bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Lifestyle Exercise After a Cardiac Event Improve Metabolic Syndrome Profile in Older Adults?
Authors: Wright Kathy D. , Moore-Schiltz Laura , Sattar Abdus , Josephson Richard , Moore Shirley M. 
Published: April 2018

Background:
Exercise is a common recommendation to reduce the risk factors of metabolic syndrome, yet there are limited data on the influence of lifestyle exercise after cardiac events on metabolic syndrome factors.

Objective:
The purpose of this study was to determine whether lifestyle exercise improves metabolic syndrome profile in older adults after a cardiac event.

Methods:
Participants were from a post–cardiac-event lifestyle exercise study. Five metabolic syndrome factors were assessed: waist circumference, triglycerides, high-density lipids, glucose, and systolic and diastolic blood pressure. Objective measures of exercise were obtained from heart rate monitors over a year. Logistic regression was used to determine whether participants who engaged in the minimum recommendation of 130 hours of exercise or greater during the 12-month period improved their metabolic syndrome profile by improving at least 1 metabolic syndrome factor.

Results:
In the sample of 116 participants (74% men; average age, 67.5 years), 43% exercised at the recommended amount (≥130 h/y) and 28% (n = 33) improved their metabolic syndrome profile. After controlling for confounding factors of age, gender, race, diabetes, functional ability, and employment, subjects who exercised at least 130 hours a year were 3.6 times more likely to improve at least 1 metabolic syndrome factor (95% confidence interval, 1.24–10.49). Of the 28% who improved their metabolic syndrome profile, 72% increased their high-density lipoprotein and 60.6% reduced their waist circumference and glucose.

Conclusions:
After a cardiac event, older patients who engage in lifestyle exercise at the recommended amount have improvement in their metabolic syndrome profile.
Clinical Outcome After Lateral Ulnar Collateral Ligament Reconstruction in an Adolescent Baseball Player: A Case Report
Authors: Saper Michael G. , Andrews James R. 
Published: April 2018

Abstract:
Lateral ulnar collateral ligament (LUCL) reconstruction is a commonly used surgical procedure to treat posterolateral rotatory instability (PLRI) of the elbow. We report a 17-year-old right-handed pitcher with symptomatic PLRI after an injury to his LUCL during a baseball game. Having failed 8 months of conservative treatment, a LUCL reconstruction using the modified O'Driscoll technique was performed with the contralateral gracilis autograft. At 5-year follow-up, an excellent patient-reported outcome was achieved and the patient continued to play baseball at the recreational level. This type of injury is rarely reported in adolescent baseball players, and improving our knowledge of the long-term outcomes is crucial to assist clinicians in counseling patients about expectations after surgery.
Efficacy of Intra-Articular Polynucleotides Associated With Hyaluronic Acid Versus Hyaluronic Acid Alone in the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Controlled Clinical Trial
Authors: Dallari Dante , Sabbioni Giacomo , Del Piccolo Nicolandrea , Carubbi Chiara , Veronesi Francesca , Torricelli Paola , Fini Milena 
Published: April 2018

Objective:
Pain and range of motion loss are the main clinical features of osteoarthritis (OA). Hyaluronic acid (HA) is one of the infiltrative therapies for OA treatment; however, its effectiveness is a matter of an ongoing debate in clinical practice. Polynucleotides (PNs), a DNA-derived macromolecule with natural origin and trophic activity, were found to favor cell growth and collagen production, in preclinical and clinical studies regarding cartilage regeneration. This study aimed at evaluating whether injection of PNs, in combination with HA [PNs associated with HA (PNHA)], can ameliorate pain and function of knees affected by OA, more than HA alone.

Design:
A randomized, double-blind, controlled clinical trial.

Patients:
The study enrolled 100 patients, then randomized to receive PNHA or HA alone (3 weekly knee I.A. injections).

Interventions and Main Outcome Measures:
Pain reduction, decrease of proinflammatory synovial fluid (SF) factors, and improvement in knee function were evaluated by Knee Society Score and WOMAC scores, after 2, 6, and 12 months and by biochemical and immunoenzymatic analyses of SF at the end of the treatment.

