bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Feeding in Mice Promotes Colonic Hyperpermeability and Changes in Colonic Organoid Stem Cell Fate
Authors: Forsyth Christopher B. , Shaikh Maliha , Bishehsari Faraz , Swanson Garth , Voigt Robin M. , Dodiya Hemraj , Wilkinson Peter , Samelco Beata , Song Shiwen , Keshavarzian Ali
Published: October 2017

Background

Alcohol increases intestinal permeability to proinflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol.

Methods

Mice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis–inflammation, and stool short‐chain fatty acids (SCFAs) were measured. Jejunum and colonic organoids and tissue were stained for stem cell, cell lineage, and apical junction markers with assessment of mRNA by PCR and RNA‐seq. ChIP‐PCR analysis was carried out for Notch1 using an antibody specific for acetylated histone 3.

Results

Alcohol‐fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis, and decreased butyrate/total SCFA ratio in stool. Stem cell, cell lineage, and apical junction marker staining in tissue or organoids from jejunum tissue were not impacted by alcohol. Only chromogranin A (Chga) was increased in jejunum organoids by qPCR. However, colonic tissue and organoid staining exhibited an alcohol‐induced significant decrease in cytokeratin 20+  (Krt20+) absorptive lineage enterocytes, a decrease in occludin and E‐cadherin apical junction proteins, an increase in Chga, and an increase in the Lgr5 stem cell marker. qPCR revealed an alcohol‐induced decrease in colonic organoid and tissue Notch1, Hes1, and Krt20 and increased Chga, supporting an alteration in stem cell fate due to decreased Notch1 expression. Colonic tissue ChIP‐PCR revealed alcohol feeding suppressed Notch1 mRNA expression (via deacetylation of histone H3) and decreased Notch1 tissue staining.

Conclusions

Data support a model for alcohol‐induced colonic hyperpermeability via epigenetic effects on Notch1, and thus Hes1, suppression through a mechanism involving histone H3 deacetylation at the Notch1 locus. This decreased enterocyte and increased enteroendocrine cell colonic stem cell fate and decreased apical junctional proteins leading to hyperpermeability.
Microdissection testicular sperm extraction in Finland – results of the first 100 patients
Authors: Klami Rauni , Mankonen Harri , Perheentupa Antti
Published: October 2017

Introduction

Testicular microdissection sperm extraction (MD‐TESE) combined with intracytoplasmic sperm injection (ICSI) has made biological fatherhood possible for many men with the most severe form of male infertility, non‐obstructive azoospermia. MD‐TESE was introduced in Turku in 2008, and by 2015, 100 Finnish men with non‐obstructive azoospermia have been operated on.

Material and methods

The average age of the men was 33 years at the time of surgery. Forty‐eight had a needle biopsy previously and 56% had a testicular size <15 mL. The most common diagnoses were idiopathic (n = 65), Klinefelter syndrome (n = 15), operated cryptorchidism or torsion (n = 10), and Y chromosome microdeletion (n = 7). The pregnancy outcomes were followed.

Results

The sperm recovery rate (SRR) overall was 42%: 31% for idiopathic non‐obstructive azoospermia, 40% for Klinefelter syndrome, 57% for Y chromosome microdeletion AZFc, 90% for previous testicular surgery (mostly for cryptorchidism; n = 10) and 67% for previous cytotoxic treatment (n = 3). SRR with histopathologic diagnosis Sertoli‐cell‐only was 29%, and 44% for spermatogenic arrest. Age did not affect the outcome of the surgery. Small testicular size seemed to predict a higher SRR. A previous needle biopsy did not predict a lower SRR. Surgical complications were rare. Of couples, 32 had at least one ICSI attempt, and 22 at least one live birth, giving a cumulative live birth rate of 69%. No major pregnancy complications occurred.

Conclusions

Our SRR is comparable with international results, and the cumulative live birth rate similar to other ICSI indications in Finland. Physicians and specialists need to be made aware of new treatment options to enable biological fatherhood for men with non‐obstructive azoospermia.
Ontogenetic allometry of the digital rays of the leopard gecko (Gekkota: Eublepharidae; Eublepharis macularius)
Authors: Powell George Lawrence , Osgood Geoffrey J. , Russell Anthony P.
Published: October 2017

The role of allometry in producing the variation in autopodial morphology observed among the lizards is not well understood. Allometry of metapodial and digit lengths in the manus and pes of the primitively padless gekkotan (Eublepharis macularius) is explored using maximum‐likelihood repeated‐measures ANCOVAs with body length as the covariate. Estimated variance–covariance matrices differed significantly within and between autopodia, and integration was stronger among the metapodials than the digits. The first metapodial and the first digit of each autopodium exhibit the strongest covariances with each of the remaining components in each variance–covariance matrix, suggesting that the lengths of the first rays are important for allometric integration of both manus and pes. Metapodials scale isometrically and digits negatively allometrically; both display allometric heterogeneity among themselves in both autopodia. Both autopodia exhibit changes in proportion over the ontogenetic size range, attributable to variation in scaling among the components of the rays. Allometric coefficients do not vary among pedal digits, despite differences in phalanx number, although phalanx number is associated with differences in slope in the manual digits. This is suggestive of heterogeneity in allometry among the manual phalanges, which thus may be associated with variation in phalanx length within gekkotan digits.
Changes in white matter microstructure predict lithium response in adolescents with bipolar disorder
Authors: Kafantaris Vivian , Spritzer Linda , Doshi Vishal , Saito Ema , Szeszko Philip R
Published: October 2017

Objectives

To investigate whether response to lithium treatment in pediatric bipolar disorder can be predicted by changes in white matter microstructure in key cortico‐limbic tracts involved in emotion regulation.

