the functional interactions between parietal and prefrontal cortices commonly observed in rs-fMRI studies are not symmetrical, but consists of directional connectivity from parietal areas to prefrontal cortices rather than vice versa. These effects are localized within the same hemisphere and do not generalize to cross-hemispheric functional interactions. Our data are consistent with neurophysiological evidence that posterior parietal cortices involved in processing and integration of multi-sensory information modulate the function of more anterior prefrontal regions implicated in action control and goal-directed behaviour. The directionality of functional connectivity can provide an additional layer of information in interpreting rs-fMRI studies both in health and disease.
Epigenetic alterations to Polycomb targets precede malignant transition in a mouse model of breast cancer
Authors: Cai Ying , Lin Jhih-Rong , Zhang Quanwei , O’Brien Kelly , Montagna Cristina , Zhang Zhengdong D. 
Published: March 2018

AbstractMalignant breast cancer remains a major health threat to women of all ages worldwide and epigenetic variations on DNA methylation have been widely reported in cancers of different types. We profiled DNA methylation with ERRBS (Enhanced Reduced Representation Bisulfite Sequencing) across four main stages of tumor progression in the MMTV-PyMT mouse model (hyperplasia, adenoma/mammary intraepithelial neoplasia, early carcinoma and late carcinoma), during which malignant transition occurs. We identified a large number of differentially methylated cytosines (DMCs) in tumors relative to age-matched normal mammary glands from FVB mice. Despite similarities, the methylation differences of the premalignant stages were distinct from the malignant ones. Many differentially methylated loci were preserved from the first to the last stage throughout tumor progression. Genes affected by methylation gains were enriched in Polycomb repressive complex 2 (PRC2) targets, which may present biomarkers for early diagnosis and targets for treatment.
Rudhira/BCAS3 is essential for mouse development and cardiovascular patterning
Authors: Shetty Ronak , Joshi Divyesh , Jain Mamta , Vasudevan Madavan , Paul Jasper Chrysolite , Bhat Ganesh , Banerjee Poulomi , Abe Takaya , Kiyonari Hiroshi , VijayRaghavan K. , Inamdar Maneesha S. 
Published: March 2018

AbstractRudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein that promotes directional cell migration and angiogenesis in vitro and is implicated in human carcinomas and coronary artery disease. To study the role of Rudhira during development in vivo, we generated the first knockout mouse for rudhira and show that Rudhira is essential for mouse development. Rudhira null embryos die at embryonic day (E) 9.5 accompanied by severe vascular patterning defects in embryonic and extra-embryonic tissues. To identify the molecular processes downstream of rudhira, we analyzed the transcriptome of intact knockout yolk sacs. Genome-wide transcriptome analysis showed that Rudhira functions in angiogenesis and its related processes such as cell adhesion, extracellular matrix organization, peptidase activity and TGFβ signaling. Since Rudhira is also expressed in endothelial cells (ECs), we further generated Tie2Cre-mediated endothelial knockout (CKO) of rudhira. CKO embryos survive to E11.5 and similar to the global knockout, display gross vascular patterning defects, showing that endothelial Rudhira is vital for development. Further, Rudhira knockdown ECs in culture fail to sprout in a spheroid-sprouting assay, strongly supporting its role in vascular patterning. Our study identifies an essential role for Rudhira in blood vessel remodeling and provides a mouse model for cardiovascular development.
Metformin adapts its cellular effects to bioenergetic status in a model of metabolic dysfunction
Authors: Auger Christopher , Sivayoganathan Thibacg , Abdullahi Abdikarim , Parousis Alexandra , Pang Bo Wen , Jeschke Marc G. 
Published: March 2018