Results:
Knee Society Score total score and pain item significantly ameliorated in both groups, showing better results in PNHA- than in the HA-treated group. A significant reduction in the WOMAC score was observed over time for both groups. No significant adverse events were reported in either group.

Conclusions:
These findings suggest that I.A. injection of PNs, in combination with HA, is more effective in improving knee function and pain, in a joint affected by OA, compared with HA alone.
Permeation Enhancers for Intratympanically-applied Drugs Studied Using Fluorescent Dexamethasone as a Marker
Authors: Li Wei , Hartsock Jared J. , Dai Chunfu , Salt Alec N. 
Published: April 2018

Hypothesis:
Entry of locally applied drugs into the inner ear can be enhanced by chemical manipulations.

Background:
Perilymph drug concentrations achieved by intratympanic applications are well below the applied concentration due to limited entry through the round window (RW) membrane and stapes. Chemical manipulations to increase entry permeability could increase the effectiveness of drug therapy with local applications.

Methods:
Dexamethasone-fluorescein (F-dex) was used as an entry marker. F-dex was applied to the RW niche of guinea pigs as a 20 μL bolus of 1 mM solution. After a 1 hour application, 10 samples of perilymph were collected sequentially from the lateral semicircular canal, allowing F-dex distribution throughout the perilymph to be quantified. Entry was also measured with the applied solution additionally containing dimethyl sulfoxide (DMSO), N-methylpyrrolidone (NMP), saponin, caprate, benzyl alcohol (BA) or poloxamer 407 (P407). Combinations of saponin or BA with P407 were also compared.

Results:
In control experiments, F-dex entered the inner ear slowly at both the RW and stapes. The total F-dex recovered in all 10 samples from each animal averaged 2.1 pMoles for controls, 1.71 pMoles for 17% P407, 3.70 pMoles for caprate, 8.04 pMoles for DMSO, 16.32 pMoles for NMP, 31.0 pMoles for saponin, and 67.3 pMoles for 4% BA. Entry with DMSO, NMP, saponin and 4% BA were all significantly higher than the controls (one-way ANOVA).

Conclusion:
These studies confirm that entry of drugs into the ear can be markedly enhanced with the use of chemical permeation-enhancing agents.
A Comparison of Repeatability and Usability of Semi-Automated Volume Segmentation Tools for Measurement of Vestibular Schwannomas
Authors: MacKeith Samuel A. C. , Das Tilak , Graves Martin , Patterson Andrew , Donnelly Neil , Mannion Richard , Axon Patrick , Tysome James 
Published: April 2018

Objective:
Semi-automated volume segmentation tools (SAVST) offer a less time consuming technique compared with manual volume segmentation method. No data exists to suggest which of the available applications are optimal for use with vestibular schwannomas (VS). This study aims to compare repeatability and usability of three different SAVST for measurement of VS.

Study Design:
Experimental comparison of three SAVST.

Setting:
Tertiary skull base unit.

Patients:
Twenty-four patients with a unilateral VS imaged with T1-weighted Gadolinium enhanced MRI.

Intervention:
Repeated measurements made to determine intra and inter-observer agreement. This was repeated using three different SAVST.

Main Outcome Measures:
1) Intra- and inter-observer intraclass correlation coefficients (ICC), repeatability coefficients (RC), and relative smallest detectable differences (%SDD).
2) Usability as determined by the mean number of steps and time required per tumor measurement and the proportion of cases where manual editing was required.

Results:
Intra-observer ICCs were significantly better for SliceOmatic and OleaSphere than AW VolumeShare (0.998 versus 0.994, p < 0.05). Inter-observer ICCs were also better for SliceOmatic (0.994) and OleaSphere (0.989) compared with AW VolumeShare (0.976), however, this was only significant for SliceOmatic (p = 0.012). SliceOmatic had a poorer usability profile requiring more manual editing, time, and individual steps per measurement but its “watershed segmentation” algorithm was better at measuring cystic or heterogenous tumors.

