bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Complement Retards Ankylosing Spondylitis Progression
Authors: Yang Chaoqun , Ding Peipei , Wang Qingkai , Zhang Long , Zhang Xin , Zhao Jianquan , Xu Enjie , Wang Na , Chen Jianfeng , Yang Guang , Hu Weiguo , Zhou Xuhui 
Published: October 2016

AbstractAnkylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-β1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal ofextracellularfibrinogen-binding protein ofStaphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-β1 and RANKL, were elevated uponin vitrocomplement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy.
High-resolution 3D volumetry versus conventional measuring techniques for the assessment of experimental lymphedema in the mouse hindlimb
Authors: Frueh Florian S. , Körbel Christina , Gassert Laura , Müller Andreas , Gousopoulos Epameinondas , Lindenblatt Nicole , Giovanoli Pietro , Laschke Matthias W. , Menger Michael D. 
Published: October 2016

AbstractSecondary lymphedema is a common complication of cancer treatment characterized by chronic limb swelling with interstitial inflammation. The rodent hindlimb is a widely used model for the evaluation of novel lymphedema treatments. However, the assessment of limb volume in small animals is challenging. Recently, high-resolution three-dimensional (3D) imaging modalities have been introduced for rodent limb volumetry. In the present study we evaluated the validity of microcomputed tomography (μCT), magnetic resonance imaging (MRI) and ultrasound in comparison to conventional measuring techniques. For this purpose, acute lymphedema was induced in the mouse hindlimb by a modified popliteal lymphadenectomy. The 4-week course of this type of lymphedema was first assessed in 6 animals. In additional 12 animals, limb volumes were analyzed by μCT, 9.4 T MRI and 30 MHz ultrasound as well as by planimetry, circumferential length and paw thickness measurements. Interobserver correlation was high for all modalities, in particular for μCT analysis (r = 0.975, p < 0.001). Importantly, caliper-measured paw thickness correlated well with μCT (r = 0.861), MRI (r = 0.821) and ultrasound (r = 0.800). Because the assessment of paw thickness represents a time- and cost-effective approach, it may be ideally suited for the quantification of rodent hindlimb lymphedema.
Exome sequencing in the knockin mice generated using the CRISPR/Cas system
Authors: Nakajima Kazuo , Kazuno An-a , Kelsoe John , Nakanishi Moe , Takumi Toru , Kato Tadafumi 
Published: October 2016

AbstractKnockin (KI) mouse carrying a point mutation has been an invaluable tool for disease modeling and analysis. Genome editing technologies using the CRISPR/Cas system has emerged as an alternative way to create KI mice. However, if the mice carry nucleotide insertions and/or deletions (InDels) in other genes, which could have unintentionally occurred during the establishment of the KI mouse line and potentially have larger impact than a point mutation, it would confound phenotyping of the KI mice. In this study, we performed whole exome sequencing of multiple lines of F1 heterozygousNtrk1KI mice generated using the CRISPR/Cas system in comparison to that of a wild-type mouse used as a control. We found three InDels in four KI mice but not in a control mouse.In vitrodigestion assay suggested that each InDel occurred as a de novo mutation, was carried-over from the parental mice, or was incorporated through the Cas9 nuclease mediated off-target cleavage. These results suggest that frequency of InDels found in KI mice generated by the CRISPR/Cas technology is not high, but cannot be neglected and careful assessment of these mutations is warranted.
Dose Schedule and Enhanced Conversational Recast Treatment for Children With Specific Language Impairment
Authors: Meyers-Denman Christina N. , Plante Elena 
Published: October 2016

Purpose
Dosage has been identified as an important element of treatment that may affect treatment efficacy. The purpose of this study was to examine the role of dose schedule for treatment of grammatical morphology deficits in children with specific language impairment (SLI).

Method

Sixteen 4-to-5-year-old children with SLI participated in a 5-week intervention consisting of equivalent daily Enhanced Conversational Recast treatment (Plante et al., 2014) targeting grammatical morphology. Half of the children received treatment in one 30-min session (
massed
condition). Half received treatment in three 10-min sessions (
spaced
condition) within one 4-hr period. Progress was assessed 3 times weekly by probing a child's use of his or her treatment morpheme and untreated morpheme (a maturational control) in untreated contexts.

