bluuebunny/crossref_metadata_2025 huggingface dataset:
Seizures After Pediatric Vilazodone Ingestion
Authors: Del Pizzo Jeannine , Fernandez Elon K. , Kopec Kathryn T. , Wenger Jesse , Noyes Erin M. , Salzman Matthew , Henretig Fred M.
Published: June 2017

Vilazodone hydrochloride is the first member in a new class of antidepressants called indolealkylamines and was approved for use in the United States in 2011 for major depressive disorder. It has a combined mechanism of action of a selective serotonin reuptake inhibitor and a partial agonist of serotonin 5-HT1A receptors. It has not been approved for use in the pediatric population, and toxicity from exploratory vilazodone ingestion has been rarely described to date. We describe 2 children with laboratory-confirmed vilazodone ingestions that led to significant toxicity including refractory status epilepticus in 1 patient and likely transient seizure activity in the other. Both patients required multiple doses of benzodiazepines; in the more severe case, barbiturates were added to control seizure activity. These children returned to baseline and had no prolonged neurologic complications. Pediatric experience with vilazodone is limited; however, the literature demonstrates 3 additional case reports of children experiencing seizure after vilazodone ingestion. With the 2 new cases presented here, it seems prudent to educate prescribers and families of the potential dangers of ingestion of vilazodone tablets by young children.
“It's Not a Tumor”
Authors: Augenstein Julie A. , Chapman Teresa , McNeil Michael J. , Lo Mark D.
Published: June 2017

Cerebral developmental venous anomalies (DVAs) are benign anatomical variants of the venous system and are commonly described as an incidental finding without clinical significance. Neurologic symptoms or abnormal examination findings are rare and usually attributed to hemorrhagic complications related to coexisting cavernous malformations. There have been limited case reports of symptomatic, uncomplicated DVAs described in the literature. The following case describes a previously healthy child who presented to the emergency department with an acute onset of altered mental status, headache, and focal neurologic examination abnormalities. Magnetic resonance imaging revealed a prominent cerebellar DVA. There was no evidence of a cavernous angioma, hemorrhage, or acute parenchymal injury. This case report illustrates a clinically symptomatic, uncomplicated posterior fossa DVA. It provides additional evidence regarding the potential for a cerebral venous malformation in causing focal neurologic deficits.
Huge Hepatic Fungal Inflammatory Pseudotumor Misdiagnosed as Primary Hepatocellular Carcinoma
Authors: Xian Meng Fei , Lan Wen Tong , Huang Hui , Zeng Dan , Xu Zuo Feng
Published: June 2017

Fungal inflammatory pseudotumor (FIPT) of the liver is a rare disease that may be mistaken for a malignant tumor. It is difficult to diagnose because of its nonspecific clinical and imaging features. We report the case of a 46-year-old Asian man who presented with a mass in the right upper quadrant of the abdomen. The patient had undergone transcatheter arterial chemoembolization therapy at another institution 6 months earlier, but the mass had continued to enlarge. He had no history of chronic hepatitis B, and the serum α-fetoprotein was negative. Contrast-enhanced ultrasonography and computed tomography images were suggestive of hepatocellular carcinoma. However, ultrasound-guided biopsy revealed features of chronic inflammation. The mass was resected and found to be an FIPT. We discuss the details of the case and review related articles.
Current management of metastatic renal cell carcinoma: evolving new therapies
Authors: Kumar Ravi , Kapoor Anil
Published: June 2017

Purpose of review

Targeted therapies have recently replaced cytokine treatments as the gold standard for management of metastatic renal cell carcinoma (mRCC). Currently approved treatments include the tyrosine kinase inhibitors sunitinib, pazopanib, axitinib, sorafenib, cabozantinib and lenvatinib; the vascular endothelial growth factor (VEGF) inhibitor bevacizumab; the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus; and the immunologic nivolumab. The purpose of this review is to provide an updated analysis of the clinical data supporting the use of these agents in the first-line and second-line setting.

Recent findings

In the first-line setting, pazopanib may be better tolerated than sunitinib, an individualized dosing sunitinib regimen based on toxicity might improve survival and cabozantinib appears to be an emerging option. In the second-line setting, three new therapies (cabozantinib, lenvatinib/everolimus and nivolumab) have shown superiority against everolimus, the previous standard therapy. The International Metastatic RCC Database Consortium prognostic model may be useful in guiding the selection of subsequent therapy and patients eligible for metastasectomy.

Targeted therapies are the standard treatment for mRCC. Despite advancements in survival, progression-free survival and tolerability, these targeted therapies remain largely noncurative. Further characterization of the RCC oncogenic pathway, and the ongoing clinical trials should help optimize the management of mRCC.
Optimal timing for repair of peripheral nerve injuries
Authors: Wang Eugene , Inaba Kenji , Byerly Saskya , Escamilla Diandra , Cho Jayun , Carey Joseph , Stevanovic Milan , Ghiassi Alidad , Demetriades Demetrios
Published: June 2017

BACKGROUND

Data regarding outcomes after peripheral nerve injuries is limited, and the optimal management strategy for an acute injury is unclear. The aim of this study was to examine timing of repair and specific factors that impact motor-sensory outcomes after peripheral nerve injury.

