bluuebunny/crossref_metadata_2025 huggingface dataset:
The qSOFA Score: A Simple and Accurate Predictor of Outcome in Patients with Glyphosate Herbicide Poisoning
Authors: Cho Yong Soo , Chun Byeong Jo , Moon Jeong Mi
Published: May 2018

This study aimed to investigate whether the quick Sequential Organ Failure Assessment (qSOFA) score at emergency department (ED) presentation can help improve the risk assessment of glyphosate‐surfactant herbicide (GlySH) poisoning complications. A total of 150 patients presenting with acute glyphosate herbicide ingestion were enrolled in this retrospective observational study. The qSOFA scores at presentation, ΔqSOFA (calculated by subtracting the worst qSOFA score from 1 hr after admission from the qSOFA score at presentation), baseline characteristics, clinical courses and outcome were collected and analysed. A total of 41 patients had life‐threatening complications (27.3%), and 14 patients died (9.3%). Patients with a qSOFA score of 0 at presentation had a 1.5% incidence rate of complications. As the qSOFA score at presentation increased from 1 to 3, the rate of life‐threatening complications significantly increased from 29.6% to 100%. Patients with a ΔqSOFA of 1 had a higher frequency of complications than did patients with a ΔqSOFA of 0. The qSOFA score (OR: 8.39, 95% CI: 3.51–26.67) and ΔqSOFA (OR: 27.60, 95% CI: 3.87–575.67) were associated with the development of life‐threatening complications in the multivariate analysis. The qSOFA score showed high sensitivity (97.56%), and the ΔqSOFA score showed high specificity (99.08%). The values of area under the curve were significantly higher in the models using the qSOFA and ΔqSOFA than they were in the models using previously known prognostic factors (p < 0.01). The clinician should pay more attention to patients with high qSOFA scores at presentation or an increase in the qSOFA score 1 hr after admission.
Rho Kinase and Protein Kinase C Pathways are Responsible for Enhanced Carbachol Contraction in Permeabilized Detrusor in a Rat Model of Cystitis
Authors: Denizalti Merve , Durlu‐Kandilci Nezahat Tugba , Simsek Gul , Bozkurt Turgut Emrah , Sahin‐Erdemli Inci
Published: May 2018

Interstitial cystitis is a syndrome characterized by detrusor overactivity and chronic inflammation of the bladder. The mechanisms responsible for the altered smooth muscle contractility remain poorly understood. The aim of the study was to investigate the role of intracellular signalling pathways in carbachol‐induced detrusor contraction in a rat model of interstitial cystitis. Cyclophosphamide (150 mg/kg, dissolved in saline) was injected to rats (Sprague–Dawley, female, 200–250 g) intraperitoneally once a day on days 1, 4 and 7 to induce interstitial cystitis. Control groups were injected with saline (0.9% NaCl). Detrusor smooth muscle strips were mounted in 1‐ml organ baths containing HEPES‐buffered modified Krebs’ solution and permeabilized with 40 μM β‐escin for 30 min. Carbachol‐induced contractions were significantly increased from 21.2 ± 1.6% (saline‐treated) to 44 ± 4.4% in cyclophosphamide‐treated group. The Rho kinase inhibitor Y‐27632 (8.8 ± 2%) and the protein kinase C inhibitor GF‐109203X (11.7 ± 2.8%) inhibited the increased contractile response (44 ± 4.4%) in rats with cystitis. The increased carbachol‐induced contraction (44 ± 4.4%) was also significantly inhibited by the sarcoplasmic reticulum ryanodine channel blocker ryanodine (25.8 ± 3.2%) and the sarcoplasmic reticulum IP3 receptor blocker heparin (17.2 ± 2.2%) in cystitis. RhoA protein levels in the bladder of cyclophosphamide‐treated rats were significantly increased while pan‐protein kinase C (α, β and γ isoforms) protein expression was unaltered between experimental groups. Carbachol‐induced calcium sensitization at constant and clamped calcium (pCa 6) was also increased in cystitis (from 15.8 ± 2.2% to 24.7 ± 2.8%). This increased response (24.7 ± 2.8%) was significantly inhibited by both Y‐27632 (7.9 ± 0.7%) and GF‐109203X (4.4 ± 1.5%). We conclude that interstitial cystitis is characterized by an enhanced carbachol contractile response as well as by calcium sensitization of the detrusor smooth muscle. Activation of Rho kinase and protein kinase C pathways may be the molecular culprits responsible for the augmented muscarinic response observed in cystitis.
Effect of Adding Magnesium Sulphate to Epidural Bupivacaine and Morphine on Post‐Thoracotomy Pain Management: A Randomized, Double‐Blind, Clinical Trial
Authors: Farzanegan Behrooz , Zangi Mahdi , Saeedi Kimia , Khalili Ali , Rajabi Mehdi , Jahangirifard Alireza , Emami Habib , Mahboobipour Amir Ali , Baniasadi Shadi
Published: May 2018