Results
Pre- to posttreatment morpheme usage differed significantly for children regardless of dosage condition, and pre to post usage of an untreated morpheme was unchanged, demonstrating overall treatment efficacy. There were no differences in treatment effects for the massed and spaced conditions.

Conclusions
The study adds to evidence that Enhanced Conversational Recast can produce positive results in a short period of time for children with SLI. Furthermore, clinicians may have some flexibility in terms of the dose schedule they use to deliver this treatment in an evidence-based manner.
Mint3 potentiates TLR3/4- and RIG-I–induced IFN-β expression and antiviral immune responses
Authors: Huai Wanwan , Song Hui , Yu Zhongxia , Wang Wenwen , Han Lihui , Sakamoto Takeharu , Seiki Motoharu , Zhang Lining , Zhang Qunye , Zhao Wei 
Published: October 2016

Significance
Optimal productions of type I IFNs are crucial for maintaining immune homeostasis and elimination of invading viruses. A couple of enhancers of host antiviral innate immunity are induced following vial infection and then potentiate type I IFN production. Here, we identified munc18-1–interacting protein 3 (Mint3) as a viral infection-induced physiological enhancer of antiviral immune responses. Viral infection and IFN-β secretion induced Mint3 expression in the virus-infected cells, and Mint3 then feedback-promoted Toll-like recptor- and retinoic acid-inducible gene-I–induced IFN-β expression. These results will be valuable for understanding the crosstalk between virus and host immune systems. Furthermore, as IFN-β has manifested in diverse pathogenic autoimmune diseases, control of IFN-β production via suppressing Mint3 will be a potential target for designing therapeutic strategies against autoimmune disorders.
StimulatingS-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK
Authors: Ogawa Takafumi , Tsubakiyama Ryohei , Kanai Muneyoshi , Koyama Tetsuya , Fujii Tsutomu , Iefuji Haruyuki , Soga Tomoyoshi , Kume Kazunori , Miyakawa Tokichi , Hirata Dai , Mizunuma Masaki 
Published: October 2016

SignificanceCalorie restriction (CR) or methionine (Met) restriction extends the lifespan of diverse model organisms. Here we carefully examined how Met metabolites influenced aging in yeast. We showed that stimulatingS-adenosyl-l-methionine (AdoMet) synthesis, which consumes both ATP and Met, resulted in an extended lifespan and was epistatic to CR. Indeed, stimulating AdoMet synthesis led to AMP-activated protein kinase activation and increased lifespan. Furthermore, we revealed an effect ofS-adenosyl-l-homocysteine that contributed to longevity with a higher accumulation of AdoMet. The most common CR regimen involves reducing caloric intake, an unpopular trade-off. We have shown that stimulating AdoMet synthesis per se in yeast could produce physiological conditions that mimicked CR.
Simplified derivation of the gravitational wave stress tensor from the linearized Einstein field equations
Authors: Balbus Steven A. 
Published: October 2016

Significance
Gravitational radiation provides a probe of unprecedented power with which to elucidate important astrophysical processes that are otherwise completely dark (e.g., black hole mergers) or impenetrable (e.g., supernova and early universe dynamics). Historically, the gap between propagating fluctuations in the spacetime metric and classical dynamical concepts such as energy and angular momentum conservation has bedeviled this subject. By now, there is a vast literature on this topic, and there are many powerful methods available. Because of their mathematical sophistication, however, they are not used in introductory texts, which are forced instead to a follow a much more cumbersome path. We present here a derivation of the most widely used form of the stress energy tensor of gravitational radiation, using elementary methods only.
Diagnostic Accuracy of the Inferior Vena Cava Collapsibility to Predict Fluid Responsiveness in Spontaneously Breathing Patients With Sepsis and Acute Circulatory Failure
Authors: Preau Sebastien , Bortolotti Perrine , Colling Delphine , Dewavrin Florent , Colas Vincent , Voisin Benoit , Onimus Thierry , Drumez Elodie , Durocher Alain , Redheuil Alban , Saulnier Fabienne 
Published: October 2016

Objective:
To investigate whether the collapsibility index of the inferior vena cava recorded during a deep standardized inspiration predicts fluid responsiveness in nonintubated patients.

