bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations for the Development and Reform of Microtia and Atresia Services
Authors: Mazeed Ahmed S. , Saied Samia , Abulezz Tarek , Youssef Gamal , Bulstrode Neil W. 
Published: February 2019

Background:
The initial step in setting up standardized microtia-atresia service is investigating the current status of the service and comparing this to internationally recognized guidelines or care standards. In many countries, documented information about microtia care is lacking. This study is an initiative to guide reform efforts of national microtia service in any country. The UK care standards for microtia-atresia can be a useful model to help set up a comprehensive microtia-atresia service.

Methods:
The authors conducted a survey to investigate different aspects of microtia service in Egypt. The major plastic surgery centers (n = 22) were surveyed by a structured questionnaire. The results were compared with the UK care standards for microtia-atresia to identify the aspects that need improvement. Thorough analysis of the main problems in microtia-atresia service is presented.

Results:
The authors found that microtia service is fragmented between the surveyed centers with 65% of the centers treating less than 10 microtia cases annually. Multiple surgeons are responsible for ear reconstruction in 90% of centers and only 25% of them practise a multidisciplinary team approach. None of the centers uses validated tools of aesthetic or psychological patient-reported outcome measures.

Recommendations:
These 5 recommendations are the keys to reforming microtia service in any country:
(1) Establishing nationally designated centers to concentrate the required expertise.
(2) Assigning fewer high-volume surgeons to optimize the surgical outcomes.
(3) Providing treatment by experienced multidisciplinary teams.
(4) Using validated tools of patient-reported outcome measures.
(5) Collecting and keeping standardized records for regular audit and intercenter studies.
Clinical and Radiological Comparison of Effects of Platelet-Rich Plasma, Hyaluronic Acid, and Corticosteroid Injections on Temporomandibular Joint Osteoarthritis
Authors: Gokçe Kutuk Sinem , Gökçe Gökçen , Arslan Muhammet , Özkan Yasemin , Kütük Mustafa , Kursat Arikan Osman 
Published: February 2019

Abstract
There are few studies in the literature that comparatively evaluate the use of intra-articular orticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP). In this study, the authors aimed to compare the clinical results of intra-articular CS, HA, and PRP injections in patients who presented to the authors’ clinic with temporomandibular joint (TMJ) pain and clinically diagnosed with TMJ-osteoarthritis. Patients were evaluated in 2 groups as those patients who felt pain on lateral (n = 31), and posterior (n = 43) palpation. Patients who were evaluated in the study were randomly assigned to 3 different treatment groups as Group 1 (PRP), Group 2 (HA), and Group 3 (CS). Pain felt on the TMJ on lateral and posterior palpation was assessed before treatment and every month for 3 months using a 5-point pain scale. Presence of crepitation, loss of function, and loss of strength were assessed before treatment and every month for 3 months. Significant changes were observed in the PRP and HA groups when the patients were evaluated according to the VAS scores evaluated at different follow-up times for TMJ pain on lateral palpation. Significant changes were observed in the PRP, HA, and CS groups when VAS scores were evaluated according to the patients’ follow-up times for TMJ pain on lateral palpation. In conclusion, the findings of this study have shown that intra-articular PRP injections decreased TMJ palpation pain more effectively compared with the HA and CS groups.
Use of Porous Implants for the Prosthetic Rehabilitation of Fibula Free Flap Reconstructed Patients
Authors: Brauner Edoardo , Di Carlo Stefano , Ciolfi Alessandro , Pompa Giorgio , Jamshir Sara , De Angelis Francesca , Della Monaca Marco , Valentini Valentino 
Published: February 2019

