bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robotic Radiosurgery for Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence (CYBER-SPACE)—A Single-Center Prospective Randomized Trial
Authors: El Shafie Rami A , Paul Angela , Bernhardt Denise , Lang Kristin , Welzel Thomas , Sprave Tanja , Hommertgen Adriane , Krisam Johannes , Schmitt Daniela , Klüter Sebastian , Schubert Kai , Klose Christina , Kieser Meinhard , Debus Jürgen , Rieken Stefan 
Published: January 2018

Abstract

BACKGROUND
Stereotactic radiosurgery (SRS) of brain metastases (BM) is recommended in oligometastatic scenarios as a less toxic treatment alternative to whole-brain radiotherapy. Recent findings support SRS for patients with multiple (>3) BM. Furthermore, advances in MR imaging have facilitated the detection of very small BM, as advances in SRS technology have facilitated the highly conformal and simultaneous treatment of multiple target lesions.

OBJECTIVE
To compare efficacy and toxicity of repeated frameless robotic SRS of up to 10 simultaneous BM through a single-center prospective randomized trial.

METHODS
Two hundred patients will be randomized and receive imaging and treatment based on either the highly sensitive SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) or the MPRAGE (magnetization-prepared rapid gradient-echo) magnetic resonance imaging sequence. If during follow-up new metastases are detected, treatment is repeated. The primary endpoint is reached when a patient develops more than 10 simultaneous new BM and is thus deemed unsuitable for further SRS. Overall survival will be assessed as secondary endpoint. Quality of life and neurocognition will be evaluated every 3 mo using CANTAB tests and EORTC (European Organisation for Research and Treatment of Cancer) questionnaires.

EXPECTED OUTCOMES
We expect to show that repeated SRS based on sensitive imaging can delay intracranial dissemination while preserving neurocognitive function and quality of life.

DISCUSSION
The present study is the first to prospectively assess the benefit of sensitive imaging and repeated stereotactic irradiation in the treatment of patients with multiple BM. It represents a novel approach, where in a palliative setting advanced technology in treatment and diagnostics is employed to improve tumor control while also reducing toxicity and preserving quality of life.
Internal Carotid Artery Bifurcation Aneurysms: Microsurgical Strategies and Operative Nuances for Different Aneurysmal Directions
Authors: Savardekar Amey R , Patra Devi Prasad , Narayan Vinayak , Bollam Papireddy , Guthikonda Bharat , Nanda Anil 
Published: January 2018

Abstract

BACKGROUND
Internal carotid artery bifurcation aneurysms (ICAbifAs), comprising approximately 5% of intracranial aneurysms, are characterized clinically by their tendency to occur at a younger age and surgically by the technical difficulties posed by their domes being adherent to the frontal lobe, their location at the apex of the sylvian fissure, and their relation to myriad perforator complexes.

OBJECTIVE
To review the nuances of technique and operative strategy specific to aneurysmal direction in the light of our experience with ICAbifAs.

METHODS
ICAbifAs managed at our institute from January 2001 to July 2016 were analyzed. Detailed analysis of clinical data, pre- and postoperative radiology, operative notes and videos, and clinical outcome was done.

RESULTS
Fifty-one patients with ICAbifAs were treated in the study period out of which 40 patients underwent microsurgical clipping. The median age was 48 yr (range 14-68 yr). Nearly 95% of the patients presented in a good clinical grade (World Federation of Neurological Surgeons grade 1 and 2). At 6-mo follow-up, 36 patients (90%) had good clinical outcome (Glasgow Outcome Scale 4 and 5). According to their direction, ICAbifAs were grouped as anteriorly directed (10 cases), superiorly directed (23 cases), and posteriorly directed (7 cases). Operative techniques and nuances utilized depend on aneurysmal direction and are presented here.

CONCLUSION
An appropriate surgical strategy based on the direction of ICAbifAs as per the preoperative radiology, meticulous dissection of aneurysmal wall from adjacent perforators, and clip application with the aim of remodeling the ICA bifurcation are integral to achieving a good outcome.
MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR–TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Mantel Irmela , Dirani Ali , Zola Marta , Parvin Parmis , De Massougnes Sophie , Bergin Ciara 
Published: January 2018

Purpose:
To investigate factors associated with macular atrophy (MA) incidence in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept in an Observe-and-Plan variable dosing regimen.