Design:
Prospective, nonrandomized study.

Setting:
ICUs at a general and a university hospital.

Patients:
Nonintubated patients without mechanical ventilation (n = 90) presenting with sepsis-induced acute circulatory failure and considered for volume expansion.

Interventions:
We assessed hemodynamic status at baseline and after a volume expansion induced by a 30-minute infusion of 500-mL gelatin 4%.

Measurements and Main Results:
We measured stroke volume index and collapsibility index of the inferior vena cava under a deep standardized inspiration using transthoracic echocardiography. Vena cava pertinent diameters were measured 15–20 mm caudal to the hepatic vein junction and recorded by bidimensional imaging on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep standardized inspiration followed by passive exhalation. The collapsibility index expressed in percentage equaled the ratio of the difference between end-expiratory and minimum-inspiratory diameter over the end-expiratory diameter. After volume expansion, a relevant (≥ 10%) stroke volume index increase was recorded in 56% patients. In receiver operating characteristic analysis, the area under curve for that collapsibility index was 0.89 (95% CI, 0.82–0.97). When such index is superior or equal to 48%, fluid responsiveness is predicted with a sensitivity of 84% and a specificity of 90%.

Conclusions:
The collapsibility index of the inferior vena cava during a deep standardized inspiration is a simple, noninvasive bedside predictor of fluid responsiveness in nonintubated patients with sepsis-related acute circulatory failure.
Longitudinal analysis of changes in weight and waist circumference in relation to incident vasomotor symptoms: the Study of Women's Health Across the Nation (SWAN)
Authors: Gold Ellen B. , Crawford Sybil L. , Shelton Janie F. , Tepper Ping G. , Crandall Carolyn J. , Greendale Gail A. , Matthews Karen A. , Thurston Rebecca C. , Avis Nancy E. 
Published: October 2016

Abstract

Objective:
Greater body mass index (BMI) and body fat are associated with vasomotor symptoms (VMS). Thus, weight loss may prevent VMS. We analyzed whether concurrent BMI or waist circumference and/or changes in weight or waist circumference predicted incident VMS and whether these relations differed by menopause stage or race/ethnicity.

Methods:
Data from 10 follow-up visits for 1,546 participants in the Study of Women's Health Across the Nation who reported no VMS at baseline were modeled for time to first symptomatic visit in relation to concurrent BMI and waist circumference and change in weight and waist circumference during early and late menopause using discrete survival analyses, adjusting for covariates.

Results:
Greater concurrent BMI and waist circumference were significantly related to greater any and frequent (≥6 d in the last 2 wk) incident VMS in early menopause and lower VMS risk in late menopause. Percentage weight change since baseline and since the prior visit was unrelated to incident any VMS in either menopause stage. Percentage weight change since baseline had a significant shallow U-shaped association with incident frequent VMS in early menopause (P = 0.02), a shallow inverse U-shape in late menopause (P = 0.02), and a significant interaction with menopause stage (P = 0.004) but not with race/ethnicity. Recent weight change was unassociated with incident VMS in either menopause stage. Results were similar for waist change.

Conclusions:
Concurrent BMI and waist circumference were positively related to incident VMS in early menopause and negatively related in late menopause. Maintaining healthy weight in early menopause may help prevent VMS.
Evaluation of the Effect of Cycloplegia on Anterior Chamber Depth in Cataract Patients Using Optical Low-Coherence Reflectometry
Authors: Avdagic Ema , Lazzaro Douglas R. 
Published: October 2016

Purpose:
The study was performed to study the effect of cycloplegia on anterior chamber depth (ACD) in cataract eyes. One instrument (Lenstar) was used for all measurements.

Methods:
Anterior chamber depth calculations were taken with the Lenstar in cataract eyes with a mean age of 71.9±8.8 years before instilling cycloplegic drops. Two drops of Tropicamide were then instilled in each eye and measurements were retaken between 30 to 45 min later.

