bluuebunny/crossref_metadata_2025 huggingface dataset:
Endoluminal stenting for the management of leak following sleeve gastrectomy and loop duodenojejunal bypass with sleeve gastrectomy
Authors: Tsai Ying‐Nan , Wang Hsiu‐Po , Huang Chih‐Kun , Chang Po‐Chin , Lin I‐Chang , Tai Chi‐Ming
Published: September 2017

Postoperative leak is a serious complication of bariatric surgery and often results in significant morbidity and mortality. Stent placement is a less invasive alternative to surgery for the treatment of bariatric surgical leak. We evaluated the efficacy and complications of covered self‐expandable metal stents (SEMS) in the treatment of post‐bariatric surgical leak. We retrospectively reviewed patients who underwent stent placement for leak after bariatric surgery. Leak was diagnosed by upper gastrointestinal series or was visualized during the endoscopy. We examined the timing of stent placement, size of the leak, stent migration and its complications, total stent treatment duration, and treatment outcome. Between January 2011 and April 2015, seven patients underwent covered SEMS placement for leak after bariatric surgery, including laparoscopic sleeve gastrectomy (LSG) (n = 5) and laparoscopic loop duodenojejunal bypass with sleeve gastrectomy (LDJB‐SG) (n = 2). A stent was placed in one patient for infection control and bridging to revisional surgery. Among the other six patients, one patient who received stent placement one year after leak diagnosis failed to achieve leak closure, and five patients with early stent placement achieved leak closure. Three patients with small leak achieved leak closure more quickly. Stent migration was found in six patients, and associated ulcers occurred in five patients. We conclude that stenting is effective in the management of staple‐line leaks following LSG and LDJB‐SG. Stent migration and associated ulcers are common after stent placement. Early stent removal can be achieved in patients with small leaks.
Long‐Term Effects of Orthoses Use on the Changes of Foot and Ankle Joint Motions of Children With Spastic Cerebral Palsy
Authors: Liu Xue‐Cheng , Embrey David , Tassone Channing , Zvara Kim , Brandsma Brenna , Lyon Roger , Goodfriend Karin , Tarima Sergey , Thometz John
Published: September 2017

Background

Orthoses commonly are prescribed to children with cerebral palsy (CP) to provide foot correction and to improve ambulatory function. Immediate effects of ankle foot orthosis (AFOs) have been investigated, but long‐term kinematic effects are lacking clinical evidence.

Objective

To determine changes in 3‐dimensional ankle and foot segment motion in pediatric patients with CP between initial and follow‐up visits (18‐month average time differences) in both barefoot gait and gait with their AFO. We also investigated intravisit changes between barefoot and AFO gait.

Design

A prospective cohort study.

Setting

Children's Hospital of Wisconsin, Department of Orthopaedic Surgery, Medical College of Wisconsin.

Patients

A total of 23 children with CP, mean age 10.5 years (6.2‐18.1 years) were clinically prescribed either a solid ankle foot orthotic (SAFO), hinged ankle foot orthotic (HAFO), or supramalleolar orthotic.

Methods

Holes were cut in the study orthoses so that electromagnetic markers could be directly placed on the skin. A 6‐foot segment model was used.

Outcome Measurements

Kinematic and kinetic data were recorded for each patient's initial and follow‐up visit (18‐month follow‐up average, 15‐20 months range).

Results

For the SAFO group (gait with AFO), a significant decrease in dorsiflexion was found between the initial and third visit (P = .008). Furthermore, the SAFO group (barefoot gait) had an increased eversion at the midfoot for most of the gait cycle (P < .008). Sagittal forefoot range of motion was reduced for all 3 groups between the barefoot and AFO groups.

Conclusion

The use of AFOs long term either maintained or improved foot deformities or dysfunction.

Level of Evidence

Level II.
Unilateral Lower Extremity Pain Due to Malignancy Managed With Cordotomy: A Case Report
Authors: Chai Thomas , Suleiman Zakari A. , Roldan Carlos J.
Published: September 2017

Cancer pain management is comprehensive, and it generally begins with pharmacotherapy in a step‐wise approach per analgesic guidelines established decades ago by the World Health Organization. This analgesic ladder involves the prescribing of co‐analgesics, adjuvants, and opioids, with each step depending on pain severity. Although the majority of cancer pain responds to this strategy, there exist patients who do not respond adequately or experience significant side effects or intolerance to pain medications. It is in these patients whom clinicians consider interventional approaches. One approach to manage unremitting unilateral malignant pain includes evaluation for cordotomy, which is an approach that has been effective in such cases. We present a patient with breast cancer metastatic to the pelvis, with associated severe pelvic and right lower limb pain. Due to progressive disease, her pain worsened despite aggressive opioid dose escalations. She ultimately underwent percutaneous left anterolateral cervical cordotomy for malignant right leg pain, resulting in complete resolution of leg pain. We propose that, in select patients with neoplasm‐related pain, cordotomy may prove very effective.