AbstractThermal injury induces a complex immunometabolic response, characterized by hyperglycemia, extensive inflammation and persistent hypermetabolism. It has been suggested that attenuation of the hypermetabolic response is beneficial for patient wellbeing. To that effect, metformin represents an attractive therapeutic agent, as its effects on glycemia, inflammation and bioenergetics can improve outcomes in burn patients. Therefore, we studied metformin and its effects on mitochondrial bioenergetics in a murine model of thermal injury. We set out to determine the impact of this agent on mitochondrial hypermetabolism (adult mice) and mitochondrial dysfunction (aged mice). Seahorse respirometry complimented by in-gel activity assays were used to elucidate metformin’s cellular mechanism. We found that metformin exerts distinctly different effects, attenuating the hypermetabolic mitochondria of adult mice while significantly improving mitochondrial bioenergetics in the aged mice. Furthermore, we observed that these changes occur both with and without adenosine monophosphate kinase (AMPK) activation, respectively, and analyzed damage markers to provide further context for metformin’s beneficial actions. We suggest that metformin has a dual role following trauma, acting via both AMPK-dependent and independent pathways depending on bioenergetic status. These findings help further our understanding of metformin’s biomolecular effects and support the continued use of this drug in patients.
Ventilator Dependence Risk Score for the Prediction of Prolonged Mechanical Ventilation in Patients Who Survive Sepsis/Septic Shock with Respiratory Failure
Authors: Chang Ya-Chun , Huang Kuo-Tung , Chen Yu-Mu , Wang Chin-Chou , Wang Yi-Hsi , Tseng Chia-Cheng , Lin Meng-Chih , Fang Wen-Feng 
Published: March 2018

AbstractWe intended to develop a scoring system to predict mechanical ventilator dependence in patients who survive sepsis/septic shock with respiratory failure. This study evaluated 251 adult patients in medical intensive care units (ICUs) between August 2013 to October 2015, who had survived for over 21 days and received aggressive treatment. The risk factors for ventilator dependence were determined. We then constructed a ventilator dependence (VD) risk score using the identified risk factors. The ventilator dependence risk score was calculated as the sum of the following four variables after being adjusted by proportion to the beta coefficient. We assigned a history of previous stroke, a score of one point, platelet count less than 150,000/μL a score of one point, pH value less than 7.35 a score of two points, and the fraction of inspired oxygen on admission day 7 over 39% as two points. The area under the curve in the derivation group was 0.725 (p < 0.001). We then applied the VD risk score for validation on 175 patients. The area under the curve in the validation group was 0.658 (p = 0.001). VD risk score could be applied to predict prolonged mechanical ventilation in patients who survive sepsis/septic shock.
Microwave index engineering for slow-wave coplanar waveguides
Authors: Rosa Álvaro , Verstuyft Steven , Brimont Antoine , Thourhout Dries Van , Sanchis Pablo 
Published: March 2018

AbstractMicrowave index engineering has been investigated in order to properly design slow-wave coplanar waveguides suitable for a wide range of applications in microwave, photonics, plasmonics and metamaterials. The introduction and optimization of novel capacitive and inductive elements is proposed as a design approach to increase the microwave index while keeping the impedance close to 50 Ω to ensure the compatibility with external electronic devices. The contribution of inductive and capacitive elements and their influence on the performance of the slow-wave coplanar waveguide has been systematically analyzed. As a result, a microwave index as high as 11.6 has been experimentally demonstrated in a frequency range up to 40 GHz which is, to the best of our knowledge, the largest microwave index obtained so far in coplanar waveguides.
Anti-inflammatory effects in a mouse osteoarthritis model of a mixture of glucosamine and chitooligosaccharides produced by bi-enzyme single-step hydrolysis
Authors: Li Yali , Chen Liang , Liu Yangyang , Zhang Yong , Liang Yunxiang , Mei Yuxia 
Published: March 2018

AbstractWe developed a novel technique of bi-enzyme single-step hydrolysis, using recombinant chitosanase (McChoA) and exo-β-D-glucosaminidase (AorCsxA) constructed previously in our lab, to degrade chitosan. The hydrolysis product was shown by HPLC, FTIR, and chemical analyses to be a mixture (termed “GC”) composed primarily of glucosamine (80.00%) and chitooligosaccharides (9.80%). We performed experiments with a mouse osteoarthritis (OA) model to evaluate the anti-inflammatory effects of GC against OA. The three “GC groups” (which underwent knee joint damage followed by oral administration of GC at concentrations 40, 80, and 160 mg/kg·bw·d for 15 days) showed significantly downregulated serum expression of pre-inflammatory cytokines (IL-1β, IL-6, TNF-α), and significant, dose-dependent enhancement of anti-inflammatory cytokine IL-2, in comparison with Model group. Levels of C-reactive protein, which typically rise in response to inflammatory processes, were significantly lower in the GC groups than in Model group. Thymus index and levels of immunoglobulins (IgG, IgA, IgM) were higher in the GC groups. Knee joint swelling was relieved and typical OA symptoms were partially ameliorated in the GC-treated groups. Our findings indicate that GC has strong anti-inflammatory effects and potential as a therapeutic agent against OA and other inflammatory diseases.
Nonlinear inelastic electron scattering from Au nanostructures induced by localized surface plasmon resonance
Authors: Li ZheAn , Xu ChunKai , Liu WenJie , Li Meng , Chen XiangJun 
Published: March 2018

