bluuebunny/crossref_metadata_2025 huggingface dataset:
Language evolution to revolution: the leap from rich-vocabulary non-recursive communication system to recursive language 70,000 years ago was associated with acquisition of a novel component of imagination, called Prefrontal Synthesis, enabled by a mutation that slowed down the prefrontal cortex maturation simultaneously in two or more children – the Romulus and Remus hypothesis
Authors: Vyshedskiy Andrey
Published: July 2017

There is an overwhelming archeological and genetic evidence that modern speech apparatus was acquired by hominins by 600,000 years ago1. On the other hand, artifacts signifying modern imagination, such as (1) composite figurative arts, (2) bone needles with an eye, (3) construction of dwellings, and (4) elaborate burials arose not earlier than 70,000 years ago2. It remains unclear (1) why there was a long gap between acquisition of modern speech apparatus and modern imagination, (2) what triggered the acquisition of modern imagination 70,000 years ago, and (3) what role language might have played in this process. Our research into evolutionary origin of modern imagination has been driven by the observation of a temporal limit for the development of a particular component of imagination. Modern children not exposed to recursive language in early childhood never acquire the type of active constructive imagination called Prefrontal Synthesis (PFS). Unlike vocabulary and grammar acquisition, which can be learned throughout one’s lifetime, there is a strong critical period for the development of PFS and individuals not exposed to recursive language in early childhood can never acquire PFS as adults. Their language will always lack understanding of spatial prepositions and recursion that depend on the PFS ability. In a similar manner, early hominins would not have been able to learn recursive language as adults and, therefore, would not be able to teach recursive language to their children. Thus, the existence of a strong critical period for PFS acquisition creates an evolutionary barrier for behavioral modernity. An evolutionary mathematical model suggests that a synergistic confluence of three events (1) a genetic mutation that extended the critical period by slowing down the prefrontal cortex development simultaneously in two or more children, (2) invention of recursive elements of language, such as spatial prepositions, by these children and (3) their dialogic communications using these recursive elements, resulted in concurrent conversion of a non-recursive communication system of their parents to recursive language and acquisition of PFS around 70,000 years ago.
Genome-wide divergence among invasive populations ofAedes aegyptiin California
Authors: Lee Yoosook , Schmidt Hanno , Collier Travis C. , Conner William R. , Hanemaaijer Mark J. , Slatkin Montgomery , Marshall John M. , Chiu Joanna C. , Smartt Chelsea T. , Lanzaro Gregory C. , Mulligan F. Steve , Cornel Anthony J.
Published: July 2017

In the summer of 2013,Aedes aegyptiLinnaeus was first detected in three cities in central California (Clovis, Madera and Menlo Park). It has now been detected in multiple locations in central and southern CA as far south as San Diego and Imperial Counties. A number of published reports suggest that CA populations have been established from multiple independent introductions. Here we report the first population genomics analyses ofAe. aegyptibased on individual, field collected whole genome sequences. We analyzed 46Ae. aegyptigenomes to establish genetic relationships among populations from sites in California, Florida and South Africa. We identified 3 major genetic clusters within California; one that includes all sample sites in the southern part of the state (South of Tehachapi mountain range) plus the town of Exeter in central California and two additional clusters in central California. A lack of concordance between mitochondrial and nuclear genealogies suggests that the three founding populations were polymorphic for two main mitochondrial haplotypes prior to being introduced to California. One of these has been lost in the Clovis populations, possibly by a founder effect. Genome-wide comparisons indicate extensive differentiation between genetic clusters. Our observations support recent introductions ofAe. aegyptiinto California from multiple, genetically diverged source populations. Our data reveal signs of hybridization among diverged populations within CA. Genetic markers identified in this study will be of great value in pursuing classical population genetic studies which require larger sample sizes.
Structural elucidation of a hydroxy–cineole product obtained from cytochrome P450 monooxygenase CYP101J2 catalysed transformation of 1,8-cineole
Authors: Collis Gavin E. , Unterweger Birgit , Dumsday Geoff J. , Forsyth Craig M.
Published: July 2017

1,8-Cineole is an abundant natural product that has the potential to be transformed into other building blocks that could be suitable alternatives to petroleum-based chemicals. Monohydroxylation of 1,8-cineole can potentially occur at eight different carbon sites around the bicyclic ring system. Using cytochrome P450 monooxygenase CYP101J2 from Sphingobium yanoikuyae B2, the hydroxylation can be regioselectively directed at the C atom adjacent to the methyl-substituted quaternary bridgehead atom of 1,8-cineole. The unambiguous location of the hydroxyl functionality and the stereochemistry at this position was determined by X-ray crystal analysis. The monohydroxylated compound derived from this microorganism was determined to be (1S)-2a-hydroxy-1,8-cineole (trivial name) or (1S,4R,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol (V) (systematic), C10H18O2. In the solid state this compound exhibits an interesting O—H...O hydrogen-bonding motif.
Crystal structure and Hirshfeld surface analysis of diaquabis(isonicotinamide-κN)bis(2,4,6-trimethylbenzoato-κO
1)nickel(II) dihydrate
Authors: Hökelek Tuncer , Sertkaya Gizem , Ay Ezgi , Özkaya Safiye , Necefoğlu Hacali
Published: July 2017

