bluuebunny/crossref_metadata_2025 huggingface dataset:
A Shape‐Based Local Spatial Association Measure (LISShA): A Case Study in Maritime Anomaly Detection
Authors: Roberts Steven Andrew
Published: November 2018

The explicit consideration of the shape of geographic features has been largely ignored in existing spatial association measures. The primary contribution of this work is the development of a new local spatial association measure—a Local Indicator of Spatial and Shape Association (LISShA). The LISShA measure is modeled after local Geary's Spatial Autocorrelation measure with distance between shapes, calculated using the Small–Le metric, replacing difference between attribute values and the spatial neighborhood defined by Fréchet distance. We provide some explanation of these metrics and show, in detail, how the LISShA and proposed moments are calculated in a one‐dimensional context in a case study of maritime anomaly detection.
Frequency and immunophenotype of IL10‐producing regulatory B cells in optic neuritis
Authors: Lundqvist Sara , Modvig Signe , Fischer Emilie A. , Frederiksen Jette L. , Degn Matilda
Published: November 2018

Mouse models of multiple sclerosis (MS) have shown the importance of interleukin‐10 (IL‐10) ‐producing regulatory B (Breg) cells in dampening disease activity and inhibiting disease initiation and progression. In MS and other autoimmune diseases decreased frequency and functionality of Breg cells correlate with disease activity and the percentage of IL‐10‐producing Breg cells decreases during relapse and normalizes in remission. Optic neuritis (ON) is a common first clinical manifestation of MS and IL‐10‐producing Breg cells may be crucial in the transition from ON to MS, we therefore investigate the frequency and function of Breg cells in ON as a clinical model of early demyelinating disease. B cells were purified from 27 patients with ON sampled close to symptom onset (median 23 days, range 7–41 days) and 13 healthy controls. The B cells were stimulated and cultured for 48 hr with CD40 ligand and CpG before measurement of intracellular IL‐10 and the surface markers CD19, CD1d, CD5, CD24, CD38 and CD27 by flow cytometry. The frequency of B‐cell subsets was analysed in peripheral blood and cerebral spinal fluid (CSF) of patients. Sixty‐five per cent of the IL‐10‐producing Breg cells co‐expressed CD24 and CD38, and only 14% were CD24high CD27+, suggesting that the naive B cells are the primary source of IL‐10 in the B‐cell culture, followed by memory cells in both healthy controls and patients. The frequency of naive CD19+ CD24+ CD38+ Breg cells was higher in patients with ON compared with controls. The ability of Breg cells to produce IL‐10 was at normal levels in both ON patients with high risk and those with low risk of progression to MS. We found no correlation between Breg cell function and the presence of brain white matter lesions by magnetic resonance imaging or CSF oligoclonal bands indicative of ON patients carrying a higher risk of conversion to MS. The frequencies of IL‐10‐producing B cells did not correlate with the conversion to MS at 2‐year follow up. Interleukin‐10 was primarily produced by naive and memory B cells. The frequency of IL‐10‐secreting B cells did not correlate with risk factors of MS. Breg cell function at clinical onset of ON is not a determining factor for conversion to MS.
Trauma exposure and post‐traumatic stress disorder in people with intellectual disabilities: A Delphi expert rating
Authors: Rittmannsberger Doris , Kocman Andreas , Weber Germain , Lueger‐Schuster Brigitte
Published: November 2018

Background

There is a lack of research on trauma in people with intellectual disabilities. This study assessed expert consensus on the traumatic potential of a broader range of adverse life events, and differences in symptom manifestation and behavioural symptom equivalents of post‐traumatic stress disorder (PTSD) symptoms.

Method

The present authors conducted a three‐step Delphi survey using a mixed‐methods design. Twenty‐nine expert raters participated in the survey, and 16 persisted to the final round. Consensus was calculated using the interquartile range.

Results

Traumatic potential was attributed to adverse life events, particularly revolving around sexuality and autonomy. DSM‐5 symptoms of PTSD were rated as partially adequate, with behavioural symptom expression being the main difference to the general population.

Conclusion

The range of traumatic events should be broadened for people with intellectual disabilities. A specific subset of events need to be defined in future research. Detection of PTSD depends upon determining specific symptom correlates of challenging behaviour.
Fibroblast growth factor 21 facilitates peripheral nerve regeneration through suppressing oxidative damage and autophagic cell death
Authors: Lu Yingfeng , Li Rui , Zhu Junyi , Wu Yanqing , Li Duohui , Dong Lupeng , Li Yiyang , Wen Xin , Yu Fangzheng , Zhang Hongyu , Ni Xiao , Du Shenghu , Li Xiaokun , Xiao Jian , Wang Jian
Published: November 2018

Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention. Fibroblast growth factor 21 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation. Furthermore, local FGF21 application attenuated the excessive activation of oxidative stress, which was accompanied with the activation of nuclear factor erythroid‐2‐related factor 2 (Nrf‐2) transcription and extracellular regulated protein kinases (ERK) phosphorylation. We detected FGF21 also suppressed autophagic cell death in SCs. Additionally, treatment with the ERK inhibitor U0126 or autophagy inhibitor 3‐MA partially abolishes anti‐oxidant effect and reduces SCs death. Taken together, these results indicated that the role of FGF21 in remyelination and nerve regeneration after PNI was probably related to inhibit the excessive activation of ERK/Nrf‐2 signalling‐regulated oxidative stress and autophagy‐induced cell death. Overall, our work suggests that FGF21 administration may provide a new therapy for PNI.
TRPV4 regulates matrix stiffness and TGFβ1‐induced epithelial‐mesenchymal transition
Authors: Sharma Shweta , Goswami Rishov , Zhang David X. , Rahaman Shaik O.
Published: November 2018