METHODS

This was a single-center, retrospective study. Patients with traumatic peripheral nerve injury from January 2010 to June 2015 were included. Patients who died, required amputation, suffered brachial plexus injury, or had missing motor-sensory examinations were excluded. Motor-sensory examinations were graded 0 to 5 by the Modified British Medical Research Council system. Operative repair of peripheral nerves was analyzed for patient characteristics, anatomic nerve injured, level of injury, associated injuries, days until repair, and repair method.

RESULTS

Three hundred eleven patients met inclusion criteria. Two hundred fifty-eight (83%) patients underwent operative management, and 53 (17%) underwent nonoperative management. Those who required operative intervention had significantly more penetrating injuries 85.7% versus 64.2% (p < 0.001), worse initial motor scores 1.19 versus 2.23 (p = 0.004), and worse initial sensory examination scores 1.75 versus 2.28 (p = 0.029). Predictors of improved operative motor outcomes on univariate analysis were Injury Severity Score less than 15 (p = 0.013) and male sex (p = 0.006). Upper arm level of injury was a predictor of poor outcome (p = 0.041). Multivariate analysis confirmed male sex as a predictor of good motor outcome (p = 0.014; Adjusted Odds Ratio, 3.88 [1.28–11.80]). Univariate analysis identified distal forearm level of injury (p = 0.026) and autograft repair (p = 0.048) as predictors of poor sensory outcome. Damage control surgery for unstable patients undergoing laparotomy (p = 0.257) and days to nerve repair (p = 0.834) did not influence motor-sensory outcome. Outcomes did not differ significantly in patients who underwent repair 24 hours or longer versus those who were repaired later.

CONCLUSION

Outcomes were primarily influenced by patient characteristics and injury level rather than operative characteristics. Peripheral nerve injuries can be repaired after damage control surgery without detriment to outcomes.

LEVEL OF EVIDENCE

Prognostic study, level III.
Mammalian genomic regulatory regions predicted by utilizing human genomics, transcriptomics and epigenetics data
Authors: Nguyen Quan H. , Tellam Ross L. , Naval-Sanchez Marina , Porto-Neto Laercio R. , Barendse William , Reverter Antonio , Hayes Benjamin , Kijas James , Dalrymple Brian P.
Published: June 2017

Genome sequences for hundreds of mammalian species are available, but an understanding of their genomic regulatory regions, which control gene expression, is only beginning. A comprehensive prediction of potential active regulatory regions is necessary to functionally study the roles of the majority of genomic variants in evolution, domestication, and animal production. We developed a computational method to predict regulatory DNA sequences (promoters, enhancers and transcription factor binding sites) in production animals (cows and pigs) and extended its broad applicability to other mammals. The method utilizes human regulatory features identified from thousands of tissues, cell lines, and experimental assays to find homologous regions that are conserved in sequences and genome organization and are enriched for regulatory elements in the genome sequences of other mammalian species. Importantly, we developed a filtering strategy, including a machine learning classification method, to utilize a very small number of species-specific experimental datasets available to select for the likely active regulatory regions. The method finds the optimal combination of sensitivity and accuracy to unbiasedly predict regulatory regions in mammalian species. Furthermore, we demonstrated the utility of the predicted regulatory datasets in cattle for prioritizing variants associated with multiple production and climate change adaptation traits, and identifying potential genome editing targets.
A cell-free platform for rapid synthesis and testing of active oligosaccharyltransferases
Authors: Schoborg Jennifer A. , Hershewe Jasmine , Stark Jessica C. , Kightlinger Weston , Kath James E. , Jaroentomeechai Thapakorn , Natarajan Aravind , DeLisa Matthew P. , Jewett Michael C.
Published: June 2017

Protein glycosylation, or the attachment of sugar moieties (glycans) to proteins, is important for protein stability, activity, and immunogenicity. However, understanding the roles and regulations of site-specific glycosylation events remains a significant challenge due to several technological limitations. These limitations include a lack of available tools for biochemical characterization of enzymes involved in glycosylation. A particular challenge is the synthesis of oligosaccharyltransferases (OSTs), which catalyze the attachment of glycans to specific amino acid residues in target proteins. The difficulty arises from the fact that canonical OSTs are large (>70 kDa) and possess multiple transmembrane helices, making them difficult to overexpress in living cells. Here, we address this challenge by establishing a bacterial cell-free protein synthesis platform that enables rapid production of a variety of OSTs in their active conformations. Specifically, by using lipid nanodiscs as cellular membrane mimics, we obtained yields of up to 440 µg/mL for the single-subunit OST enzyme, ‘Protein glycosylation B’ (PglB) fromCampylobacter jejuni, as well as for three additional PglB homologs fromCampylobacter coli, Campylobacter lari, andDesulfovibrio gigas. Importantly, all of these enzymes catalyzedN-glycosylation reactionsin vitrowith no purification or processing needed. Furthermore, we demonstrate the ability of cell-free synthesized OSTs to glycosylate multiple target proteins with varyingN-glycosylation acceptor sequons. We anticipate that this broadly applicable production method will advance glycoengineering efforts by enabling preparative expression of membrane-embedded OSTs from all kingdoms of life.
Ancient genomes from southern Africa pushes modern human divergence beyond 260,000 years ago
Authors: Schlebusch Carina M. , Malmström Helena , Günther Torsten , Sjödin Per , Coutinho Alexandra , Edlund Hanna , Munters Arielle R. , Steyn Maryna , Soodyall Himla , Lombard Marlize , Jakobsson Mattias
Published: June 2017