Methods

Eighteen clinically referred lithium‐naive patients (mean age 15.5 years) were administered clinical rating scales and diffusion tensor imaging (DTI) examinations at baseline and following 4 weeks of lithium treatment. Clinical ratings were repeated following 8 weeks of treatment. Patients with Clinical Global Impressions (CGI) ratings of 1 (“very much improved”) or 2 (“much improved”) were classified as responders. Ten healthy volunteers received baseline and follow‐up DTI examinations. Using the ENIGMA pipeline, we investigated the relationship between changes in fractional anisotropy (FA) in the cingulum hippocampus (CGH) and clinical response to lithium.

Results

Patients demonstrated significantly lower FA compared to healthy volunteers in the left and right CGH white matter at baseline. Following 4 weeks of lithium treatment, FA in the left CGH increased in patients, but no significant changes in FA were observed among the untreated healthy volunteers. Lithium responders had a significantly greater increase in FA compared to non‐responders. Moreover, baseline (pre‐treatment) FA in the left CGH white matter significantly predicted week 8 overall CGI severity score, with post hoc analyses indicating that these effects were evident for both severity of depression and mania.

Conclusions

Our findings suggest that response to lithium treatment in pediatric bipolar disorder is associated with normalization of white matter microstructure in regions associated with emotion processing.
A GLM-based Latent Variable Ordination Method for Microbiome Samples
Authors: Sohn Michael B. , Li Hongzhe
Published: October 2017

Distance-based ordination methods, such as principal coordinates analysis (PCoA), are widely used in the analysis of microbiome data. However, these methods are prone to pose a potential risk of misinterpretation about the compositional difference in samples across different populations if there is a difference in dispersion effects. Accounting for high sparsity and overdispersion of microbiome data, we propose a GLM-based Ordination Method for Microbiome Samples (GOMMS) in this article. This method uses a zero-inflated quasi–Poisson (ZIQP) latent factor model. An EM algorithm based on the quasi-likelihood is developed to estimate parameters. It performs comparatively to the distance-based approach when dispersion effects are negligible and consistently better when dispersion effects are strong, where the distance-based approach sometimes yields undesirable results. The estimated latent factors from GOMMS can be used to associate the microbiome community with covariates or outcomes using the standard multivariate tests, which can be investigated in future confirmatory experiments. We illustrate the method in simulations and an analysis of microbiome samples from nasopharynx and oropharynx.
Neuropsychiatric comorbidity among adolescents with psoriasis
Authors: Galili E. , Barzilai A. , Shreberk-Hassidim R. , Merdler I. , Caspi T. , Astman N.
Published: October 2017

Background

Psoriasis is a known risk factor for neuropsychiatric diseases among adults. Less is known about the impact on adolescents.

Objectives

To investigate the association between psoriasis and neuropsychiatric comorbidity and social skills among adolescents.

Methods

A population-based cross-sectional study between 1 January 1999 and 1 January 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate-to-severe psoriasis, respectively. The psoriasis patients were diagnosed by a dermatologist. Neuropsychiatric diseases were diagnosed by a neurologist and a psychiatrist, as appropriate. Social skills were evaluated using psychosocial assessment. Patients with psoriasis were compared with 884 653 healthy controls by a multivariate analysis adjusted for age, sex, country of origin, socioeconomic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity that could only be evaluated for part of the recruitment years, using a univariate analysis.

Results

Overall chronic headaches (8·1% vs. 3·4%), intermediate frequency migraine (4·8% vs. 1·6%), low-frequency migraine and nonmigraine headaches (3·4% vs. 1·8%) were associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted odds ratios (OR) 1·9, 95% confidence interval (CI) 1·6–2·4; 2·3, 95% CI 1·8–3·0 and 1·5, 95% CI 1·1–2·1, respectively]. Anxiety disorders (2·1% vs. 0·8%) and impaired social adjustment skills (7·5% vs. 4·2%) were also associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted ORs 2·9, 95% CI 1·6–5·5 and 1·9, 95% CI 1·3–2·6 (of 466 vs. 265 023), respectively].