Substrate stiffness (or rigidity) of the extracellular matrix has important functions in numerous pathophysiological processes including fibrosis. Emerging data support a role for both a mechanical signal, for example, matrix stiffness, and a biochemical signal, for example, transforming growth factor β1 (TGFβ1), in epithelial‐mesenchymal transition (EMT), a process critically involved in fibrosis. Here, we report evidence showing that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive channel, is the likely mediator of EMT in response to both TGFβ1 and matrix stiffness. Specifically, we found that: (a) genetic ablation or pharmacological inhibition of TRPV4 blocked matrix stiffness and TGFβ1‐induced EMT in normal mouse primary epidermal keratinocytes (NMEKs) as determined by changes in morphology, adhesion, migration and alterations of expression of EMT markers including E‐cadherin, N‐cadherin (NCAD) and α‐smooth muscle actin (α‐SMA), and (b) TRPV4 deficiency prevented matrix stiffness‐induced EMT in NMEKs over a pathophysiological range. Intriguingly, TRPV4 deletion in mice suppressed expression of mesenchymal markers, NCAD and α‐SMA, in a bleomycin‐induced murine skin fibrosis model. Mechanistically, we found that: (a) TRPV4 was essential for the nuclear translocation of YAP/TAZ (yes‐associated protein/transcriptional coactivator with PDZ‐binding motif) in response to matrix stiffness and TGFβ1, (b) TRPV4 deletion inhibited both matrix stiffness‐ and TGFβ1‐induced expression of YAP/TAZ proteins and (c) TRPV4 deletion abrogated both matrix stiffness‐ and TGFβ1‐induced activation of AKT, but not Smad2/3, suggesting a mechanism by which TRPV4 activity regulates EMT in NMEKs. Altogether, these data identify a novel role for TRPV4 in regulating EMT.
Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families
Authors: Reis Sabrina T. , Leite Katia R. M. , Marchini Giovanni S. , Guimarães Ronaldo M. , Viana Nayara I. , Pimenta Ruan C. A. , Torricelli Fabio C. , Danilovic Alexandre , Vicentini Fábio Carvalho , Nahas William Carlos , Srougi Miguel , Mazzucchi Eduardo
Published: November 2018

The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome‐Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0‐fold (P = 0.036). Pre‐B‐cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3‐fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild‐type homozygote genotype had overexpression of PBX1. There is a 3‐fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.
Clinical association of metabolic syndrome, C‐reactive protein and testosterone levels with clinically significant prostate cancer
Authors: Gómez‐Gómez Enrique , Carrasco‐Valiente Julia , Campos‐Hernández Juan Pablo , Blanca‐Pedregosa Ana Maria , Jiménez‐Vacas Juan Manuel , Ruiz‐García Jesus , Valero‐Rosa Jose , Luque Raul Miguel , Requena‐Tapia María José
Published: November 2018

Recently, the influence that metabolic syndrome (MetS), hormonal alterations and inflammation might have on prostate cancer (PCa) risk has been a subject of controversial debate. Herein, we aimed to investigate the association between MetS‐components, C‐reactive protein (CRP) and testosterone levels, and the risk of clinically significant PCa (Sig‐PCa) at the time of prostate biopsy. For that, men scheduled for transrectal ultrasound guided biopsy of the prostate were studied. Clinical, laboratory parameters and criteria for MetS characterization just before the biopsy were collected. A total of 524 patients were analysed, being 195 (37.2%) subsequently diagnosed with PCa and 240 (45.8%) meet the diagnostic criteria for MetS. Among patients with PCa, MetS‐diagnosis was present in 94 (48.2%). Remarkably, a higher risk of Sig‐PCa was associated to MetS, greater number of MetS‐components and higher CRP levels (odds‐ratio: 1.83, 1.30 and 2.00, respectively; P < 0.05). Moreover, higher circulating CRP levels were also associated with a more aggressive Gleason score in PCa patients. Altogether, our data reveal a clear association between the presence of MetS, a greater number of MetS‐components or CRP levels >2.5 mg/L with an increased Sig‐PCa diagnosis and/or with aggressive features, suggesting that MetS and/or CRP levels might influence PCa pathophysiology.
Osterix promotes the migration and angiogenesis of breast cancer by upregulation of S100A4 expression
Authors: Qu Shuang , Wu Jiahui , Bao Qianyi , Yao Bing , Duan Rui , Chen Xiang , Li Lingyun , Yuan Hongyan , Jin Yucui , Ma Changyan
Published: November 2018

