bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mandibular Condyle Reconstruction With Fibula Free-Tissue Transfer: The Role of the Masseter Muscle
Authors: Gravvanis Andreas , Anterriotis Dimitrios , Kakagia Despoina 
Published: September 2017

Background:
Free fibula flap is an option for primary restoration after disarticulation mandibular resection, though literature on technique refinements is scarce. The authors hypothesized that inset of the masseter, the key mandibular elevator muscle, at the reconstructed mandible may optimize functional recovery.

Methods:
All patients undergoing reconstruction of mandibulectomy–condylectomy defect (January 2009 to January 2014) by means of a fibular flap were prospectively studied. The neocondyle was formed by the distal portion of the fibula and placed directly into the glenoid fossa with preservation of the temporomandibular disc. The deep portion of the masseter was inset at the angle of the reconstructed mandible.
Condylar position was postoperatively evaluated by panoramic radiographs. Patients self-evaluated speech, chewing, swallowing, and facial appearance.

Results:
Two patients had immediate and 3 delayed reconstruction involving condyle ramus body, in the study period. During a mean follow-up of 32 months, 4 patients had satisfactory occlusion, 1 patient had an open-bite deformity, but was able to masticate solid food and maintain an oral diet. Although no significant condyle dislocation was recorded, 2 patients had slight ipsilateral deviation on mouth opening. Nevertheless, cosmesis was satisfactory and all patients maintained intelligible speech. Functional score was 13.6 ± 1.14 and facial appearance score was 4 ± 0.7.

Conclusion:
The free fibula transfers with direct seating of the fibula into the condylar fossa followed by masseter muscle reinsertion provides acceptable functional reconstruction of the mandibulectomy–condylectomy defect.
Bariatric Surgery and the Risk of Cancer in a Large Multisite Cohort
Authors: Schauer Daniel P. , Feigelson Heather Spencer , Koebnick Corinna , Caan Bette , Weinmann Sheila , Leonard Anthony C. , Powers J. David , Yenumula Panduranga R. , Arterburn David E. 
Published: September 2017

Objective:
To determine whether bariatric surgery is associated with a lower risk of cancer.

Background:
Obesity is strongly associated with many types of cancer. Few studies have examined the relationship between bariatric surgery and cancer risk.

Methods:
We conducted a retrospective cohort study of patients undergoing bariatric surgery between 2005 and 2012 with follow-up through 2014 using data from a large integrated health insurance and care delivery systems with 5 study sites. The study included 22,198 subjects who had bariatric surgery and 66,427 nonsurgical subjects matched on sex, age, study site, body mass index, and Elixhauser comorbidity index. Multivariable Cox proportional-hazards models were used to examine incident cancer up to 10 years after bariatric surgery compared to the matched nonsurgical patients.

Results:
After a mean follow-up of 3.5 years, we identified 2543 incident cancers. Patients undergoing bariatric surgery had a 33% lower hazard of developing any cancer during follow-up [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.60, 0.74, P < 0.001) compared with matched patients with severe obesity who did not undergo bariatric surgery, and results were even stronger when the outcome was restricted to obesity-associated cancers (HR 0.59, 95% CI 0.51, 0.69, P < 0.001). Among the obesity-associated cancers, the risk of postmenopausal breast cancer (HR 0.58, 95% CI 0.44, 0.77, P < 0.001), colon cancer (HR 0.59, 95% CI 0.36, 0.97, P = 0.04), endometrial cancer (HR 0.50, 95% CI 0.37, 0.67, P < 0.001), and pancreatic cancer (HR 0.46, 95% CI 0.22, 0.97, P = 0.04) was each statistically significantly lower among those who had undergone bariatric surgery compared with matched nonsurgical patients.