Post‐thoracotomy pain is very severe and may cause pulmonary complications. Thoracic epidural analgesia can greatly decrease the pain experience and its consequences. However, finding new methods to decrease the amount of administered opioids is an important issue of research. We aimed to evaluate the effect of adding epidural magnesium sulphate to bupivacaine and morphine on pain control and the amount of opioid consumption after thoracotomy. Eighty patients undergoing thoracotomy at a tertiary cardiothoracic referral centre were enrolled in a randomized, double‐blind trial. Patients were randomly allocated to two groups. Bupivacaine (12.5 mg) and morphine (2 mg) were administered epidurally to all patients at the end of operation. Patients in the magnesium (Mg) group received epidural magnesium sulphate (50 mg), and patients in the control (C) group received normal saline as an adjuvant. Visual analogue scale (VAS) score and the amount of morphine consumption were measured during 24 hr post‐operation. Thirty‐nine patients in the Mg group and 41 patients in the C group completed the study. Patients in the Mg group had significantly less VAS score at recovery time (p < 0.05), 2 hr (p < 0.01) and 4 hr (p < 0.05) after surgery. The patient‐controlled analgesia pump was started earlier in the C group than in the Mg group (p < 0.05). The amount of morphine needed in the Mg group was significantly lower than in the C group (5.64 ± 1.69 mg/24 hr versus 8.44 ± 3.98 mg/24 hr; p < 0.001). Pruritus was seen in the C group (9.7%) and absent in the Mg group (p < 0.05). Co‐administration of magnesium sulphate with bupivacaine and morphine for thoracic epidural analgesia after thoracotomy leads to a reduction in post‐operative pain score and the need for opioid administration.
Four‐year follow‐up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL)
Authors: Jain Preetesh , Romaguera Jorge , Srour Samer A. , Lee Hun J. , Hagemeister Frederick , Westin Jason , Fayad Luis , Samaniego Felipe , Badillo Maria , Zhang Liang , Nastoupil Lorreta , Kanagal‐Shamanna Rashmi , Fowler Nathan , Wang Michael L.
Published: May 2018

Ibrutinib has shown significant activity in patients with relapsed or refractory mantle cell lymphoma (RR‐MCL). We report the long‐term outcome and safety profile of a single‐centre, single arm, open‐label, phase 2 study of RR‐MCL treated with IR. Overall, the median follow‐up time was 47 months (range 1–52 months), median duration on treatment was 16 months (range 1–53 months) and median number of treatment cycles was 17 (range 1–56). Twenty‐nine patients (58%) achieved complete remission and of these, 12 patients continue on study. Thirty‐eight patients discontinued treatment, 14 due to disease progression (2 transformed). Patients with blastoid morphology, high risk MCL International Prognostic Index score and high Ki67% had inferior survival. The commonest grade 1–2 toxicities were fatigue, diarrhoea, nausea, arthralgias and myalgias. None had long term toxicities. Median progression‐free survival was 43 months. Eighteen patients (36%) died (14 deaths were MCL‐related). The median overall survival has not been reached. Treatment with IR can provide durable remissions in a subset of patients with RR‐MCL, especially those with low Ki67%. The possible benefit of adding other therapies in combination with IR in RR‐MCL is under exploration.
Non‐Standard Time Wage Premiums and Employment Effects: Evidence from an Australian Natural Experiment
Authors: Yu Serena , Peetz David
Published: May 2018

We examine the effect of increasing Sunday wage premiums on retail industry employment in Australia, exploiting a quasi‐experimental policy change across two neighbouring states. Using both aggregate and individual‐level data, we adopt a difference‐in‐difference regression framework to estimate the causal impact of the policy change on employment outcomes. We find no evidence of changes in the total number of employees, and no effect on hours per employee in the years following the policy implementation. However, there appeared to be a decline in hours per employee in the announcement year of the policy change. Overall, it appears that in an industry dominated by part‐time and casual employment, any adjustment to the new Sunday wage rates occurred principally through flexibility in hours, rather than in the number of employees.
Increase in incidental detection of thyroid cancer in Osaka, Japan
Authors: Toyoda Yasuhiro , Tabuchi Takahiro , Nakata Kayo , Morishima Toshitaka , Nakayama Tomio , Miyashiro Isao , Hojo Shigeyuki , Yoshioka Setsuko
Published: May 2018