As a key transcription factor required for bone formation, osterix (OSX) has been reported to be overexpressed in various cancers, however, its roles in breast cancer progression remain poorly understood. In this study, we demonstrated that OSX was highly expressed in metastatic breast cancer cells. Moreover, it could upregulate the expression of S100 calcium binding protein A4 (S100A4) and potentiate breast cancer cell migration and tumor angiogenesis in vitro and in vivo. Importantly, inhibition of S100A4 impaired OSX‐induced cell migration and capillary‐like tube formation. Restored S100A4 expression rescued OSX‐short hairpin RNA‐suppressed cell migration and capillary‐like tube formation. Moreover, the expression levels of OSX and S100A4 correlated significantly in human breast tumors. Our study suggested that OSX acts as an oncogenic driver in cell migration and tumor angiogenesis, and may serve as a potential therapeutic target for human breast cancer treatment.
Endogenous reduction of miR‐185 accelerates cardiac function recovery in mice following myocardial infarction via targeting of cathepsin K
Authors: Li Chuan‐Chang , Qiu Xue‐Ting , Sun Quan , Zhou Ji‐Peng , Yang Hui‐Jun , Wu Wan‐Zhou , He Ling‐Fang , Tang Can‐E , Zhang Guo‐Gang , Bai Yong‐Ping
Published: November 2018

Angiogenesis is critical for re‐establishing the blood supply to the surviving myocardium after myocardial infarction (MI) in patients with acute coronary syndrome (ACS). MicroRNAs are recognised as important epigenetic regulators of endothelial function. The aim of this study was to determine the roles of microRNAs in angiogenesis. Eighteen circulating microRNAs including miR‐185‐5p were differently expressed in plasma from patients with ACS by high‐throughput RNA sequencing. The expressional levels of miR‐185‐5p were dramatically reduced in hearts isolated from mice following MI and cultured human umbilical vein endothelial cells (HUVECs) under hypoxia, as determined by fluorescence in situ hybridisation and quantitative RT‐PCR. Evidence from computational prediction and luciferase reporter gene activity indicated that cathepsin K (CatK) mRNA is a target of miR‐185‐5p. In HUVECs, miR‐185‐5p mimics inhibited cell proliferations, migrations and tube formations under hypoxia, while miR‐185‐5p inhibitors performed the opposites. Further, the inhibitory effects of miR‐185‐5p up‐regulation on cellular functions of HUVECs were abolished by CatK gene overexpression, and adenovirus‐mediated CatK gene silencing ablated these enhancive effects in HUVECs under hypoxia. In vivo studies indicated that gain‐function of miR‐185‐5p by agomir infusion down‐regulated CatK gene expression, impaired angiogenesis and delayed the recovery of cardiac functions in mice following MI. These actions of miR‐185‐5p agonists were mirrored by in vivo knockdown of CatK in mice with MI. Endogenous reductions of miR‐185‐5p in endothelial cells induced by hypoxia increase CatK gene expression to promote angiogenesis and to accelerate the recovery of cardiac function in mice following MI.
Engineering of TIMP‐3 as a LAP‐fusion protein for targeting to sites of inflammation
Authors: Alberts Ben M. , Sacre Sandra M. , Bush Peter G. , Mullen Lisa M.
Published: November 2018

Tissue inhibitor of metalloproteinase (TIMP)‐3 is a natural inhibitor of a range of enzymes that degrade connective tissue and are involved in the pathogenesis of conditions such as arthritis and cancer. We describe here the engineering of TIMP‐3 using a novel drug‐delivery system known as the ‘LAP technology’. This involves creating therapeutic proteins in fusion with the latency‐associated peptide (LAP) from the cytokine TGF‐? to generate proteins that are biologically inactive until cleavage of the LAP to release the therapy. LAP‐TIMP‐3 was successfully expressed in mammalian cells and the presence of the LAP resulted in a 14‐fold increase in the quantity of recombinant TIMP‐3 produced. LAP‐TIMP‐3 was latent until release from the LAP by treatment with matrix metalloproteinase when it could inhibit proteases of the adamalysins and adamalysins with thrombospondin motifs families, but not matrix metalloproteinases, indicating that this version of TIMP‐3 is a more specific inhibitor than the native protein. There was sufficient protease activity in synovial fluid from human joints with osteoarthritis to release TIMP‐3 from the LAP fusion. These results demonstrate the potential for development of TIMP‐3 as a novel therapy for conditions where upregulation of catabolic enzymes are part of the pathology.
Evaluation of medical and surgical treatments for hidradenitis suppurativa using real‐life data from the Scandinavian registry (HISREG)
Authors: Grimstad Ø. , Tzellos T. , Dufour D.N. , Bremnes Ø. , Skoie I.M. , Snekvik I. , Jarnæss E. , Kyrgidis A. , Ingvarsson G.
Published: November 2018

Background

Hidradenitis suppurativa (HS) substantially affects health‐related quality‐of‐life outcomes. Most treatment options are supported by low quality of evidence without validated outcomes.

Objective

The aim of this study was to evaluate the efficacy of surgical and medical interventions using physician‐ and patient‐reported outcomes registered in HISREG.

Methods

Data were extracted for all adult patients registered in HISREG between January 2013 and April 2016. Primary endpoints included Dermatology Life Quality Index (DLQI) scores, pain as measured using a numeric rating scale (NRS), Sartorius score and Hurley classification. Minimum clinically important differences (MCIDs) for DLQI and NRS pain were analysed. Secondary endpoints included comparisons among different treatment groups, safety and complications of various treatments.