Southern Africa is consistently placed as one of the potential regions for the evolution ofHomo sapiens. To examine the region’s human prehistory prior to the arrival of migrants from East and West Africa or Eurasia in the last 1,700 years, we generated and analyzed genome sequence data from seven ancient individuals from KwaZulu-Natal, South Africa. Three Stone Age hunter-gatherers date to ~2,000 years ago, and we show that they were related to current-day southern San groups such as the Karretjie People. Four Iron Age farmers (300–500 years old) have genetic signatures similar to present day Bantu-speakers. The genome sequence (13x coverage) of a juvenile boy from Ballito Bay, who lived ~2,000 years ago, demonstrates that southern African Stone Age hunter-gatherers were not impacted by recent admixture; however, we estimate that all modern-day Khoekhoe and San groups have been influenced by 9–22% genetic admixture from East African/Eurasian pastoralist groups arriving >1,000 years ago, including the Ju|‘hoansi San, previously thought to have very low levels of admixture. Using traditional and new approaches, we estimate the population divergence time between the Ballito Bay boy and other groups to beyond 260,000 years ago. These estimates dramatically increases the deepest divergence amongst modern humans, coincide with the onset of the Middle Stone Age in sub-Saharan Africa, and coincide with anatomical developments of archaic humans into modern humans as represented in the local fossil record. Cumulatively, cross-disciplinary records increasingly point to southern Africa as a potential (not necessarily exclusive) ‘hot spot’ for the evolution of our species.
The Effects of Central Nervous System Stimulants onDrosophila melanogasterReproduction
Authors: Blake McMahon A.S.
Published: June 2017

Stimulant drugs are used everyday by people around the world. The effect stimulants have on developing human fetuses is widely unknown. The fruit flyDrosophila melanogasterhas become a valuable system to model the complex effects and properties of drugs in mammals. In this study,Drosophilais used to analyze the effects of stimulant exposure on reproduction to determine if stimulants cause a significant decrease in the number of offspring produced by parent generations. Caffeine, nicotine, and pseudoephedrine hydrochloride were found to significantly decrease the number of offspring in experimental populations. Further experimentation is necessary to understand the mechanisms underlying these results.
Construction of an exome-wide risk score for schizophrenia based on a weighted burden test
Authors: Curtis David
Published: June 2017

Polygenic risk scores obtained as a weighted sum of associated variants can be used to explore association in additional data sets and to assign risk scores to individuals. The methods used to derive polygenic risk scores from common SNPs are not suitable for variants detected in whole exome sequencing studies. Rare variants which may have major effects are seen too infrequently to judge whether they are associated and may not be shared between training and test subjects. A method is proposed whereby variants are weighted according to their frequency, their annotations and to the genes they affect. A weighted sum across all variants provides an individual risk score. Scores constructed in this way are used in a weighted burden test and are shown to be significantly different between schizophrenia cases and controls using a five-way cross validation procedure. This approach represents a first attempt to summarise exome sequence variation into a summary risk score, which could be combined with risk scores from common variants and from environmental factors. It is hoped that the method could be developed further.
Metabolic changes of the host-pathogen environment in aCryptosporidiuminfection
Authors: Miller Christopher N. , Panagos Charalampos G. , Kváč Martin , Howard Mark J. , Tsaousis Anastasios D.
Published: June 2017

Cryptosporidiumis an important gut microbe whose contributions towards infant and immunocompromise patient mortality rates are steadily increasing. Current techniques for diagnosing, curing or simply understanding the biology of the parasite are few and far between, relying on a combination ofin-silicopredictions modelled on a varied and unique group of organisms and medical reports. The development of anin-vitroculture system, using COLO-680N cells, has provided theCryptosporidiumcommunity with the opportunity to expand its toolkit for investigating this disease. One area in particular that is sorely overlooked is the metabolic alterations upon infection. Existing research is extremely limited and has already shown that significant variation can be found between the metabolome of different infected host species. Using a1H Nuclear Magnetic Resonance approach to metabolomics, we have explored the nature of the mouse gut metabolome as well as providing the first insight into the metabolome of an infected cell line. Through a combination of Partial Least Squares Discriminant Analysis and predictive modelling, we exhibit new and potentially game changing insights into the effects of aCryptosporidium parvuminfection, while verifying the presence of known metabolic changes. Of particular note is the potential contribution of host derived taurine to the diuretic aspects of the disease previously attributed to a solely parasite based alteration of the gut environment. This practical and informative approach can spearhead our understanding of theCryptosporidium-host metabolic exchange and thus provide novel targets for tackling this deadly parasite.
The importance of Chargaff’s second parity rule for genomic signatures in metagenomics
Authors: Gori Fabio , Mavroeidis Dimitrios , Jetten Mike SM , Marchiori Elena
Published: June 2017

An important problem in metagenomic data analysis is to identify the source organism, or at least taxon, of each sequence. Most methods tackle this problem in two steps by using an alignment-free approach: first the DNA sequences are represented as points of a real n-dimensional space via a mapping function then either clustering or classification algorithms are applied. Those mapping functions require to be genomic signatures: the dissimilarity between the mapped points must reflect the degree of phylogenetic similarity of the source species. Designing good signatures for metagenomics can be challenging due to the special characteristics of metagenomic sequences; most of the existing signatures were not designed accordingly and they were tested only on error-free sequences sampled from a few dozens of species.

