bluuebunny/crossref_metadata_2025_split huggingface dataset:
5‐HT2A receptor activation enhances NMDA receptor‐mediated glutamate responses through Src kinase in the dendrites of rat jaw‐closing motoneurons
Authors: Dantsuji Masanori , Nakamura Shiro , Nakayama Kiyomi , Mochizuki Ayako , Park Sook Kyung , Bae Yong Chul , Ozeki Masahiko , Inoue Tomio 
Published: March 2019

Key points
5‐HT increases the excitability of brainstem and spinal motoneurons, including the jaw‐closing motoneurons, by depolarizing the membrane potential and decreasing the medium‐duration afterhyperpolarization.
In this study, we focused on how 5‐HT enhances postsynaptic glutamatergic responses in the dendrites of the jaw‐closing motoneurons.
We demonstrate that 5‐HT augments glutamatergic signalling by enhancing the function of the GluN2A‐containing NMDA receptor (NMDAR) through the activation of 5‐HT2A receptors (5‐HT2ARs) and Src kinase.
To enhance glutamatergic responses, activation of the 5‐HT2ARs must occur within ∼60 μm of the location of the glutamate responses.
5‐HT inputs to the jaw‐closing motoneurons can significantly vary their input–output relationship, which may contribute to wide‐range regulation of contractile forces of the jaw‐closing muscles.
AbstractVarious motor behaviours are modulated by 5‐HT. Although the masseter (jaw‐closing) motoneurons receive both glutamatergic and serotonergic inputs, it remains unclear how 5‐HT affects the glutamatergic inputs to the motoneuronal dendrites. We examined the effects of 5‐HT on postsynaptic responses evoked by single‐ or two‐photon uncaging of caged glutamate (glutamate responses) to the dendrites of masseter motoneurons in postnatal day 2–5 rats of either sex. Application of 5‐HT induced membrane depolarization and enhanced the glutamate‐response amplitude. This enhancement was mimicked by the 5‐HT2A receptor (5‐HT2AR) agonist and was blocked by the 5‐HT2A/2CR antagonist. However, neither the 5‐HT2BR nor the 5‐HT2CR agonists altered glutamate responses. Blockade of the NMDA receptors (NMDARs), but not AMPA receptors, abolished the 5‐HT‐induced enhancement. Furthermore, the selective antagonist for the GluN2A subunit abolished the 5‐HT‐induced enhancement. 5‐HT increased GluN2A phosphorylation, while the Src kinase inhibitor reduced the 5‐HT‐induced enhancement and GluN2A phosphorylation. When exposure to the 5‐HT2AR agonist was targeted to the dendrites, the enhancement of glutamate responses was restricted to the loci of the dendrites near the puff loci. Electron microscopic immunohistochemistry revealed that both the NMDARs and the 5‐HT2ARs were close to each other in the same dendrite. These results suggest that activation of dendritic 5‐HT2ARs enhances the function of local GluN2A‐containing NMDARs through Src kinase. Such enhancement of the glutamate responses by 5‐HT may contribute to wide‐range regulation of contractile forces of the jaw‐closing muscles.
Basal forebrain GABAergic innervation of olfactory bulb periglomerular interneurons
Authors: Sanz Diez Alvaro , Najac Marion , De Saint Jan Didier 
Published: March 2019