In the title NiII complex, [Ni(C10H11O2)2(C6H6N2O)2(H2O)2]·2H2O, the divalent Ni ion occupies a crystallographically imposed centre of symmetry and is coordinated by two O atoms from the carboxylate groups of two 2,4,6-trimethylbenzoate (TMB) ligands [Ni—O = 2.0438 (12) Å], two N atoms from the pyridyl groups of two isonicotinamide (INA) ligands [Ni—N = 2.1506 (15) Å] and two water molecules [Ni—O = 2.0438 (12) Å] in a slightly distorted octahedral geometry. The coordinating water molecules are hydrogen bonded to the non-coordinating carboxylate O atom of the TMB ligand [O...O = 2.593 (3) Å], enclosing an S(6) hydrogen-bonding motif. Two solvent water molecules are also present in the formula unit. In the crystal, a network of intermolecular N—H...O and O—H...O hydrogen bonds link the complexes into a three-dimensional array. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H...H (59.8%), O...H/H...O (20.2%) and C...H/H...C (13.7%) interactions.
6-Chloro-1,4-diethylquinoxaline-2,3(1H,4H)-dione
Authors: El Janati Ali , Kandri Rodi Youssef , Jasinski Jerry P. , Kaur Manpreet , Ouzidan Younes , Essassi El Mokhtar
Published: July 2017

In the title compound, C12H13ClN2O2, the terminal C atoms of the ethyl groups deviate from the mean plane of the quinoxaline-2,3(1H,4H)-dione ring (r.m.s. deviation = 0.016 Å) in opposite directions by −1.451 (2) and 1.472 (2) Å. In the crystal, weak C—H...O interactions link the molecules into [100] chains and aromatic π–π stacking interactions [shortest centroid–centroid separation = 3.6631 (9) Å] are also observed.
Tracking restoration of population diversity via the portfolio effect
Authors: Yamane Lauren , Botsford Louis W. , Kilduff D. Patrick
Published: July 2017

Declines in diversity among populations managed together have diminished aggregate stability through a decreased portfolio effect. Although the portfolio effect has been quantified in a variety of ways, management recommendations for the recovery of lost diversity rarely specify the stability benefits possible through such improvements.

We introduce a metric, the Diversity Deficit (DD), that relates past losses and potential gains in aggregate stability to the changes in population diversity (i.e. covariability among population time series). We illustrate the use of this metric in retrospective analyses of the aggregate Sacramento River Fall‐run Chinook salmon stock (Oncorhynchus tshawytscha), and project potential future improvements in stability through population diversity.

In the retrospective analysis, we removed individual time series from the stability calculations to determine their effects on times and locations of past losses in diversity and stability. We found an early threefold loss in stock stability resulting from the presence of a single tributary, the Sacramento River mainstem. Other shifts in stability resulted from an increase in variability of a single population, and from the synchronizing effects of low ocean survival that led to the 2008–2009 fishery closure. Only one, smaller increase in the DD (i.e. in lost stability) was due to portfolio‐wide increases in covariabilities among tributary abundances.

In a prospective analysis using the DD applied to California salmon, we found that increasing biodiversity to the point of population independence and to its early high value would have reduced the probability of triggering a fishery closure.

Synthesis and applications. Analyses with the Diversity Deficit (DD) metric illustrate a way to identify the times and locations of losses in population diversity, and to quantify how much restoration of population diversity could increase stability, and thus benefit resource services. In our research, the benefit was a reduction in the probability of falling below a critical management threshold leading to fishery closure, but other tangible benefits (e.g. reduction in probability of extinction) would also be possible.
Overyielding in young tree plantations is driven by local complementarity and selection effects related to shade tolerance
Authors: Van de Peer Thomas , Verheyen Kris , Ponette Quentin , Setiawan Nuri N. , Muys Bart
Published: July 2017

Overyielding in mixed‐species forests has been demonstrated in a vast body of literature, and the focus of functional biodiversity research is now shifting towards a mechanistic understanding of these observations.

We explored diversity–productivity relationships at two sites of a large‐scale tree diversity experiment, with harsh (Ged) and benign (Zed) environmental conditions for plantation establishment. Additive partitioning methodologies were adopted to detect phenomenological patterns in the productivity data, and the trait structure of mixed communities was used to advance insights into compositional effects.

After 6 years of plantation development, biomass productivity was significantly higher in mixtures compared to the monocultures of component species. We observed that processes operated through direct tree–tree interactions, as the diversity signal disappeared where trees in mixed stands were surrounded by conspecific neighbours only. This result is particularly relevant for mixed‐species plantation systems, as trees are commonly planted in monospecific patches to simplify management.

Partitioning unveiled strong selection effects at both plantation sites. However, at the harsh Ged‐site this was caused by competitive dominance of species with fast young growth, whereas at the benign Zed‐site, species with slow young growth improved their performances but not at the expense of others (i.e. trait‐dependent complementarity). Species tolerance to shading is an influential trait for predicting biodiversity effects, with community‐weighted means in shade tolerance mediating dominance effects (Ged) and functional diversity in shade tolerance mediating (trait‐dependent) complementarity effects (Zed).

Synthesis. This study highlights that biodiversity effects in young tree plantations could be explained by the functional composition of mixed communities, with a key role for species levels of shade tolerance. As contrasting results between plantation sites were observed, future research should target the context‐dependency of diversity–productivity relationships.
The role of species pools in determining species diversity in spatially heterogeneous communities
Authors: Ron Ronen , Fragman‐Sapir Ori , Kadmon Ronen
Published: July 2017

The “habitat‐specific species pool hypothesis” proposes that differences between habitats in the sizes of their species pools are the main drivers of diversity responses to habitat heterogeneity. Empirical tests of this hypothesis are not trivial as species might be missing from ecologically suitable habitats due to limited dispersal, while others may occur in unsuitable habitats by means of source–sink dynamics and mass effect.