Results

Two hundred and fifty‐five patients were included in the study: 31, 188, and 36 patients had Hurley stages I, II and III disease, respectively. Treatment with CO2 lasers was the most common treatment modality. One hundred and forty‐nine patients (58.4%) were treated with surgical intervention, 87 (34.1%) received antibiotics and/or anti‐inflammatory treatments, and 19 (7.5%) were treated with both surgery and medical intervention. No patients received biologic treatment. In patients with surgical treatments, Sartorius scores were significantly improved compared with baseline (P = 0.001), 83 patients (55%) achieved a DLQI MCID, and 75 patients (49.7%) achieved an NRS pain MCID. In patients with medical treatments, Sartorius scores were not significantly improved compared with baseline (P = 0.582); 25 patients (28%) achieved a DLQI MCID and 28 patients (31%) achieved an NRS pain MCID. In patients treated with surgical and medical combination, 9 (48%) achieved DLQI and NRS pain MCIDs and Sartorius scores were significantly improved.

Conclusions

CO2 laser treatment is more effective than the non‐biologic medical treatments in this analysis based on physician‐ and patient‐derived outcomes. The study provides limited evidence for the combination of medical and surgical therapies in patients with HS.
Apremilast for moderate hidradenitis suppurativa: no significant change in lesional skin inflammatory biomarkers
Authors: Vossen A.R.J.V. , van der Zee H.H. , Davelaar N. , Mus A.M.C. , van Doorn M.B.A. , Prens E.P.
Published: November 2018

Background

Treatment with apremilast has recently demonstrated clinically meaningful improvement in moderate hidradenitis suppurativa (HS).

Objective

To evaluate the change in expression of inflammatory markers in lesional skin of HS patients receiving apremilast 30 mg twice daily (n = 15) for 16 weeks compared with placebo (n = 5).

Methods

At baseline, 5‐mm punch biopsies were obtained from an index lesion (HSL) and non‐lesional (HSN) skin in the same anatomical area. Subsequent HSL samples were taken as close as possible to the previously biopsied site at week 4 and week 16. After sampling, biopsies were split; one half was processed for in vivo mRNA analysis using real‐time quantitative PCR; the other half was cultured for ex vivo protein analysis using a proximity extension assay (Olink). Linear mixed effects models were calculated to compare the levels of inflammatory markers in HSL skin between apremilast and placebo over time.

Results

At baseline, 17 proteins with a fold change >2 in HSL vs. HSN skin were identified in 20 patients. The top five were IL‐17A (5), S100A12, CST5, IL‐12/23p40, CD6 (1) with fold changes ranging from 6.6 to 1638, respectively (FDR <0.044). Linear mixed effects models for 75 assays were calculated. Protein levels of S100A12 decreased during treatment in the apremilast group compared with the placebo group (p = 0.014, FDR = 0.186). None of the 14 genes exhibited significant changes in expression over time. However, an evident downward trend in relative mRNA expression of IL‐17A and IL‐17F was demonstrated in patients receiving apremilast.

Conclusion

We did not detect statistically significant changes in inflammatory markers in HSL skin of HS patients receiving apremilast compared with placebo, despite clinical improvement in the apremilast group. Nonetheless, S100A12 and IL‐17A were significantly elevated in HSL skin and showed a decrease in response to apremilast. The translational model in clinical trials involving HS clearly needs further improvement.
The Disaster of Wording
Authors: Gogol Manfred
Published: November 2018

See the Reply by Leng et al.
Chronic over‐expression of ubiquitin impairs learning, reduces synaptic plasticity, and enhances GRIA receptor turnover in mice
Authors: Vaden Jada H. , Tian Tina , Golf Samantha , McLean John W. , Wilson Julie A. , Wilson Scott M.
Published: November 2018

Ubiquitin is an essential signaling protein that controls many different cellular processes. While cellular ubiquitin levels normally cycle between pools of free and conjugated ubiquitin, the balance of these ubiquitin pools can be shifted by exposure to a variety of cellular stresses. Altered ubiquitin pools are also observed in several neurological disorders, suggesting that imbalances in ubiquitin homeostasis may contribute to neuronal dysfunction. To examine the effects of increased ubiquitin levels on the mammalian nervous system, we generated transgenic mice that express ubiquitin under the control of the Thy1.2 promoter. While we did not detect global changes in levels of ubiquitin conjugates in the hippocampus, we found that increasing ubiquitin levels reduced AMPA (GRIA1‐4) receptor expression without affecting the levels of NMDA (GRIN) or GABAA receptors. Ubiquitin over‐expression also negatively impacted hippocampus‐dependent learning and memory as well as baseline excitability and synaptic plasticity at hippocampal CA3‐CA1 synapses. These changes occurred in a dose‐dependent manner in that mice with the highest levels of ubiquitin over‐expression had the greatest deficits in synaptic function and were the most impaired in the learning and memory tasks. As chronic elevation of ubiquitin expression in neurons is sufficient to cause changes in synaptic function and cognition, altered ubiquitin homeostasis may be an important contributor to the stress‐induced changes observed in neurological disorders.