Key points
Basal forebrain long‐range projections to the olfactory bulb are important for olfactory sensitivity and odour discrimination.
Using optogenetics, it was confirmed that basal forebrain afferents mediate IPSCs on granule and deep short axon cells. It was also shown that they selectively innervate specific subtypes of periglomerular (PG) cells.
Three different subtypes of type 2 PG cells receive GABAergic IPSCs from the basal forebrain but not from other PG cells.
Type 1 PG cells, in contrast, do not receive inputs from the basal forebrain but do receive inhibition from other PG cells.
These results shed new light on the complexity and specificity of glomerular inhibitory circuits, as well as on their modulation by the basal forebrain.
AbstractOlfactory bulb circuits are dominated by multiple inhibitory pathways that finely tune the activity of mitral and tufted cells, the principal neurons, and regulate odour discrimination. Granule cells mediate interglomerular lateral inhibition between mitral and tufted cells’ lateral dendrites whereas diverse subtypes of periglomerular (PG) cells mediate intraglomerular lateral inhibition between their apical dendrites. Deep short axon cells form broad intrabulbar inhibitory circuits that regulate both populations of interneurons. Little is known about the extrabulbar GABAergic circuits that control the activity of these various interneurons. We examined this question using patch‐clamp recordings and optogenetics in olfactory bulb slices from transgenic mice. We showed that axonal projections emanating from diverse basal forebrain GABAergic neurons densely project in all layers of the olfactory bulb. These long‐range GABAergic projections provide a prominent synaptic input on granule and short axon cells in deep layers as well as on selective subtypes of PG cells. Specifically, three different subclasses of type 2 PG cells receive robust and target‐specific basal forebrain inputs but have little local interactions with other PG cells. In contrast, type 1 PG cells are not innervated by basal forebrain fibres but do interact with other PG cells. Thus, attention‐regulated basal forebrain inputs regulate inhibition in all layers of the olfactory bulb with a previously overlooked synaptic complexity that further defines interneuron subclasses.
Tensor Train Accelerated Solvers for Nonsmooth Rigid Body Dynamics
Authors: Corona Eduardo , Gorsich David , Jayakumar Paramsothy , Veerapaneni Shravan 
Published: March 2019

Abstract
In the last two decades, increased need for high-fidelity simulations of the time evolution and propagation of forces in granular media has spurred a renewed interest in the discrete element method (DEM) modeling of frictional contact. Force penalty methods, while economic and widely accessible, introduce artificial stiffness, requiring small time steps to retain numerical stability. Optimization-based methods, which enforce contacts geometrically through complementarity constraints leading to a differential variational inequality problem (DVI), allow for the use of larger time steps at the expense of solving a nonlinear complementarity problem (NCP) each time-step. We review the latest efforts to produce solvers for this NCP, focusing on its relaxation to a cone complementarity problem (CCP) and solution via an equivalent quadratic optimization problem with conic constraints. We distinguish between first-order methods, which use only gradient information and are thus linearly convergent and second-order methods, which rely on a Newton type step to gain quadratic convergence and are typically more robust and problem-independent. However, they require the approximate solution of large sparse linear systems, thus losing their competitive advantages in large scale problems due to computational cost. In this work, we propose a novel acceleration for the solution of Newton step linear systems in second-order methods using low-rank compression based fast direct solvers, leveraging on recent direct solver techniques for structured linear systems arising from differential and integral equations. We employ the quantized tensor train (QTT) decomposition to produce efficient approximate representations of the system matrix and its inverse. This provides a versatile and robust framework to accelerate its solution using this inverse in a direct or a preconditioned iterative method. We demonstrate compressibility of the Newton step matrices in primal dual interior point (PDIP) methods as applied to the multibody dynamics problem. Using a number of numerical tests, we demonstrate that this approach displays sublinear scaling of precomputation costs, may be efficiently updated across Newton iterations as well as across simulation time steps, and leads to a fast, optimal complexity solution of the Newton step. This allows our method to gain an order of magnitude speedups over state-of-the-art preconditioning techniques for moderate to large-scale systems, hence mitigating the computational bottleneck of second-order methods.
Clinical and sonographic characteristics of Warthin-like variant papillary thyroid carcinomas
Authors: Ning Chunping , Koo Ja Seung , Kim Eun-Kyung , Lee Suji 
Published: March 2019