We tested the habitat‐specific species pool hypothesis in a local, environmentally heterogeneous community of annual plants using a novel “ecological selection” experiment. Mixtures of seeds representing the whole community were sown in each habitat, and the emerging species were exposed to six generations of selection by environmental filtering and competition while being blocked from dispersal. A comparison of the total number of species that were able to survive in each habitat (i.e. to pass the selection test) with data on species richness in the natural community allowed us to test the degree to which observed differences in species richness between habitats could be explained by differences in the sizes of the respective species pools.

Results supported the species pool hypothesis, showing that differences in the sizes of the habitat‐specific species pools were important in determining diversity responses to habitat heterogeneity. Moreover, species richness showed a unimodal response to local‐scale gradients in habitat productivity, and this response could be attributed to underlying differences in species pool sizes. Both results were robust to properties of the data and the method of analysis.

Synthesis. Our results provide a strong experimental evidence that differences in the sizes of habitat‐specific species pools might be important in shaping the diversity of local communities. Future theoretical and empirical studies in community ecology should explore the potential sources and implications of such differences.
Effects of nitric oxide on large‐conductance Ca2+‐activated K+ currents in human cardiac fibroblasts through PKA and PKG‐related pathways
Authors: Bae Hyemi , Lim Inja
Published: July 2017

The human cardiac fibroblast (HCF) is the most abundant cell type in the myocardium, and HCFs play critical roles in maintaining normal cardiac function. However, unlike cardiomyocytes, the electrophysiology of HCFs is not well established. In the cardiovascular system, Ca2+‐activated K+ (KCa) channels have distinct physiological and pathological functions, and nitric oxide (NO) plays a key role. In this study, we investigated the potential effects of NO on KCa channels in HCFs. We recorded strong oscillating, well‐maintained outward K+ currents without marked inactivation throughout the test pulse period and detected outward rectification in the I‐V curve; these are all characteristics that are typical of KCa currents. These currents were blocked with iberiotoxin (IBTX, a BKCa blocker) but not with TRAM‐34 (an IKCa blocker). The amplitudes of the currents were increased with SNAP (an NO donor), and these increases were inhibited with IBTX. The SNAP‐stimulating effect on the BKCa currents was blocked by pretreatment with KT5823 (a protein kinase G [PKG] inhibitor) or 1 H‐[1,‐2, ‐4] oxadiazolo‐[4,‐3‐a] quinoxalin‐1‐one (ODQ; a soluble guanylate cyclase inhibitor). Additionally, 8‐bromo‐cyclic guanosine 3’,5’‐monophosphate (8‐Br‐cGMP) stimulated the BKCa currents, and pretreatment with KT5720 (a protein kinase A [PKA] inhibitor) and SQ22536 (an adenylyl cyclase inhibitor) blocked the NO‐stimulating effect on the BKCa currents. Furthermore, 8‐bromo‐cyclic adenosine 3’,5’‐monophosphate (8‐Br‐cAMP) activated the BKCa currents. These data suggest that BKCa current is the main subtype of the KCa current in HCFs and that NO enhances these currents through the PKG and PKA pathways.
Growth inhibitory effect of β‐eudesmol on cholangiocarcinoma cells and its potential suppressive effect on heme oxygenase‐1 production, STAT1/3 activation, and NF‐κB downregulation
Authors: Mathema Vivek B , Chaijaroenkul Wanna , Karbwang Juntra , Na‐Bangchang Kesara
Published: July 2017

Cholangiocarcinoma (CCA) is a progressively fatal form of cancer originating from the malignant transformation of hepatic biliary cholangiocytes. The present study reports for the first time in vitro growth inhibitory activities of β‐eudesmol, the bioactive sesquiterpenoid present in the rhizome of Atractylodes lancea (Thunb) DC., with respect to its underlying potential effects on heme oxygenase‐1 (HO‐1) production, STAT1/3 phosphorylation, and NF‐κB protein expression in human CCA cell line CL‐6. The cytotoxic effect of β‐eudesmol on CL‐6 cells was evaluated by MTT assay using normal human embryonic fibroblast (OUMS) as a control cell line. Results indicated that β‐eudesmol exhibited selective cytotoxicity towards CL‐6 compared to OUMS with mean (±SD) IC50 (concentration that inhibits cell growth by 50%) values of 166.75 ± 3.69 and 240.01 ± 16.54 μmol/L, respectively. In addition, it also significantly suppressed colony forming and wound healing ability of CL‐6 cells in a concentration‐dependent manner. Western blot analysis indicated that β‐eudesmol treatment resulted in significant suppression of HO‐1 production in CL‐6 cells. Its inhibitory effects on the phosphorylation of STAT1/3 proteins and expression of NF‐κB (p65 and p50) proteins were concentration‐dependent. Taken together, these results suggest that β‐eudesmol exerts significant growth inhibitory activity on CL‐6 cells that may be linked to its inhibitory effect on the production of HO‐1, phosphorylation of STAT1/3, and expression of major NF‐κB proteins.
Specific α7 nicotinic acetylcholine receptor agonist ameliorates isoproterenol‐induced cardiac remodelling in mice through TGF‐β1/Smad3 pathway
Authors: Yang Yong‐Hua , Fang Huan‐Le , Zhao Ming , Wei Xiang‐Lan , Zhang Ning , Wang Shun , Lu Yi , Yu Xiao‐Jiang , Sun Lei , He Xi , Li Dong‐Ling , Liu Jin‐Jun , Zang Wei‐Jin
Published: July 2017