Conclusions:
In this large, multisite cohort of patients with severe obesity, bariatric surgery was associated with a lower risk of incident cancer, particularly obesity-associated cancers, such as postmenopausal breast cancer, endometrial cancer, and colon cancer. More research is needed to clarify the specific mechanisms through which bariatric surgery lowers cancer risk.
Pervasive epistasis modulates neurodevelopmental defects of the autism-associated 16p11.2 deletion
Authors: Iyer Janani , Singh Mayanglambam Dhruba , Jensen Matthew , Patel Payal , Pizzo Lucilla , Huber Emily , Koerselman Haley , Weiner Alexis T. , Lepanto Paola , Vadodaria Komal , Kubina Alexis , Wang Qingyu , Talbert Abigail , Yennawar Sneha , Badano Jose , Manak J. Robert , Rolls Melissa M. , Krishnan Arjun , Girirajan Santhosh 
Published: September 2017

ABSTRACTAs opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods inDrosophilaRNAi lines, we identified a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We tested 565 pairwise knockdowns in the developing eye, and identified 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppressed or enhanced cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways were also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for genetic interactions within CNVs and identifies potential therapeutic targets for neurodevelopmental disorders.
Acute Social Stress Engages Synergistic Activity of Stress Mediators in the VTA to Promote Pavlovian Reward Learning
Authors: Tovar-Diaz Jorge , Pomrenze Matthew B. , Pahlavan Bahram , Kan Russell , Drew Michael R. , Morikawa Hitoshi 
Published: September 2017

ABSTRACTStressful events rapidly trigger activity-dependent synaptic plasticity in certain brain areas, driving the formation of aversive memories. However, it remains unclear how stressful experience affects plasticity mechanisms to regulate learning of appetitive events, such as intake of addictive drugs or palatable foods. Using rats, we show that two acute stress mediators, corticotropin-releasing factor (CRF) and norepinephrine (NE), enhance plasticity of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA) through their differential effects on inositol 1,4,5-triphosphate (IP)-dependent Ca2+signaling. In line with this, acute social defeat stress engages convergent CRF and NE signaling in the VTA to enhance learning of cocaine-paired cues. Furthermore, defeat stress enables learning of a food-paired cue with no delay between the cue onset and food delivery. We propose that acute stress mediators synergistically regulate IP3-Ca2+signaling in the VTA to promote appetitive Pavlovian conditioning, likely enabling learning of cues with no predictive value.
Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure
Authors: Rodriguez-Barraquer Isabel , Arinaitwe Emmanuel , Jagannathan Prasanna , Kamya Moses R , Rosenthal Philip J. , Rek John , Dorsey Grant , Nankabirwa Joaniter , Staedke Sarah G. , Kilama Maxwell , Drakeley Chris , Ssewanyana Isaac , Smith David L , Greenhouse Bryan 
Published: September 2017

AbstractMalaria immunity is complex and multi-faceted, and fundamental gaps remain in our understanding of how it develops. Here, we use detailed clinical and entomological data from three parallel cohort studies conducted across the malaria transmission spectrum in Uganda to quantify the development of immunity against symptomaticPlasmodium falciparumas a function of age and transmission intensity. We focus on: anti-parasite immunity (i.e; ability to control parasite densities) and anti-disease immunity (i.e; ability to tolerate higher parasite densities without fever). Our findings suggest a strong effect of age on both types of immunity, that remains significant after adjusting for cumulative exposure. They also show a non-linear effect of transmission intensity, where children experiencing the lowest transmission appear to develop immunity faster than those experiencing higher transmission. These findings illustrate how anti-parasite and anti-disease immunity develop in parallel, reducing the probability of experiencing symptomatic malaria upon each subsequentP. falciparuminfection.
Genetic drivers of repeat expansion disorders localize to 3-D chromatin domain boundaries
Authors: Sun James , Zhou Linda , Emerson Daniel J. , Gilgenast Thomas G. , Titus Katelyn , Beagan Jonathan A. , Phillips-Cremins Jennifer E. 
Published: September 2017