Aim: To summarize the clinical, ultrasonographic (US) and pathological characteristics of Warthin-like variant papillary thyroid carcinomas (WVPTC).Material and methods: Medical records and US images of 32 cases of WVPTCs diagnosed between December, 2006 and September, 2018 were reviewed. Clinical, pathological and US characteristics of these cases were collected and summarized. ACR TI-RADS was followed during the analysis of the US features of the lesions. Results: Totally, 32 patients with 33 WVPTC nodules were reviewed. WVPTC was more often seen in female patients (27/32,84.4%) with a relatively high age (mean age, 51.0±10.8 years old). Hyperthyroidism was observed in 14 patients; 2 patients were diagnosed as subclinical hyperthyroidism and 1 patient as subclinical hypothyroidism. Abnormal thyroglobulin antibody was detected in 22 patients. Mean size of the nodule was 1.2±0.5 cm (range, 0.5~2.99 cm) on US. Pathologically, tumor margin of 63.6% carcinomas were infiltrative but most (72.9%) of the enrolled carcinomas were intra-thyroidal. Lymphocytic thyroiditis was detected in 87.5% (28/32) patients. On US, most WVPTCs were solid or almost complete solid (32/33, 97.0%) and very hypoechoic (26/33, 78.8%). Taller-than-wide shape (6/33, 18.2%) and punctate echogenic foci (9/33, 27.3%) were not popular. All the nodules were scored higher than 5 points according to the ACR TI-RADS, including 9 nodules that were classified into TR4 and 24 nodules as TR5. Follow-up information was available in 31 patients and no recurrence or distal metastasis was detected.Conclusions: WVPTC is a rare variant of PTCs with favorable outcomes. Very hypoechoic echogenicity, solid or almost complete solid composition are the vital indicators for biopsy, even though the nodule may be wider-than-tall and have a lack of punctuate echoic foci.
Relationship between sociodemographic factors and specialty destination of UK trainee doctors: a national cohort study
Authors: Kumwenda Ben , Cleland Jennifer , Prescott Gordon , Walker Kim , Johnston Peter 
Published: March 2019

ObjectivesMany countries are driving forward policies to widen the socioeconomic profile of medical students and to train more medical students for certain specialties. However, little is known about how socioeconomic origin relates to specialty choice. Nor is there a good understanding of the relationship between academic performance and specialty choice. To address these gaps, our aim was to identify the relationship between socioeconomic background, academic performance and accepted offers into specialty training.DesignLongitudinal, cohort study using data from the UK Medical Education Database (https://www.ukmed.ac.uk/).Participants6065 (60% females) UK doctors who accepted offers to a specialty training (residency) post after completing the 2-year generic foundation programme (UK Foundation Programme) between 2012 and 2014.Main outcome measuresΧ2tests were used to examine the relationships between sociodemographic characteristics, academic ability and the dependent variable, specialty choice. Multiple data imputation was used to address the issue of missing data. Multinomial regression was employed to test the independent variables in predicting the likelihood of choosing a given specialty.ResultsParticipants pursuing careers in more competitive specialties had significantly higher academic scores than colleagues pursuing less competitive ones. After controlling for the presence of multiple factors, trainees who came from families where no parent was educated to a degree level had statistically significant lower odds of choosing careers in medical specialties relative to general practice (OR=0.78, 95% CI, 0.67 to 0.92). Students who entered medical school as school leavers, compared with mature students, had odds 1.2 times higher (95% CI, 1.04 to 1.56) of choosing surgical specialties than general practice.ConclusionsThe data indicate a direct association between trainees’ sociodemographic characteristics, academic ability and career choices. The findings can be used by medical school, training boards and workforce planners to inform recruitment and retention strategies.
Use of performance reports among trauma medical directors and programme managers in the American College of Surgeons’ Trauma Quality Improvement Program: a qualitative analysis
Authors: Gotlib Conn Lesley , Hoeft Christopher , Neal Melanie , Nathens Avery 
Published: March 2019

BackgroundThe American College of Surgeons’ Trauma Quality Improvement Program (TQIP) provides trauma centres with performance reports on their processes and outcomes of care relative to their peers. This study explored how performance reports are used by trauma centre leaders to engage in performance improvement and perceived barriers to use.Study designQualitative focus group study with trauma medical directors (TMDs) and trauma programme managers (TPMs) in US trauma centres. Consistent with qualitative descriptive analysis, data collection and interpretation were inductively and iteratively completed. Major themes were derived using a constant comparative technique.ResultsSix focus groups were conducted involving 22 TMDs and 22 TPMs. Three major themes were captured: (1) technical uses of performance reports; (2) cultural uses of performance reports; (3) opportunities to enhance the role and value of TQIP. First, technical uses included using reports to assess data collection procedures, data quality and areas of poor performance relative to peers. In this domain, barriers to report use included not trusting others’ data quality and challenges with report interpretation. Second, reports were used to influence practice change by fostering inter-specialty discussions, leveraging resources for quality improvement, community engagement and regional collaboratives. Perceived lack of specialist engagement was viewed as an impediment in this domain. Lastly, identified opportunities for TQIP to support report use involved clarifying the relationship between verification and performance reports, and increasing partnerships with nursing associations.ConclusionTrauma centre improvement leaders indicated practical and social uses of performance reports that can affect intention and ability to change. Recommendations to optimise programme participation include a focus on data quality, adequate resource provision and enhanced support for regional collaboratives.
Epidemiology and implications of concurrent diagnosis of eosinophilic oesophagitis and IBD based on a prospective population-based analysis
Authors: Limketkai Berkeley N , Shah Shailja C , Hirano Ikuo , Bellaguarda Emanuelle , Colombel Jean-Frederic 
Published: March 2019