Using Osaka Cancer Registry data, we examined age‐specific and age‐adjusted incidence rates of thyroid cancer according to the route of thyroid cancer detection from 1992 to 2012. The detection routes were categorized into “symptomatic” and “incidental detection.” Age‐specific incidence rates of incidentally‐detected thyroid cancer consistently increased during the study period, especially after 2001, for all sex and age groups other than childhood. The rate of symptomatic thyroid cancer did not largely differ among groups. Age‐adjusted incidence rates of symptomatic thyroid cancer were around 1.5 and 4.5 per 100 000 among men and women, respectively. The rate of incidentally‐detected thyroid cancer increased from 0.1 and 0.1 per 100 000 person‐years among men and women in 1992‐1994 to 2.0 and 4.9, respectively, in 2010‐2012. Age‐adjusted mortality rates among both sexes during the study period leveled off. This finding suggests that the thyroid cancer incidence rate in Osaka increased with incidental detection. We need to continue careful monitoring to confirm these findings.
Design, synthesis and evaluation of a novel series of inhibitors reversing P‐glycoprotein‐mediated multidrug resistance
Authors: Ghaleb Hesham , Li Huilan , Kairuki Mutta , Qiu Qianqian , Bi Xinzhou , Liu Chunxia , Liao Chen , Li Jieming , Hezam Kamal , Huang Wenlong , Qian Hai
Published: May 2018

Multidrug resistance (MDR) is still the main barrier to attaining effective results with chemotherapy. Discovery of new chemo‐reversal agents is needed to overcome MDR. Our study focused on a better way to obtain novel drugs with triazole rings that have an MDR reversal ability through click chemistry. Among 20 developed compounds, compound 19 had a minimal cytotoxic effect compared to tariquidar and verapamil (VRP) and showed a higher reversal activity than VRP through increased accumulation in K562/A02 cells. Compound 19 also played an important role in the P‐gp efflux function of intracellular Rh123 and doxorubicin (DOX) accumulation in K562/A02 cells. Moreover, compound 19 exhibited a long lifetime of approximately 24 hr. These results indicated that compound 19 is a potential lead compound for the design of new drugs to overcome cancer MDR.
Intergroup Contact Attitudes Across Peer Networks in School: Selection, Influence, and Implications for Cross‐Group Friendships
Authors: Rivas‐Drake Deborah , Saleem Muniba , Schaefer David R. , Medina Michael , Jagers Robert
Published: May 2018

This study offers new insights into the power of peer networks for shaping intergroup relations in a diverse school. Data were drawn from a longitudinal study of sixth–eighth graders (N = 524; MageT1 = 11.87; 48% girls; 9% Asian American/Pacific Islander, 28% African American, 13% Latino, 1% Native American, 31% White, 5% Other, and 11% Multiracial) in the Midwestern United States. Students with more positive intergroup contact attitudes (ICA) were most likely to be friends with similarly minded students. Students with more positive ICA were less likely to select friends of the same race/ethnicity than those with less positive ICA. Finally, students’ ICA became more similar to their friends’ ICA over time. Results implicate school‐level norms and contagion in students’ ICA.
Novel genes and insights in complete asthma remission: A genome‐wide association study on clinical and complete asthma remission
Authors: Vonk J. M. , Nieuwenhuis M. A. E. , Dijk F. N. , Boudier A. , Siroux V. , Bouzigon E. , Probst‐Hensch N. , Imboden M. , Keidel D. , Sin D. , Bossé Y. , Hao K. , van den Berge M. , Faiz A. , Koppelman G. H. , Postma D. S.
Published: May 2018

Background

Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome‐wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission.

Objective

We performed a GWA study to develop insights in asthma remission.

Methods

Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long‐term follow‐up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium.

Results

Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow‐up of 15.5 (range 3.3‐47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta‐analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta‐analysis of the replication cohorts. The top‐hit, rs6581895, almost reached genome‐wide significance (P‐value 4.68 × 10−7) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis‐eQTL in lung tissue for IL1RL1 and IL18R1 and a trans‐eQTL for IL13.

Conclusions and Clinical Relevance

By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.
DYNAMIC ENTRY WITH DEMAND AND SUPPLY SIDE SPILLOVERS
Authors: Tan Yong
Published: May 2018

Supply side spillovers have been used to explain firms' entry behavior in the pharmaceutical industry. In contrast, demand side spillovers have received less attention. This paper identifies supply and demand spillovers using a dynamic model of strategic interaction. The results indicate that demand side spillovers are more significant than the supply side spillovers to generic drug firms, and the demand side spillovers increase a firm's market share by 3%–4% on average in subsequent market entry. In addition, with supply side spillovers alone, lowering entry barriers can increase future entry rates, while in the case of demand side spillovers, lowering entry barriers will have the opposite effect. (JEL L110, L130, D220)
The Mental Representation of Human Action
Authors: Levine Sydney , Leslie Alan M. , Mikhail John
Published: May 2018