Methods:
Information was obtained from two identical prospective treatment protocols using ranibizumab or aflibercept in a variable dosing regimen termed “Observe and Plan.” Eyes without MA at baseline were included. New atrophy at the final 2-year visit was investigated with univariate and multivariate analysis to identify associated risk factors, focusing on treatment factors.

Results:

De novo MA developed in 63 (42%) of 149 eyes/patients (mean age 79.0 years), in 70 eyes treated using aflibercept and 79 eyes using ranibizumab. The univariate analysis showed multiple associations of MA with baseline factors, of which the following were confirmed as independent risk factors after multivariate stepwise logistic regression: lower number of anti–vascular endothelial growth factors injections (P = 0.011), depigmentation (P = 0.0004), reticular pseudodrusen (P = 0.0005), lower baseline visual acuity (P = 0.0006), and retinal angiomatous proliferation (P = 0.001). The drug type showed no significant association with MA incidence (P = 0.21).

Conclusion:
Within the variable dosing regimen, MA incidence was higher when fewer injections were required. More injections, if required by disease activity, did not increase the risk for MA.
Association of aortic valve disease with intestinal angioectasia: data from the Nationwide Inpatient Sample
Authors: Jehangir Asad , Pathak Ranjan , Ukaigwe Anene , Donato Anthony A. 
Published: January 2018

Objective
Since the description of a correlation between aortic stenosis and angioectasia, controversy has persisted about whether these diseases are truly associated or coincidental findings of older age. Our objective was to determine the association of aortic valve disease and bleeding intestinal angioectasia from a large database.

Patients and methods
We used the 2011 Nationwide Inpatient Sample database to identify hospitalizations in the USA in patients with bleeding intestinal angioectasia. International Classification of Diseases, 9th revision, Clinical Modification codes were used to identify patients with aortic valve disease, mitral valve disease, and known risk factors for angioectasia (including diagnosed von Willebrand disease, left ventricular assist device, and chronic kidney disease). Univariate and multivariate logistic regression were used to determine the odds of association between the valvular diseases and angioectasia.

Results
A total of 32 079 intestinal angioectasia-related hospitalizations were identified of which 7.02% (n=2253) cases had coexistent aortic valve disease. The unadjusted odds of aortic valve disease in association with bleeding intestinal angioectasia versus those without bleeding angioectasia was 4.95 [95% confidence interval: (CI): 4.43–5.54, P<0.001]. The association of intestinal angioectasia with mitral valve disease was not significant (odds ratio=1.56, 95% CI: 0.59–4.14, P=0.38). When adjusted for age and known risk factors, the odds of aortic valve disease in bleeding intestinal angioectasia was still significant (odds ratio=2.37, 95% CI: 2.10–2.66, P<0.001).

Conclusion
Our findings support an important association between aortic valve disease and bleeding intestinal angioectasia, not identified in valvular heart valvular diseases with lower shear stress (mitral valve disease).
Development and Validity Testing of an Arthritis Self-Management Assessment Tool
Authors: Oh HyunSoo , Han SunYoung , Kim SooHyun , Seo WhaSook 
Published: January 2018

BACKGROUND:
Because of the chronic, progressive nature of arthritis and the substantial effects it has on quality of life, patients may benefit from self-management. However, no valid, reliable self-management assessment tool has been devised for patients with arthritis.

PURPOSE:
This study was conducted to develop a comprehensive self-management assessment tool for patients with arthritis, that is, the Arthritis Self-Management Assessment Tool (ASMAT).

METHODS:
To develop a list of qualified items corresponding to the conceptual definitions and attributes of arthritis self-management, a measurement model was established on the basis of theoretical and empirical foundations. Content validity testing was conducted to evaluate whether listed items were suitable for assessing arthritis self-management. Construct validity and reliability of the ASMAT were tested. Construct validity was examined using confirmatory factor analysis and nomological validity.

RESULTS:
The 32-item ASMAT was developed with a sample composed of patients in a clinic in South Korea. Content validity testing validated the 32 items, which comprised medical (10 items), behavioral (13 items), and psychoemotional (9 items) management subscales. Construct validity testing of the ASMAT showed that the 32 items properly corresponded with conceptual constructs of arthritis self-management, and were suitable for assessing self-management ability in patients with arthritis. Reliability was also well supported.