AbstractNonlinear electron scattering is a recently-discovered physical process observed during the localized plasmonic excitation of Ag nanostructures on graphite surface. In the present work, nonlinear electron scattering phenomena is experimentally verified on Au nanostructures by measuring inelastic scattering of electrons field-emitted from tungsten tip. The relative intensity of the electron-energy-loss peak associated with the plasmonic excitation of Au shows again to increase nonlinearly with the electric field generated by the tip-sample bias, demonstrating the generality of nonlinear electron scattering process in plasmonic system. Compared to the nonlinear electron scattering phenomena observed on Ag nanostructures, the nonlinear term for Au nanostructures is about 1 to 2 orders of magnitude smaller, which is in consistent with the field enhancement factor of Au and Ag nanostructures from both the surface-enhanced Raman spectroscopy experiments and the theoretical calculations.
Antibiotikatherapie bei COPD-Exazerbationen
Authors: Rohde Gernot G.U. 
Published: March 2018

ZusammenfassungCOPD-Exazerbationen halten mehrere Wochen an und haben einen negativen Einfluss auf die Lungenfunktion und die Lebensqualität. Sie sind mit einer deutlich
erhöhten Morbidität und Mortalität assoziiert, vor allem bei Krankenhausaufnahme. Je schwerer die zugrundeliegende COPD ist, desto höher ist das Risiko für
schwere Exazerbationen, welche wiederum eine Krankhausaufnahme bedingen. Zu den Auslösern einer COPD-Exazerbation zählen Temperaturveränderungen,
Luftverschmutzung und Zigarettenrauchen. Atemwegsinfektionen, ausgelöst durch Bakterien, vor allem aber durch Viren stellen mit zusammen mehr als 80 % mit
Abstand die häufigsten Auslöser dar. Zur Standardtherapie einer COPD-Exazerbation zählt die Therapie der Atemwegsentzündung, die Therapie der Obstruktion und
die Therapie der respiratorischen Insuffizienz. Inwieweit der Einsatz von Antibiotika einen zusätzlichen Nutzen beim Management von COPD-Exazerbationen hat,
muss kontrolliert zur Standardtherapie untersucht werden. Grundsätzlich ist der Einsatz von Antibiotika auf die Fälle zu begrenzen, bei denen sicher von einer
bakteriellen Genese auszugehen ist, was häufig an der Sputum-Purulenz festgemacht werden kann. Da es keine Evidenz für den Einsatz von Antibiotika bei der
leichtgradigen Exazerbation (ambulante Therapie) gibt, sollte hier weitgehend auf den Einsatz von Antibiotika verzichtet werden. Bei mittel- bis schwergradiger
COPD und nachgewiesener Sputumpurulenz kann der Einsatz von Antibiotika erwogen werden. Bei der schwergradigen Exazerbation mit der Notwendigkeit intensivierter
Überwachung und Therapie werden in der Regel Antibiotika verordnet, wobei auch hier der Einsatz kritisch beurteilt werden muss. Wichtig ist in diesen Fällen,
wiederholte Gaben derselben Substanzklasse zu vermeiden und somit bewusst sequentiell unterschiedliche Substanzklassen einzusetzen.
Antikoagulation bei Niereninsuffizienz und Vorhofflimmern
Authors: Alscher Mark Dominik 
Published: March 2018