Level of Evidence

V
Incomplete atrioventricular dissociation and isorhythmic atrioventricular dissociation during general anesthesia with desflurane and remifentanil: A case report
Authors: Hirase Masayasu , Seto Mika , Koga Sayo , Takaoka Masao , Kita Ryosuke , Kikuta Toshihiro
Published: September 2017

We encountered a patient who experienced incomplete atrioventricular (A‐V) dissociation and isorhythmic A‐V dissociation during general anesthesia with desflurane and remifentanil. A 38‐year‐old man was scheduled to undergo extraction of both the upper and the right lower impacted wisdom teeth under general anesthesia. After anesthesia induction, we maintained anesthesia with desflurane and remifentanil. After 15min, incomplete A‐V dissociation was observed on electrocardiography (ECG). After atropine sulfate 0.3mg was administered intravenously, isorhythmic A‐V dissociation was observed. Atropine sulfate 0.2mg was administered intravenously, and we observed normal ECG findings. Subsequently, no abnormal ECG findings were observed.
Microbes May Thrive in Subsea Permafrost Long After Flooding
Authors: Stanley Sarah
Published: September 2017

Two cores from the East Siberian Arctic Shelf reveal how microbial communities develop over thousands of years as submarine permafrost slowly thaws.
A Grand Tour of the Ocean Basins
Authors: De Paor Declan
Published: September 2017

A new teaching resource facilitates plate tectonic studies using a Google Earth virtual guided tour of ocean basins around the world.
Finding the connections between a high-school chemistry curriculum and nano-scale science and technology
Authors: Blonder Ron , Sakhnini Sohair
Published: September 2017

The high-school chemistry curriculum is loaded with many important chemical concepts that are taught at the high-school level and it is therefore very difficult to add modern contents to the existing curriculum. However, many studies have underscored the importance of integrating modern chemistry contents such as nanotechnology into a high-school curriculum. When students are exposed to nanotechnology, they perceive chemistry as more relevant to their life, and more modern than the chemistry they usually study at school, and consequently, their continuous motivation to study chemistry and related subjects increases. In the current study we identified topics in the high-school chemistry curriculum in Israel into which the essential nano-scale science and technology (NST) concepts can be integrated. Insertion points for all 8 NST essential concepts were found. We discuss the importance of ways in which chemistry educators can implement the results for updating the chemistry curriculum, thus making it more modern and relevant to the actual chemistry research that is conducted.
Studying the consistency between and within the student mental models for atomic structure
Authors: Zarkadis Nikolaos , Papageorgiou George , Stamovlasis Dimitrios
Published: September 2017

Science education research has revealed a number of student mental models for atomic structure, among which, the one based on Bohr's model seems to be the most dominant. The aim of the current study is to investigate the coherence of these models when students apply them for the explanation of a variety of situations. For this purpose, a set of six tasks describing different everyday situations was given to 225 students of the 10th and 11th grades of secondary schools from Northern Greece. Quantitative analysis of the students’ responses using Latent Class Analysis (LCA) showed that there is no consistency between models across the tasks and that the context of the task affects the distribution of students’ responses across models. Qualitative analysis showed a variety of pieces of knowledge from different models that students combine when manipulating the tasks, which possibly causes a lack of consistency within each one of the models. The findings are discussed in terms of between and within model consistency, and the conclusions contribute to the debate concerning the coherentvs.fragmented knowledge hypotheses. The empirical evidence provided by the analysis clearly demonstrates that student mental models for atomic structure were not coherent when applied in different everyday situations. Implications for theory and practice are discussed.
The coproporphyrin ferrochelatase of Staphylococcus aureus: mechanistic insights into a regulatory iron-binding site
Authors: Hobbs Charlie , Reid James D. , Shepherd Mark
Published: September 2017

The majority of characterised ferrochelatase enzymes catalyse the final step of classical haem synthesis, inserting ferrous iron into protoporphyrin IX. However, for the recently discovered coproporphyrin-dependent pathway, ferrochelatase catalyses the penultimate reaction where ferrous iron is inserted into coproporphyrin III. Ferrochelatase enzymes from the bacterial phyla Firmicutes and Actinobacteria have previously been shown to insert iron into coproporphyrin, and those from Bacillus subtilis and Staphylococcus aureus are known to be inhibited by elevated iron concentrations. The work herein reports a Km (coproporphyrin III) for S. aureus ferrochelatase of 1.5 µM and it is shown that elevating the iron concentration increases the Km for coproporphyrin III, providing a potential explanation for the observed iron-mediated substrate inhibition. Together, structural modelling, site-directed mutagenesis, and kinetic analyses confirm residue Glu271 as being essential for the binding of iron to the inhibitory regulatory site on S. aureus ferrochelatase, providing a molecular explanation for the observed substrate inhibition patterns. This work therefore has implications for how haem biosynthesis in S. aureus is regulated by iron availability.
SH003 reverses drug resistance by blocking signal transducer and activator of transcription 3 (STAT3) signaling in breast cancer cells
Authors: Seo Hye-Sook , Ku Jin Mo , Lee Hee-Jae , Woo Jong-Kyu , Cheon Chunhoo , Kim Mia , Jang Bo-Hyoung , Shin Yong Cheol , Ko Seong-Gyu
Published: September 2017