In this work we analyze comparatively the goodness of existing and novel signatures based on tetranu-cleotide frequencies via statistical models and computational experiments; we also study how they are affected by the generalized Chargaff’s second parity rule (GCSPR), which states that in a given sequence longer than 50kbp, inverse oligonucleotides are approximately equally frequent. We analyze 38 million sequences of 150 bp-1,000 bp with 1% base-calling error, sampled from 1,284 microbes. Our models indicate that GCSPR reduces strand-dependence of signatures, that is, their values are less affected by the source strand; GCSPR is further exploited by some signatures to reduce the intra-species dispersion. Two novel signatures stand out both in the models and in the experiments: the combination signature and the operation signature. The former achieves strand-independence without grouping oligonucleotides; this could be valuable for alignment-free sequence comparison methods when distinguishing inverse oligonucleotides matters. Operation signature sums the frequencies of reverse, complement, and inverse tetranucleotides; having 72 features it reduces the computational intensity of the analysis.
Emerging patterns of plasmid-host coevolution that stabilize antibiotic resistance
Authors: Stalder Thibault , Rogers Linda M. , Renfrow Chris , Yano Hirokazu , Smith Zachary , Top Eva M.
Published: June 2017

Multidrug resistant bacterial pathogens have become a serious global human health threat, and conjugative plasmids are important drivers of the rapid spread of resistance to last-resort antibiotics. Whereas antibiotics have been shown to select for adaptation of resistance plasmids to their new bacterial hosts, orvice versa, a general evolutionary mechanism has not yet emerged. Here we conducted an experimental evolution study aimed at determining general patterns of plasmid-bacteria evolution. Specifically, we found that a large conjugative resistance plasmid follows the same evolutionary trajectories as its non-conjugative mini-replicon in the same and other species. Furthermore, within a single host–plasmid pair three distinct patterns of adaptive evolution led to increased plasmid persistence: i) mutations in the replication protein gene (trfA1); ii) the acquisition by the resistance plasmid of a transposon from a co-residing plasmid encoding a putative toxin-antitoxin system; iii) a mutation in the host’s global transcriptional regulator genefur. Since each of these evolutionary solutions individually have been shown to increase plasmid persistence in other plasmid-host pairs, our work points towards common mechanisms of plasmid stabilization. These could become the targets of future alternative drug therapies to slow down the spread of antibiotic resistance.
Compartmental and spatial rule-based modeling withVirtual Cell(VCell)
Authors: Blinov M. L. , Schaff J. C. , Vasilescu D. , Moraru I. I. , Bloom J. E. , Loew L. M.
Published: June 2017

In rule-based modeling, molecular interactions are systematically specified in the form of reaction rules that serve as generators of reactions. This provides a way to account for all the potential molecular complexes and interactions among multivalent or multistate molecules. Recently, we introduced rule-based modeling into the Virtual Cell (VCell) modeling framework, permitting graphical specification of rules and merger of networks generated automatically (using the BioNetGen modeling engine) with hand-specified reaction networks. VCell provides a number of ordinary differential equation (ODE) and stochastic numerical solvers for single-compartment simulations of the kinetic systems derived from these networks, and agent-based network-free simulation of the rules. In this work, compartmental and spatial modeling of rule-based models has been implemented within VCell. To enable rule-based deterministic and stochastic spatial simulations and network-free agent-based compartmental simulations, the BioNetGen and NFSim engines were each modified to support compartments. In the new rule-based formalism, every reactant and product pattern and every reaction rule are assigned locations. We also introduce the novel rule-based concept of molecular anchors. This assures that any species that has a molecule anchored to a predefined compartment will remain in this compartment. Importantly, in addition to formulation of compartmental models, this now permits VCell users to seamlessly connect reaction networks derived from rules to explicit geometries to automatically generate a system of reaction-diffusion equations. These may then be simulated using either the VCell partial differential equations (PDE) deterministic solvers or the Smoldyn stochastic simulator.
Separable Fully Connected Layers Improve Deep Learning Models For Genomics
Authors: Alexandari Amr Mohamed , Shrikumar Avanti , Kundaje Anshul
Published: June 2017

Convolutional neural networks are rapidly gaining popularity in regulatory genomics. Typically, these networks have a stack of convolutional and pooling layers, followed by one or more fully connected layers. In genomics, the same positional patterns are often present across multiple convolutional channels. Therefore, in current state-of-the-art networks, there exists significant redundancy in the representations learned by standard fully connected layers. We present a new separable fully connected layer that learns a weights tensor that is the outer product of positional weights and cross-channel weights, thereby allowing the same positional patterns to be applied across multiple convolutional channels. Decomposing positional and cross-channel weights further enables us to readily impose biologically-inspired constraints on positional weights, such as symmetry. We also propose a novel regularizer and constraint that act on curvature in the positional weights. Using experiments on simulated andin vivodatasets, we show that networks that incorporate our separable fully connected layer outperform conventional models with analogous architectures and the same number of parameters. Additionally, our networks are more robust to hyperparameter tuning, have more informative gradients, and produce importance scores that are more consistent with known biology than conventional deep neural networks.