ZusammenfassungChronische Nierenerkrankungen (CKD) nehmen weltweit zu. Es kann heute damit gerechnet werden, dass bis zu 15 % der erwachsenen Weltbevölkerung eine CKD haben.
Ein Vorhofflimmern findet sich bei CKD gehäuft. Bei Hämodialysepatienten findet sich dieses beispielsweise in bis zu 12 % der Patienten. Auch lässt sich eine
erhöhte Rate von ischämischen apoplektischen Insulten demonstrieren (um das 1,6-fache gesteigert). Eine Antikoagulation bei Vorhofflimmern bei CKD ist jedoch
umstritten. Daten zeigen einen positiven Effekt in den Stadien vor Dialysepflichtigkeit. Für Dialysepatienten konnte dies so nicht bestätigt werden, im
Gegenteil, die Nebenwirkungen der Antikoagulation, spezielle große Blutungsereignisse, waren gesteigert. Deshalb mag der Hinweis wichtig sein, dass es bei
Dialysepatienten keinen Automatismus gibt, der eine Antikoagulation bei Vorhofflimmern zwingend vorsieht. Wenn eine Antikoagulation bei Patienten mit
Dialysepflichtigkeit durchgeführt wird, muss für diese Population derzeit Phenprocoumon empfohlen werden. In den Stadien zuvor (KDIGO G1–4) wird eine
Antikoagulation bei Vorhofflimmern generell empfohlen, bis zu einer Creatinin-Clearance von (15)–30 ml/min kommen auch neuere Substanzen in Betracht
(NOAKs).
The impact of Endocuff-assisted colonoscopy on adenoma detection in an organized screening program
Authors: Cavallaro Lucas , Hassan Cesare , Lecis Pierenrico , Galliani Ermenegildo , Dal Pont Elisabetta , Iuzzolino Paolo , Roldo Claudia , Soppelsa Fabio , Germanà Bastianello 
Published: March 2018

Abstract
Background and study aims Colorectal cancer (CRC) screening with biennial fecal occult blood test has been shown to reduce CRC mortality. For the effectiveness of the CRC screening program is crucial that a high-quality colonoscopy with a high adenoma detection rate (ADR) be performed. To improve ADR, various endoscopic devices have been developed. Endocuff, an endoscopic cap with finger-like projections, has been shown to improve ADR. The aim of this study was to compare in an organized CRC screening program ADR, advanced adenoma detection rate (AADR) and mean number of adenomas per patient (MAP) using standard colonoscopy (SC) and Endocuff-assisted colonoscopy (EAC).
Patients and methods We compared performance of SC (in 2014) and EAC (in 2015) in consecutive participants in an organized CRC screening program.
Results SC and EAC were performed in 546 (284 males) and 519 (293 males) subjects, respectively (mean age 60 years). Cecal intubation rate was 97.4 % for SC and 97.1 % for EAC and not significantly different (P = 0.7). ADR was 47 % for SC and 52 % for EAC, P = 0.1. MAP in SC and EAC were 0.87 (range: 0 – 7) and 1.11 (range: 0 – 13) respectively, P = 0.02. AADR rate was 25 % and 23 % for SC and EAC, respectively, P = 0.5.
Conclusion Endocuff-assisted colonoscopy does not improve the number of patients with at least one adenoma but it may increase the number of detected adenomas per procedure.
Disparity between Preoperative and Pre-Excisional Intraoperative Parathyroid Hormone in Parathyroid Surgery
Authors: Masood Maheer , Hackman Trevor 
Published: March 2018

Introduction Intraoperative parathyroid hormone (ioPTH) testing is a widely accepted standard for assessing the parathyroid gland function. A decline of preoperative parathyroid hormone (PTH) levels by more than 50% is one accepted measure of parathyroid surgery adequacy. However, there may be a variation between preoperative PTH levels obtained at a clinic visit and pre-excisional ioPTH.
Objective Our study explores the differences between preoperative PTH and pre-excisional ioPTH levels, and the potential impact this difference has on determining the adequacy of parathyroid surgery.
Methods A retrospective study that consisted of 33 patients that had undergone parathyroid resection between September 2009 and March 2016 at a tertiary academic center was performed. Each subject's preoperative PTH levels were obtained from clinic visits and pre-excisional ioPTH levels were recorded along with the time interval between the measurements.
Results There was a significant difference between the mean preoperative PTH and the pre-excisional ioPTH levels of 147 pg/mL (95% confidence interval [CI] 11.43 to 284.47; p = 0.0396). The exclusion of four outliers revealed a further significant difference with a mean of 35.09 pg/mL (95% CI 20.27 to 49.92; p < 0.0001). The average time interval between blood draws was 48 days + 32 days. A weak correlation between the change in PTH values and the time interval between preoperative and pre-excision blood draws was noted (r2 = 0.15).
Conclusion Our study reveals a significant difference between the preoperative PTH levels obtained at clinic visits and the pre-excisional intraoperative PTH levels. We recommend routine pre-excisional intraoperative PTH levels, despite evidence of elevated preoperative PTH levels, in order to more accurately assess the adequacy of surgical resection.
Reconstrucción de esquina posteromedial: reporte de 30 casos
Authors: Leon Agustin , Mena Adolfo , Figueroa Francisco , Tuca Maria Jesús , Ferrer Gonzalo , Espinoza Gonzalo 
Published: March 2018