It is well‐accepted that inflammation plays an important role in the development of cardiac remodelling and that therapeutic approaches targeting inflammation can inhibit cardiac remodelling. Although a large amount of evidence indicates that activation of α7 nicotinic acetylcholine receptor (α7nAChR) causes an anti‐inflammatory effect, the role of α7nAChR in cardiac remodelling and the underlying mechanism have not been established. To investigate the effect of the specific α7nAChR agonist, PNU282987, on cardiac remodelling induced by isoproterenol (ISO 60 mg/kg per day) in mice, the cardiomyocyte cross‐sectional area (CSA) and collagen volume fraction were evaluated by hematoxylin and eosin (HE) and Masson staining, respectively. Cardiac function and ventricular wall thickness were measured by echocardiography. The protein expressions of collagen I, matrix metalloproteinase 9 (MMP‐9), transforming growth factor β1 (TGF‐β1), and Smad3 were analyzed by Western blot. ISO‐induced cardiac hypertrophy, characterized by an increase in the heart weight/body weight ratio, CSA and ventricular wall thickness. Moreover, cardiac fibrosis indices, such as collagen volume fraction, MMP‐9 and collagen I protein expression, were also increased by ISO. PNU282987 not only attenuated cardiac hypertrophy but also decreased the cardiac fibrosis induced by ISO. Furthermore, PNU282987 suppressed TGF‐β1 protein expression and the phosphorylation of Smad3 induced by ISO. In conclusion, PNU282987 ameliorated the cardiac remodelling induced by ISO, which may be related to the TGF‐β1/Smad3 pathway. These data imply that the α7nAChR may represent a novel therapeutic target for cardiac remodelling in many cardiovascular diseases.
Transcriptomic insights into the alternative splicing‐mediated adaptation of the entomopathogenic fungus Beauveria bassiana to host niches: autophagy‐related gene 8 as an example
Authors: Dong Wei‐Xia , Ding Jin‐Li , Gao Yang , Peng Yue‐Jin , Feng Ming‐Guang , Ying Sheng‐Hua
Published: July 2017

Alternative splicing (AS) regulates various biological processes in fungi by extending the cellular proteome. However, comprehensive studies investigating AS in entomopathogenic fungi are lacking. Based on transcriptome data obtained via dual RNA‐seq, the first overview of AS events was developed for Beauveria bassiana growing in an insect haemocoel. The AS was demonstrated for 556 of 8840 expressed genes, accounting for 5.4% of the total genes in B. bassiana. Intron retention was the most abundant type of AS, accounting for 87.1% of all splicing events and exon skipping events were rare, only accounting for 2.0% of all events. Functional distribution analysis indicated an association between alternatively spliced genes and several physiological processes. Notably, B. bassiana autophagy‐related gene 8 (BbATG8), an indispensable gene for autophagy, was spliced at an alternative 5′ splice site to generate two transcripts (BbATG8‐α and BbATG8‐β). The BbATG8‐α transcript was necessary for fungal autophagy and oxidation tolerance, while the BbATG8‐β transcript was not. These two transcripts differentially contributed to the formation of conidia or blastospores as well as fungal virulence. Thus, AS acts as a powerful post‐transcriptional regulatory strategy in insect mycopathogens and significantly mediates fungal transcriptional adaption to host niches.
The importance of adoption of formal client feedback in therapy: a narrative review
Authors: Lappan Sara , Shamoon Zain , Blow Adrian
Published: July 2017

Couple and family therapy has well‐established benefits. Although the majority of clients benefit, some worsen, some show no positive change, and some drop out early. This suggests that existing treatment modalities require further advancement. One promising avenue to achieve advancement involves instituting, as the standard of care, formalized client feedback, which has been shown to improve outcomes. This paper is a non‐systematic review that outlines several formalized feedback systems currently available and highlights each system's utility with application to couple and family therapy. While couple and family therapists have unique obstacles in therapy due to multiple therapeutic alliances, the use of formalized feedback has potential to strengthen alliances and improve outcomes for all clients who participate. We advocate for the use of formalized feedback in the training of new therapists and to augment the supervision process.

Practitioner points

Encourage the couple and family therapy field to implement the use of formalized client feedback systems both clinically and in research

Demonstrate the importance of implementing formalized client feedback systems to decrease premature termination and improve client outcomes

Provide information about existing client feedback systems to give practitioners the opportunity to choose a method that most benefits their clients
The Automation of Regression Modeling in Osteometric Sorting: An Ordination Approach
Authors: Lynch Jeffrey James
Published: July 2017

This study compares the original osteometric sorting association method with an ordination approach across all combinations of the humerus, ulna, radius, femur, tibia, and fibula. This includes both the original prediction interval and t‐statistic approaches. Standard measurements are utilized in the models with full measurements combined and without length measurements. The sample is the osteometric sorting reference from the Defense POW/MIA Accounting Agency. A full set of performance statistics is provided. Results indicate the ordination approach outperforms the original in the majority of bone combinations. Models with length measurements have more exclusion power than those without. It is recommended for the ordination approach to supersede the original when applied to large commingled assemblages.
Do assortative mating and immigrant inviability help maintain population genetic structuring of an herbivore on a crop and a wild relative?
Authors: Ramirez‐Romero Ricardo , Garibay‐Benítez Delia , Vargas‐Ponce Ofelia , Joyce Andrea , Bernal Julio S.
Published: July 2017