Availability

Implementation:https://github.com/kundajelab/keras/tree/keras_1

A gist illustrating model setup is at:goo.gl/gYooaa
Analytical Fingerprint of Wolframite Ore Concentrates
Authors: Gäbler Hans‐Eike , Schink Wilhelm , Goldmann Simon , Bahr Andreas , Gawronski Timo
Published: June 2017

Ongoing violent conflicts in Central Africa are fueled by illegal mining and trading of tantalum, tin, and tungsten ores. The credibility of document‐based traceability systems can be improved by an analytical fingerprint applied as an independent method to confirm or doubt the documented origin of ore minerals. Wolframite (Fe,Mn)WO4 is the most important ore mineral for tungsten and is subject to artisanal mining in Central Africa. Element concentrations of wolframite grains analyzed by laser ablation‐inductively coupled plasma‐mass spectrometry are used to establish the analytical fingerprint. The data from ore concentrate samples are multivariate, not normal or log‐normal distributed. The samples cannot be regarded as representative aliquots of a population. Based on the Kolmogorov–Smirnov distance, a measure of similarity between a sample in question and reference samples from a database is determined. A decision criterion is deduced to recognize samples which do not originate from the declared mine site.
Facial Age Synthesis Using Sparse Partial Least Squares (The Case of Ben Needham)
Authors: Bukar Ali M. , Ugail Hassan
Published: June 2017

Automatic facial age progression (AFAP) has been an active area of research in recent years. This is due to its numerous applications which include searching for missing. This study presents a new method of AFAP. Here, we use an active appearance model (AAM) to extract facial features from available images. An aging function is then modelled using sparse partial least squares regression (sPLS). Thereafter, the aging function is used to render new faces at different ages. To test the accuracy of our algorithm, extensive evaluation is conducted using a database of 500 face images with known ages. Furthermore, the algorithm is used to progress Ben Needham's facial image that was taken when he was 21 months old to the ages of 6, 14, and 22 years. The algorithm presented in this study could potentially be used to enhance the search for missing people worldwide.
FACIAL PROFILING: RACE, PHYSICAL APPEARANCE, AND PUNISHMENT*
Authors: JOHNSON BRIAN D. , KING RYAN D.
Published: June 2017

We investigate the associations among physical appearance, threat perceptions, and criminal punishment. Psychological ideas about impression formation are integrated with criminological perspectives on sentencing to generate and test unique hypotheses about the associations among defendant facial characteristics, subjective evaluations of threatening appearance, and judicial imprisonment decisions. We analyze newly collected data that link booking photos, criminal histories, and sentencing information for more than 1,100 convicted felony defendants. Our findings indicate that Black defendants are perceived to be more threatening in appearance. Other facial characteristics, such as physical attractiveness, baby‐faced appearance, facial scars, and visible tattoos, also influence perceptions of threat, as do criminal history scores. Furthermore, some physical appearance characteristics are significantly related to imprisonment decisions, even after controlling for other relevant case characteristics. These and other findings are discussed as they relate to psychological research on impression formation, criminological theories of court actor decision‐making, and sociological work on race and punishment.
Morphological characterization and biological control of Alitropus typus (Isopoda: Aegidae)
Authors: Shah Syed Aizaz Ali , Ashraf Asma , Qureshi Naveeda Akhtar
Published: June 2017

The Alitropus typus infestation has a serious influence on fish farming in Pakistan. The present study focuses on the external morphology and control of highly infested ectoparasitic isopod Alitropus typus. Sixteen morphological parameters of the whole body were measured and statistically analyzed for mean, standard error and coefficient of variation by using the student t test. Non‐significant variations were observed in the size of pereopods which depict the significance of swimming and attached to its host. For biological control, different concentrations (1000, 5000 and 10 000 ppm) of a leaf extract of four plants (i.e. Euphorbia helioscopia, Ajuga bracteosa, Cannabis sativa and Callistemon citrinus) were tested against A. typus, and the mortality rates were recorded after 12, 24 and 36 h. One way Anova and Tukey tests were used to analyze the results. The recorded percentage mortality was in the order of E. helioscopia > A. bracteosa > C. sativa, whereas C. citrinus did not showed any toxicity. Concentrations of biochemical components like carbohydrates (mg/g), proteins (mg/g), and lipids (mg/dL) of treated isopods were estimated by the phenol‐sulfuric acid process, Lowry's method and biochemistry analyzer, respectively. The protein contents of the insects tested had decreased markedly as compared to control rates, and this might be due to insecticidal stress caused by the extracts. In another biocontrol experiment, crabs were introduced along with isopods into an aquarium. It was then noted that one crab consumes an average of seven isopods/week and can act as a scavenger for dead organisms.
Improved sample preparation for direct quantitative detection of Escherichia coli O157 in soil using qPCR without pre‐enrichment
Authors: Highmore Callum J. , Rothwell Steve D. , Keevil Charles W.
Published: June 2017