Objetivo Reportar la experiencia, después de 1 año de seguimiento, de una serie de 30 pacientes sometidos a reconstrucción de la esquina posteromedial (EPM) con la técnica descrita por La Prade.
Método Cohorte retrospectiva de 30 pacientes con lesión de EPM operados por el mismo equipo quirúrgico. Criterios de inclusión: diagnóstico clínico, radiografía con estrés y resonancia magnética compatibles con lesión de EPM, inestabilidad grado III luego de 3 meses de tratamiento ortopédico, técnica de reconstrucción de La Prade, al menos 12 meses de seguimiento. Criterios de exclusión: discordancia entre clínica e imagenología, inestabilidad grado I o II, y otra técnica quirúrgica. Evaluación con IKDC y Lysholm antes de la cirugía, a los 6 y 12 meses de seguimiento postcirugía.
Resultados 30 pacientes cumplieron los criterios de inclusión. Promedio de edad 43 años (24–69). Veintiocho pacientes presentaron lesiones de alta energía, 20 pacientes fueron diagnosticados en agudo, mientras que 10 fueron diagnosticados luego de malos resultados en reconstrucción de otros ligamentos. Veintiocho presentaron lesiones asociadas: 11 casos asociados a lesión de ligamento cruzado anterior, 3 casos asociados a lesión de ligamento cruzado posterior, 3 casos en asociación con lesiones meniscales, 9 casos con lesión asociada de ligamento cruzado anterior y posterior, y 2 casos en asociación con ligamento cruzado anterior, posterior y ligamento colateral lateral. Promedio de tiempo hasta la reconstrucción de EPM fue de 5 meses (rango 2–32). Puntuación en Lysholm e IKDC (preoperatorio 18,2 y 24,3 respectivamente), mejoraron a 76,7 y 70,7 después de 1 año de seguimiento. Al fin del seguimiento, el rango articular promedio era 113° (90–140), la mayoría de los pacientes (24) tuvieron estabilidad tipo A según IKDC.
Conclusión La reconstrucción de lesiones de EPM mejora los resultados clínicos en pacientes con inestabilidad crónica posteromedial de rodilla. Se observó mejoría en la estabilidad y scores funcionales de todos los pacientes.
Accuracy of probe-based confocal laser endomicroscopy (pCLE) compared to random biopsies during endoscopic surveillance of Barrett’s esophagus
Authors: Shah Tilak , Lippman Robert , Kohli Divyanshoo , Mutha Pritesh , Solomon Sanjeev , Zfass Alvin 
Published: March 2018

Abstract
Background For surveillance of Barrett’s esophagus (BE), the current standard of random 4-quadrant biopsies misses 10 – 50 % of esophageal neoplasms, and does not permit real-time decision-making. Probe-based confocal laser endomicroscopy (pCLE) permits real-time in vivo histologic assessment of esophageal mucosa during upper endoscopy. Prospective studies comparing the accuracy of pCLE to 4-quadrant biopsies in routine clinical practice are lacking.
Methods Consecutive patients with BE underwent high definition white light and narrow-band imaging followed by pCLE and targeted biopsy or mucosal resection. Four-quadrant biopsies were obtained during the same session. Baseline variables, real-time pCLE interpretation, and histology results were prospectively recorded. Blinded expert review of pCLE sequences and histology specimens was performed. A sample size of 64 patients was calculated a priori based on 3 % estimated prevalence of high grade dysplasia (HGD) or cancer.
Results In total, 66 patients were included in the study. The prevalence of HGD or cancer was 4.55 %. Both real-time and blinded pCLE correctly identified all cases of cancer. For the primary outcome, real-time pCLE was 98 % specific but only 67 % sensitive for HGD/cancer compared to non-blinded pathologist interpretation. For HGD and cancer, inter-observer agreement was substantial between real-time and blinded endomicroscopists (kappa = 0.6). pCLE identified dysplasia in 75 % of cases where both blinded and unblinded pathology interpretation was low grade dysplasia.
Conclusions pCLE demonstrates high specificity for detecting dysplasia and cancer, but lower sensitivity may limit its utility in routine BE surveillance. pCLE may have a role in confirming LGD in real-time before eradication therapy.