CONCLUSION:
The ASMAT devised in the present study may aid the evaluation of patient self-management ability and the effectiveness of self-management interventions. The authors believe the developed tool may also aid the identification of problems associated with the adoption of self-management practice, and thus improve symptom management, independence, and quality of life of patients with arthritis.
Laparoscopic Hilar Lymph Node Sampling in Patients With Biliary Tract Cancers That are Rarely Associated With Nodal Metastasis
Authors: Kobayashi Shogo , Tomokuni Akira , Takahashi Hidenori , Akita Hirofumi , Marubashi Shigeru , Gotoh Kunihito , Yanagimoto Yoshitomo , Takahashi Yusuke , Sugimura Keijiro , Miyoshi Norikatsu , Moon Jeong Ho , Yasui Masayoshi , Omori Takeshi , Miyata Hiroshi , Ohue Masayuki , Fujiwara Yoshiyuki , Yano Masahiko , Sakon Masato 
Published: January 2018

Purpose:
Among the various types of biliary tract cancer, patients with single, small (<5 cm), peripheral intrahepatic cholangiocarcinoma (ICC), or small (<2 cm) gallbladder tumors (GBTs) rarely develop lymph node (LN) metastasis. We investigated a laparoscopic approach for hilar LN sampling in such cases.

Methods:
Among the 176 patients with biliary tract cancer who were treated from January 2012 to March 2017, 21 (ICC, n=4; GBT, n=17) met the above indications.

Results:
All patients were treated by a laparoscopic approach with R0 resection. After determining the pathologic diagnosis, 9 patients with GBT and all 4 patients with ICC underwent laparoscopic LN sampling; the mean numbers of sampled LNs were 2.6 and 7.3, respectively; no patients had metastasis. The mean operating times for GBT and ICC were 223 and 379 minutes, respectively; the mean blood loss was 23 mL and 171 mL. With the exception of 1 patient who developed intrahepatic metastasis of ICC at the opposite liver lobe, all of the patients were recurrence free.

Conclusions:
A laparoscopic approach could be safely applied under our indications.
Synergistic binding of bHLH transcription factors to the promoter of the maize NADP-ME gene used in C4 photosynthesis is based on an ancient code found in the ancestral C3 state
Authors: Borba Ana Rita , Serra Tânia S. , Górska Alicja , Gouveia Paulo , Cordeiro André M. , Reyna-Llorens Ivan , Kneřová Jana , Barros Pedro M. , Abreu Isabel A. , Oliveira M. Margarida , Hibberd Julian M. , Saibo Nelson J.M. 
Published: January 2018

AbstractC4 photosynthesis has evolved repeatedly from the ancestral C3 state to generate a carbon concentrating mechanism that increases photosynthetic efficiency. This specialised form of photosynthesis is particularly common in the PACMAD clade of grasses, and is used by many of the world’s most productive crops. The C4 cycle is accomplished through cell-type specific accumulation of enzymes but cis-elements and transcription factors controlling C4 photosynthesis remain largely unknown. Using the NADP-Malic Enzyme (NADP-ME) gene as a model we aimed to better understand molecular mechanisms associated with the evolution of C4 photosynthesis. Two basic Helix-Loop-Helix (bHLH) transcription factors, ZmbHLH128 and ZmbHLH129, were shown to bind the C4NADP-ME promoter from maize. These proteins form heterodimers and ZmbHLH129 impairs trans-activation by ZmbHLH128. Electrophoretic mobility shift assays indicate that a pair of cis-elements separated by a seven base pair spacer synergistically bind either ZmbHLH128 or ZmbHLH129. This pair of cis-elements is found in both C3 and C4 species of the PACMAD clade. Our analysis is consistent with this cis-element pair originating from a single motif present in the ancestral C3 state. We conclude that C4 photosynthesis has co-opted an ancient C3 regulatory code built on G-box recognition by bHLH to regulate the NADP-ME gene. More broadly, our findings also contribute to the understanding of gene regulatory networks controlling C4 photosynthesis.
Prodiginine Production inStreptomyces coelicolorCorrelates Temporally and Spatially to Programmed Cell Death
Authors: Tenconi Elodie , Traxler Matthew F. , Hoebreck Charline , Van Wezel Gilles P. , Rigali Sébastien 
Published: January 2018