Various theories of moral cognition posit that moral intuitions can be understood as the output of a computational process performed over structured mental representations of human action. We propose that action plan diagrams—“act trees”—can be a useful tool for theorists to succinctly and clearly present their hypotheses about the information contained in these representations. We then develop a methodology for using a series of linguistic probes to test the theories embodied in the act trees. In Study 1, we validate the method by testing a specific hypothesis (diagrammed by act trees) about how subjects are representing two classic moral dilemmas and finding that the data support the hypothesis. In Studies 2–4, we explore possible explanations for discrete and surprising findings that our hypothesis did not predict. In Study 5, we apply the method to a less well‐studied case and show how new experiments generated by our method can be used to settle debates about how actions are mentally represented. In Study 6, we argue that our method captures the mental representation of human action better than an alternative approach. A brief conclusion suggests that act trees can be profitably used in various fields interested in complex representations of human action, including law, philosophy, psychology, linguistics, neuroscience, computer science, robotics, and artificial intelligence.
Lexical Learning May Contribute to Phonetic Learning in Infants: A Corpus Analysis of Maternal Spanish
Authors: Swingley Daniel , Alarcon Claudia
Published: May 2018

In their first year, infants begin to learn the speech sounds of their language. This process is typically modeled as an unsupervised clustering problem in which phonetically similar speech‐sound tokens are grouped into phonetic categories by infants using their domain‐general inference abilities. We argue here that maternal speech is too phonetically variable for this account to be plausible, and we provide phonetic evidence from Spanish showing that infant‐directed Spanish vowels are more readily clustered over word types than over vowel tokens. The results suggest that infants’ early adaptation to native‐language phonetics depends on their word‐form lexicon, implicating a much wider range of potential sources of influence on infants’ developmental trajectories in language learning.
In vitro formation of the Merkel cell‐neurite complex in embryonic mouse whiskers using organotypic co‐cultures
Authors: Ishida Kentaro , Saito Tetsuichiro , Mitsui Toshiyuki
Published: May 2018

A Merkel cell‐neurite complex is a touch receptor composed of specialized epithelial cells named Merkel cells and peripheral sensory nerves in the skin. Merkel cells are found in touch‐sensitive skin components including whisker follicles. The nerve fibers that innervate Merkel cells of a whisker follicle extend from the maxillary branch of the trigeminal ganglion. Whiskers as a sensory organ attribute to the complicated architecture of the Merkel cell‐neurite complex, and therefore it is intriguing how the structure is formed. However, observing the dynamic process of the formation of a Merkel cell‐neurite complex in whiskers during embryonic development is still difficult. In this study, we tried to develop an organotypic co‐culture method of a whisker pad and a trigeminal ganglion explant to form the Merkel cell‐neurite complex in vitro. We initially developed two distinct culture methods of a single whisker row and a trigeminal ganglion explant, and then combined them. By dissecting and cultivating a single row from a whisker pad, the morphogenesis of whisker follicles could be observed under a microscope. After the co‐cultivation of the whisker row with a trigeminal ganglion explant, a Merkel cell‐neurite complex composed of Merkel cells, which were positive for both cytokeratin 8 and SOX2, Neurofilament‐H‐positive trigeminal nerve fibers and Schwann cells expressing Nestin, SOX2 and SOX10 was observed via immunohistochemical analyses. These results suggest that the process for the formation of a Merkel cell‐neurite complex can be observed under a microscope using our organotypic co‐culture method.
Longitudinal growth of receptive language in children with cerebral palsy between 18 months and 54 months of age
Authors: Hustad Katherine C , Sakash Ashley , Broman Aimee Teo , Rathouz Paul J
Published: May 2018

Aim

We examined receptive language developmental trajectories between 18 months and 54 months for three clinical speech‐language profile groups of children with cerebral palsy (those with speech motor involvement, without speech motor involvement, and with anarthria) and quantified differences from age‐level expectations. We identified latent classes of comprehension development, related these classes to clinical profile groups, and examined how well early receptive language predicted outcomes.

Method

We used a prospective longitudinal design. Eighty‐five children with cerebral palsy (43 females, 42 males) were followed longitudinally from 18 to 54 months of age. Children were seen two to eight times (322 data points). Children were classified into clinical profile groups. Language comprehension age‐equivalent scores were the primary measures of interest.

Results

Children with anarthria had significant language delays, limited developmental change over time, and comprised their own latent class. Children with speech motor impairment had slight receptive language delays over time. Children with no speech motor impairment had age‐appropriate receptive language over time. Early language comprehension scores were highly predictive of later latent profile group membership.

Interpretation

Early language comprehension abilities are highly predictive of language comprehension growth trajectory and suggest that children with early language delay, particularly those who are non‐speaking, should receive language intervention to support development.

What this paper adds

There are two growth trajectories for language comprehension among children with cerebral palsy.

Children with speech motor impairment had a constant 6‐month receptive language delay.

Children without speech motor impairment had age‐appropriate receptive language.