Conclusions:
This is the first study to compare three SAVST for measurement of VS. While SliceOmatic had the highest repeatability, Olea Sphere combined comparable repeatability with improved usability and a greater degree of automation and was, therefore, deemed optimal for use in routine clinical practice.
Measuring the value of endoscopic retrograde cholangiopancreatography activity: an opportunity to stratify endoscopists on the basis of their value
Authors: Parihar Vikrant , Moran Carthage , Maheshwari Pardeep , Cheriyan Danny , O’Toole Aoibhlinn , Murray Frank , Patchett Stephen E. , Harewood Gavin C. 
Published: April 2018

Introduction
As finite healthcare resources come under pressure, the value of physician activity is assuming increasing importance. The value in healthcare can be defined as patient health outcomes achieved per monetary unit spent. Even though some attempts have been made to quantify the value of clinician activity, there is little in the medical literature describing the importance of endoscopists’ activity. This study aimed to characterize the value of endoscopic retrograde cholangiopancreatography (ERCP) performance of five gastroenterologists.

Patients and methods
We carried out a retrospective–prospective cohort study using the databases of patients undergoing ERCP between September 2014 and March 2017. We collected data from 1070 patients who underwent ERCP comparing value among the ERCPists at index ERCP. Procedure value was calculated using the formula Q/(T/C), where Q is the quality of procedure, T is the duration of procedure and C is the adjusted for complexity level. Quality and complexity were derived on a 1–4 Likert scale on the basis of American Society for Gastrointestinal Endoscopy criteria; time was recorded (in min) from intubation to extubation. Endoscopist time calculated from procedure time was considered a surrogate marker of cost as individual components of procedure cost were not itemized.

Results
In total, 590 procedures were analysed: 465 retrospectively over 24 months and 125 prospectively over 6 months. There was a 32% variation in the value of endoscopist activity in a more substantial retrospective cohort, with an even more considerable 73% variation in a smaller prospective arm.

Conclusion
In an analysis of greater than 1000 ERCPs by a small cohort of experienced ERCPists, there was a wide variation in the value of endoscopist activity. Although the precision of estimating procedural costs needs further refinement, these findings show the ability to stratify ERCPists on the basis of the value their activity. As healthcare costs are scrutinized more closely, such value measurements are likely to become more relevant.
The Influence of Volume and Anatomic Location of Optic Disc Drusen on the Sensitivity of Autofluorescence
Authors: Loft Frederik Cornelius , Malmqvist Lasse , Wessel Lindberg Anne-Sofie , Hamann Steffen 
Published: April 2018

Background:
Optic disc drusen (ODD) are acellular deposits in the optic nerve head. ODD can be diagnosed using different imaging modalities, including enhanced depth imaging optical coherence tomography (EDI-OCT) and autofluorescence (AF). It is unknown which factors determine the sensitivity of AF. The aim of this study was to investigate the effect of volume and anatomic location of ODD on the sensitivity of AF.

Methods:
Cross-sectional study.

Results:
A total of 38 patients (75 eyes) with ODD were included. In 12 of 75 eyes (16%) and in 11 of 38 patients (29%), EDI-OCT detected ODD that were not detected by AF. In 24 distinctly solitary ODD, both increase in ODD volume (P = 0.0388) and a more superficial ODD location (P < 0.0001) increased the possibility of AF detection of ODD, when performing a multivariate analysis.

Conclusions:
EDI-OCT is superior to AF in the diagnosis of ODD. Volume and anatomic location of ODD have a significant impact on the sensitivity of AF.
An Automated Bayesian Pipeline for Rapid Analysis of Single-Molecule Binding Data
Authors: Smith Carlas S. , Jouravleva Karina , Huisman Maximiliaan , Jolly Samson M. , Zamore Phillip D. , Grunwald David 
Published: April 2018