ObjectiveEosinophilic oesophagitis (EoO) and IBD are immune-mediated diseases of the gastrointestinal tract with possible overlapping pathogenic mechanisms. Our aim was to define the epidemiology and clinical implications of concurrent EoO and IBD diagnoses.DesignWe conducted a prospective cohort analysis using the Truven MarketScan database (2009–2016) to estimate the incidence and prevalence of EoO in patients with Crohn’s disease (CD) or UC and vice versa. Cox proportional hazards and Kaplan-Meier methods were used to estimate the risk of EoO-related or IBD-related complications among patients with concurrent diagnoses.ResultsAmong 134 013 536 individuals, the incidence of EoO, CD and UC were 23.1, 51.2 and 55.2 per 100 000 person-years, respectively. The risk of EoO was higher among patients with CD (incidence rate ratio [IRR] 5.4, p<0.01; prevalence ratio (PR) 7.8, p<0.01) or UC (IRR 3.5, p<0.01; PR 5.0, p<0.01), while the risk of IBD was higher among patients with EoO (CD: IRR 5.7, p<0.01; PR 7.6, p<0.01; UC: IRR 3.4, p<0.01; PR 4.9, p<0.01) versus individuals without either diagnosis. Concurrent diagnosis of EoO and IBD was associated with greater composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.09, p=0.01; UC: aHR 1.10, p=0.04) but lower composite risk of EoO-related complications (aHR 0.59; p<0.01).ConclusionBased on a population-based prospective cohort analysis, the risk of EoO is significantly higher among patients with IBD and vice versa. Concurrent diagnoses might modify the risk of IBD-related and EoO-related complications. Studies defining the mechanisms underlying these observations are needed.
Increased serum/plasma fibroblast growth factor 21 in type 2 diabetes mellitus: a systematic review and meta-analysis
Authors: Wang Yun-Sheng , Ye Jun , Cao Yong-Hong , Zhang Rong , Liu Yan , Zhang Su-Wan , Dai Wu , Zhang Qiu 
Published: March 2019

AbstractObjectivesFibroblast growth factor-21 (FGF-21) plays an important role in glucose and lipid metabolism. This study aims to systemically review the evidence regarding the relationship between the FGF-21 levels and type 2 diabetes mellitus (T2DM), as well as the related influential factors.MethodsResearch related to plasma/serum FGF-21 levels in patients with T2DM and healthy controls were searched in PubMed, EMBASE and The Cochrane Library databases (up to 31 March 2017). Pooled standard mean difference (SMD) with 95% CI was calculated by fixed-effect or random-effect model analysis. Heterogeneity test was performed by the Q-statistic and quantified using I2, and publication bias was evaluated using a funnel plot and Egger’s linear regression test.ResultsIn total, 317 articles were obtained after searching databases, and 11 studies with 866 patients with T2DM and 629 controls were finally included. Meta-analysis revealed that, compared with the control group, the T2DM group had a significantly higher plasma/serum FGF-21 level (p &lt; 0.001), with the SMD of 1.34% and 95% CI (0.70 to 1.98). Meta-regression analysis and subgroup analyses suggested that body mass index (BMI), triglycerides (TG) and total cholesterol (TC) were likely related to the observed FGF-21 differences between two groups.ConclusionsOverall, our study suggests that patients with T2DM have significantly higher plasma/serum FGF-21 levels, and the FGF-21 levels were influenced by BMI, TC and TG.
Syphilitic hepatitis and neurosyphilis: an observational study of Danish HIV-infected individuals during a 13-year period
Authors: Salado-Rasmussen Kirsten , Wessman Maria , Cowan Susan A , Gerstoft Jan , Katzenstein Terese Lea 
Published: March 2019