Non‐speaking children had significant receptive language delay.

Early language comprehension change was highly predictive of later trajectory group.
More patients reach glycaemic control with a fixed‐ratio combination of insulin glargine and lixisenatide (iGlarLixi) than with basal insulin at 12 weeks of treatment: A post hoc time‐to‐control analysis of LixiLan‐O and LixiLan‐L
Authors: Frias Juan , Puig Domingo Manuel , Meneghini Luigi , Napoli Raffaele , Liu Minzhi , Soltes Rak Erika , Aroda Vanita R.
Published: May 2018

The present post hoc analysis of two 30‐week clinical trials compared efficacy and hypoglycaemia outcomes at early study visits with iGlarLixi (insulin glargine U100 [iGlar] and lixisenatide) vs iGlar alone in patients with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs; LixiLan‐O trial) or basal insulin (LixiLan‐L trial). Time to control, defined as days to achieve glycated haemoglobin (HbA1c) <53 mmol/mol (<7%) or fasting plasma glucose (FPG) ≤7.2 mmol/L, was estimated using the Kaplan–Meier method. In the LixiLan‐O and LixiLan‐L trials, 60% and 46% of patients, respectively, reached HbA1c <53 mmol/mol (<7%) with iGlarLixi at 12 weeks, vs 45% and 24%, respectively, with iGlar. In the LixiLan‐O trial, the median time to target HbA1c was approximately half with iGlarLixi vs iGlar (85.0 vs 166.0 days; P < .0001). In the LixiLan‐L trial, the median time to target HbA1c was 153.0 days with iGlarLixi, while target HbA1c was never reached by 50% of patients with iGlar (P < .0001). Time‐to‐target FPG and hypoglycaemia outcomes were similar between treatments. In T2D uncontrolled on OADs or basal insulin, iGlarLixi resulted in glycaemic control in more patients than did iGlar at early treatment time points.
Wing morphology and migration status, but not body size, habitat or Rapoport's rule predict range size in North‐American dragonflies (Odonata: Libellulidae)
Authors: Outomuro David , Johansson Frank
Published: May 2018

Understanding why species range sizes vary is important for predicting the impact of environmental change on biodiversity. Here we use a multi‐variable approach in a phylogenetic comparative context to understand how four morphological, two ecological, and two eco‐geographical variables are associated with range size, latitudinal range and longitudinal range in 81 species of North‐American libellulid dragonflies. Our results show that: 1) migratory species and species with a more expanded basal hindwing lobe have a larger range size; 2) opposite to Rapoport's rule, latitudinal range is negatively correlated with mid‐range latitude; 3) longitudinal range is predicted by wing morphology and migration; 4) body size and larval habitat are not correlated with range size, latitudinal range or longitudinal range. These results suggest that dispersal‐related traits, such as wing shape and migratory status, are important factors in predicting the range size of libellulid dragonflies. In addition, the reverse Rapoport's rule suggests that more northern‐centred species might be more specialized than more southern‐centred species. We suggest that the variables predicting range size are likely imposed by taxon‐specific morphological, ecological, physiological and behavioural traits. Taxon‐specific knowledge is thus necessary to understand the dynamics of range sizes and is important to implement successful restoration and conservation plans of threatened species.
Dealing with food shortage: larval dispersal behaviour and survival on non‐prey food of the hoverfly Episyrphus balteatus
Authors: Vosteen Ilka , Gershenzon Jonathan , Kunert Grit
Published: May 2018

1. Predatory larvae often have to face food shortages during their development, and thus the ability to disperse and find new feeding sites is crucial for survival. However, the dispersal capacity of predatory larvae, the host finding cues employed, and their use of alternative food sources are largely unknown. These aspects of the foraging behaviour of the aphidophagous hoverfly (Episyrphus balteatus De Geer) larvae were investigated in the present study.

2. It was shown that these hoverfly larvae do not leave a plant as long as there are aphids available, but that dispersing larvae are able to find other aphid colonies in the field. Dispersing hoverfly larvae accumulated on large aphid colonies, but did not distinguish between different pea aphid race–plant species combinations. Large aphid colonies might be easier to detect because of intensified searching by hoverfly larvae following the encounter of aphid cues like honeydew that accumulate around large colonies.

3. It was further shown that non‐prey food, such as diluted honey or pollen, was insufficient for hoverfly larvae to gain weight, but prolonged the survival of the larvae compared with unfed individuals. As soon as larvae were switched back to an aphid diet, they rapidly gained weight and some pupated after a few days. Although pupation and adult hatching rates were strongly reduced compared with hoverflies continuously fed with aphids, the consumption of non‐prey food most probably increases the probability that hoverfly larvae find an aphid colony and complete their development.
Targeted next generation sequencing for the diagnosis of patients with rare congenital anemias
Authors: Shefer Averbuch Noa , Steinberg‐Shemer Orna , Dgany Orly , Krasnov Tanya , Noy‐Lotan Sharon , Yacobovich Joanne , Kuperman Amir A. , Kattamis Antonis , Ben Barak Ayelet , Roth‐Jelinek Batia , Chubar Evgeni , Shabad Evelyn , Dufort Gustavo , Ellis Martin , Wolach Ofir , Pazgal Idit , Abu Quider Abed , Miskin Hagit , Tamary Hannah
Published: May 2018

Background

Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes.