Overcoming drug resistance is an important task for investigators and clinician to achieve successful chemotherapy in cancer patients. Drug resistance is caused by various factors, including the overexpression of P-glycoprotein (P-gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. SH003 is extracted from the mixture of three different herbs, and its anticancer effect has been revealed in different cancer cell types. In the present study, we investigated whether SH003 is able to reverse drug resistance using paclitaxel-resistant breast cancer cells (MCF-7/PAC). In our experiments, SH003 significantly decreased cell growth and colony formation in MCF-7/PAC cells and parental MCF-7 cells. This growth inhibition was related to the accumulation of cells in the sub-G0/G1 apoptotic population and an increase in the number of apoptotic cells. SH003 reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated proteins (MRPs) in MCF-7/PAC cells. SH003 also down-regulated the expression of P-gp. SH003 reversed drug efflux from MCF-7/PAC cells, resulting in rhodamine123 (Rho123) accumulation. Inhibition of drug resistance by SH003 is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. SH003 decreased STAT3 activation (p-STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP-2, which are STAT3 target genes. An STAT3 inhibitor, JAK inhibitor I and an HIF-1α inhibitor decreased cell growth in MCF-7 and MCF-7/PAC cells. Taken together, these results demonstrate that SH003 can overcome drug resistance, and SH003 might be helpful for chemotherapy in cancer patients.
MicroRNA sequence analysis identifies microRNAs associated with peri-implantitis in dogs
Authors: Wu Xiaolin , Chen Xipeng , Mi Wenxiang , Wu Tingting , Gu Qinhua , Huang Hui
Published: September 2017

Peri-implantitis, which is characterized by dense inflammatory infiltrates and increased osteoclast activity, can lead to alveolar bone destruction and implantation failure. miRNAs participate in the regulation of various inflammatory diseases, such as periodontitis and osteoporosis. Therefore, the present study aimed to investigate the differential expression of miRNAs in canine peri-implantitis and to explore the functions of their target genes. An miRNA sequence analysis was used to identify differentially expressed miRNAs in peri-implantitis. Under the criteria of a fold-change >1.5 and P<0.01, 8 up-regulated and 30 down-regulated miRNAs were selected for predictions of target genes and their biological functions. Based on the results of Gene Ontology (GO) and KEGG pathway analyses, these miRNAs may fine-tune the inflammatory process in peri-implantitis through an intricate mechanism. The results of quantitative real-time PCR (qRT-PCR) revealed that let-7g, miR-27a, and miR-145 may play important roles in peri-implantitis and are worth further investigation. The results of the present study provide insights into the potential biological effects of the differentially expressed miRNAs, and specific enrichment of target genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway was observed. These findings highlight the intricate and specific roles of miRNAs in inflammation and osteoclastogenesis, both of which are key aspects of peri-implantitis, and thus may contribute to future investigations of the etiology, underlying mechanism, and treatment of peri-implantitis.
Homocysteine inhibits angiogenesis through cytoskeleton remodeling
Authors: Pan Lemen , Yu Guanfeng , Huang Jingyong , Zheng Xiangtao , Xu Yinghua
Published: September 2017

Homocysteine (Hcy) is an intermediate non-diet amino acid connecting methionine and folate cycles. Elevated total Hcy level in blood, denoted as hyperhomocysteinemia, has emerged as a prevalent and strong risk factor for multiple diseases including atherosclerotic vascular disease in coronary, cerebral, and peripheral vessels. Its detrimental effect on vascular system implies the potential application as an inhibitor of angiogenesis. However, the detailed mechanism is unveiled. Inhibitory effect of Hcy was assessed on vascular endothelial growth factor (VEGF) induced cell proliferation and migration with endothelial cell (EC) culture system. Its effect on angiogenesis was further examined in vitro and in vivo. After Hcy treatment, key angiogenic factors were measured by RT-qPCR. Cellular skeletal structure was also evaluated by actin stress fiber staining. VEGF-induced human umbilical vein EC (HUVEC) proliferation and migration were dramatically down-regulated by Hcy in a dose-responsive manner. Hcy treatment significantly inhibited the VEGF-induced angiogenesis in vitro by tube formation assay and chick chorioallantoic membrane (CAM) vessel formation in vivo. Key angiogenic factors like VEGFR1/2 and angiopoietin (Ang)1/2 were substantially reduced by Hcy in HUVEC- and VEGF-induced actin stress fiber cytoskeletal structure was abolished. We demonstrated that Hcy could inhibit angiogenesis by targetting key angiogenic factor and disruption of actin cytoskeleton which is crucial for cell migration.
TVPRNN for image caption generation
Authors: Yang Liang , Hu Haifeng
Published: September 2017

