bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical Stimulation Increases Knee Meniscus Gene RNA-level Expression in Adipose-derived Stromal Cells
Authors: Meier Elizabeth M. , Wu Bin , Siddiqui Aamir , Tepper Donna G. , Longaker Michael T. , Lam Mai T. 
Published: September 2016

Background:
Efforts have been made to engineer knee meniscus tissue for injury repair, yet most attempts have been unsuccessful. Creating a cell source that resembles the complex, heterogeneous phenotype of the meniscus cell remains difficult. Stem cell differentiation has been investigated, mainly using bone marrow mesenchymal cells and biochemical means for differentiation, resulting in no solution. Mechanical stimulation has been investigated to an extent with no conclusion. Here, we explore the potential for and effectiveness of mechanical stimulation to induce the meniscal phenotype in adipose-derived stromal cells.

Methods:
Human adipose-derived stromal cells were chosen for their fibrogenic nature and conduciveness for chondrogenesis. Biochemical and mechanical stimulation were investigated. Biochemical stimulation included fibrogenic and chondrogenic media. For mechanical stimulation, a custom-built device was used to apply constant, cyclical, uniaxial strain for up to 6 hours. Strain and frequency varied.

Results:
Under biochemical stimulation, both fibrogenic (collagen I, versican) and chondrogenic (collagen II, Sox9, aggrecan) genes were expressed by cells exposed to either fibrogenic or chondrogenic biochemical factors. Mechanical strain was found to preferentially promote fibrogenesis over chondrogenesis, confirming that tensile strain is an effective fibrogenic cue. Three hours at 10% strain and 1 Hz in chondrogenic media resulted in the highest expression of fibrochondrogenic genes. Although mechanical stimulation did not seem to affect protein level expression, biochemical means did affect protein level presence of collagen fibers.

Conclusion:
Mechanical stimulation can be a useful differentiation tool for mechanoresponsive cell types as long as biochemical factors are also integrated.
A Unique Case of Allogeneic Fat Grafting Between Brothers
Authors: Kim Samuel , Edelson Richard L. , Sumpio Brandon , Kwei Stephanie , Narayan Deepak 
Published: September 2016

Summary:
We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient’s unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain. Our unique case study supports the use of fat grafting for its restorative purposes and for its ability to alleviate chronic neuropathic pain. Additionally, it appears that our case provides a basis of a general approach to the treatment of radiation-induced ulcers in chimeric patients with lymphoid malignancies.
The impact of peripheral nerve blocks on perioperative outcome in hip and knee arthroplasty—a population-based study
Authors: Memtsoudis Stavros G. , Poeran Jashvant , Cozowicz Crispiana , Zubizarreta Nicole , Ozbek Umut , Mazumdar Madhu 
Published: September 2016

Abstract
The role of anesthesia techniques on perioperative outcomes on a population level has recently gained widespread interest. Although mainly neuraxial vs general anesthesia has been addressed, population-level data on the impact of peripheral nerve blocks (PNBs) are still lacking. Therefore, we investigated the association between PNB use and outcomes using retrospective data on 1,062,152 recipients of hip and knee arthroplasties (total hip arthroplasty [THA]/total knee arthroplasty [TKA]) from the national Premier Perspective database (2006-2013). Multilevel multivariable logistic regression models measured associations between PNB use and outcomes. Complications included cardiac, pulmonary, gastrointestinal and renal complications, cerebrovascular events, infections, wound complications, thromboembolic complications, inpatient falls, and mortality. Resource utilization variables included blood transfusions, intensive care unit admissions, opioid consumption, cost, and length of stay. Overall, 12.5% of patients received a PNB, with an increase over time particularly among TKAs. Peripheral nerve block use was associated with lower odds for most adverse outcomes mainly among patients with THA. Notable beneficial effects were seen for wound complications (odds ratio 0.60 [95% confidence interval, 0.49-0.74]) among THA recipients and pulmonary complications (odds ratio 0.83 [95% confidence interval, 0.72-0.94]) in patients with TKA. Peripheral nerve block use was significantly (P < 0.0001) associated with a −16.2% and −12.7% reduction in opioid consumption for patients with THA and TKA, respectively. In conclusion, our results indicate that PNBs might be associated with superior perioperative population-level outcomes. In light of the inability to establish a causal relationship and the presence of residual confounding, we strongly advocate for further prospective investigation, ideally in multicenter, randomized trials, to establish the potential impact of PNBs on outcomes on a population level.
Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study
Authors: Wodarski Rachel , Delaney Ada , Ultenius Camilla , Morland Rosie , Andrews Nick , Baastrup Catherine , Bryden Luke A. , Caspani Ombretta , Christoph Thomas , Gardiner Natalie J. , Huang Wenlong , Kennedy Jeffrey D. , Koyama Suguru , Li Dominic , Ligocki Marcin , Lindsten Annika , Machin Ian , Pekcec Anton , Robens Angela , Rotariu Sanziana M. , Voß Sabrina , Segerdahl Marta , Stenfors Carina , Svensson Camilla I. , Treede Rolf-Detlef , Uto Katsuhiro , Yamamoto Kazumi , Rutten Kris , Rice Andrew S.C. 
Published: September 2016