AbstractMore than 25 inherited neurological disorders are caused by the unstable expansion of repetitive DNA sequences termed short tandem repeats (STRs). A fundamental unresolved question is why specific STRs are susceptible to unstable expansion leading to severe pathology, whereas tens of thousands of normal-length repeat tracts across the human genome are relatively stable. Here, we unexpectedly discover that nearly all STRs associated with repeat expansion diseases are located at boundaries demarcating 3-D chromatin domains. We find that boundaries exhibit markedly higher CpG island density compared to loci internal to domains. Importantly, disease-associated STRs are specifically localized to ultra-dense CpG island-rich boundaries, suggesting that these loci might be hotspots for epigenetic instability and topological disruption upon unstable expansion. In Fragile X Syndrome, mutation-length expansion at theFmr1gene results in severe disruption of the boundary between TADs. Our data uncover higher-order chromatin architecture as a new dimension in understanding the mechanistic basis of repeat expansion disorders.
Functional Brain Network Estimation with Time Series Self-scrubbing
Authors: Li Weikai , Qiao Lishan , Wang Zhengxia , Shen Dinggang 
Published: September 2017

AbstractFunctional brain network (FBN) has been becoming an increasingly important measurement for exploring the cerebral working mechanism and mining informative biomarkers for assisting diagnosis of some neurodegenerative disorders. Despite its potential performance in discovering the valuable patterns hidden in the brains, the estimated FBNs are often heavily influenced by the quality of the observed data (e.g., BOLD signal series). In practice, a preprocessing pipeline is usually employed for improving the data quality prior to the FBN estimation; but, even so, some data points in the time series are still not clean enough, possibly including original artifacts (e.g., micro head motion), non-resting functional disturbing (e.g., mind-wandering), and new “noises” caused by the preprocessing pipeline per se. Therefore, not all data points in the time series can contribute to the subsequent FBN estimation. To address this issue, in this paper, we propose a novel FBN estimation method by introducing a latent variable as an indicator of the data quality, and develop an alternating optimization algorithm for scrubbing the data and estimating FBN simultaneously in a single framework. As a result, we can obtain more accurate FBNs with the self-scrubbing data. To illustrate the effectiveness of the proposed method, we conduct experiments on two publicly available datasets to identify mild cognitive impairment (MCI) patients from normal control (NC) subjects based on the estimated FBNs. Experimental results show that the proposed FBN modelling method can achieve higher classification accuracy, significantly outperforming the baseline methods.
TMS SMART – Scalp Mapping of Annoyance Ratings and Twitches caused by Transcranial Magnetic Stimulation
Authors: Meteyard Lotte , Holmes Nicholas 
Published: September 2017

AbstractThe magnetic pulse generated during Transcranial magnetic stimulation [TMS] also stimulates cutaneous nerves and muscle fibres, with the most commonly reported side effect being muscle twitches and sometimes painful sensations. These sensations affect behaviour during experimental tasks, presenting a potential confound for ‘online’ single-pulse TMS studies. Our objective was to systematically map the degree of disturbance (ratings of annoyance, pain, and muscle twitches) caused by TMS at 43 locations across the scalp. Ten participants provided ratings whilst completing a choice reaction time task, and ten participants provided ratings whilst completing a ‘flanker’ reaction time task. TMS over frontal and inferior regions resulted in the highest ratings of annoyance, pain, and muscle twitches caused by TMS. In separate analyses we predicted the difference in reaction times (RT) under TMS by scalp location and subjective ratings. Frontal and inferior scalp locations showed the greatest cost to RTs under TMS (i.e., slowing), with midline sites showing no or minimal slowing. Increases in subjective ratings of disturbance predicted longer RTs under TMS. Critically, ratings were a better predictor of the cost of TMS than scalp location or scalp-to-cortex distance, and the more difficult ‘flanker’ task showed a greater effect of subjective disturbance. The peripheral sensations and discomfort caused by TMS pulses significantly and systematically influence RTs during single-pulse, online TMS experiments. We provide the data as an online resource (www.tms-smart.info) so that researchers can select control sites that account for the level of general interference in task performance caused by online single-pulse TMS.
Wine yeast phenomics: a standardized fermentation method for assessing quantitative traits ofSaccharomyces cerevisiaestrains in enological conditions
Authors: Peltier Emilien , Bernard Margaux , Trujillo Marine , Prodhomme Duyên , Barbe Jean-Christophe , Gibon Yves , Marullo Philippe 
Published: September 2017