Image caption generation has attracted considerable interest in computer vision and natural language processes. However, existing methods usually use convolution neural network (CNN) for extracting image feature and recurrent NN (RNN) to predict next produced word, which may make the obtained features unadaptable to the word generated at current time. A new time‐varying parallel RNN (TVPRNN) to deal with this task is proposed. TVPRNN uses two classical CNNs (i.e. VggNet and inception v3) for extracting global image feature, jointly with RNN to obtain time‐varying feature at each time step, which are used for representing current word. Visual and textual representation in a multimodal space is fused. Moreover, visual attention mechanism is introduced to guild the proposed network. The approach is evaluated using the benchmark Flickr8k, Flickr30k and MSCOCO datasets. The experimental results show that TVPRNN achieves better or on par with the state‐of‐the‐art methods.
Iterative sparse channel estimation and demodulation for blind equalisation
Authors: Kim Geumbee , Lee Jeongwon , Nam Haewoon , Park Daeyoung
Published: September 2017

The authors formulate a blind equalisation problem minimising the residual that is difference between the received signal and the predicted signal. Since both channel impulse responses and transmitted symbols are unknown, the authors regard the problem as a kind of dictionary learning problem. The authors divide the problem into two sub‐problems and iteratively find the channel impulse response and the demodulated symbols. Since the wireless channels with a large bandwidth tend to have a sparse multipath structure, the authors apply the compressive sensing technique to the channel estimation sub‐problem. Numerical results show that the proposed algorithm achieves the Genie‐aided lower‐bound performance.
Gait features fusion for efficient automatic age classification
Authors: Mansouri Nabila , Aouled Issa Mohammed , Ben Jemaa Yousra
Published: September 2017

Far from the camera, image resolution is significantly degraded and person cannot cooperate with the acquisition equipment. So, the classical intrusive biometrics approach could not be applied. As a non‐intrusive biometric, gait analysis gained the attention of the computer vision community for number of potential applications such as age estimation. Since, that gait is very sensitive to ageing, gait analysis is the suitable solution for age estimation at a great distance from the camera. Given the complexity of this task, the authors propose in this study a new approach based on descriptors cascade. The proposed approach is to use a fusion of some efficient contour and silhouette descriptors. Indeed, they introduce the proposed descriptor based on silhouette projection model (SM) in the first time. In the second time, the proposed descriptor is merged with the best existing ones in order to enhance the classification performances. Despite that age classification using gait is a very challenging task, experiments conducted on OU‐ISIR database show that their proposed descriptors fusion approach enhances considerably the recognition rate.
Measuring the driver's perception error in the traffic accident risk evaluation
Authors: Eboli Laura , Mazzulla Gabriella , Pungillo Giuseppe
Published: September 2017

The perception of risk, as the expectation of being involved in a traffic accident, is evaluated mainly in a subjective manner being perceptions as highly individual, and depending on experiences with accidents. However, both individual driver characteristics and driving behaviour entail certain perception errors in the risk level evaluation; as a consequence, drivers are very often not aware of the actual risk they are taking. For this aim, the paper presents a methodology for measuring the driver's perception error in the traffic accidents risk level evaluation based on the comparison between a measure of the risk perception subjectively obtained, and an objective measure obtained from kinematic parameters defining the driving style. Starting from a procedure that describes the relationship between lateral and longitudinal accelerations and speeds, we classified car drivers’ behaviour as safe or unsafe. Then, we defined three levels of risk of being involved in a road accident (low, medium, and high risk). The subjective measure of the risk perception is obtained by the judgements of drivers regarding their driving behaviour.
Model predictive stator current control of doubly fed induction generator during network unbalance
Authors: Cheng Chenwen , Cheng Peng , Nian Heng , Sun Dan
Published: September 2017

This study proposes a model predictive stator current control (MPSCC) strategy of doubly fed induction generator (DFIG) under unbalanced grid voltage conditions. Sinusoidal and balanced stator currents injected into the power grid can be ensured due to the direct control of stator currents rather than rotor currents. Model predictive control instead of traditional vector control is adopted, which can increase the current loop bandwidth and obtain faster dynamic responses. Conventional resonant regulators such as second‐order generalised integrators or second‐order vector integrators that are usually used to eliminate unbalanced components in stator currents can also be avoided. Moreover, both extractions of negative sequence components in rotor or stator currents and calculation of commanded rotor current are avoided, which simplifies the control scheme. The proposed MPSCC strategy can also implement the grid connection by introducing the virtual stator currents without any changes in the control scheme. Finally, experimental results based on a 1 kW lab DFIG system are provided to validate the effectiveness of the proposed control strategy.
Cbfβ governs osteoblast−adipocyte lineage commitment through enhancing β-catenin signaling and suppressing adipogenesis gene expression
Authors: Wu Mengrui , Wang Yiping , Shao Jian-Zhong , Wang Jue , Chen Wei , Li Yi-Ping
Published: September 2017