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The role of hippocampus in the retrieval of autobiographical memories in patients with amnestic Mild Cognitive Impairment due to Alzheimer's disease
Authors: Serra Laura , Bozzali Marco , Fadda Lucia , De Simone Maria Stefania , Bruschini Michela , Perri Roberta , Caltagirone Carlo , Carlesimo Giovanni A.
Published: November 2018

The role of the hippocampus and neocortical areas in the retrieval of past memories in pre‐dementia Alzheimer's disease (AD) patients was investigated. The aim was to assess whether the hippocampus has a temporary role in memory trace formation, according to the Cortical Reallocation Theory (CRT), or whether it continuously updates and enriches memories, according to the Multiple Trace Theory. According to the former theory, hippocampal damage should affect more recent memories, whereas the association cortex is expected to affect memories of the entire lifespan. In the second case, damage to either the hippocampus or the association cortices should affect memories of the entire lifespan. Seventeen patients with amnestic Mild Cognitive Impairment due to AD were submitted to autobiographical (i.e., episodic and semantic personal) memory assessment. Patients underwent MRI for the acquisition of T1‐weighted brain volumes. Voxel‐based morphometry was used to assess correlations between grey matter (GM) volumes and autobiographical memory. Correlation analyses revealed a strict association between GM volumes in the hippocampus and patients’ ability to retrieve the most recent but not the oldest autobiographical memories in both aspects, episodic and semantic. Moreover, patients’ GM volumes in the pre‐frontal and temporal polar areas were associated with recollection of episodic and semantic events, respectively. Finally, GM volumes in the precuneus and occipital cortex were associated with retrieval of the most recent episodic events. These findings indicate that the hippocampus has a specific time‐dependent role; thus, they support the CRT.
Ligamentous structures in human glans penis
Authors: Lee Shin‐Hyo , Ha Tae‐Jun , Koh Ki‐Seok , Song Wu‐Chul
Published: November 2018

The corpus spongiosum reportedly occupies a larger proportion of the human glans penis than does the penile body, embedding the end of the corpus cavernosus (CC). However, anatomic descriptions about the fibrous structures of glans penis in the literature cause confusion during dissection and reconstructive surgery. Forty‐five penises of formalin‐embalmed cadavers were dissected sagittally along the course of the distal urethra and observed macroscopically. Dense connective tissues adjacent to the fossa navicularis and spongiosum parts of the glans were cropped, and underwent Masson's trichrome and Verhoeff‐Van‐Gieson staining. Most (55.5%) of the specimens had distinct fibrous bands toward the distal tips of the glans penis, which elongated from the tunica albuginea of the CC. They comprised longitudinal collagen bundles continuous to the outer longitudinal layer of the tunica albuginea covering the CC and were intermingled with sparse elastic fibres. This architecture either did not reach the distal end of the glans penis (35.5% of cases), or was obscure or dispersed in all directions (9.0% of cases). The structural dimorphism and the variations in the ratio of dense connective tissue components of the fibrous skeleton are considered to contribute to the varying degrees of flexibility, distensibility and rigidity of the human glans penis.
Dose‐dependent effects of continuous positive airway pressure for sleep apnea on weight or metabolic function: Individual patient‐level clinical trial meta‐analysis
Authors: Hoyos Camilla M. , Murugan Swati M. , Melehan Kerri L. , Yee Brendon J. , Phillips Craig L. , Killick Roo , Cayanan Elizabeth A. , Wong Keith K. , Liu Peter Y. , Grunstein Ronald R. , Marshall Nathaniel S.
Published: November 2018

Therapeutic‐continuous positive airway pressure seems to increase weight compared with placebo‐continuous positive airway pressure. It is not known whether weight gain with therapeutic‐continuous positive airway pressure dose is dependent or whether it causes metabolic dysfunction. Data synthesis of three randomised placebo‐continuous positive airway pressure‐controlled trials (2–3 months) was performed to test whether there is a dose‐dependent effect of continuous positive airway pressure on weight. Fasting glucose, insulin, insulin resistance (homeostatic model assessment), lipids and visceral abdominal fat were also tested to determine any effect on metabolic function. Mixed‐model analysis of variance was used to quantify these effects. One‐hundred and twenty‐eight patients were analysed. Overall there was a small increase in weight with therapeutic‐continuous positive airway pressure use compared with placebo‐continuous positive airway pressure (difference: 1.17 kg; 0.37–1.97, p = 0.005), which was greater with high‐use therapeutic‐continuous positive airway pressure compared with high‐use placebo‐continuous positive airway pressure (1.45 kg; 0.10–2.80, p = 0.04). Continuous positive airway pressure use as a continuous variable was also significantly associated with weight change in continuous positive airway pressure users (0.30 kg hr−1 night−1; 0.04–0.56, p = 0.001), but not in placebo users (0.04 kg hr−1 night−1; −0.22 to 0.26, p = 0.76). Neither therapeutic‐continuous positive airway pressure nor the dose of therapeutic‐continuous positive airway pressure caused any changes to metabolic outcomes. The weight gain effects of medium‐term therapeutic‐continuous positive airway pressure appear modest and are not accompanied by any adverse metabolic effects.
Upper airway stimulation in obstructive sleep apnea improves glucose metabolism and reduces hedonic drive for food
Authors: Steffen Armin , Chamorro Rodrigo , Buyny Laura , Windjäger Anne , Wilms Britta , Hasselbacher Katrin , Wollenberg Barbara , Lehnert Hendrik , Schmid Sebastian M.
Published: November 2018