AbstractProgrammed cell death (PCD) is a common feature of multicellularity and morphogenesis in bacteria. While cell death has been well documented whenStreptomycesspecies switch from vegetative (nutrition) to aerial (reproduction) growth, lethal determinants are yet to be discovered to unveil the genetic basis of PCD in mycelial bacteria. In this work we used prodiginines ofStreptomyces coelicoloras model to test the hypothesis that a bacterium uses ‘self-made’ antiproliferative DNA-damaging agents as toxins of their PCD process. Spatio-temporal visualisation of the autofluorescence of prodiginines reveals that their biosynthesis is triggered in the dying zone of the colony prior to morphological differentiation of the mycelium. A prodiginine nonproducer showed hyper-accumulation of viable filaments, with increased RNA and proteins synthesis when most of the mycelium of the wild-type strain was dead when prodiginine accumulated. Addition of a prodiginine synthesis inhibitor also strongly favoured viable over dead filaments. As self-toxicity has also been reported for other producers of DNA-damaging agents we propose that cytotoxic metabolites synthetized during the morphological transition of filamentous bacteria may be used to execute PCD.Significance StatementActinobacteria are prolific producers of compounds with antiproliferative activity, but why these bacteria synthetize metabolites with this bioactivity has so far remained a mystery. Using prodiginines (PdGs) as model system, we revealed that the spatio-temporal synthesis of these molecules correlates to cell death of the producerStreptomyces coelicolorand that inhibition of their synthesis results in hyper-accumulation of viable filaments. Since PdGs potentiate death ofS. coelicolorrecurrently prior to morphological differentiation, this is a form of programmed cell death (PCD). Hence, next to weapons in competition between organisms or signals in inter- and intra-species communications, we propose a third role for secondary metabolites i.e., elements required for self-toxicity in PCD processes.
Intracranial fluid dynamics changes in idiopathic intracranial hypertension: pre and post therapy
Authors: Agarwal N. , Contarino C. , Bertazzi L. , Limbucci N. , Toro E. F. 
Published: January 2018

AbstractIdiopathic intracranial hypertension (IIH) is a condition of unknown etiology frequently associated with dural sinus stenosis. There is emerging evidence that venous sinus stenting is an effective treatment. We use phase contrast cine MRI to observe changes in flow dynamics of multiple intracranial fluids and their response to different treatments in a patient with IIH. We quantified the following parameters at the level of the aqueduct of Sylvius and the cervical C2C3: cerebrospinal fluid (CSF), arterial and venous flow; CSF velocity amplitude; artero-venous delay (AVD); artero-CSF delay and percentage of venous outflow normalized to total arterial inflow (tIJV/tA). Analyses were run before lumbar puncture (LP) (A), after LP (B), after medical therapy (C) and after venous stent placements deployed at two separate times (D and E). AVD and tIJV/tA improved only after CSF removal and after stent placements. CSF velocity amplitude remained elevated. Arterial flow profile showed a dramatic reduction after LP with improvement in mean venous flow. This report is the first to demonstrate interactive changes in intracranial fluid dynamics that occur before and after different therapeutic interventions in IIH. We discuss how increased intracranial venous blood could be “tumoral” in IIH and facilitating its outflow could be therapeutic.
Neonatal gut and respiratory microbiota: coordinated development through time and space
Authors: Grier Alex , McDavid Andrew , Wang Bokai , Qiu Xing , Java James , Bandyopadhyay Sanjukta , Yang Hongmei , Holden-Wiltse Jeanne , Kessler Haeja A. , Gill Ann L. , Huyck Heidie , Falsey Ann R. , Topham David J. , Scheible Kristin M. , Caserta Mary T. , Pryhuber Gloria S. , Gill Steven R. 
Published: January 2018