The prominence of fresh produce as a vehicle for foodborne pathogens such as enterohaemorrhagic Escherichia coli (EHEC) O157 is rising, where disease cases can cause hospitalization and in some cases death. This rise emphasises the necessity for accurate and sensitive methods for detection of pathogens in soil, potential sources of contamination of fresh produce. The complexity of the soil matrix has previously proven prohibitive to pathogen detection via molecular methods without the use of a culture enrichment step, thereby excluding the detection of viable but non‐culturable cells. Here, a sample preparation procedure to facilitate a direct qPCR assay is developed for the detection of E. coli O157 in soil, bypassing culture steps in favour of sample separation through pulsification release and filtration. In sand and peat‐based compost, the method is sensitive to 10 CFU g−1 soil. When testing soils from agricultural sites, it was found that several were qPCR positive for E. coli O157 while being culture‐negative, with peat‐based compost possessing a concentration of 200 tir gene copies per gram. This procedure offers a rapid, quantitative assessment of the potential presence of E. coli O157 in soils which can act as a prescreen of their suitability to grow fresh produce safely.
Thermal sensitivity of bacteriocytes constrains the persistence of intracellular bacteria in whitefly symbiosis under heat stress
Authors: Shan Hong‐Wei , Deng Wen‐Hao , Luan Jun‐Bo , Zhang Min‐Jing , Zhang Zhen , Liu Shu‐Sheng , Liu Yin‐Quan
Published: June 2017

Temperature affects the persistence of diverse symbionts of insects. Our previous study indicates that the whitefly symbionts confined within bacteriocytes or scattered throughout the body cavity outside bacteriocytes may have differential thermal sensitivity. However, the underlying mechanisms remain largely unknown. Here, we report that following continuous heat stress, Portiera and Hamiltonella were almost completely depleted in two species of Middle East‐Asia Minor 1 (MEAM1) and Mediterranean (MED) of the Bemisia tabaci whitefly cryptic species complex. Meanwhile, proliferation of bacteriocytes was severely inhibited and approximately 50% of the nymphs had lost one of the two bacteriomes. While cell size of bacteriocytes was increased, cell number was severely decreased leading to reduction of total volume of bacteriocytes. Moreover, bacteriocyte organelles and associated symbionts were lysed, and huge amount of electron‐dense inclusions accumulated. Eventually, Portiera and Hamiltonella failed to be transmitted to the next generation. In contrast, Rickettsia could be detected although at a reduced level, and successfully transmitted to eggs. The results suggest that the thermal sensitivity of bacteriocytes may limit thermal tolerance and vertical transmission of the associated symbionts, and consequently different patterns of distribution of symbionts may affect their capacity to tolerate unfavourable temperatures and persistence in the host.
A discussion on disease severity index values. Part I: warning on inherent errors and suggestions to maximise accuracy
Authors: Chiang K.S. , Liu H.I. , Bock C.H.
Published: June 2017

A special type of ordinal scale comprising a number of intervals of known numeric ranges can be used when estimating severity of a plant disease. The interval ranges are most often based on the percent area with symptoms [e.g. the Horsfall–Barratt (H–B) scale]. Studies in plant pathology and plant breeding often use this type of ordinal scale. The disease severity is estimated by a rater as a value on the scale and has been used to determine a disease severity index (DSI) on a percentage basis, where DSI (%) = [sum (class frequency × score of rating class)]/[(total number of plants) × (maximal disease index)] × 100. However, very few studies have investigated the effects of different scales on accuracy of the DSI. Therefore, the objectives of this study were to investigate the process of calculating a DSI on a percentage basis from ordinal scale data, and to use simulation approaches to explore the effect of using different methods for calculation of the interval range and the nature of the ordinal scales used on the DSI estimates (%). We found that the DSI is particularly prone to overestimation when using the above formula if the midpoint values of the rating class are not considered. Moreover, the results of the simulation studies show that, if rater estimates are unbiased, compared with other methods tested in this study, the most accurate method for estimation of a DSI is to use the midpoint of the severity range for each class with an amended 10% ordinal scale (an ordinal scale based on a 10% linear scale emphasising severities ≤50% disease, with additional grades at low severities). As for biased conditions, the accuracy for calculating DSI estimates (%) will depend mainly on the degree and direction of the rater bias relative to the actual mean value.
Advances in Therapeutic Approaches to Extend Healthspan: a perspective from the 2nd Scripps Symposium on the Biology of Aging
Authors: Robbins Paul D. , Niedernhofer Laura J.
Published: June 2017

The 2nd Scripps Florida Symposium on The Biology of Aging entitled ‘Advances in Therapeutic Approaches to Extend Healthspan’ was held on January 22nd–25th, 2017 at The Scripps Research Institute in Jupiter, Florida. The meeting highlighted a variety of therapeutic approaches in animal models of aging that either are or soon will be in clinic trials. For example, drugs targeting senescent cells, metformin, rapalogs, NAD precursors, young plasma, mitochondrial‐targeted free radical scavengers, stem cells, and stem cell factors all have shown significant preclinical efficacy. This perspective, based on presentations and discussions at the symposium, outlines the current and future state of development of therapeutic approaches to extend human healthspan.
Use of the optical disector in canine mammary simple and complex carcinomas
Authors: Santos Marta , Dias‐Pereira Patrícia , Correia‐Gomes Carla , Marcos Ricardo , de Matos Augusto , Rocha Eduardo , Lopes Carlos
Published: June 2017