Upper airway stimulation is a new and effective second‐line treatment for obstructive sleep apnea, but possible consequences on glucose metabolism and central regulation of food intake are unclear. Twenty patients were prospectively studied before and 12 months after obstructive sleep apnea treatment by upper airway stimulation. Respiratory parameters and daytime sleepiness were assessed to document effectiveness of treatment. Glucose metabolism was assessed by the oral glucose tolerance test, and hedonic versus homeostatic drive to eat was characterized. At 12 months, upper airway stimulation significantly improved measures of obstructive sleep apnea (all p < 0.01). Despite no change in body weight, fasting C‐peptide insulin resistance index (p = 0.01) as well as insulin and C‐peptide levels at 60 min during the oral glucose tolerance test (p < 0.02) were reduced. Hedonic drive to eat was strongly reduced (p < 0.05), while leptin and ghrelin remained unchanged (p > 0.15). Upper airway stimulation is effective in treatment of obstructive sleep apnea and improves glucose metabolism. Reduced hedonic drive to eat might contribute to these metabolic improvements. These promising findings are in need for long‐term controlled evaluation of metabolic sequelae of upper airway stimulation and to mechanistically evaluate the metabolic benefits of upper airway stimulation in patients with obstructive sleep apnea.
Age and Cultural Gender Equality as Moderators of the Gender Difference in the Importance of Religion and Spirituality: Comparing the United Kingdom, France, and Germany
Authors: Robinson Oliver C. , Hanson Karina , Hayward Guy , Lorimer David
Published: November 2018

A range of research studies has found that women report greater importance of religion and spirituality in their lives than men do. This study extends the literature on this phenomenon, and the theories that aim to explain it, by looking at whether gender differences in the three European countries (the United Kingdom, France, and Germany) differ by adult age group (young adults 18–39, midlifers 40–59, and older adults 60+), and by the cultural gender equality of the countries in question. Participants provided data on the importance of religiosity and spirituality to their life. Significant gender differences were found within all three countries, for each of the three age groups. In line with predictions based on Global Gender Gap Report 2016, Germany showed the smallest difference, followed by France and the United Kingdom. Gender differences were smaller in the young adult samples than for midlife adults or older adults.
Tree selection is linked to locomotor performance and associated noise production in a lizard
Authors: MacLeod Kirsty J. , Freidenfelds Nicole A. , Leighton Gavin M. , Langkilde Tracy
Published: November 2018

Microhabitat preference can be an important determinant of individual fitness. Differential use of microhabitats (such as substrate type) can confer or facilitate increased ability to evade or escape predators, and catch prey, for example by influencing sprint speed and noise produced by movement. However, there have been few studies that demarcate whether substrate use influences traits like these. Additionally, the importance of auditory crypsis and locomotor performance for microhabitat selection has been historically under‐studied, especially when compared to the importance of facilitating visual crypsis. We investigate substrate (tree) type use, and the influence of substrate types on both sprint performance and level of noise produced by movement, in fence lizards (Sceloporus undulatus). In our study sites, fence lizards inhabit mixed woodland where deciduous and coniferous trees exist at approximately equal frequency. We show a strong bias in tree use, with lizards being found more frequently on deciduous trees. Using acoustic and video recordings of lizards moving on trees of both types, we demonstrate that lizards sprint faster and their movement appears to generate less noise on deciduous trees, providing a possible basis for their increased use of this tree type. These data suggest that lizards use substrates on which they are more likely to evade auditory detection and can sprint quickly to refuge or capture prey. We conclude that factors other than visual camouflage may be important in determining substrate use and should also be considered in studies of microhabitat selection.
A Systematic Analysis of Experimental Studies Targeting Fractions for Students with Mathematics Difficulties
Authors: Hwang Jiwon , Riccomini Paul J. , Hwang Seok Yoon , Morano Stephanie
Published: November 2018

Developing an understanding of fractions is critical and is an educational focus, as reflected in national standards and principles. This study conducted a quantitative synthesis of 22 experimental studies to investigate the overall efficacy of previously conducted fraction interventions compared to standard instruction. Instruction type and achievement level were used to examine variations of the effect sizes. The results indicated that intervention was more effective than standard instruction only in problem‐solving domains, and the effects were differentiated by instruction type and achievement level. This study provides a diagnostic view of the current state of U.S. mathematics education on fractions, along with insights for future directions in fraction instruction, particularly focusing on students with mathematics difficulties. Educational implications and limitations are discussed.
Use of Delphi approach to develop indicators and preferences for restoration of balance in Dal Lake fisheries
Authors: Qureshi Neha W. , Krishnan M. , Srinivasa Aditya K.
Published: November 2018

Dal Lake, Kashmir, is the jewel in the crown of India. The present study addresses the issue of lake sustainability by conducting a two‐round Delphi survey to elicit views and build consensus on the relative importance of the impacts of restoration of Dal Lake and its fisheries. The Friedman and Kendall W tests, along with post hoc Wilcoxon signed‐rank test, were used to detect the presence of rank patterns and rank convergence. The general consensus among the experts was a call for the restoration of the Schizothorax fishery in Dal Lake. The survey also called for a drastic reduction in the spread and intensity of vegetable farming practices, as well as containing an inherent appeal for easing tourism‐based development of Dal Lake area. The survey also supports controlled vegetable farming as a supplementary income source.
Bathymetric survey of Lake Naivasha and its satellite Lake Oloiden in Kenya; using acoustic profiling system
Authors: Maina Caroline W. , Sang Joseph K. , Mutua Benedict M. , Raude James M.
Published: November 2018