Abstract
Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.
Hepatitis B virus infection and risk of gallstones: a systematic review and meta-analysis
Authors: Wijarnpreecha Karn , Thongprayoon Charat , Panjawatanan Panadeekarn , Manatsathit Wuttiporn , Ungprasert Patompong 
Published: September 2016

Background/objectives
Gallstone disease and its complications are common, particularly in Western populations. Recent studies have reported a significantly increased risk of gallstones among hepatitis C virus-infected patients. However, the data on patients with hepatitis B virus (HBV) infection are still limited. This meta-analysis was carried out with the aim of summarizing all available evidence.

Patients and methods
A literature search was performed using MEDLINE and the EMBASE database from inception to May 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of gallstones among HBV-infected patients versus patients without HBV infection were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse-variance method.

Results
Nine studies fulfilled our eligibility criteria and were included in the analysis. We found no significant association between HBV infection and the risk of gallstones, with a pooled OR of 1.10 (95% CI, 0.91–1.33). The statistical heterogeneity was moderate, with an I
2 of 69%. Subgroup analysis was carried out. The pooled OR of cross-sectional studies was 1.01 (95% CI, 0.91–1.12; I
2 0%), whereas the pooled OR of case–control studies was 1.53 (95% CI, 0.85–2.74; I
2 80%).

Conclusion
A significant association between HBV infection and the risk of gallstones was not observed in this study.
A novel lozenge containing bupivacaine as topical alleviation of oral mucositis pain in patients with head and neck cancer: a pilot study
Authors: Mogensen Stine , Treldal Charlotte , Sveinsdottir Kolbrún , Jensen Kenneth , Kristensen Claus A. , Mogensen Torben S. , Petersen Janne , Andersen Ove 
Published: September 2016

Abstract

Introduction: Oral mucositis induces severe oral pain in head and neck cancer patients. There is at this point no effective pain treatment without considerable side effects.

Objective: The aim of this pilot study was to investigate pain reduction in oral cavity and pharynx in patients with head and neck cancer (HNC) with oral mucositis, the location of anesthetic effect, and duration of pain relief, after a single-dose administration of a 25 mg bupivacaine lozenge.

Methods: Ten patients with HNC suffering from oral mucositis pain were included. The patients assessed pain in the oral cavity and pharynx on a visual analogue scale (from 0 to 100 mm) at baseline and up to 3 hours after the lozenge was dissolved. Possible adverse events were registered.

Results: The baseline pain was 51 mm (range: 30–73 mm) in the oral cavity and 58 mm (range: 35–70 mm) in the pharynx. When the lozenge was dissolved, both oral (−27 mm; range: −3 to −52 mm; P = 0.0003) and pharynx pain (−20 mm; range: −3 to −45 mm; P = 0.008) were significantly reduced. After 180 minutes, the mean reduction in pain was significant in the oral cavity (−18 mm; range: −8 to −30 mm; P < 0.0001) but not in the pharynx (−8 mm; range: +4 to −23 mm; P = 0.12). No adverse events were observed.

Conclusion: The results indicate that the bupivacaine lozenge has a clinically significant and long-lasting pain-relieving effect on pain because of oral mucositis in patients with HNC.
Medical Students Raising Concerns
Authors: Druce Maralyn R. , Hickey Andrea , Warrens Anthony N. , Westwood Olwyn M.R. 
Published: September 2016

Abstract
After a number of high-profile incidents and national reports, it has become clear that all health professionals and all medical students must be able to raise concerns about a colleague’s behavior if this behavior puts patients, colleagues, or themselves at risk.
Detailed evidence from medical students about their confidence to raise concerns is limited, together with examples of barriers, which impair their ability to do so. We describe a questionnaire survey of medical students in a single-center, examining self-reported confidence about raising concerns in a number of possible scenarios. Thematic analysis was applied to comments about barriers identified.
Although 80% of respondents felt confident to report a patient safety issue, students were less confident around issues of probity, attitude, and conduct. This needs to be addressed to create clear mechanisms to raise concerns, as well as support for students during the process.
Cerebellar Control of Eye Movements
Authors: Beh Shin C. , Frohman Teresa C. , Frohman Elliot M. 
Published: September 2016

Background:
The cerebellum plays a central role in the online, real-time control, and long-term modulation of eye movements.