Results:
Cycloplegia with a mild agent used routinely in this practice location showed a statically significant effect on increasing ACD by 0.0647±0.01 in the OD and 0.0758±0.02 in the OS.

Conclusions:
Anterior chamber depth can be important in the final refractive result postcataract surgery. The results of a change in effective lens position would be most significant in higher intraocular lens powers.
A Grounded Theory Qualitative Analysis of Interprofessional Providers' Perceptions on Caring for Critically Ill Infants and Children in Pediatric and General Emergency Departments
Authors: Gangadharan Sandeep , Tiyyagura Gunjan , Gawel Marcie , Walsh Barbara M. , Brown Linda L. , Lavoie Megan , Tay Khoon-Yen , Auerbach Marc A. 
Published: October 2016

Objective
The objective of this study was to explore pediatric emergency department (PED) and general emergency department (GED) providers' perceptions on caring for critically ill infants and children.

Methods
This study utilized qualitative methods to examine the perceptions of emergency department providers caring for critically ill infants and children. Teams of providers participated in 4 in situ simulation cases followed by facilitated debriefings. Debriefings were recorded and professionally transcribed. The transcripts were reviewed independently and followed by group coding discussions to identify emerging themes. Consistent with grounded theory, the team iteratively revised the debriefing script as new understanding was gained. A total of 188 simulation debriefings were recorded in 24 departments, with 15 teams participating from 8 PEDs and 32 teams from 16 GEDs.

Results
Twenty-four debriefings were audiotaped and professionally transcribed verbatim. Thematic saturation was achieved after 20 transcripts. In our iterative qualitative analysis of these transcripts, we observed 4 themes: (1) GED provider comfort with algorithm-based pediatric care and overall comfort with pediatric care in PED, (2) GED provider reliance on cognitive aids versus experience-based recall by PED providers, (3) GED provider discomfort with locating and determining size or dose of pediatric-specific equipment and medications, and (4) PED provider reliance on larger team size and challenges with multitasking during resuscitation.

Conclusions
Our qualitative analysis produced several themes that help us to understand providers' perceptions in caring for critically ill children in GEDs and PEDs. These data could guide the development of targeted educational and improvement interventions.
Craniectomy and Traumatic Brain Injury in Children on Extracorporeal Membrane Oxygenation Support
Authors: Anton-Martin Pilar , Braga Bruno , Megison Stephen , Journeycake Janna , Moreland Jessica 
Published: October 2016

Abstract
Severe trauma may cause refractory life-threatening respiratory failure requiring extracorporeal membrane oxygenation (ECMO). Concurrent traumatic brain injury, however, complicates the use of ECMO because of the major risk of intracranial bleeding with systemic anticoagulation. Craniotomy and/or craniectomy for hematoma evacuation during ECMO are extremely high-risk procedures secondary to ongoing anticoagulation, and there are only a few such case reports in the literature. We present the case of a child with multiple thoracic injuries and life-threatening respiratory failure supported on ECMO. She developed an intracranial hemorrhage while systemically heparinized that required emergent decannulation and bedside craniectomy for hematoma extraction. She survived with an excellent neurologic outcome. We also review the relevant literature regarding the use of ECMO in patients with polytrauma and the occurrence of craniectomy on extracorporeal support, with a focus on pediatric publications. Patients with polytrauma with brain injury can be supported on ECMO, but extreme precaution must be taken regarding anticoagulation. The intracranial complications of ECMO in this population are not infrequent, but our case report and review of the literature suggest that neurosurgical intervention should be considered in life-threatening conditions when no other alternatives are available.
Quantification of Chronic Oxaliplatin-Induced Hypesthesia in Two Areas of the Hand
Authors: Andriamamonjy Mihary , Delmotte Jean-Baptiste , Savinelli Francesco , Beaussier Hélène , Coudoré François 
Published: October 2016

Purpose:
Oxaliplatin is a platinum derivate widely used in cancer treatment but producing dose-limiting peripheral neurotoxicity. Acute neuropathy is characterized by a transient cold-induced distal allodynia, whereas chronic neuropathy leads to sensory loss. To design a method for quantitative assessment of oxaliplatin-induced peripheral neuropathy, we developed a study that aims to characterize the most appropriate skin area of the hand to perform sensory tests.