Lakes and reservoirs play important roles as freshwater sources for domestic, industrial, agricultural, fisheries and recreational purposes. However, for the lakes to be sustainably exploited, there is need to understand their bathymetric characteristics by conducting bathymetric surveys. This aids in generating information that can guide lakes stakeholders and managers in establishing the volume of available water. It is recommended, therefore, that bathymetric surveys be conducted at ten‐year intervals. Such continuous bathymetric information is lacking in many lakes, especially in developing countries. One example is Lake Naivasha in Kenya, which is largely exploited for various socio‐economic purposes. Despite its importance, its most recent published bathymetric data were collected in 1991. The goal of the present study, therefore, was to conduct a bathymetric survey of Lake Naivasha and its satellite Lake Oloiden, using an Acoustic Profiling System (APS) to generate Depth–Area–Volume relationships for the lakes. The survey results indicate the in the year 2016 mean depth, volume and surface area of the lake were 4.68 m, 722 × 106 m3 and 154.17 × 106 m2, respectively. Because of limited information from the 1991 survey, the 2016 survey results were comparable with those of 1983. The difference in the lakes mean, and maximum depth for the 1983 and 2016 survey was less by 0.23 and 2 m, respectively. This could be an indicator the lake is being affected by anthropogenic activities or environmental changes. The established Depth–Area–Volume relationships are crucial since they provide invaluable information to lake and water resources managers for making informed decisions regarding management of the lake's water resources.
Temperature‐induced range expansion of a subtropical crab along the California coast
Authors: Sadowski Jason S. , Gonzalez Julie A. , Lonhart Steve I. , Jeppesen Rikke , Grimes Tracy M. , Grosholz Edwin D.
Published: November 2018

We describe the range expansion and first occurrence of the subtropical crab Portunus xantusii (Stimpson, 1860) in northern California during 2016 and link the range expansion to the regional extreme water temperature event during this time. We collected P. xantusii occurrence data from crab trapping surveys conducted along the California coast as well as incidental observations by fishermen and SCUBA divers. We then analyzed 10 years of regional offshore temperature patterns using National Data Buoy Center data around the trapping region. We also examined evidence of northern California warm water refugia using sensors monitoring Tomales Bay, Elkhorn Slough, and San Francisco Bay. We found that P. xantusii was present in every major estuary north of Monterey Bay and as far north as Tomales Bay and that the documented range expansion was likely due to the unusual oceanographic event that occurred northern California during this time period. Mean offshore temperatures and mean nearshore temperatures during 2014–2016 were about 2°C (one standard deviation) higher than the 2006–2013 mean, with extreme temperatures reaching three standard deviations above the 2006–2013 mean. We suggest that this unusual warm water event permitted survival of dispersing larvae of P. xantusii larvae northward via coastal currents, and that the extended warm water period allowed P. xantusii to complete its development. Long‐term crab trapping programs in place since 1994 within this region provide robust support for the absence of P. xantusii prior to 2016. Temperature data indicate that the estuaries in which adult P. xantusii was found could allow persistence of adult P. xantusii in northern California.
The temporal relationship of daily life stress, emotions, and bowel symptoms in irritable bowel syndrome—Diarrhea subtype: A smartphone‐based experience sampling study
Authors: Chan Yawen , So Suzanne Ho‐wai , Mak Arthur Dun Ping , Siah Kewin Tien Ho , Chan Wai , Wu Justin C. Y.
Published: November 2018

Background

The current study aimed to model the moment‐to‐moment relationship between daily life stress, emotions, and bowel symptoms among patients with irritable bowel syndrome—diarrhea subtype (IBS‐D) in the flow of daily life using a smartphone‐based experience sampling method (ESM).

Methods

Patients with IBS‐D (N = 27) and healthy controls (HC; N = 30) completed ESM ratings of their real‐time daily life stress, which was defined as subjective stress related to daily activities, both positive and negative emotions, as well as bowel symptoms eight times a day for 14 consecutive days, following a baseline interview measuring bowel and mood symptoms. Moment‐to‐moment association between ESM variables was tested within and between groups using multilevel regression modeling.

Key Results

Patients with IBS‐D reported more severe bowel symptoms and lower positive affect than HCs, but levels of daily life stress and negative affect were comparable between groups. Time‐lagged analysis of ESM data revealed that, among patients with IBS‐D, daily life stress predicted a decrease in abdominal pain and urgency to defecation at a subsequent time point, whereas severity of bowel symptoms and occurrence of diarrhea predicted a subsequent increase in negative affect and daily life stress. The above associations were not found among HCs.