SummarySingle-molecule binding assays enable the study of how molecular machines assemble and function. Current algorithms can identify and locate individual molecules, but require tedious manual validation of each spot. Moreover, no solution for high-throughput analysis of single-molecule binding data exists. Here, we describe an automated pipeline to analyze single-molecule data over a wide range of experimental conditions. We benchmarked the pipeline by measuring the binding properties of the well-studied, DNA-guided DNA endonuclease, TtAgo, an Argonaute protein from the Eubacterium Thermus thermophilus. We also used the pipeline to extend our understanding of TtAgo by measuring the protein’s binding kinetics at physiological temperatures and for target DNAs containing multiple, adjacent binding sites.
Validation of a library of cGMP-compliant human pluripotent stem cell lines for use in liver therapy
Authors: Blackford Samuel J I , Ng Soon Seng , Segal Joe M , King Aileen J F , Moore Jennifer , Sheldon Michael , Ilic Dusko , Dhawan Anil , Mitry Ragai , Rashid S Tamir 
Published: April 2018

AbstractRecent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment of patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC-Heps generated using a chemically defined four-step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D PEG-DA fabricated inverted colloid crystal (ICC) scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate. This is the first report we are aware of demonstrating cGMP-compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications.
The Relation Between White Matter Microstructure and Network Complexity: Implications for Processing Efficienc
Authors: McDonough Ian M. , Siegel Jonathan T. 
Published: April 2018

AbstractBrain structure has been proposed to facilitate as well as constrain functional interactions within brain networks. Simulation models suggest that integrity of white matter (WM) microstructure should be positively related to the complexity of BOLD signal—a measure of network interactions. Using 121 young adults from the Human Connectome Project, we empirically tested whether greater WM integrity would be associated with greater complexity of the BOLD signal during rest via multiscale entropy. Multiscale entropy measures the lack of predictability within a given time series across varying time scales, thus being able to estimate fluctuating signal dynamics within brain networks. Using multivariate analysis techniques (Partial Least Squares), we found that greater WM integrity was associated with greater network complexity at fast time scales, but less network complexity at slower time scales. These findings implicate two separate pathways through which WM integrity affects brain function in the prefrontal cortex—an executive-prefrontal pathway and a perceptuo-occipital pathway. In two additional samples, the main patterns of WM and network complexity were replicated. These findings support simulation models of WM integrity and network complexity and provide new insights into brain structure-function relationships.
Endogenous fluctuations of OCT4 and SOX2 bias pluripotent cell fate decisions
Authors: Strebinger Daniel , Deluz Cédric , Friman Elias T. , Govindan Subashika , Alber Andrea B. , Suter David M. 
Published: April 2018

AbstractSOX2 and OCT4 are pioneer transcription factors playing a key role in embryonic stem (ES) cell self-renewal and differentiation. However, how temporal fluctuations in their expression levels bias lineage commitment is unknown. Here we generated knock-in reporter fusion ES cell lines allowing to monitor endogenous SOX2 and OCT4 protein fluctuations in living cells and to determine their impact on mesendodermal and neuroectodermal commitment. We found that small differences in SOX2 and OCT4 levels impact cell fate commitment in G1 but not in S phase. Elevated SOX2 levels modestly increased neuroectodermal commitment and decreased mesendodermal commitment upon directed differentiation. In contrast, elevated OCT4 levels strongly biased ES cell towards both neuroectodermal and mesendodermal fates. Using ATAC-seq on ES cells gated for different endogenous SOX2 and OCT4 levels, we found that high OCT4 levels increased chromatin accessibility at differentiation-associated enhancers. This suggests that small endogenous fluctuations of pioneer transcription factors can bias cell fate decisions by concentration-dependent priming of differentiation-associated enhancers.
Combinatorial Approaches to Viral Attenuation
Authors: Paff Matthew L. , Jack Benjamin R. , Smith Bartram L. , Bull James J. , Wilke Claus O. 
Published: April 2018