Abstract
Vascularized free flaps represent today the gold standard in Maxillo-Facial reconstructive treatment of the upper and lower compromised maxillas.
The aim of this study is to perform the advantages and disadvantages of the vascularized fibula free flap and the available rehabilitation options with porous implants.
In this study the authors analyzed 45 patients with 211 inserted implants treated and reconstructed with vascularized fibula flaps. The authors compared the use of 103 titanium tapered implants (with micro rough surface) versus 108 tantalum-titanium porous implants to evaluate the bone reabsorption and implant survival. Immediate implant stability, the peri-implant reabsorption, and the survival were evaluated. The follow-up was after 3, 6, 12, and 24 months.
The authors found that for the 108 Zimmer TM they had an average bone loss of 1 mm ± 0.2 mm after 1 year of follow-up, compared with the other implants where the average bone loss was 2.27 mm ± 0.4.
This study demonstrated that the problems caused by different fibula flaps level, compared with the mandibula or, with adjacent teeth in the maxilla, can be solved using TM porous implants that almost duplicate the fixture surface and guarantees long life prognosis to the authors’ prosthetic devices.
Donepezil's Effects on Brain Functions of Patients With Alzheimer Disease: A Regional Homogeneity Study Based on Resting-State Functional Magnetic Resonance Imaging
Authors: Cheng Jianan , Yang Hua , Zhang Jiangtao 
Published: February 2019

Purpose
Donepezil is known to increase cholinergic synaptic transmission in Alzheimer disease (AD), although how it affects cortical brain activity and how it consequently affects brain functions need further clarification. To investigate the therapeutic mechanism of donepezil underlying its effect on brain function, regional homogeneity (ReHo) technology was used in this study.

Patients and methods
This study included 11 mild-to-moderate AD patients who completed 24 weeks of donepezil treatment and 11 matched healthy controls. All participants finished neuropsychological assessment and resting-state functional magnetic resonance imaging scanning to compare whole-brain ReHo before and after donepezil treatment.

Results
Significantly decreased Alzheimer's Disease Assessment Scale–Cognitive Subscale scores (P = 0.010) and increased Mini-Mental State Examination scores (P = 0.043) were observed in the AD patients. In addition, in the right gyrus rectus (P = 0.021), right precentral gyrus (P = 0.026), and left superior temporal gyrus (P = 0.043) of the AD patients, decreased ReHo was exhibited.

Conclusion
Donepezil-mediated improvement of cognitive function in AD patients is linked to spontaneous brain activities of the right gyrus rectus, right precentral gyrus, and left superior temporal gyrus, which could be used as potential biomarkers for monitoring the therapeutic effect of donepezil.
Effect of Duloxetine for the Treatment of Chronic Central Poststroke Pain
Authors: Kim Na Young , Lee Sang Chul , Kim Yong Wook 
Published: February 2019

Objectives
Central poststroke pain (CPSP) is the neuropathic pain in areas of the body corresponding to stroke lesions. It is often refractory to treatment, reduces quality of life, and impedes rehabilitation. The pharmacological treatment of CPSP is challenging. Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is known to be effective against neuropathic pain. The current study describes the efficacy of duloxetine in reducing pain severity in CPSP patients.

Subjects and Methods
For the purpose of this study, CPSP was defined as spontaneous pain within an area of the body corresponding to the brain lesion that emerged at or after stroke onset. Any previously prescribed medical therapy for the patients was not changed or stopped; duloxetine 30 mg was added to their ongoing treatment. Pain was assessed at baseline and thereafter at 1 and 3 weeks using Numeric Rating Scale (NRS) and Short-form MC Gill Pain Questionnaire scores. At the first follow-up, scores were reviewed and dose was doubled if no improvement or adverse effects were observed.

Results
From a total of 37 patients, 4 were withdrawn because of adverse effects including nausea, agitation, and somnolence. The mean elapsed time of observed symptoms since stroke onset was 3.1 ± 4.1 years. There was a significant difference between the mean values of Short-form MC Gill Pain Questionnaire and NRS scores at baseline and those at the follow-up assessment. Twenty-six (70.3%) of the patients showed at least 30% reduction of NRS compared with baseline at the third week.