Population genetic structuring is common among herbivorous insects and frequently is associated with divergent host plants, such as crops and their wild relatives. Previous studies showed population genetic structuring in corn leafhopper Dalbulus maidis in Mexico, such that the species consists of two sympatric, host plant‐associated populations: an abundant and widespread “pestiferous” population on maize (Zea mays mays), and a small and localized “wild” population on perennial teosinte (Zea diploperennis), a maize wild relative with a limited distribution. This study addressed whether assortative mating and immigrant inviability mediate genetic structuring of corn leafhopper by comparing the mating and reproductive successes of pestiferous and wild females that colonize their nonassociated host plants against the successes of females colonizing their associated host plants. Assortative mating was assessed by comparing mating frequencies and premating and mating times among females of each population on each host plant; immigrant inviability was assessed by comparing, across two generations, the fecundity, survival, development time, sex ratio, and population growth rate among leafhopper populations and host plants. Our results showed that on maize, and compared to resident, pestiferous females, wild females were more likely to mate, and greater proportions of their offspring survived to adult stage and were daughters; consequently, the per‐generation population growth rate on maize was greater for immigrant, wild leafhoppers compared to resident, pestiferous leafhoppers. Our results suggested that wild leafhoppers emigrating to maize have a fitness advantage over resident, pestiferous leafhoppers, while immigrant pestiferous and resident wild leafhoppers on teosinte have similar fitnesses.
Inhibition of Shigella sonnei and Shigella flexneri in Hummus Using Citric Acid and Garlic Extract
Authors: Olaimat Amin N. , Al‐Holy Murad A. , Abu‐Ghoush Mahmoud H. , Osaili Tareq M. , Al‐Nabulsi Anas A. , Rasco Barbara A.
Published: July 2017

Hummus (chickpea dip) is a ready‐to‐eat product that may pose a significant risk to human if pathogens are present. Several organisms including Shigella spp. have been isolated from hummus. However, studies on the survival and inhibition of Shigella spp. in food are scarce. This study investigated the growth pattern of Sh. sonnei and Sh. flexneri in hummus at different temperatures (4, 10, and 24 °C). Additionally, the inhibitory activity of different concentrations of citric acid (CA) (0.5%, 1.0%, and 2.0%) and garlic extract (GE) (1.0%, 2.0%, and 3.0%) against Sh. sonnei and Sh. flexneri inoculated into hummus and stored at 4 and 10 °C was investigated. Both Shigella spp. survived well at 4 °C, while both grew to >7.0 log10 after 4 d at 10 °C or 1 d at 24 °C. At 4 °C, CA at 0.5% and 1.0% resulted in a slight reduction in the count (approximately 1.0 log10); a complete elimination of Sh. sonnei was attained by using 2.0% CA. However, approximately 3.0 log10 reduction in Sh. sonnei was obtained at 10 °C. For Sh. flexneri, CA at 0.5% and 1.0% resulted in a bacteriostatic inhibition. GE at 1.0% and 2.0% resulted in approximately 1.0 to 2.0 log10 reduction in Sh. sonnei count at 4 °C, while at 3.0% GE, approximately 4.0 and 3.0 log10 reductions were obtained at 4 and 10 °C, respectively. In comparison, the 2.0% and 3.0% GE resulted in a bacteriostatic effect against Sh. flexneri at 4 and 10 °C.
Efficacy of abatacept in patients with rheumatoid arthritis, as assessed by magnetic resonance imaging of bilateral hands
Authors: Kukida Yuji , Kasahara Akiko , Seno Takahiro , Inoue Takuya , Sagawa Risa , Kida Takashi , Nakabayashi Amane , Nagahara Hidetake , Murakami Ken , Sugitani Toshifumi , Morita Satoshi , Ito Hirotoshi , Oda Ryo , Fujiwara Hiroyoshi , Kohno Masataka , Kawahito Yutaka
Published: July 2017

Aim

To examine the efficacy of abatacept in patients with rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of bilateral hands.

Method

This prospective study included 35 RA patients. MRI of bilateral hands was performed at baseline and after 12 months of treatment with intravenous abatacept. MRI images were scored for synovitis, osteitis, erosion and joint space narrowing (JSN) according to the RA MRI Scoring System (RAMRIS). The primary endpoint was the change in RAMRIS score from baseline. Repair of erosion was defined as a negative change in the erosion score that was greater than the smallest detectable changes (SDCs).

Results

Thirty‐one patients completed the study. Median synovitis and osteitis scores showed statistically significant reductions at Month 12 when compared to baseline (synovitis score, −5.5 [P < 0.0001]; osteitis score, −0.5 [P = 0.03]). However, median erosion and JSN scores did not significantly change. At Month 12, 83% of patients showed no progression of erosion scores and repair of erosion was observed in 11% of patients. All patients with repair of erosion achieved functional remission (Health Assessment Questionnaire‐Disability Index ≤ 0.5). The Simplified Disease Activity Index response rate at Month 1 was identified as an independent factor predicting changes in the erosion scores at Month 12.