ABSTRACTBackground:Postnatal development of the microbiota in early life influences immunity, metabolism, neurodevelopment and long-term infant health. Microbiome development occurs at multiple body sites, each with distinct community compositions and functions. Associations between microbiota at multiple sites represent an unexplored influence on the infant microbiome. Here, we examined co-occurrence patterns of gut and respiratory microbiota in pre- and full-term infants over the first year of life, a period critical to neonatal development and risk of respiratory diseases.Results:Gut and respiratory microbiota collected as longitudinal rectal, throat and nasal samples from 38 pre-term and 44 full-term infants were first clustered into community state types (CSTs) on the basis of their composition. Multiple methods were used to relate the occurrence of CSTs to several measures of infant maturity, including gestational age (GA) at birth, week of life (WOL), and post menstrual age (PMA: equal to GA plus WOL). Manifestation of CSTs followed one of three patterns with respect to infant maturity. First,chronological: independent of infant maturity (GA) at birth, and strongly associated with post-natal age (WOL). Second,idiosyncratic: primarily dependent on maturity (GA) at birth, with persistent differences in CST occurrence between pre- and full-term infants through the first year of life. Third,convergent: CSTs appear earlier in infants with greater maturity (GA) at birth, but after a sufficient post-natal interval their occurrence in pre-term infants reaches parity with full-term infants. The composition of CSTs was highly dissimilar between different body sites, but the CST of any one body site was highly predictive of the CSTs at other body sites. There were significant associations between the abundance of individual taxa at each body site and the CSTs of the other body sites, which persisted after stringent control for the non-linear effects of infant maturity. Significant canonical correlations exist between the microbiota composition at each pair of body sites, with the strongest correlations between more proximal locations.Conclusion:Cross-body site associations of developing infant microbiota suggest the importance of research and clinical practices that focus on dynamic interactions between multiple microbial communities to elucidate and promote systemic microbiota development.
Genome-Encoded Cytoplasmic Double-Stranded RNAs, Found in C9ORF72 ALS-FTD Brain, Provoke Propagated Neuronal Death
Authors: Rodriguez Steven , Schrank Benjamin R. , Sahin Asli , Al-Lawati Hawra , Costantino Isabel , Benz Eric , Fard Darian , Albers Alefiya D. , Cao Luxiang , Gomez Alexis C. , Ratti Elena , Cudkowicz Merit , Frosch Matthew P. , Talkowski Michael , Sorger Peter K. , Hyman Bradley T. , Albers Mark W. 
Published: January 2018

SUMMARYInnate immune signaling activation and DNA damage are pathological hallmarks of aging that may herald multiple adult-onset neurodegenerative diseases. Here, we report that both cell autonomous and non-autonomous neuronal death are triggered by the production of cytoplasmic double-stranded RNA (cdsRNA) from a regulated, disarticulated transgene in the setting of type I interferon (IFN-I) signaling. CdsRNA is a pathogen associated molecular pattern that induces IFN-I in many cell types. Transfection of a dsRNA mimetic into cultured human neurons also induces IFN-I signaling and cell death in a dose-dependent manner. Direct relevance to human disease is found in neurons of ALS-FTD patients carrying C9ORF72 intronic hexanucleotide expansions; cdsRNA isolated from these tissues is comprised of repeat sequences. Together, these findings implicate cdsRNA generated from genomic sequences in neurons as a trigger for sterile, viral-mimetic IFN-I induction and propagated neuronal death within in a neural circuit in the aging nervous system.
Treemmer: a tool to reduce large phylogenetic datasets with minimal loss of diversity
Authors: Menardo Fabrizio , Loiseau Chloé , Brites Daniela , Coscolla Mireia , Gygli Sebastian M. , Rutaihwa Liliana K. , Trauner Andrej , Beisel Christian , Borrell Sonia , Gagneux Sebastien 
Published: January 2018

AbstractLarge sequence datasets are difficult to visualize and handle. Additionally, they are often not an adequate representation of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer from redundancy and sampling biases. Here we present Treemmer, a simple tool to evaluate the redundancy of phylogenetic trees and reduce their complexity by eliminating leaves that contribute the least to the tree diversity.Treemmer can reduce the size of datasets with different phylogenetic structures and levels of redundancy while maintaining a sub-sample that is representative of the original diversity.
The effect of education on adult mortality, health, and income: triangulating across genetic and policy reforms
Authors: Davies Neil M , Dickson Matt , Davey Smith George , Windmeijer Frank , van den Berg Gerard J 
Published: January 2018

1AbstractOn average, educated people are healthier, wealthier and have higher life expectancy than those with less education. Numerous studies have attempted to determine whether these differences are caused by education, or are merely correlated with it and are ultimately caused by another factor. Previous studies have used a range of natural experiments to provide causal evidence. Here we exploit two natural experiments, perturbation of germline genetic variation associated with education which occurs at conception, known as Mendelian randomization, and a policy reform, the raising of the school leaving age in the UK in 1972. Previous studies have suggested that the differences in outcomes associated with education may be due to confounding. However, the two independent sources of variation we exploit largely imply consistent causal effects of education on outcomes much later in life.