Conclusions
Our findings suggest that duloxetine can be effective for managing CPSP.
Spatial Correlation and Breast Cancer Risk
Authors: Fowler Erin E. E. , Hathaway Cassandra , Tillman Fabryann , Weinfurtner Robert , Sellers Thomas A. , Heine John 
Published: February 2019

AbstractWe present a novel method for evaluating the spatial correlation structure in two-dimensional (2D) mammograms and evaluate its merits for risk prediction. Two matched case-control studies were analyzed. Study 1 included women (N = 588 pairs) with mammograms acquired with either Hologic Selenia full field digital mammography (FFDM) units or Hologic Dimensions digital breast tomosynthesis units. Study 2 included women (N =180 pairs) with mammograms acquired with a General Electric Senographe 2000D FFDM unit. Matching variables included age, HRT usage/duration, screening history, and mammography unit. The local autocorrelation function was determined with Fourier analysis and compared with template defined as 2D double-sided exponential function with one spatial extent parameter: n = 4, 12, 24, 50, 74, 100, and 124 defined in pixel widths. The difference between local correlation and template was gauged within a kernel with an adjustable parameter and summarized, producing two measures: the mean (mn+1), and standard (sn+1). Both adjustable parameters were varied in Study 1. Select measures that produced significant associations with breast cancer were translated to Study 2. Breast cancer associations were evaluated with conditional logistic regression, adjusted for body mass index and ethnicity. Odds ratios (ORs) were estimated as per standard increment with 95% confidence intervals (CIs).Two measures were selected for breast cancer association analysis in Study 1: m75 and s25. Both measures revealed significant associations with breast cancer: OR = 1.45 (1.23, 1.66) for m75 and OR = 1.30 (1.14, 1.49) for s25. When translating to Study 2, these measures also revealed significant associations: OR = 1.49 (1.12, 1.96) for m75 and OR = 1.34 (1.06, 1.69) for s25.Novel correlation metrics presented in this work revealed significant associations with breast cancer risk. This approach is general and may have applications beyond mammography.
SLCs contribute to endocrine resistance in breast cancer: role of SLC7A5 (LAT1)
Authors: Sevigny Catherine M. , Sengupta Surojeet , Luo Zhexun , Liu Xiaoyi , Hu Rong , Zhang Zhen , Jin Lu , Pearce Dominic , Demas Diane , Shajahan-Haq Ayesha N. , Clarke Robert 
Published: February 2019

AbstractResistance to endocrine therapies remains a major challenge for the successful management of patients with estrogen receptor-positive (ER+) breast cancers. Central to the development of resistance is the adaptive reprogramming of cellular metabolism in response to treatment. Solute carriers (SLCs) play a key role in metabolic reprogramming by transporting sugars, amino acids, and other nutrients and regulating their abundance within the cell and its subcellular organelles. We found 109 SLC mRNAs to be differentially expressed between endocrine sensitive and resistant breast cancer cells. In univariate analyses, 55 of these SLCs were associated with poor outcome in ER+ breast cancer patients. Data from TMT and SILAC studies then led us to focus on SLC7A5 (LAT1). In complex with SLC3A2 (CD98), LAT1 is the primary transporter of large, neutral amino acids including leucine and tyrosine. LAT1 expression is estrogen-regulated in endocrine sensitive cells but this regulation is lost in resistant cells. Pharmacologic inhibition or genetic depletion of LAT1 each suppressed growth in two models of endocrine resistant breast cancer. Autophagy was activated with LAT1 inhibition, but cells failed to degrade p62 showing that flux was blocked. Overexpression of the LAT1 cDNA increased protein synthesis and high LAT1 expression correlated with poor disease-free survival in ER+ breast cancer patients. This study uncovers a novel LAT1 mediated adaptive response that contributes to the development of endocrine resistance. Blocking LAT1 function may offer a new avenue for effective therapeutic intervention against endocrine resistant ER+ breast cancers.
Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease
Authors: Vogel Jacob W. , Iturria-Medina Yasser , Strandberg Olof T. , Smith Ruben , Evans Alan C. , Hansson Oskar ,   for the Alzheimer’s Disease Neuroimaging Initiative, and the Swedish BioFinder Study
Published: February 2019