AbstractAttenuated viruses have numerous applications, in particular in the context of live viral vaccines. However, purposefully designing attenuated viruses remains challenging, in particular if the attenuation is meant to be resistant to rapid evolutionary recovery. Here we develop and analyze a new attenuation method, promoter ablation, using an established viral model, bacteriophage T7. Ablating promoters of the two most highly expressed T7 proteins (scaffold and capsid) led to major reductions in transcript abundance of the affected genes, with the effect of the double knockout approximately additive of the effects of single knockouts. Fitness reduction was moderate and also approximately additive; fitness recovery on extended adaptation was partial and did not restore the promoters. The fitness effect of promoter knockouts combined with a previously tested codon deoptimization of the capsid gene was less than additive, as anticipated from their competing mechanisms of action. In one design, the engineering created an unintended consequence that led to further attenuation, the effect of which was studied and understood in hindsight. Overall, the mechanisms and effects of genome engineering on attenuation behaved in a predictable manner. Therefore, this work suggests that the rational design of viral attenuation methods is becoming feasible.ImportanceLive viral vaccines rely on attenuated viruses that can successfully infect their host but have reduced fitness or virulence. Such attenuated viruses were originally developed through trial- and-error, typically by adaptation of the wild-type virus to novel conditions. That method was haphazard, with no way of controlling the degree of attenuation, the number of attenuating mutations, or preventing evolutionary reversion. Synthetic biology now enables rational design and engineering of viral attenuation, but rational design must be informed by biological principles to achieve stable, quantitative attenuation. This work shows that in a model system for viral attenuation, bacteriophage T7, attenuation can be obtained from rational design principles, and multiple different attenuation approaches can be combined for enhanced overall effect.
Intra-host symbiont diversity and extended symbiont maintenance in photosymbiotic Acantharea (clade F)
Authors: Brisbin Margaret Mars , Mesrop Lisa Y. , Grossmann Mary M. , Mitarai Satoshi 
Published: April 2018

AbstractPhotosymbiotic protists contribute to surface primary production in low-nutrient, open-ocean ecosystems and constitute model systems for studying plastid acquisition via endosymbiosis. Little is known, however, about host-symbiont dynamics in these important relationships, and whether these symbioses constitute mutualisms is debated. In this study, we applied single-cell sequencing methods and advanced fluorescent microscopy to investigate host-symbiont dynamics in clade F acantharians, a major group of photosymbiotic protists in oligotrophic subtropical gyres. We amplified the 18S rRNA gene from single acantharian hosts and environmental samples to assess intra-host symbiont diversity and to determine whether intra-host symbiont community composition directly reflects the available symbiont community in the surrounding environment. Our results demonstrate that clade F acantharians simultaneously host multiple species from the haptophyte generaPhaeocystisandChrysochromulina. The intra-host symbiont community composition was distinct from the external free-living symbiont community, suggesting that these acantharians maintain symbionts for extended periods of time. After selective staining of digestive organelles, fluorescent confocal microscopy showed that symbionts were not being systematically digested, which is consistent with extended symbiont maintenance within hosts. Extended maintenance within hosts may benefit symbionts through protection from grazing or viral lysis, and therefore dispersal, provided that symbionts retain reproductive capacity.
SORLA-driven endosomal trafficking regulates the oncogenic fitness of HER2
Authors: Pietilä Mika , Sahgal Pranshu , Peuhu Emilia , Jäntti Niklas , Paatero Ilkka , Andersen Olav M. , Padzik Artur , Blomqvist Matias , Saarinen Immi , Boström Peter , Taimen Pekka , Ivaska Johanna 
Published: April 2018

AbstractHuman epidermal growth factor receptor 2 (HER2) is an oncogene targeted by several kinase inhibitors and therapeutic antibodies. Endosomal trafficking of many other receptor tyrosine kinases regulates their oncogenic signaling, but the prevailing view is that HER2 is retained on the cell surface. Here we reveal that in cancer cells Sortilin related receptor 1 (SORLA; SORL1) forms a complex with HER2 and regulates its subcellular distribution by promoting recycling of endosomal HER2 back to plasma membrane. Expression of SORLA in cancer cell lines and bladder cancers correlates with HER2 levels. Depletion of SORLA targets HER2 to late endosomal/lysosomal compartments, impairs HER2-driven signaling and in vivo tumor growth. SORLA silencing also disrupts normal lysosome function and sensitizes anti-HER2 therapy sensitive and resistant cancer cells to lysosome-targeting cationic amphiphilic drugs. These findings reveal potentially important SORLA-dependent endosomal trafficking-linked vulnerabilities in HER2-driven cancers.