Significance

Age-associated increased marrow adiposity is often coupled with increased bone loss, presenting a significant age-associated osteoporosis health problem. Here, we examined the mechanisms underlying how transcription factors regulate mesenchymal stem cell lineage determination and showed that
Cbfβ
plays a critical role in stimulating osteogenesis and inhibiting adipogenesis through activating Wnt10b/β-catenin signaling and inhibiting adipogenesis regulatory gene (
c/ebpα
) expression. The insights resulting from this study will fill an important knowledge gap and may facilitate the development of novel bone loss therapeutics that minimize the adverse side effects on bone homeostasis.
Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation
Authors: Gao Xiaofei , Lee Hsiang-Ying , Li Wenbo , Platt Randall Jeffrey , Barrasa M. Inmaculada , Ma Qi , Elmes Russell R. , Rosenfeld Michael G. , Lodish Harvey F.
Published: September 2017

Significance

We have long known that thyroid hormone (TH) stimulates formation of red blood cells and patients with thyroid diseases are often anemic, but the underlying molecular mechanisms are unclear. This study uses pharmacologic and genetic approaches in primary cells and animal models to demonstrate essential roles of nuclear receptor coactivator 4 (NCOA4) and TH in late erythropoiesis. We show that TH is essential for the last steps in formation of red cells in culture, and that treatment of cells with drugs that activate a particular nuclear TH receptor, TRβ, stimulates erythroid differentiation and alleviates anemic symptoms in a chronic anemia mouse model, indicating potential clinical applications. Further, we show that TRβ functions together with NCOA4 to regulate red cell formation.
Clinical decision support alert malfunctions: analysis and empirically derived taxonomy
Authors: Wright Adam , Ai Angela , Ash Joan , Wiesen Jane F , Hickman Thu-Trang T , Aaron Skye , McEvoy Dustin , Borkowsky Shane , Dissanayake Pavithra I , Embi Peter , Galanter William , Harper Jeremy , Kassakian Steve Z , Ramoni Rachel , Schreiber Richard , Sirajuddin Anwar , Bates David W , Sittig Dean F
Published: September 2017

Objective

To develop an empirically derived taxonomy of clinical decision support (CDS) alert malfunctions.

Materials and Methods

We identified CDS alert malfunctions using a mix of qualitative and quantitative methods: (1) site visits with interviews of chief medical informatics officers, CDS developers, clinical leaders, and CDS end users; (2) surveys of chief medical informatics officers; (3) analysis of CDS firing rates; and (4) analysis of CDS overrides. We used a multi-round, manual, iterative card sort to develop a multi-axial, empirically derived taxonomy of CDS malfunctions.

Results

We analyzed 68 CDS alert malfunction cases from 14 sites across the United States with diverse electronic health record systems. Four primary axes emerged: the cause of the malfunction, its mode of discovery, when it began, and how it affected rule firing. Build errors, conceptualization errors, and the introduction of new concepts or terms were the most frequent causes. User reports were the predominant mode of discovery. Many malfunctions within our database caused rules to fire for patients for whom they should not have (false positives), but the reverse (false negatives) was also common.

Discussion

Across organizations and electronic health record systems, similar malfunction patterns recurred. Challenges included updates to code sets and values, software issues at the time of system upgrades, difficulties with migration of CDS content between computing environments, and the challenge of correctly conceptualizing and building CDS.

Conclusion

CDS alert malfunctions are frequent. The empirically derived taxonomy formalizes the common recurring issues that cause these malfunctions, helping CDS developers anticipate and prevent CDS malfunctions before they occur or detect and resolve them expediently.
Defining the Role of the MADS-Box Gene, Zea Agamous-like1, a Target of Selection During Maize Domestication
Authors: Wills David M , Fang Zhou , York Alessandra M , Holland James B , Doebley John F
Published: September 2017