Conclusion

Abatacept treatment reduced synovitis and osteitis scores and did not worsen erosion and JSN scores at Month 12. Over 10% of patients experienced repair of erosion.
Influence of trainee involvement on procedural characteristics for linear endobronchial ultrasound
Authors: Nguyen Sébastien , Ferland Nancy , Beaudoin Stéphane , Martel Simon , Simon Mathieu , Laberge Francis , Lampron Noel , Fortin Marc , Delage Antoine
Published: July 2017

Background

Linear endobronchial ultrasound (EBUS) is a safe and effective method for the diagnostic sampling of mediastinal lymph nodes. However, there is a learning curve associated with the procedure and operator experience influences diagnostic yield. We sought to determine if trainee involvement during EBUS influences procedural characteristics, complication rate, and diagnostic yield.

Methods

We performed a retrospective analysis of 220 subjects who underwent an EBUS procedure at our center from December 2012 to June 2013. Procedures were performed by six different interventional pulmonologists with substantial experience with EBUS or by a trainee under their direct supervision. Procedural characteristics and complications were recorded. Diagnostic yield and specimen adequacy were compared between groups.

Results

EBUS was performed in 220 patients with a trainee involved (n = 116) or by staff physician alone (n = 104). Patient characteristics, and the number and size of lymph node stations sampled were similar. EBUS duration was longer (16.0 vs. 13.7 minutes; P = 0.002) and the total dose of lidocaine used was higher (322.3 vs. 304.2 mg; P = 0.045) when a trainee was involved. The rate of adequate specimens sampled was comparable between the groups (92.0 vs. 92.0%; P = 0.60). Diagnostic yield was lower when a trainee was involved in the EBUS procedure (52.6 vs. 68.3%; P = 0.02).

Conclusion

Trainee involvement significantly increased EBUS duration and the dose of local anesthesia used for the procedure. Diagnostic yield was lower when a trainee was involved. Factors accounting for this difference in yield, despite adequate samples being obtained, warrant further investigation.
Hartmann's reversal: a comparative study between laparoscopic and open approaches
Authors: Kwak Han Deok , Kim Jin , Kang Dong Woo , Baek Se‐Jin , Kwak Jung Myun , Kim Seon‐Hahn
Published: July 2017

Background

A reversal of Hartmann's procedure can be performed using either a laparoscopic or open approach. However, laparoscopic reversal (LR) of Hartmann's procedure is challenging. This study was designed to compare the results between open and laparoscopic approaches.

Methods

This was a retrospective study of prospectively collected data. We analysed 29 patients who received Hartmann's reversal at Korea University Anam Hospital between April 2007 and September 2014. All patients underwent either LR (n = 17) or open reversal (OR, n = 12).

Results

Patient characteristics were similar between the LR and OR groups. There was also no difference in mean operation time (212.5 versus 251.8 min), diversion ileostomy, length of hospital stay, postoperative analgesic days, time to diet resumption (3.9 versus 6.2 days) or complication rate. Although the time to resuming a solid diet was not different between the two groups (P = 0.053), bowel movement occurred faster in LR patients (LR versus OR, 1.8 versus 2.8 days, P = 0.020). Patients in the LR group also had less blood loss during surgery (114.1 versus 594.2 mL, P = 0.026). There were no mortalities in this study.

Conclusion

LR of Hartmann's procedure resulted in faster bowel function recovery than the open method. Laparoscopic approaches are feasible even for patients who received an open Hartmann's procedure.
Interleukin 17A gene polymorphism rs2275913 is associated with osteitis after the Bacillus Calmette‐Guérin vaccination
Authors: Liehu‐Martiskainen Milla , Korppi Matti , Teräsjärvi Johanna , Vuononvirta Juho , Huhtala Heini , Nuolivirta Kirsi , Kröger Liisa , Peltola Ville , Pöyhönen Laura , He Qiushui
Published: July 2017

Aim

Interleukin‐17 (IL‐17) appears to promote the host's defence against mycobacterial infections. This study evaluated the association between IL17A gene polymorphism and the risk of Bacillus Calmette‐Guérin (BCG) osteitis after newborn vaccination and between IL17A gene polymorphism and IL‐17A concentrations in serum.

Methods

IL17A rs2275913 gene polymorphisms and serum IL‐17A concentrations were studied in 132 adults aged 21–49 years from across Finland, who had BCG osteitis in infancy after a newborn BCG vaccination. The subjects were recruited in 2007–2008, and their whole‐blood samples were sent to the National Institute for Health and Welfare, Turku, Finland. Their genotypes and minor allele frequencies were compared with 405 population‐based unvaccinated controls aged two to three months from a prospective birth cohort study.

Results

The genotypes and allele frequencies of IL17A rs2275913 differed significantly between the former BCG osteitis patients and controls. The genotype was variant in 75.8% of cases and 64.0% of controls (p = 0.012), and the minor allele frequency was 50.0% in the cases and 41.6% of the controls (p = 0.009). Serum IL‐17 concentrations did not differ significantly between the cases with wild or variant genotypes.