Grading of canine mammary carcinomas (CMC) is associated to subjective assessments made by the pathologists. Due to its unbiased nature, stereology can be used to objectively quantify morphological parameters associated with grading and malignancy. However, the use of stereology in CMC has not been fully disclosed. The nuclear numerical density [NV (nuclei, tumor)] is a cellularity‐associated parameter that can be estimated by the optical disector. Herein, it was estimated in 44 CMC and its association with clinicopathologic factors – such as tumor size, histological subtype and grade, vascular/lymph node invasion, nuclear pleomorphism, and survival – was evaluated. Considering all the cases, the mean NV (nuclei, tumor) was 1.6 × 106 ± 0.5 × 106 nuclei/mm3. Lower values were attained in complex carcinomas, comparing to simple carcinomas, in tumors smaller than 5 cm, with low mitotic activity and in those with high nuclear pleomorphism. No statistically significant association with grade or vascular/lymph node invasion was observed, but tumors with disease progression had lower nuclear densities. The NV (nuclei, tumor) and the correlated parameters mirror to some extension those in human breast cancer, suggesting an interesting interspecies agreement. This first estimation of the nuclear numerical density in CMC highlights the feasibility of the optical disector and their utility for objective morphological assessments in CMC. The association between nuclear numerical density and disease progression warrants future studies.
Psychometric evaluation of a 6‐item Chinese version of the Hamilton Depression Rating Scale: Mokken scaling and item analysis
Authors: Lee Chin‐Pang , Liu Chia‐Yih , Hung Ching‐I
Published: June 2017

Background

It is unclear whether the 6‐item Melancholia subscale of the Hamilton Depression Rating Scale (HAM‐D6) has better psychometric properties than the parental 17‐item version (HAM‐D17) in the Chinese populations.

Methods

The study was to check the Chinese HAM‐D17 and HAM‐D6 for reliability and validity with Mokken scale analysis and item analysis. We reanalyzed a clinical sample of adult psychiatric outpatients (N = 214; age, mean (SD) = 38.3 (10.5) years; 63.1% female) in Taiwan.

Results

Our Mokken scale analysis showed that the HAM‐D6 was a moderate unidimensional scale (Hs = 0.44) while the HAM‐D17 was not (Hs = 0.26). The 5 items of the HAM‐D6 had strong invariant item ordering (HT = 0.58). The HAM‐D17 and HAM‐D6 had comparable reliability (α = 0.79) and validity (r = 0.91), and the HAM‐D6 was more homogenous than the HAM‐D17. To predict depression in remission (HAM‐D17 ≤ 7), the best cutoff of the HAM‐D6 was 4 (specificity, 87.5%; sensitivity, 100%; positive predictive value, 56.0%; negative predictive value, 100%).

Discussion

The Chinese HAM‐D6 was a reliable, valid, and unidimensional scale of depression.
Combined interventional sialendoscopy and intraductal steroid therapy for recurrent sialadenitis in Sjögren's syndrome: Results of a pilot monocentric trial
Authors: Capaccio P. , Canzi P. , Torretta S. , Rossi V. , Benazzo M. , Bossi A. , Vitali C. , Cavagna L. , Pignataro L.
Published: June 2017

Objectives

To evaluate the effectiveness of interventional sialendoscopy alone or combined with outpatient intraductal steroid irrigations in patients with sialadenitis due to Sjögren's syndrome (SS).

Design

A pilot therapeutic study.

Setting

ENT Clinics, Universities of Milan and Pavia.

Study Population

We included 22 patients with SS of whom 12 underwent interventional sialendoscopy followed by intraductal steroid irrigations (group A), and 10 interventional sialendoscopy alone (group B).

Outcomes Measures

The following outcome measures were considered and recorded before and after the therapeutic intervention: (i) number of episodes of glandular swelling, (ii) cumulative prevalence of patients with glandular swelling assessed by the specific domain, the EULAR SS Disease Activity Index (ESSDAI), (iii) severity of pain by means of a 0‐10 pain visual analogue scale (VAS), (iv) severity of xerostomia and other disease symptoms assessed by the EULAR SS Patient Reported Index (ESSPRI) and the Xerostomia Inventory questionnaire.

Results

The postoperative reduction in the mean number of episodes of glandular swelling was 87% (95% CI: 77‐93) and 75% (95% CI: 47%‐88%) in the groups A and B, respectively. The percentage of patients with glandular swelling decreased from 41.7% to 0.0% in the group A and from 30.0% to 0.0% in the group B, respectively. Most of the patients experienced a subjective clinical improvement documented by the statistically significant reductions in the postoperative mean pain VAS (group A P<.001; group B P=.004), Xerostomia Inventory (P<.001 and P=.003) and ESSPRI scores (P<.001 and P=.008). Interventional sialendoscopy followed by outpatient intraductal steroid irrigations was more effective than interventional sialendoscopy alone, when pain VAS, Xerostomia Inventory and ESSPRI scores before and after treatment were analysed together using the multivariate Hotelling T2 test (P=.0173).