Genomic scans for genes that show the signature of past selection have been widely applied to a number of species and have identified a large number of selection candidate genes. In cultivated maize (Zea mays ssp. mays) selection scans have identified several hundred candidate domestication genes by comparing nucleotide diversity and differentiation between maize and its progenitor, teosinte (Z. mays ssp. parviglumis). One of these is a gene called zea agamous-like1 (zagl1), a MADS-box transcription factor, that is known for its function in the control of flowering time. To determine the trait(s) controlled by zagl1 that was (were) the target(s) of selection during maize domestication, we created a set of recombinant chromosome isogenic lines that differ for the maize versus teosinte alleles of zagl1 and which carry cross-overs between zagl1 and its neighbor genes. These lines were grown in a randomized trial and scored for flowering time and domestication related traits. The results indicated that the maize versus teosinte alleles of zagl1 affect flowering time as expected, as well as multiple traits related to ear size with the maize allele conferring larger ears with more kernels. Our results suggest that zagl1 may have been under selection during domestication to increase the size of the maize ear.
An ensemble algorithm for Kohonen self-organizing map with different sizes
Authors: Pasa Leandro Antonio , Costa José Alfredo F. , Medeiros Marcial Guerra de
Published: September 2017

Data Clustering aims to discover groups within the data based on similarities, with a minimal, if any, knowledge of their structure. Variations in the results may occur due to many factors, including algorithm parameters, initialization and stopping criteria. The usage of different attributes or even different subsets of data usually lead to different results. Self-organizing maps (SOM) has been widely used for a variety of tasks regarding data analysis, including data visualization and clustering. A machine committee, or ensemble, is a set of neural networks working independently with some system that enable the combination of individual results into a single output, with the aim to achieve a better generalization compared to a unique neural network. This article presents a new ensemble method that uses SOM networks. Cluster validity indexes are used to combine neuron weights from different maps with different sizes. Results are shown from simulations with real and synthetic data, from the UCI Repository and Fundamental Clustering Problems Suite. The proposed method presented promising results, with increased performance compared with conventional single Kohonen map.
Pneumocystis PCR: It Is Time to Make PCR the Test of Choice
Authors: Doyle Laura , Vogel Sherilynn , Procop Gary W
Published: September 2017

Background

The testing strategy for Pneumocystis at the Cleveland Clinic changed from toluidine blue staining to polymerase chain reaction (PCR). We studied the differences in positivity rates for these assays and compared each with the detection of Pneumocystis in companion specimens by cytology and surgical pathology.

Methods

We reviewed the results of all Pneumocystis test orders 1 year before and 1 year after the implementation of a Pneumocystis-specific PCR. We also reviewed the corresponding cytology and surgical pathology results, if performed. Finally, we reviewed the medical records of patients with rare Pneumocystis detected by PCR in an effort to differentiate colonization vs true disease.

Results

Toluidine blue staining and surgical pathology had similar sensitivities and negative predictive values, both of which were superior to cytology. There was a >4-fold increase in the annual detection of Pneumocystis by PCR compared with toluidine blue staining (toluidine blue staining: 11/1583 [0.69%] vs PCR: 44/1457 [3.0%]; chi-square P < .001). PCR detected 1 more case than surgical pathology and was far more sensitive than cytology. Chart review demonstrated that the vast majority of patients with rare Pneumocystis detected were immunosuppressed, had radiologic findings supportive of this infection, had no other pathogens detected, and were treated for pneumocystosis by the clinical team.

Conclusion

PCR was the most sensitive method for the detection of Pneumocystis and should be considered the diagnostic test of choice. Correlation with clinical and radiologic findings affords discrimination of early true disease from the far rarer instances of colonization.
Effect of Xenon Anesthesia Compared to Sevoflurane and Total Intravenous Anesthesia for Coronary Artery Bypass Graft Surgery on Postoperative Cardiac Troponin Release
Authors: Hofland Jan , Ouattara Alexandre , Fellahi Jean-Luc , Gruenewald Matthias , Hazebroucq Jean , Ecoffey Claude , Joseph Pierre , Heringlake Matthias , Steib Annick , Coburn Mark , Amour Julien , Rozec Bertrand , Liefde Inge de , Meybohm Patrick , Preckel Benedikt , Hanouz Jean-Luc , Tritapepe Luigi , Tonner Peter , Benhaoua Hamina , Roesner Jan Patrick , Bein Berthold ,   for the Xenon-CABG Study Group
Published: September 2017

Background

Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models.

Methods

In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia.

Results

The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was −0.09 ng/ml (95% CI, −0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns.

Conclusions

In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.
A Random-allocation Graded Dose–Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery
Authors: Ngan Kee Warwick D.
Published: September 2017

Background

Norepinephrine has been investigated as a potential alterative to phenylephrine for maintaining blood pressure during spinal anesthesia for cesarean delivery with the advantage of less depression of maternal heart rate and cardiac output. However, the relative potencies of these two vasopressors have not been fully determined in this context.

Methods

In a random-allocation, graded dose–response study, 180 healthy patients undergoing spinal anesthesia for elective cesarean delivery received a single bolus of norepinephrine in one of six different doses ranging from 4 to 12 µg or phenylephrine in one of six different doses ranging from 60 to 200 µg to treat the first episode of hypotension. The magnitude of response was measured as the percentage of full restoration of systolic blood pressure to the baseline value. Dose–response analysis was performed using nonlinear regression to derive four-parameter logistic dose–response curves, which were compared to determine relative potency.