Evidence acquisition:
We reviewed the latest (fifth) edition of Leigh and Zee's textbook, The Neurology of Eye Movements, and literature in PUBMED using the following terms: cerebellum, flocculus, paraflocculus, vermis, oculomotor vermis, dorsal vermis, caudal fastigial nucleus, fastigial oculomotor region, uvula, nodulus, ansiform lobule, eye movements, saccades, ipsipulsion, contrapulsion, smooth pursuit, vergence, convergence, divergence, gaze-holding, down beat nystagmus, vestibulo-ocular reflex (VOR), angular VOR, translational VOR, skew deviation, velocity storage.

Results:
The cerebellum is vital in optimizing the performance of all classes of gaze-shifting and gaze-stabilizing reflexes. The flocculus-paraflocculus are crucial to VOR gain and direction, pulse-step matching for saccades, pursuit gain, and gaze-holding. The ocular motor vermis and caudal fastigial nuclei are essential in saccadic adaptation and accuracy, and pursuit gain. The nodulus and ventral uvula are involved in processing otolothic signals and VOR responses, including velocity storage.

Conclusions:
The cerebellum guarantees the precision of ocular movements to optimize visual performance and occupies a central role in all classes of eye movements both in real-time control and in long-term calibration and learning (i.e., adaptation).
Synaesthesia lost and found: Two cases of person- and music-colour synaesthesia
Authors: Farina Francesca R , Mitchell Kevin J , Roche Richard AP 
Published: September 2016

AbstractSynaesthesia is a developmental condition involving cross-communication between sensory modalities or substreams whereby an inducer (e.g. a sound) automatically evokes a concurrent percept in another modality (e.g. a colour). Whether this condition arises due to atypical structural connectivity (e.g., between normally unconnected cortical areas) or altered neurochemistry remains a central question. We report the exceptional cases of two synaesthetes – subjects AB and CD – both of whom experience coloured auras around individuals, as well as coloured perceptions in response to music. Both subjects have, in recent years, suffered a complete loss or reduction of their synaesthetic experiences, one (AB) through successive head traumas, including a lightning strike, followed by a number of medications, and the other (CD) while taking anxiolytic medications. Using semi-structured interviews and data from the Synaesthesia Battery and a colourpicker task, we characterise the phenomenological characteristics of their pre-loss synaesthesia, as well as the subsequent restoration of each subject's synaesthetic experiences (in the months post-trauma for AB, and after cessation of medication for CD). Even after years of suppression, the patterns of associations were highly consistent with those experienced pre-injury. The phenomenological experience of synaesthesia can, thus, like most conscious experiences, be modulated by pharmacologically diverse medications or head injury. However, the underlying neural substrates mediating specific synaesthetic pairings appear remarkably “hard-wired” and can persist over very long periods even under conditions that alter or completely suppress the conscious synaesthetic experience itself.
Enhancing pre-defined workflows withad hocanalytics using Galaxy, Docker and Jupyter
Authors: Grüning Björn A. , Rasche Eric , Rebolledo-Jaramillo Boris , Eberhard Carl , Houwaart Torsten , Chilton John , Coraor Nate , Backofen Rolf , Taylor James , Nekrutenko Anton 
Published: September 2016

AbstractWhat does it take to convert a heap of sequencing data into a publishable result? First, common tools are employed to reduce primary data (sequencing reads) to a form suitable for further analyses (i.e., list of variable sites). The subsequent exploratory stage is much moread hocand requires development of custom scripts making it problematic for biomedical researchers. Here we describe a hybrid platform combining common analysis pathways with exploratory environments. It aims at fully encompassing and simplifying the “raw data-to-publication” pathway and making it reproducible.
State-dependent modulation of functional connectivity in early blind individuals
Authors: Pelland Maxime , Orban Pierre , Dansereau Christian , Lepore Franco , Bellec Pierre , Collignon Olivier 
Published: September 2016