ObjectiveSyphilis is an STI that potentially affects any organ. Syphilitic hepatitis and neurosyphilis have been reported in both HIV-uninfected and HIV-infected individuals. The aim of this study was to investigate syphilitic hepatitis and neurosyphilis among HIV-infected individuals during a 13-year period.MethodsThis retrospective study included all HIV-infected individuals ≥18 years diagnosed with syphilis between 1 May 2004 and 31 December 2016 in Copenhagen, Denmark. We used the unique 10-digit personal identification number assigned to all individuals in Denmark to link data from two nationwide registers to identify the patients. Patient files were revised to obtain clinical and laboratory data.ResultsA total of 509 episodes of syphilis were diagnosed in 427 HIV-infected individuals attending three hospitals in Copenhagen, Denmark. The majority of the patients were men (99.5%), and the majority of men were men who have sex with men (96%). Twenty-seven patients (6%) met the criteria for neurosyphilis, and the neurological symptoms included ocular and auditory abnormalities, headache, paraesthesia, vertigo, facial paresis, motor weakness and unexplained pain in the legs. The patients with neurosyphilis were diagnosed in the secondary stage (84%) and in the early latent (8%) or late latent (8%) stage. Among the patients tested for liver affection, 41% met the criteria for syphilitic hepatitis. The patients with syphilitic hepatitis were diagnosed in the secondary stage (82%), primary stage (10%), and in the early latent (5%) or late latent (3%) stage.ConclusionsThe study emphasises that patients with syphilis, also those seen at STI clinics, should undergo a thorough clinical examination and questioning to reveal neurological symptoms. Identification of patients with neurosyphilis is crucial since these patients undergo a different treatment. The study also emphasises that syphilis should be considered as a diagnosis in sexually active patients with liver .
Esophageal perforations: one is bad, two is worse
Authors: Price Dustin , Skarupa David 
Published: March 2019

A 48-year-old man was admitted for medical management of recurrentClostridium difficile(C-dif) colitis. One month prior to presentation, he underwent right thoracotomy and lower lobectomy for a carcinoid tumor at another hospital. His postoperative course was complicated by C-dif colitis, gastroesophageal reflux, and epigastric pain. He underwent two esophagogastroduodenoscopy (EGD) procedures demonstrating mild esophagitis on the first procedure, followed by a linear ulcer on the second procedure 2 weeks later. On hospital day 9 of his current admission, he developed an acute abdomen and underwent an urgent exploratory laparotomy for presumed fulminant colitis. Findings included a healthy-appearing colon with only moderate distension, so a loop ileostomy was created for antegrade colonic irrigation. Postoperatively, a chest X-ray demonstrated a tension-appearing left pleural effusion, prompting tube thoracostomy placement. Initial output was greater than 2L of thin dark-brown fluid. An esophagram demonstrated a distal esophageal perforation (EP) and EGD was performed. Two medium-sized EPs were identified which appeared to arise from chronic-appearing ulcerations, one at 39 cm and one at 45 cm from the incisors (figure 1). A single 19mm×100 mm EndoMAXX fully covered stent was placed. Video-assisted thoracoscopic (VATS) drainage of the left hemithorax was performed in addition to placement of a right tube thoracostomy. Due to continued high output from the left thoracostomy tube, the stent was exchanged for a longer 23mm×100mm EndoMAXX fully covered stent. The patient stabilized for several days but again developed worsened sepsis, with EGD demonstrating inadequate coverage of the proximal perforation.Figure 1Endoscopic photograph showing left-sided esophageal perforation/fistula (black arrow). Gastroesophageal junction indicated by white arrow. NG, Nasogastric tube.What would you have done?Repeat esophageal stenting with wide drainage of the thoracic cavity.Esophageal T-tube placement and wide drainage of the thoracic cavity.Esophageal resection with gastrostomy drainage and proximal diversion.Bilateral tube thoracostomies and antibiotic/antifungal therapy.