AbstractThis work describes the set up of a small scale fermentation methodology for measuring quantitative traits of hundreds of samples in an enological context. By using standardized screw cap vessels, the alcoholic fermentation kinetics ofSaccharomyces cerevisiaestrains were measured by following the weight loss over time. Preliminary results showed that the kinetic parameters measured are in agreement with those observed in larger scale vats. The small volume used did not impair any analysis of the strain performance. Indeed, this fermentation system was coupled with robotized enzymatic assays and 8 end-point metabolites of enological interest were measured accurately. Moreover, the vessel used offers the possibility to assay 32 volatiles compounds using a headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry approach. Data presented demonstrates that the shaking conditions significantly impacted the mean and the variance of kinetic parameters, primary metabolites, and the production of volatile compounds. This effect was likely due to an enhanced transfer of dissolved oxygen during the first hours of the alcoholic fermentation. To test the efficiency of this experimental design, the phenotypic response of 35 wine industrial starters was measured in five grape juices from the Bordeaux area. A multivariate analysis illustrated that strains were better discriminated by some grape must, than others. The technological performances as well as the phenotypic robustness of these strains was measured and discussed. The optimized methodology developed allows investigating multiple fermentation traits for numerous yeast strains and conditions and greatly contributes in achieving quantitative genetics studies as well as yeast selection programs.
Superior stimulation of female fecundity by subordinate males provides a mechanism for telegony
Authors: Pascoal Sonia , Jarrett Benjamin J. M. , Evans Emma , Kilner Rebecca M. 
Published: September 2017

SummaryWhen females mate promiscuously, sperm compete within females to fertilise the ova. In theory, a male can increase his success at siring offspring by inducing the female to lay more eggs, as well as by producing more competitive sperm. Here we report that the evolutionary consequences of fecundity stimulation extend beyond rival males, by experimentally uncovering effects on offspring. With experiments on the burying beetleNicrophorus vespilloides, we show that smaller subordinate males are better able to stimulate female fecundity than larger, dominant males. Furthermore dominant males also benefit from the greater fecundity induced by smaller males, and so gain from the female’s earlier promiscuity just as predicted by theory. By inducing females to produce more offspring on a limited resource, smaller males cause each larva to be smaller, even those they do not sire themselves. Fecundity stimulation thus promotes the non-genetic inheritance of offspring body size, and provides a mechanism for telegony.
Enhanced food-related responses in the ventral medial prefrontal cortex in orexin-deficient patients
Authors: van Holst Ruth Janke , Janssen Lieneke K. , van Mierlo Petra , Lammers Gert Jan , Cools Roshan , Overeem Sebastiaan , Aarts Esther 
Published: September 2017

AbstractBackgroundNarcolepsy Type 1 is a chronic sleep disorder caused by a deficiency of orexin (hypocretin). In addition to sleep regulation, orexin is important for motivated control processes. Weight gain and obesity are common in narcolepsy. However, the neurocognitive processes associated with food-related control and overeating in orexin-deficient patients are unknown. We explored the neural correlates of general and food-related attentional control in narcolepsy patients (n=23) and healthy BMI-matched controls (n=20). In secondary analyses, we included patients with idiopathic hypersomnia (n=15) to assess sleepiness-related influences.MethodsWe measured attentional bias to food words with a Food Stroop task and general executive control with a Classic Stroop task during fMRI. Moreover, with correlational analyses, we assessed the relative contribution of the neural findings on the Food Stroop and Classic Stroop tasks to spontaneous snack intake.ResultsRelative to healthy controls, narcolepsy patients showed enhanced ventral medial prefrontal cortex responses and connectivity with motor cortex during the Food Stroop task, but attenuated dorsal medial prefrontal cortex responses during the Classic Stroop task. The ventral medial prefrontal cortex responses on the Food Stroop task, not the dorsal medial prefrontal cortex responses on the Classic Stroop task, were a significant predictor of snack intake. Comparing the narcolepsy patients with idiopathic hypersomnia patients revealed similar results.ConclusionsThese findings demonstrate that orexin deficiency is associated with decreased dorsal medial prefrontal cortex responses during general executive control and enhanced ventral medial prefrontal cortex responses during food-driven attention, with the latter predicting increases in food intake.Statement of SignificancePatients with orexin (hypocretin) deficient narcolepsy type-1 often suffer from obesity as well as increased food craving, in addition to the sleep symptoms. However, whether and how orexin deficiency relates to neural differences in food-directed attention is unclear. We employed a Food Stroop task during fMRI and provide experimental evidence that the ventral medial prefrontal cortex responds more strongly to food words in narcolepsy patients than in controls. The hypothesis that this mechanism contributes to weight problems in narcolepsy is strengthened by the observation that ventral medial prefrontal cortex responses during the Food Stroop task were predictive of snack intake. These mechanistic data might thus advance the development of treatment targets for obesity in narcolepsy.
Tolerance of chronic HDACi-administration used for treatment of neurological and visceral disease including lung pathogenesis
Authors: Alam Md. Suhail , Cooper Bruce , Haldar Kasturi 
Published: September 2017