Results

Data were analyzed for 180 patients. The estimated ED50 values (dose giving a 50% response) were norepinephrine 10 µg (95% CI, 6 to 17 µg) and phenylephrine 137 µg (95% CI, 79 to 236 µg). The estimated relative potency ratio for the two drugs was 13.1 µg (95% CI, 10.4 to 15.8 µg).

Conclusions

Comparative dose–response analysis was completed for norepinephrine and phenylephrine given as a bolus to treat the first episode of hypotension in patients undergoing spinal anesthesia for cesarean delivery. The estimated dose equivalent to phenylephrine 100 µg was norepinephrine 8 µg (95% CI, 6 to 10 µg). These results may be useful to inform the design of future comparative studies.
Interpretable dimensionality reduction of single cell transcriptome data with deep generative models
Authors: Ding Jiarui , Condon Anne , Shah Sohrab P.
Published: September 2017

Single-cell RNA-sequencing has great potential to discover cell types, identify cell states, trace development lineages, and reconstruct the spatial organization of cells. However, dimension reduction to interpret structure in single-cell sequencing data remains a challenge. Existing algorithms are either not able to uncover the clustering structures in the data, or lose global information such as groups of clusters that are close to each other. We present a robust statistical model, scvis, to capture and visualize the low-dimensional structures in single-cell gene expression data. Simulation results demonstrate that low-dimensional representations learned by scvis preserve both the local and global neighbour structures in the data. In addition, scvis is robust to the number of data points and learns a probabilistic parametric mapping function to add new data points to an existing embedding. We then use scvis to analyze four single-cell RNA-sequencing datasets, exemplifying interpretable two-dimensional representations of the high-dimensional single-cell RNA-sequencing data.
Neural source dynamics of brain responses to continuous stimuli: speech processing from acoustics to comprehension
Authors: Brodbeck Christian , Presacco Alessandro , Simon Jonathan Z.
Published: September 2017

Human experience often involves continuous sensory information that unfolds over time. This is true in particular for speech comprehension, where continuous acoustic signals are processed over seconds or even minutes. We show that brain responses to such continuous stimuli can be investigated in detail, for magnetoencephalography (MEG) data by combining linear kernel estimation with minimum norm source localization. Previous research has shown that the requirement to average data over many trials can be overcome by modeling the brain response as a linear convolution of the stimulus and a kernel, or response function, and estimating a kernel that predicts the response from the stimulus. However, such analysis has been typically restricted to sensor space. Here we demonstrate that this analysis can also be performed in neural source space. We first computed distributed minimum norm current source estimates for continuous MEG recordings, and then computed response functions for the current estimate at each source element, using the boosting algorithm with cross-validation. Permutation tests can then assess the significance of individual predictor variables as well as features of the corresponding spatio-temporal response functions. We demonstrate the viability of this technique by computing spatio-temporal response functions for speech stimuli, using predictor variables reflecting acoustic, lexical and semantic processing. Results indicate that processes related to comprehension of continuous speech can be differentiated anatomically as well as temporally: acoustic information engaged auditory cortex at short latencies, followed by responses over the central sulcus and inferior frontal gyrus, possibly related to somatosensory/motor cortex involvement in speech perception; lexical frequency was associated with a left-lateralized response in auditory cortex and subsequent bilateral frontal activity; and semantic composition was associated with bilateral temporal and frontal brain activity. We conclude that this technique can be used to study the neural processing of continuous stimuli in time and anatomical space with the millisecond temporal resolution of MEG. This suggests new avenues for analyzing neural processing of naturalistic stimuli, without the necessity of averaging over artificially short or truncated stimuli.
Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity
Authors: Yee Yohan , Fernandes Darren J. , French Leon , Ellegood Jacob , Cahill Lindsay S. , Vousden Dulcie A. , Noakes Leigh Spencer , Scholz Jan , van Eede Matthijs C. , Nieman Brian J. , Sled John G. , Lerch Jason P.
Published: September 2017

An organizational pattern seen in the brain, termedstructural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings.

Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed.