AbstractTau is one of the two pathological hallmarks of Alzheimer’s disease, and bears a much closer relationship to local neurodegeneration and cognitive impairment than the other hallmark, β-amyloid. Cell and rodent models have shown evidence that tau spreads from cell to cell through anatomical neuronal connections, and that this process is facilitated by the presence of β-amyloid. We test this hypothesis in humans by using an epidemic spreading model (ESM) to simulate the spread of tau over human neuronal connections, and we compare the simulated pattern of progression to the observed pattern measured in the brains of 312 individuals on the Alzheimer’s disease spectrum, using PET. Fitting our model, we found that the majority of variance in the overall pattern of tau progression could be explained by diffusion of an agent through the human connectome, measured using either functional connectivity or diffusion tractography. These models far exceeded chance, and outperformed models testing the extracellular spread of tau over Euclidian space. Surprisingly, the ESM predicted the spatial patterns of tau irrespective of whether subjects demonstrated evidence for brain β-amyloid. In addition, in β-amyloid-positive subjects only, regions with greater amyloid burden showed greater tau than predicted by connectivity patterns, suggesting a role of amyloid in accelerating the spread of tau in certain isocortical regions. Altogether, our results provide strong evidence that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain β-amyloid.
Left-handedness is associated with greater fighting success in humans
Authors: Richardson Thomas , Gilman R. Tucker 
Published: February 2019

AbstractLeft-handedness is a costly, sexually dimorphic trait found at low frequencies in all human populations. How the handedness polymorphism is maintained is unclear. The fighting hypothesis argues that left-handed men have a negative frequency-dependent advantage in violent intrasexual competition giving them a selective advantage. In support of this, many studies have found that left-handed men are overrepresented among modern professional fighters, but studies typically find no difference in fighting success between left and right-handed fighters. We studied over 13,800 professional boxers and mixed martial artists of varying abilities in three of the largest samples to test this hypothesis to date, finding robust evidence that left-handed fighters have greater fighting success. This held for both male and female fighters, and for both percentage of fights won and an objective measure of fighting ability. We replicated previous results showing that left-handed fighters are strongly overrepresented in professional combat sports, but left-handed fighters did not show greater variance in fighting ability, a hypothesis suggested in previous studies. Overall we find strong evidence consistent with the fighting hypothesis.
Oxidation state dependent conformational changes of HMGB1 regulates the formation of the CXCL12/HMGB1 heterocomplex
Authors: Fassi Enrico M. A. , Sgrignani Jacopo , D’Agostino Gianluca , Cecchinato Valentina , Garofalo Maura , Grazioso Giovanni , Uguccioni Mariagrazia , Cavalli Andrea 
Published: February 2019

AbstractHigh-mobility Group Box 1 (HMGB1) is an abundant protein present in all mammalian cells and involved in several processes. During inflammation or tissue damage, HMGB1 is released in the extracellular space and, depending on its redox state, can form a heterocomplex with CXCL12. The heterocomplex acts exclusively on the chemokine receptor CXCR4 enhancing leukocyte recruitment.Here, we used multi-microsecond molecular dynamics (MD) simulations to elucidate the effect of the disulfide bond on the structure and dynamics of HMGB1.The results of the MD simulations show that the presence or lack of the disulfide bond between Cys23 and Cys45 modulates the conformational space explored by HMGB1, making the reduced protein more suitable to form a complex with CXCL12.
Microfluidic protein isolation and sample preparation for high-resolution cryo-EM
Authors: Schmidli Claudio , Albiez Stefan , Rima Luca , Righetto Ricardo , Mohammed Inayatulla , Oliva Paolo , Kovacik Lubomir , Stahlberg Henning , Braun Thomas 
Published: February 2019

AbstractHigh-resolution structural information is essential to understand protein function. Protein-structure determination needs a considerable amount of protein, which can be challenging to produce, often involving harsh and lengthy procedures. In contrast, the several thousands to a few million protein particles required for structure-determination by cryogenic electron microscopy (cryo-EM) can be provided by miniaturized systems. Here, we present a microfluidic method for the rapid isolation of a target protein and its direct preparation for cryo-EM. Less than 1 μL of cell lysate is required as starting material to solve the atomic structure of the untagged, endogenous human 20S proteasome. Our work paves the way for high-throughput structure determination of proteins from minimal amounts of cell lysate and opens new opportunities for the isolation of sensitive, endogenous protein complexes.
Sox6: A new modulator of renin expression during physiological conditions
Authors: Saleem Mohammad , Hodgkinson Conrad P. , Contreras Ela W. , Xiao Liang , Gimenez-Bastida Juan A. , Foss Jason , Payne Alan J. , Mirotsou Maria , Gama Vivian , Dzau Victor J. , Gomez Jose A. 
Published: February 2019

ABSTRACTJuxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells which give rise to JG cells or a subset of smooth muscle cells of the renal afferent arteriole. During periods of dehydration and salt deprivation JG cells undergo expansion. Gene expression profiling comparing resident renal Mesenchymal Stromal Cells (MSCs) with JG cells indicate that the transcription factor Sox6 is highly expressed in JG cells in the adult kidney. In vitro, loss of Sox6 expression reduces differentiation of renal MSCs to renin producing cells. In vivo, Sox6 expression is up-regulated during JG cell expansion. Importantly, knockout of Sox6 in Ren1d+ cells halts the increase in renin expressing cells normally seen during JG cell expansion as well as the typical increase in renin. These results support a previously undefined role for Sox6 in renin expression during normal and pathophysiological conditions.
U.S. imperiled species are most vulnerable to habitat loss on private lands
Authors: Eichenwald Adam J. , Evans Michael J. , Malcom Jacob W. 
Published: February 2019

AbstractTo stem the ongoing loss of biodiversity, there is an urgent need to distinguish between effective and ineffective approaches for protecting species habitats. Using Google Earth Engine and 30 years of Landsat images, we quantify habitat change for 24 vertebrates on the U.S. Endangered Species List (ESA) and IUCN Red List across different categories of land ownership (e.g., federal, state, and private) that are subject to different conservation-focused legal restrictions. These estimates exclude changes due to agricultural conversion and burned areas. Imperiled species evaluated lost the least habitat (3.6%) on federal lands, while losses on private lands without conservation easements were more than twice as great (8.1%). Differences in annual percent loss before and after species were placed on the Endangered Species List, and between ESA and Red List species suggest that the ESA limited habitat loss and was most effective on federal lands. These results emphasize the importance of federal lands for protecting habitat for imperiled species and highlight the need to improve habitat protection on private lands for long-term conservation.
SIPA1L2 controls trafficking and signaling of TrkB-containing amphisomes at presynaptic terminals
Authors: Andres-Alonso Maria , Ammar Mohamed Raafet , Butnaru Ioana , Gomes Guilherme M. , Sanhueza Gustavo Acuna , Raman Rajeev , Yuanxiang PingAn , Borgmeyer Maximilian , Lopez-Rojas Jeffrey , Raza Syed Ahsan , Brice Nicola , Hausrat Torben J. , Macharadze Tamar , Diaz-Gonzalez Silvia , Carlton Mark , Failla Antonio Virgilio , Stork Oliver , Schweizer Michaela , Gundelfinger Eckart D. , Kneussel Matthias , Spilker Christina , Karpova Anna , Kreutz Michael R. 
Published: February 2019

SummaryAmphisomes are transient organelles that derive from fusion of autophagosomes with late endosomes. They rapidly transform into degradative autolysosomes, whereas non-degradative roles of the autophagic pathway have been barely described. Here we show that in neurons BDNF/TrkB receptor bearing Rab7 / Light chain 3 (LC3) - positive amphisomes signal at presynaptic boutons during retrograde trafficking to the soma. Local signaling and inward transport essentially require the Rap GTPase-activating (RapGAP) protein SIPA1L2, which directly binds to TrkB and Snapin to connect TrkB-containing amphisomes to dynein. Association with LC3 regulates the RapGAP activity of SIPA1L2 and thereby retrograde trafficking. Following induction of presynaptic plasticity amphisomes dissociate from dynein at boutons, and this enables local signaling and promotes transmitter release. Accordingly,sipa1l2knockout mice show impaired BDNF-dependent presynaptic plasticity. Collectively, the data suggest that TrkB-signaling endosomes are in fact amphisomes that during retrograde transport have local signaling capacity in the context of presynaptic plasticity.