AbstractHistone deacetylase (HDAC) inhibitors are of significant interest as drugs. However, their use in neurological disorders has raised concern because HDACs are required for brain function. We have previously shown that a triple combination formulation (TCF) of the pan HDACi vorinostat (Vo) improves pharmacokinetic exposure and entry of Vo into the brain. TCF treatment significantly delayed both neurodegeneration and death in the Npc1nmf164 murine model of Niemann Pick Type C (NPC) disease. The TCF induces no metabolic toxicity, but it’s risk to normal brain functions and potential utility in treating lung disease, a major NPC clinical complication, remain unknown. Here we report that TCF administered for 8-10 months was not detrimental to brain or neuromuscular functions of healthy mice, based on quantitative analyses of major Purkinje neurons in the cerebellum, inflammation in the hippocampus and symptoms of progressive neurocognitive/muscular disease. The TCF was also not injurious to lung tissue but rather improved delivery of Vo to lungs and reduced accumulation of foamy macrophages in Npc1nmf164 mice. Together these data support feasibility of tolerable, chronic administration of an HDACi formulation to treat brain and systemic disease including lung pathology, a frequent cause of death in NPC and possibly other neurological diseases.
Dephosphorylation is the Mechanism of Fibroblast Growth Factor Inhibition of Guanylyl Cyclase-B
Authors: Robinson Jerid W. , Egbert Jeremy R. , Davydova Julia , Schmidt Hannes , Jaffe Laurinda A. , Potter Lincoln R. 
Published: September 2017

AbstractActivating mutations in fibroblast growth factor receptor 3 (FGFR3) and inactivating mutations of guanylyl cyclase-B (GC-B, also called NPRB or NPR2) cause dwarfism. FGF exposure inhibits GC-B activity in a chondrocyte cell line, but the mechanism of the inactivation is not known. Here, we report that FGF exposure causes dephosphorylation of GC-B in rat chondrosarcoma cells, which correlates with a rapid, potent and reversible inhibition of C-type natriuretic peptide-dependent activation of GC-B. Cells expressing a phosphomimetic mutant of GC-B that cannot be inactivated by dephosphorylation because it contains glutamate substitutions for all known phosphorylation sites showed no decrease in GC-B activity in response to FGF. We conclude that FGF rapidly inactivates GC-B by a reversible dephosphorylation mechanism, which may contribute to the signaling network by which activated FGFR3 causes dwarfism.HighlightsGuanylyl Cyclase-B is expressed in rat chondrosarcoma cellsFGF2 induces a rapid, potent, and reversible inhibition of GC-BFGF2 treatment causes GC-B dephosphorylationFGF2 does not inhibit a dephosphorylation-resistant form of GC-BDephosphorylation is the mechanism of FGF2-dependent inhibition of GC-BAbbreviationscGMPcyclic guanosine monophosphateGCguanylyl cyclaseNPnatriuretic peptidePBSphosphate buffered salineWTwild type