Methods:
We included patients treated for at least 6 months with oxaliplatin. Thermal sensory tests are assessed using the Thermotest (Somedic) and consist in measuring thermal thresholds in the thenar and in the fingertips of the opposite hand. Results are analyzed using T-Tests comparing thermal sensory thresholds between the two areas of the hand, globally and then individually.

Results:
In 7 weeks, 12 patients (7 men and 5 women; mean age: 64.5 years) were included, all treated with FOLFOX protocol. Thermal detection thresholds measured on the fingertips are 146% and 108% greater than the ones measured on the palm for cold and warm, respectively (P < 0.0001). Thermal pain thresholds are difficult to interpret. Regarding individual tests, 9/12 patients and 8/12 patients experienced hypesthesia to cold and warm, respectively.

Conclusions:
These results reveal that distal hypesthesia occurring under treatment with oxaliplatin is markedly pronounced in the fingertips; however, as thermal threshold is unknown before treatment, it is difficult to assert that fingertip thermal hypesthesia has developed under treatment. Finally, this short study may be useful to design a method for quantifying oxaliplatin-induced neuropathy.
Invariance principle and model reduction for the Fokker–Planck equation
Authors: Karlin I. V. 
Published: October 2016

The principle of dynamic invariance is applied to obtain closed moment equations from the Fokker–Planck kinetic equation. The analysis is carried out to explicit formulae for computation of the lowest eigenvalue and of the corresponding eigenfunction for arbitrary potentials.
This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’.
Mitochondrial DNA Density Homeostasis Accounts for the Threshold Effect in Human Mitochondrial Disease
Authors: Aryaman Juvid , Johnston Iain G. , Jones Nick S. 
Published: October 2016

AbstractMitochondrial dysfunction is involved in a wide array of devastating diseases but the heterogeneity and complexity of these diseases’ symptoms challenges theoretical understanding of their causation. With the explosion of -omics data, we have the unprecedented ability to gain deep understanding of the biochemical mechanisms of mitochondrial dysfunction. However, there is also a need to make such datasets interpretable, and quantitative modelling allows us to translate such datasets into intuition and suggest rational biomedical treatments. Working towards this interdisciplinary goal, we use a recently published large-scale dataset, and develop a mathematical model of progressive increase in mutant load of the MELAS 3243A>G mtDNA mutation to develop a descriptive and predictive biophysical model. The experimentally observed behaviour is surprisingly rich, but we find that a simple, biophysically-motivated model intuitively accounts for this heterogeneity and yields a wealth of biological predictions. Our findings suggest that cells attempt to maintain wild-type mtDNA density through cell volume reduction, and thus energy demand reduction, until a minimum cell volume is reached. Thereafter, cells toggle from demand reduction to supply increase, upregulating energy production pathways. Our analysis provides further evidence for the physiological significance of mtDNA density, and emphasizes the need for performing single-cell volume measurements jointly with mtDNA quantification. We propose novel experiments to verify the hypotheses made here, to further develop our understanding of the threshold effect, and connect with rational choices for mtDNA disease therapies.Author SummaryMitochondria are organelles which produce the major energy currency of the cell: ATP. Mitochondrial dysfunction is associated with a multitude of devastating diseases, from Parkinson’s disease to cancer. Large volumes of data related to these diseases are being produced, but translation of these data into rational biomedical treatment is challenged by a lack of theoretical understanding. We develop a mathematical model of progressive increase of mutant load in mitochondrial DNA, for the mutation associated with MELAS (the most common mitochondrial disease), to address this. We predict that cells attempt to maintain the ratio of healthy mtDNA to cell volume by reducing their cell volume until they reach a minimum cell volume. As mutant load continues to increase, cells switch strategy by increasing their energy supply pathways. Our work accounts for large-scale experimental data and makes testable predictions about mitochondrial dysfunction. It also provides support for increasing mitochondrial content, as well as reduction in dependence upon mitochondrial metabolism via the ketogenic diet, as relevant treatments for mitochondrial disease.