We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the visceral area. Additionally, this pattern of explained variation differed spatially across the brain, with transcriptomic similarity playing a larger role in the cortex than subcortex, while connectivity explains structural covariance best in parts of the cortex, midbrain, and hindbrain. These results suggest that both gene expression and connectivity underlie structural volume covariance, albeit to different extents depending on brain region, and this relationship is modulated by distance.
Accuracy of programs for the determination of HLA alleles from NGS data
Authors: Larjo Antti , Eveleigh Robert , Kilpeläinen Elina , Kwan Tony , Pastinen Tomi , Koskela Satu , Partanen Jukka
Published: September 2017

The human leukocyte antigen (HLA) genes code for proteins that play a central role in the function of the immune system by presenting peptide antigens to T cells. As HLA genes show extremely high genetic polymorphism, HLA typing on the allele level is demanding and is based on DNA sequencing. Determination of HLA alleles is warranted as many HLA alleles are major genetic factors that confer susceptibility to autoimmune diseases and is important for the matching of HLA alleles in transplantation. Here, we compared the accuracy of several published HLA-typing algorithms that are based on next generation sequencing (NGS) data. As genome screens are becoming increasingly routine in research, we wanted to test how well HLA alleles can be deduced from genome screens not designed for HLA typing. The accuracies were assessed using datasets consisting of NGS data produced using the ImmunoSEQ platform, including the full 4 Mbp HLA segment, from 94 stem cell transplantation patients and exome sequences from the 1000 Genomes collection. When used with the default settings none of the methods gave perfect results for all the genes and samples. However, we found that ensemble prediction of the results or modifications of the settings could be used to improve accuracy. Most of the algorithms did not perform very well for the exome-only data. The results indicate that the use of these algorithms for accurate HLA allele determination based on NGS data is not straightforward.
RNA-seq highlights parallel and contrasting patterns in the evolution of the nuclear genome of holo-mycoheterotrophic plants
Authors: Schelkunov M.I. , Penin A.A. , Logacheva M.D.
Published: September 2017

• While photosynthesis is the most notable trait of plants, several lineages of plants (so-called holo-heterotrophs) have adapted to obtain organic compounds from other sources. The switch to heterotrophy leads to profound changes at the morphological, physiological and genomic levels.

• Here, we characterize the transcriptomes of three species representing two lineages of mycoheterotrophic plants: orchids (Epipogium aphyllumandEpipogium roseum) and Ericaceae (Hypopitys monotropa). Comparative analysis is used to highlight the parallelism between distantly related holo-heterotrophic plants.

• In both lineages, we observed genome-wide elimination of nuclear genes that encode proteins related to photosynthesis, while systems associated with protein import to plastids as well as plastid transcription and translation remain active. Genes encoding components of plastid ribosomes that have been lost from the plastid genomes have not been transferred to the nuclear genomes; instead, some of the encoded proteins have been substituted by homologs. The nuclear genes of bothEpipogiumspecies accumulated mutations twice as rapidly as their photosynthetic relatives; in contrast, no increase in the substitution rate was observed inH.monotropa.

• Holo-heterotrophy leads to profound changes in nuclear gene content. The observed increase in the rate of nucleotide substitutions is lineage specific, rather than a universal phenomenon among non-photosynthetic plants.
Ldb1 and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in retina
Authors: de Melo Jimmy , Venkataraman Anand , Clark Brian S. , Zibetti Cristina , Blackshaw Seth
Published: September 2017

Precise control of the relative ratio of retinal neurons and glia generated during development is essential for visual function. We show thatLhx2, which encodes a LIM-homeodomain transcription factor essential for specification and differentiation of retinal Müller glia, also plays a critical role in the development of retinal neurons. Overexpression ofLhx2, and its transcriptional coactivatorLdb1, triggers cell cycle exit and inhibits both Notch signaling and retinal gliogenesis.Lhx2/Ldb1overexpression also induced the formation of wide-field amacrine cells (wfACs). In contrastRnf12, which encodes a negative regulator of LDB1, is necessary for the initiation of retinal gliogenesis. We also show that LHX2 protein binds upstream of multiple neurogenic bHLH factors includingAscl1andNeurog2, which are necessary for suppression of gliogenesis and wfAC formation respectively, and activates their expression. Finally, we demonstrate that the relative level of the LHX2-LDB1 complex in the retina decreases in tandem with the onset of gliogenesis. These findings show that control ofLhx2function byLdb1andRnf12acts as a molecular mechanism underpinning the coordinated differentiation of neurons and Müller glia in postnatal retina.

Significance Statement

The molecular mechanisms that control the ratio neurons and glia that are generated by neuronal progenitors remain unclear. Here we show that Lhx2, a transcription factor essential for retinal gliogenesis, also controls development of retinal neurons. The Lhx2 coactivator Ldb1 promotes Lhx2-dependent neurogenesis, while the Lhx2 corepressor Rnf12 is necessary and sufficient for retinal gliogenesis. Furthermore, Lhx2 directly regulates expression of bHLH factors that promote neural development, which are necessary for Lhx2-dependent neurogenesis. Finally, we show that levels of the LHX2-LDB1 complex, which activates transcription, drop as gliogenesis begins. Dynamic regulation of Lhx2 activity by Ldb1 and Rnf12 thus controls the relative levels of retinal neurogenesis and gliogenesis, and may have similar functions elsewhere in the developing nervous system.