Objective

We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next‐generation sequencing.

Methods

Genetic diagnosis was performed by gene capture followed by next‐generation sequencing of 76 genes known to cause anemia syndromes.

Results

Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years.

Conclusions

Targeted next‐generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients’ care and enable genetic counseling.
Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks
Authors: Sandvig Ioanna , Augestad Ingrid Lovise , Håberg Asta Kristine , Sandvig Axel
Published: May 2018

Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro‐ and anti‐inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity‐dependent and homeostatic plasticity, suggests that microglia‐mediated pro‐ and/or anti‐inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.
Soil respiration in Chinese tea gardens: autotrophic and heterotrophic respiration
Authors: Fan L. C. , Han W. Y.
Published: May 2018

To obtain an improved understanding of the response of soil respiration (RS) to soil temperature and water content, we used a trenching treatment that could divide RS into autotrophic (RA) and heterotrophic respiration (RH) components in Chinese tea gardens in 2013. The results of the linear and non‐linear relations of RH and RA with soil temperature and water content showed that temperature rather than water content was the main factor controlling the seasonality of RH and RA in Chinese tea gardens. The rates of RH and RA were fitted well in 14 models that took soil temperature or water content into account. Exponential models of soil temperature–moisture could explain the seasonal variation in RH and RA better than the single‐factor models. Temperature sensitivity (Q10) values between RH and RA were not significantly different. The relative contribution (RC) of RA to RS in the tea gardens was 50–63%. This study will facilitate the development of models to investigate components of respiration in soil in general, and also improve our understanding of the response of these components to soil temperature and moisture.

Highlights

Respiration in soil of Chinese tea gardens was partitioned to autotrophic and heterotrophic.

Autotrophic and heterotrophic respiration were fitted in 14 models with soil temperature or moisture.

Exponential temperature–moisture models fitted autotrophic and heterotrophic respiration better than single factor models.

Autotrophic respiration is as sensitive to temperature as heterotrophic respiration.
Evolution of lobar abnormalities of cerebral glucose metabolism in 41 children with drug‐resistant epilepsy
Authors: Govil‐Dalela Tuhina , Kumar Ajay , Behen Michael E. , Chugani Harry T. , Juhász Csaba
Published: May 2018

Objective

We analyzed long‐term changes of lobar glucose metabolic abnormalities in relation to clinical seizure variables and development in a large group of children with medically refractory epilepsy.

Methods

Forty‐one children (25 males) with drug‐resistant epilepsy had a baseline positron emission tomography (PET) scan at a median age of 4.7 years; the scans were repeated after a median of 4.3 years. Children with progressive neurological disorders or space‐occupying lesion–related epilepsy and those who had undergone epilepsy surgery were excluded. The number of affected lobes on 2‐deoxy‐2(18F)‐fluoro‐D‐glucose–PET at baseline and follow‐up was correlated with epilepsy variables and developmental outcome.

Results

On the initial PET scan, 24 children had unilateral and 13 had bilateral glucose hypometabolism, whereas 4 children had normal scans. On the follow‐up scan, 63% of the children showed an interval expansion of the hypometabolic region, and this progression was associated with persistent seizures. In contrast, 27% showed less extensive glucose hypometabolism at follow‐up; most of these subjects manifested a major interval decrease in seizure frequency. Delayed development was observed in 21 children (51%) at baseline and 28 (68%) at follow‐up. The extent of glucose hypometabolism at baseline correlated with developmental levels at the time of both baseline (r = .31, P = .05) and follow‐up scans (r = .27, P = .09).