Conclusion

IL17A rs2275913 gene polymorphism was associated with a risk of BCG osteitis after vaccination.
Supplementation of protease, alone and in combination with fructooligosaccharide to low protein diet for finishing pigs
Authors: Lei Xin Jian , Cheong Jin Young , Park Jae Hong , Kim In Ho
Published: July 2017

Effects of adding protease with or without fructooligosaccharide (FOS) to low protein diet on growth performance, nutrient digestibility and fecal noxious gas emission were evaluated in 160 finishing pigs (57.70 ± 1.16 kg) in a 9‐week study. Pigs were randomly divided into four dietary treatments, PC: positive control diet (15.97% crude protein (CP)); NC: negative control diet (12.94% CP); PRO: NC supplemented with 0.05% protease; PROFOS: NC supplemented with 0.05% protease and 0.1% FOS. During weeks 4–9 and weeks 0–9, gain : feed ratio was impaired (P < 0.05) in pigs fed NC diet compared with those fed PC, PRO and PROFOS diets. Pigs fed PC, PRO and PROFOS diets had higher (P < 0.05) apparent total tract digestibility (ATTD) of CP than pigs fed NC diet. Pigs fed PROFOS diet had reduced (P < 0.05) ammonia emissions compared to pigs fed NC and PRO diets. These data indicate that reducing dietary CP concentrations impaired growth performance, decreased ATTD of CP and reduced ammonia emissions. Supplementation of protease in low CP diet improved growth performance and increased ATTD of CP. Dietary supplementation with protease and FOS in low CP diet improved growth performance, increased ATTD of CP and decreased fecal ammonia emission.
Different thermotolerances in in vitro‐produced embryos derived from different maternal and paternal genetic backgrounds
Authors: Sakatani Miki , Yamanaka Kenichi , Balboula Ahmed Zaky , Takahashi Masashi
Published: July 2017

The present study evaluated the effects of genetic backgrounds on the developmental competence and thermotolerance of bovine in vitro‐produced (IVP) embryos. First, Holstein (Hol) and Japanese Black (JB) oocytes were fertilized with sperm from Hol, JB and a thermotolerant breed (Brahman), and in vitro development was evaluated when the embryos were exposed to heat shock on Day 2 (Day 0 = day of fertilization). Sperm genetic backgrounds affected the developmental competence in controls (P < 0.05). Second, the effect of sperm pre‐incubation for 4 h on subsequent in vitro fertilization was assessed using different sperm genetic backgrounds. The pre‐incubation of sperm did not decrease the embryonic development regardless of the breed of the sperm. A milder heat shock (40.0°C) effect on parthenotes (Hol and JB) and IVP embryos were evaluated. JB parthenotes showed developmental arrest after Day 4, and the rate of development to the blastocyst stage decreased by heat shock, but not in Hol parthenotes. Heat shock decreased developmental competence after cleavage of IVP embryos regardless of genetic background. The thermotolerance of IVP embryos would be controlled by both maternal and paternal factors but genetic involvement was still unclear. Further evaluation is needed to reveal the genetic contribution to thermotolerance.
CD155, an onco‐immunologic molecule in human tumors
Authors: Gao Jian , Zheng Qianqian , Xin Na , Wang Wei , Zhao Chenghai
Published: July 2017

CD155 is the fifth member in the nectin‐like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as necl‐5, or PVR. As an immunoglobulin‐like adhesion molecule, CD155 is involved in cell motility, and natural killer and T cell‐mediated immunity. CD155 is barely or weakly expressed in various normal human tissues, but frequently overexpressed in human malignant tumors. CD155 overexpression promotes tumor cell invasion and migration, and is associated with tumor progression and poor prognosis. As the ligand for both costimulatory receptor CD226 and coinhibitory receptor TIGIT and CD96 on natural killer and T cells, CD155 seems to play a dual role in oncoimmunity. However, some recent studies indicate that CD155 overexpression may induce tumor immune escape. Taken together, CD155 may be considered as a target for the treatment of tumors with CD155 overexpression.
Prospective observational study of carbon‐ion radiotherapy for non‐squamous cell carcinoma of the head and neck
Authors: Shirai Katsuyuki , Saitoh Jun‐ichi , Musha Atsushi , Abe Takanori , Kobayashi Daijiro , Takahashi Takeo , Tamaki Tomoaki , Kawamura Hidemasa , Takayasu Yukihiro , Shino Masato , Toyoda Minoru , Takahashi Katsumasa , Hirato Junko , Yokoo Satoshi , Chikamatsu Kazuaki , Ohno Tatsuya , Nakano Tatsuya ,   the Working Group on Head and Neck Tumors
Published: July 2017

To evaluate the efficacy and safety of carbon‐ion radiotherapy for non‐squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end‐point was the 3‐year local control rate, and the secondary end‐points included the 3‐year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow‐up time for all patients was 39 months. Thirty‐two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3‐year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2–3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon‐ion radiotherapy achieved excellent local control and overall survival rates for non‐squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.
Family Functioning and Children's Sleep
Authors: El‐Sheikh Mona , Kelly Ryan J.
Published: July 2017

Sleep is a pivotal correlate and predictor of many domains of child development, including socioemotional adjustment, physical health, and cognitive functioning. The family plays a major role in shaping children's sleep–wake behaviors, and developmental research on children's sleep in a family context is on the rise. As in any relatively young field, many gaps and questions remain. In this article, we aim to advance this literature by illustrating ways to examine the interconnections between family functioning and children's sleep. We also call for increasing conceptual developments and testing of transactional models, using well‐established and psychometrically sound objective and subjective measures, and expanding both the family functioning domains and sleep parameters assessed.
Prevalence of nickel allergy in Europe following the EU Nickel Directive – a review
Authors: Ahlström Malin G. , Thyssen Jacob P. , Menné Torkil , Johansen Jeanne D.
Published: July 2017