Conclusions and Inferences

ESM unveiled the dynamic relationship between bowel symptoms, stress, and emotionality. Patients with IBS‐D responded to bowel symptoms with more stress and distress momentarily. Counter‐intuitively, daily life activity stress appeared to ameliorate bowel symptoms, although a more rigorous study design is required to testify this claim. Psychological understanding of IBS‐D is discussed.
Mechanisms of plant–soil feedback: interactions among biotic and abiotic drivers
Authors: Bennett Jonathan A. , Klironomos John
Published: November 2018

Contents

Summary
91

I.
Introduction
91

II.
Primary PSF mechanisms
91

III.
Factors mediating the mechanisms of PSF
93

IV.
Conclusions and future directions
94

Acknowledgements
95

Author contributions
95

References
95

Plant–soil feedback (PSF) occurs when plants alter soil properties that influence the performance of seedlings, with consequent effects on plant populations and communities. Many processes influence PSF, including changes in nutrient availability and the accumulation of natural enemies, mutualists or secondary chemicals. Typically, these mechanisms are investigated in isolation, yet no single mechanism is likely to be completely responsible for PSF as these processes can interact. Further, the outcome depends on which resources are limiting and the other plants and soil biota in the surrounding environment. As such, understanding the mechanisms of PSF and their role within plant communities requires quantification of the interactions among the processes influencing PSF and the associated abiotic and biotic contexts.
The Gender Wage Gap in Europe: Job Preferences, Gender Convergence and Distributional Effects
Authors: Redmond Paul , Mcguinness Seamus
Published: November 2018

The gender wage gap has declined over time. However, most of the remaining gap is unexplained, partly because of gender convergence in wage‐determining characteristics. In this paper, we show the degree of convergence differs substantially across Europe. In some countries, predominantly in Eastern Europe, the gender wage gap is entirely unexplained. However, in other countries, differences between the characteristics of men and women explain a relatively large proportion of the wage gap. Gender differences in job preferences contribute 10% to the wage gap, which is more than job tenure, previous employment status or field of study. The role of job preferences is particularly strong at the top of the wage distribution.
Morphological dissection and cellular and transcriptome characterizations of bamboo pith cavity formation reveal a pivotal role of genes related to programmed cell death
Authors: Guo Lin , Sun Xuepeng , Li Zhongru , Wang Yujun , Fei Zhangjun , Jiao Chen , Feng Jianyuan , Cui Dingfan , Feng Xingyu , Ding Yulong , Zhang Chunxia , Wei Qiang
Published: November 2018

Pith cavity formation is critical for bamboo to overcome the bending force during its fast growth; however, the underlying molecular mechanisms remain largely unknown. Multiple approaches, including anatomical dissection, mathematical modelling and transcriptome profiling, were employed in this study to investigate the biology of pith cavity formation in bambooPseudosasa japonica. We found that the corruption of pith tissue occurred sequentially and asymmetrically from the top‐centre of the internode down to the bottom, which might be caused by the combined effects of asymmetrical radial and axial tensile forces during shoot‐wall cell elongation and spiral growth of bamboo internodes. Programmed cell death (PCD) in pitch manifested byTUNELpositive nuclei,DNAcleavage and degraded organelles, and potentially regulated by ethylene and calcium signalling pathway,ROSburst, cell wall modification, proteolysis and nutrient recycle genes, might be responsible for pith tissue corruption ofPs. japonica. Although similar physiological changes and transcriptome profiles were found in different bamboo species, different formation rates of pith cavity were observed, which might be caused by different pith cells across the internode that were negatively correlated with the culm diameter. These findings provided a systematical view on the formation of bamboo pith cavity and revealed thatPCDplays an important role in the bamboo pith cavity formation.
Emotion, Sophistication and Political Behavior: Evidence From a Laboratory Experiment
Authors: Lamprianou Iasonas , Ellinas Antonis A.
Published: November 2018

The way emotions affect political behavior has been a central theme in politics since ancient times, but it is only in the past few decades that it has been the focus of rigorous empirical inquiry. Recent empirical research suggests that emotions may affect different groups of people in distinct ways, but experimental evidence remains scant. Through a double‐blind experiment, this article investigates the degree to which emotions (shame and anger) motivate people with different levels of political sophistication to be more politically active. The findings are two‐fold: (1) Once treated with shame, more sophisticated individuals are more likely to change their political behavior than less sophisticated ones; and (2) once treated with anger, it is people with low levels of prior political involvement who are more likely to report a change in their behavior. The findings highlight the potential of going beyond the existing investigations by adding shame in empirical analyses of how emotions affect behavioral change. The evidence here also shows that different emotions might display different patterns of interaction with sophistication. Practically, the findings point to an emotional venue for the mobilization of citizens who are generally difficult to engage in political life.
Apology for the Theory of the State and Law: A New Concept of Law and Justice in Modern Legal Communication
Authors: Krawietz Werner
Published: November 2018

Concerning the need for a new conception of legal theory one question arises, above all, especially when external and internal observation as well as the critical reflexion on the premises and presuppositions of all dealings with the law permit a degree of distance, the question, namely, whether it is not an increasing application of scientific methods that is needed, in the sense that the development of a theory from the beginning involves the integration of a norm‐descriptive point of view and intellectual standpoint with the norm‐ prescriptive theory of law, by way of complementing each other, as it were (multilevel approach to law). This, at least, appears to be the only way of also clarifying the relationship between legal theory and philosophy and the theory and sociology of law. The inevitable consequences of the development of a theory of norms and action also have to be drawn from this.