Significance

In this PET study of unoperated children with focal epilepsy, the lobar pattern of glucose hypometabolism changed over time in 90% of the cases. The results support the notion of an expansion of metabolic dysfunction in children with persistent frequent seizures and its association with developmental delay, and support that optimized medical treatment to control seizures may contribute to better neurocognitive outcome if no surgery can be offered.
Recent evolution of the human skin barrier
Authors: Brettmann Erin A. , de Guzman Strong Cristina
Published: May 2018

The skin is the first line of defense against the environment, with the epidermis as the outermost tissue providing much of the barrier function. Given its direct exposure to and encounters with the environment, the epidermis must evolve to provide an optimal barrier for the survival of an organism. Recent advances in genomics have identified a number of genes for the human skin barrier that have undergone evolutionary changes since humans diverged from chimpanzees. Here, we highlight a selection of key and innovative genetic findings for skin barrier evolution in our divergence from our primate ancestors and among modern human populations.
A bald statement — Current approaches to manipulate miniaturisation focus only on promoting hair growth
Authors: Pantelireis Nikolaos , Higgins Claire A.
Published: May 2018

Hair plays a large part in communication and society with its role changing through time and across cultures. Most people do not leave the house before combing their hair or shaving their beard and for many hair loss or irregular hair growth can have a significant impact on their psychological health. Somewhat unsurprisingly, according to GMR Data, today’s global hair care industry is worth an estimated $87 Billion, with hair loss estimated at $2.8 Billion. Considering that no current hair loss‐related products can completely reverse hair loss, it is reasonable to believe this market could expand significantly with the discovery of a comprehensive therapy. As such, a great deal of research focuses on overcoming hair loss, and in particular, a common form of hair loss known as androgenetic alopecia (AGA) or male pattern baldness. In AGA, hair follicles miniaturise in a large step change from a terminal to a vellus state. Within this viewpoint article, we discuss how influx and efflux of cells into and out from the dermal papilla (DP) can modulate DP size during the hair cycle. As DP size is positively correlated with the size of the hair fibre produced by a follicle, we argue here that therapies for treating AGA should be developed which can alter DP size, rather than just promote hair growth. We also discuss current therapeutics for AGA and emphasise the importance of using the right model systems to analyse miniaturisation.
Community disassembly under global change: Evidence in favor of the stress‐dominance hypothesis
Authors: Kuczynski Lucie , Grenouillet Gaël
Published: May 2018

Ecological theory suggests that communities are not random combinations of species but rather the results of community assembly processes filtering and sorting species that are able to coexist together. To date, such processes (i.e., assembly rules) have been inferred from observed spatial patterns of biodiversity combined with null model approaches, but relatively few attempts have been made to assess how these processes may be changing through time. Specifically, in the context of the ongoing biodiversity crisis and global change, understanding how processes shaping communities may be changing and identifying the potential drivers underlying these changes become increasingly critical. Here, we used time series of 460 French freshwater fish communities and assessed both functional and phylogenetic diversity patterns to determine the relative importance of two key assembly rules (i.e., habitat filtering and limiting similarity) in shaping these communities over the last two decades. We aimed to (a) describe the temporal changes in both functional and phylogenetic diversity patterns, (b) determine to what extent temporal changes in processes inferred through the use of standardized diversity indices were congruent, and (c) test the relationships between the dynamics of assembly rules and both climatic and biotic drivers. Our results revealed that habitat filtering, although already largely predominant over limiting similarity, became more widespread over time. We also highlighted that phylogenetic and trait‐based approaches offered complementary information about temporal changes in assembly rules. Finally, we found that increased environmental harshness over the study period (especially higher seasonality of temperature) led to an increase in habitat filtering and that biological invasions increased functional redundancy within communities. Overall, these findings underlie the need to develop temporal perspectives in community assembly studies, as understanding ongoing temporal changes could provide a better vision about the way communities could respond to future global changes.
Defining a land boundary for sustainable livestock consumption
Authors: Van Zanten Hannah H. E. , Herrero Mario , Van Hal Ollie , Röös Elin , Muller Adrian , Garnett Tara , Gerber Pierre J. , Schader Christian , De Boer Imke J. M.
Published: May 2018

The need for more sustainable production and consumption of animal source food (ASF) is central to the achievement of the sustainable development goals: within this context, wise use of land is a core challenge and concern. A key question in feeding the future world is: how much ASF should we eat? We demonstrate that livestock raised under the circular economy concept could provide a significant, nonnegligible part (9–23 g/per capita) of our daily protein needs (~50–60 g/per capita). This livestock then would not consume human‐edible biomass, such as grains, but mainly convert leftovers from arable land and grass resources into valuable food, implying that production of livestock feed is largely decoupled from arable land. The availability of these biomass streams for livestock then determines the boundaries for livestock production and consumption. Under this concept, the competition for land for feed or food would be minimized and compared to no ASF, including some ASF in the human diet could free up about one quarter of global arable land. Our results also demonstrate that restricted growth in consumption of ASF in Africa and Asia would be feasible under these boundary conditions, while reductions in the rest of the world would be necessary to meet land use sustainability criteria. Managing this expansion and contraction of future consumption of ASF is essential for achieving sustainable nutrition security.
Accessibility Measurement in Transportation Networks and Application to the Seoul Bus System
Authors: Lee Keumsook , Park Jong Soo , Goh Segun , Choi MooYoung
Published: May 2018