Nickel contact allergy remains a problem in EU countries, despite the EU Nickel Directive. To study the prevalence of nickel allergy in EU countries following the implementation of the EU Nickel Directive, we performed a systematic search in PubMed for studies that examined the prevalence of nickel allergy in EU countries published during 2005–2016. We identified 46 studies: 10 in the general population and 36 in patch tested dermatitis patients. A significantly lower prevalence of nickel allergy after than before the implementation of the EU Nickel Directive was found in women aged 18–35 years (11.4% versus 19.8%) (p = 0.02), in female dermatitis patients aged ≤17 years (14.3% versus 29.2%) (p < 0.0001), and in dermatitis patients aged 18–30 years (women: 20.2% versus 36.6%) (p < 0.0001) (men: 4.9% versus 6.6%) (p < 0.0001). Overall, the prevalence was higher in southern than in northern EU countries, and generally remained high, affecting 8–18% of the general population. A consistent pattern of decreasing prevalence of nickel allergy in some EU countries was observed, although the prevalence among young women remains high. Steps should be taken for better prevention of nickel allergy in EU countries.
UMBRELLA DAMAGES: TOWARD A COHERENT ANTITRUST POLICY
Authors: Blair Roger D. , Durrance Christine Piette
Published: July 2017

Price‐fixing cartels usually do not involve all members of an industry. To the extent that the nonconspiring industry members set their prices under the price umbrella of the cartel, the customers of the nonconspiring firms suffer overcharges just like customers of the conspiring firms. Whether these so‐called umbrella plaintiffs have standing to sue for antitrust damages is an unresolved policy question, because the Supreme Court has not spoken on “umbrella damages.” In this article, we identify the judicial concerns regarding umbrella damage claims, which can be traced to Mid‐West Paper and Petroleum Products Antitrust Litigation. These decisions raise concerns that the fact of injury is conjectural and the measurement of the damages is speculative. We first review the divided judicial treatment of standing for umbrella plaintiffs. Next, we describe the economics of umbrella pricing, which reveals that umbrella claims are not inherently conjectural. We then examine the econometric analysis necessary to estimate damages, demonstrating that umbrella damage estimates are not inherently speculative. We also examine some difficulties that exist in damage estimation generally and for umbrella plaintiffs in particular. Finally, we argue that granting standing to umbrella plaintiffs is consistent with the goals of antitrust policy. (JEL L1, L4, K2)
The role of the cytopathologist in subtyping and epidermal growth factor receptor testing in non‐small cell lung cancer: An institutional experience
Authors: Sekar A. , Gupta N. , Rajwanshi A. , Chaturvedi R. , Singh N. , Lal A.
Published: July 2017

Objective

Approximately 10% of non‐small‐cell lung cancer (NSCLC) remains unclassifiable as NSCLC‐not otherwise specified (NOS), after using a panel of immunomarkers. The present study was undertaken to assess sensitivity and specificity of immunomarkers in sub‐typing NSCLC on fine needle aspiration cytology (FNAC). Epidermal growth factor receptor (EGFR) mutations were also detected in these samples.

Methods

Sixty cases of NSCLC including 15 squamous cell carcinoma (SCC), 15 adenocarcinomas (ADC) and 30 NSCLC‐NOS reported on FNAC were included in the study. A panel of CK7, CK5/6, TTF‐1 and p63 was applied in these cases. DNA was extracted from 54 cases including 14 effusion samples, and EGFR mutations were detected.

Results

Classic ADC cases (n=15) showed 73.3% TTF‐1 positivity and 100% CK7 positivity. Two cases of ADC showed aberrant expression of p63 and 2 cases showed CK5/6 positivity. 80% of classic SCC cases (n=15) showed strong nuclear p63 positivity and 86.6% were positive for CK5/6. TTF‐1 was seen exclusively in ADC cases. Immunohistochemistry (IHC) using two immunomarkers (TTF‐1 and p63) helped in subtyping 24/30(80%) cases of NSCLC. EGFR mutations were detected in 9/54 (16.7%) cases, and the most common mutation was short in‐frame deletion in Exon 19.

Conclusions

More than 90% of NSCLC can be sub‐typed on cytology samples with the help of immunochemistry. The sensitivity of TTF‐1, p63, CK5/6 and CK7 was 73.3%, 80%, 100% and 100%, respectively. The specificity of TTF‐1, p63, CK5/6 and CK7 was 100%, 86.6%, 86.6% and 93.3%, respectively. TTF‐1 is highly specific, and almost 80% of NSCLC‐NOS cases can be sub‐typed using TTF‐1 and p63. EGFR mutations can be detected in cytology samples, and 16.7% samples were positive for EGFR mutations.
Supplier Innovation Strategy and Performance: A Matter of Supply Chain Market Positioning
Authors: Mackelprang Alan W. , Bernardes Ednilson , Burke Gerard J. , Welter Chris
Published: July 2017

Extant research consistently illustrates the positive benefits customers get from having more innovative suppliers. However, do suppliers benefit financially from positioning themselves as leading innovators? Utilizing a secondary dataset of 1039 supplier to customer base observations, and grounding our study in the structure‐conduct‐performance framework, we examine the extent to which suppliers are able to benefit from pursuing a more leading or lagging innovation strategy within their industry. While in general we find that suppliers employing a leading innovator strategy have higher levels of financial performance, such an effect is not universal. Rather, the ability of the supplying firm to leverage their innovation strategy into increased performance is highly contingent upon not only the innovation levels of their own industry, but also the innovation levels of the industries which they supply. Our results, therefore, suggest that it would be advantageous for suppliers to take a supply chain perspective and strategically incorporate the innovation characteristics of their customers when determining whether to pursue a leading or lagging innovation strategy.