Conclusions

This pilot study confirms that interventional sialendoscopy with steroid duct irrigation significantly reduces the number of painful episodes of sialadenitis and improves the subjective sensation of oral dryness and other disease symptoms in patients with SS. The study results also suggest that the improvement is greater when interventional sialendoscopy is combined with a cycle of outpatient steroid ductal irrigations. Larger controlled randomised studies are certainly needed to confirm these preliminary data.
Allergic rhinitis, rather than asthma, is a risk factor for dental caries
Authors: Chuang C.Y. , Sun H.L. , Ku M.S.
Published: June 2017

Objectives

The association between AS (asthma) and dental caries is controversial, while that between allergic rhinitis (AR) and caries has not been established. This study aimed to verify the relationship among AR, AS and dental caries.

Design

Retrospective cohort study.

Setting

Data from Health Insurance Database of the Taiwan's National Health Insurance Research Database.

Participants

Nine thousand and thirty‐eight children born in 2004 were obtained. Their claims data were evaluated from birth to the age of 9 years.

Main outcome measures

The frequencies of clinical visits for dental caries were calculated for primary teeth (age 1‐5) and for dental transitional period (age 6‐9). Differences in the frequencies of clinical visits for caries in AR vs non‐AR and AS vs non‐AS children were compared. Correlation between AR, AS and caries frequencies was studied, and the influences of AR drugs on the development of caries were evaluated.

Results

After adjusting for confounding factors and AS case, the frequencies of clinical visits for caries were higher in AR (increased by 13%‐25% and P<.001 at different age periods). The AR frequencies significantly correlated with caries frequencies in children with AR. Different AR drugs also correlated with caries formation. After adjusting for confounding factors and AR case, there was no relationship between AS and caries in children.

Conclusion

Asthma is not associated with dental caries, but AR can increase the frequency of clinical visits for caries. Medications for AR may also play a role in caries formation. Thus, AR may be a risk factor for childhood dental caries.
A New Measure of Hallucinatory States and a Discussion of REM Sleep Dreaming as a Virtual Laboratory for the Rehearsal of Embodied Cognition
Authors: Speth Clemens , Speth Jana
Published: June 2017

Hallucinatory states are experienced not only in connection with drugs and psychopathologies but occur naturally and spontaneously across the human circadian cycle: Our nightly dreams bring multimodal experiences in the absence of adequate external stimuli. The current study proposes a new, tighter measure of these hallucinatory states: Sleep onset, REM sleep, and non‐REM sleep are shown to differ with regard to (a) motor imagery indicating interactions with a rich imaginative world, and (b) cognitive agency that could enable sleepers to recognize their hallucinatory state. Mentation reports from the different states were analysed quantitatively with regard to two grammatical–semantic constructs, motor agency and cognitive agency. The present results support earlier physiological and psychological evidence in revealing a decline in cognitive functions and an increase in simulated interactions with a hallucinatory world, en route to normal REM sleep. This leads us to introduce the hypothesis that REM sleep, which exhibits remarkably high levels of (simulated) sensorimotor processes, may have evolved to serve as a virtual laboratory for the development and rehearsal of embodied cognition. The new measure of hallucinatory states presented here may also hold implications for the study of executive functions and (meta‐)cognitions, which might be interesting, for example, for the investigation of lucid dreaming.
Reproducibility of the plasma glucose response to moderate‐intensity exercise in adolescents with Type 1 diabetes
Authors: Abraham M. B. , Davey R. J. , Cooper M. N. , Paramalingam N. , O'Grady M. J. , Ly T. T. , Jones T. W. , Fournier P. A. , Davis E. A.
Published: June 2017

Aims

The aim of the study was to evaluate the reproducibility of the plasma glucose response to moderate‐intensity exercise performed on different days under controlled conditions in adolescents with Type 1 diabetes.

Methods

Eight adolescents with Type 1 diabetes on continuous subcutaneous insulin infusion completed two exercise sessions, each on two separate days, under basal insulin and fasting conditions. On each day, participants cycled twice for 30 min at 55% of their peak rate of oxygen consumption, with each exercise session separated by a 30‐min rest.

Results

Plasma insulin levels were similar between testing days and exercise sessions. The mean absolute drop in plasma glucose from the commencement to the end of exercise was 1.6 ± 0.5 mmol/l on day 1 and 1.9 ± 0.7 mmol/l on day 2 (P = 0.3). In response to the first exercise session, plasma glucose levels relative to baseline did not change significantly (0.2 ± 0.6 and –0.2 ± 0.5 mmol/l on days 1 and 2). By contrast, the change in plasma glucose during the second exercise session was –1.1 ± 0.7 and –1.3 ± 0.7mmol/l on days 1 and 2, respectively. The mean absolute intra‐individual difference in the change in plasma glucose between testing days were 0.7 ± 0.5 [95% confidence interval (CI) 0.4–1.0] and 0.7 ± 0.4 (95% CI 0.4–1.0) mmol/l, at the end of the first and second exercise sessions respectively.

Conclusions

The plasma glucose response to moderate‐intensity exercise under similar glycaemic and basal insulin conditions can be reproducible in adolescents with Type 1 diabetes.