This study presents an algorithm for measuring the time‐distance accessibility based on the flow data of actual transportation networks and examines resulting accessibility distributions. Specifically, we construct an extended graph of the transportation network to take into account not only the average speed and transfer time extracted from the data set but also various possible trajectories taken via transfers. Employing the modified Floyd algorithm which finds the shortest time distance, we compute the time‐distance accessibility of every bus stop in the Seoul bus system, which yields distinctive skew distributions. We then introduce a time‐distance cutoff to focus on effective connections and probe the emergent spatial distributions as the cutoff is varied. Revealed are the characteristic scales as well as spatial structures of the system. It is suggested that the time‐distance accessibility can serve as a significant measure to describe and predict the urban land use pattern.
Sonic geographies: Themes, concepts, and deaf spots
Authors: Paiva Daniel
Published: May 2018

This article poses a straightforward question: What has geography been listening to? Sonic geographies have been established as a relevant subfield in Human Geography in the last decades. During this period, a significant amount of work has been published, but there are still few reviews of these works, and most of them focus solely on Anglophone geography. In this article, I attempt to address this gap by providing an overview of the themes and concepts that have been studied within the emerging subfield of sonic geographies. My intention is to reunite a large range of works that are becoming increasingly scattered and specialized, in order to make sense of the subfield as a whole. With this in mind, I am particularly interested in identifying the “deaf spots” of the subfield, that is, the subjects, concepts, or fields that have not yet been explored thoroughly by sonic geographies.
Use of proton pump inhibitors is associated with increased mortality due to nosocomial pneumonia in bedridden patients receiving tube feeding
Authors: Hamai Kosuke , Iwamoto Hiroshi , Ohshimo Shinichiro , Wakabayashi Yu , Ihara Daisuke , Fujitaka Kazunori , Hamada Hironobu , Ono Koichi , Hattori Noboru
Published: May 2018

Aim

To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding.

Methods

A total of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non‐PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan–Meier approach and the log–rank test.

Results

A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non‐PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2‐year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non‐PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups.

Conclusion

The use of PPI in bedridden tube‐fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non‐significant lower incidence of gastrointestinal bleeding than the non‐PPI group. Geriatr Gerontol Int 2018; 18: 1215–1218.
Metagenomic study of bacterial microbiota in persistent endodontic infections using Next‐generation sequencing
Authors: Sánchez‐Sanhueza G. , Bello‐Toledo H. , González‐Rocha G. , Gonçalves A. T. , Valenzuela V. , Gallardo‐Escárate C.
Published: May 2018

Aim

To determine the bacterial microbiota in root canals associated with persistent apical periodontitis and their relationship with the clinical characteristics of patients using next‐generation sequencing (NGS).

Methodology

Bacterial samples from root canals associated with teeth having persistent apical periodontitis were taken from 24 patients undergoing root canal retreatment. Bacterial DNA was extracted, and V3–V4 variable regions of the 16S rRNA gene were amplified. The amplification was deep sequenced by Illumina technology to establish the metagenetic relationships among the bacterial species identified. The composition and diversity of microbial communities in the root canal and their relationships with clinical features were analysed. Parametric and nonparametric tests were used to analyse differences between patient characteristics and microbial data.

Results

A total of 86 different operational taxonomic units (OTUs) were identified and Good's nonparametric coverage estimator method indicated that 99.9 ± 0.00001% diversity was recovered per sample. The largest number of bacteria belonged to the phylum Proteobacteria. According to the medical history from the American Society of Anesthesiologists (ASA) Classification System, ASA II–III had higher richness estimates and distinct phylogenetic relationships compared to ASA I individuals (P < 0.05). Periapical index (PAI) score 5 was associated with increased microbiota diversity in comparison to PAI score 4, and this index was reduced in symptomatic patients.

Conclusions

Based on the findings of this study, it is possible to suggest a close relationship between several clinical features and greater microbiota diversity with persistent endodontic infections. This work provides a better understanding on how microbial communities interact with their host and vice versa.
Residual thermal stresses prediction for CVD coating/substrate system based on a numerical model
Authors: Wang Yang , Chen Zhaofeng , Pan Ning , Li Binbin , Yu Shengjie , Cui Sheng
Published: May 2018

For a chemical vapor deposition (CVD) coating/substrate system, an improved and optimized numerical model is established to predict the residual thermal stresses. This model takes into account both the normal and bending strains and is developed based on the concept of a misfit strain between coating and substrate. Comparisons are presented between predictions from this model and from finite element analysis. The effects of coating thickness, elastic modulus, temperature difference, and multiple deposition on the residual stresses in the coating/substrate system have also been analyzed in detail. Furthermore, some confirmatory CVD SiC experiments with different layers have also been conducted according to the analysis model. The predictions that the multiple deposition system can relieve the residual thermal stresses and reduce the microcracks in the outermost coating effectively, are consistent with the numerical model.