AbstractResting-state functional connectivity (RSFC) studies have highlighted how visual experience influences the brain’s functional architecture. Reduced RSFC coupling between occipital (visual) and temporal (auditory) regions has been reliably observed in early blind individuals (EB) at rest. In contrast, task-dependent activation studies have repeatedly demonstrated enhanced co-activation and connectivity of occipital and temporal regions during auditory processing in EB. To investigate this apparent discrepancy, the functional coupling between temporal and occipital networks at rest was directly compared to that of an auditory task in both EB and sighted controls (SC). Functional brain clusters shared across groups and cognitive states (rest and auditory task) were defined. In EBs, we observed higher occipito-temporal correlations in activity during the task than at rest. The reverse pattern was observed in SC. We also observed higher temporal variability of occipito-temporal RSFC in EB suggesting that occipital regions in this population may play a role of multiple demand system. Our study reveals how the connectivity profile of sighted and early blind people is differentially influenced by their cognitive state, bridging the gap between previous task-dependent and RSFC studies. Our results also highlight how inferring group-differences in functional brain architecture solely based on resting-state acquisition has to be considered with caution.HighlightsOccipito-temporal functional connectivity is modified by cognitive states.This modulation is different in blind and sighted individuals.Blind participants have higher occipito-temporal temporal variability at rest.The group difference in variability at rest explains the differences in modulation.Inferring group differences with resting-state data should be subject to caution.
Single variant bottleneck in the early dynamics ofH. influenzaebacteremia in neonatal rats questions the theory of independent action
Authors: Shao Xinxian , Levin Bruce , Nemenman Ilya 
Published: September 2016

AbstractThere is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (SmSand SmR) and otherwise isogenic stains ofHaemophilus influenzaetype b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, SmSor SmR. After rulling out other possibilities through years of related experiments, the field seems to have settled on a plausible explanation for this phenomenon: the first bacterium to invade the host activates the host immune response that ‘shuts the door’ on the second invading strain. To explore this hypothesis in a necessarily quantitative way, we modeled this process with a set of mixed stochastic and deterministic differential equations. Our analysis of the properties of this model with realistic parameters suggests that this hypothesis cannot explain the experimental results of Moxon and Murphy, and in particular the observed relationship between the frequency of different types of blood infections (bacteremias) and the inoculum size. We propose modifications to the model that come closer to explaining these data. However, the modified and better fitting model contradicts the common theory of independent action of individual bacteria in establishing infections. We discuss the implications of these results.
Length control of filamentous structures in cells by the limiting pool mechanism
Authors: Mohapatra Lishibanya , Lagny Thibaut J. , Harbage David , Jelenkovic Predrag R. , Kondev Jane 
Published: September 2016

AbstractHow the size of organelles in cells is controlled despite a constant turnover of their constituent parts is a central problem in cell biology. A general mechanism has been proposed based on the idea that an organelle grows by self-assembly of molecular subunits that freely diffuse in the cytoplasm. Assembly continues until the available pool of subunits is depleted to the point when the stochastic addition and removal of subunits is balanced, leading to a structure of well-defined size. Here we focus on length control of multiple filamentous structures in cells, such as actin cables and flagella. Using queueing theory and computation we show that the limiting pool mechanism leads to three different phases of assembly, starting with a rapid growth phase when all filaments quickly accumulate a large number of available subunits. Then, the slower growing filamentous structures enter a disassembly phase as they gradually lose all of their subunits to the faster growing structures. Finally, when multiple, equivalent fast-growing filaments are present, their lengths undergo protracted diffusive dynamics due to the stochastic swapping of subunits between them. This eventually leads to a broad, power-law distribution of filament lengths in steady state. Our findings demonstrate that the limiting-pool mechanism is incapable of controlling lengths of multiple filamentous structures that are assembled from a common pool of subunits, and at best, can produce only one filament of a well-defined size. Overall, our theoretical results reveal physical limitations of the limiting-pool mechanism of organelle size control.Significance StatementWhat determines the size of organelles in cells is a classic problem in cell biology. Recent experiments on mitotic spindles, and nucleolus have singled out the limiting-pool mechanism of size control. As these structures assemble, they deplete a finite pool of subunits present in the cell, thereby reducing the rate of subunit addition. Eventually the stochastic addition and removal of subunits are balanced and a well-defined size is achieved. We find that, while the limiting-pool mechanism does control the size of an individual structure, it fails when multiple structures are competing for the same pool of subunits. In that case we predict large size fluctuations and that the fastest growing structure takes up practically all the subunits from the pool.
Bursting deep dorsal horn neurons: the pharmacological target for the anti-spastic effects of Zolmitriptan?
Authors: Carlsen Eva Meier , Rasmussen Rune 
Published: September 2016

AbstractIn a recent publication, Thaweerattanasinp and colleagues employed an in vitro preparation and electrophysiology to investigate firing properties of deep dorsal horn neurons following spinal cord injury during NMDA or zolmitriptan application. Deep dorsal horn neurons were classified into bursting, simple or tonic, with bursting neurons showing NMDA and zolmitriptan sensitivity. Here, we discuss the findings in a methodological framework and propose future experiments of importance for translating the results into a physiological setting.