Conclusions

Psoriasis among adolescents is associated with neuropsychiatric comorbidity and impaired adjustment skills, depending on disease severity.
The prevalence of psychological comorbidity in people with vitiligo: a systematic review and meta-analysis
Authors: Osinubi O. , Grainge M.J. , Hong L. , Ahmed A. , Batchelor J.M. , Grindlay D. , Thompson A.R. , Ratib S.
Published: October 2017

Background

Vitiligo is a chronic disorder causing skin depigmentation with global prevalence varying from 0·2% to 1·8%. U.K. guidelines recommend assessment of psychological state during clinical evaluation of vitiligo. However, the prevalence of psychological comorbidity in people with vitiligo has not been described.

Objectives

To establish the prevalence of psychological symptoms or disorders in people with vitiligo and describe the outcome measures used.

Methods

We performed a comprehensive search of MEDLINE, Embase, CINAHL and PsycINFO to identify observational studies assessing the prevalence of psychological symptoms or disorders (December 2016). DerSimonian and Lard random-effects models were used to estimate the overall pooled prevalence.

Results

We identified 29 studies with 2530 people with vitiligo. Most studies included a measure of either depression (n =25) or anxiety (n =13). The commonest tools were the Hospital Anxiety and Depression Scale and the Centre for Epidemiology Studies Depression Scale. Ten studies provided information on 13 other psychological outcomes. Pooled prevalence using depression-specific and anxiety-specific questionnaires was 0·29 [95% confidence interval (CI) 0·21–0·38] and 0·33 (95% CI 0·18–0·49), respectively. Prevalence was lower for clinically diagnosed depression (0·21, 95% CI 0·15–0·28) and anxiety (0·15, 95% CI 0·06–0·24). When nonspecific tools were used the prevalence remained similar for depression (0·27, 95% CI 0·08–0·46) but increased for anxiety (0·46, 95% CI 0·39–0·52). High heterogeneity was observed.

Conclusions

A range of psychological outcomes are common in people with vitiligo. The prevalence of anxiety was influenced by type of screening tool, suggesting the need for validation of psychological outcome screening tools in the field of dermatology.
Immunoparesis defined by heavy+light chain suppression is a novel marker of long‐term outcomes in cardiac AL amyloidosis
Authors: Sachchithanantham Sajitha , Berlanga Oscar , Alvi Azra , Mahmood Shameem A. , Lachmann Helen J. , Gillmore Julian D. , Hawkins Philip N. , Harding Stephen , Wechalekar Ashutosh D.
Published: October 2017

Cardiac involvement and presenting dFLC (difference between involved and uninvolved free light chains) are independent predictors of outcome in systemic AL amyloidosis. These markers have limited prognostic utility in patients surviving the initial months following diagnosis. Here we assessed immunoparesis, as determined by novel heavy+light chain (HLC) immunoassays, as a prognostic marker for survival in AL amyloidosis. HLC measurements identified immunoparesis of at least one immunoglobulin (Ig) isotype in 145 (85%) patients; and severe immunoparesis (≥2 Ig isotypes suppressed by >50% below normal levels) in 29 (17%) patients. Median overall survival (OS) on intention to treat (ITT) analysis was 26·2 months. In the ITT cohort, dFLC >180 mg/l was associated with shorter OS (P = 0·05); whereas HLC immunoparesis was not prognostic. On a landmark analysis of 127 patients alive at 6 months, presenting dFLC was not prognostic for OS (P = 0·33) and severe HLC immunoparesis trended towards poorer survival (20·2 vs. 42·8 months; P = 0·09). In the subset of patients with cardiac involvement, severe HLC immunoparesis conferred very poor outcome (median OS 8·8 vs. 29·9 months, P = 0·007). In conclusion, severe HLC immunoparesis is an independent marker of long‐term poor prognosis in AL patients with cardiac involvement. The pathophysiological significance of this observation needs further study.
Impact of low alcohol verbal descriptors on perceived strength: An experimental study
Authors: Vasiljevic Milica , Couturier Dominique‐Laurent , Marteau Theresa M.
Published: October 2017

Objectives

Low alcohol labels are a set of labels that carry descriptors such as ‘low’ or ‘lighter’ to denote alcohol content in beverages. There is growing interest from policymakers and producers in lower strength alcohol products. However, there is a lack of evidence on how the general population perceives verbal descriptors of strength. The present research examines consumers’ perceptions of strength (%ABV) and appeal of alcohol products using low or high alcohol verbal descriptors.

Design

A within‐subjects experimental study in which participants rated the strength and appeal of 18 terms denoting low (nine terms), high (eight terms) and regular (one term) strengths for either (1) wine or (2) beer according to drinking preference.

Methods

Thousand six hundred adults (796 wine and 804 beer drinkers) sampled from a nationally representativeUKpanel.

Results

Low, Lower, Light, Lighter,andReducedformed a cluster and were rated as denoting lower strength products thanRegular, but higher strength than the cluster with intensifiers consisting ofExtra Low, Super Low, Extra Light,andSuper Light. Similar clustering in perceived strength was observed amongst the high verbal descriptors.Regularwas the most appealing strength descriptor, with the low and high verbal descriptors using intensifiers rated least appealing.

Conclusions

The perceived strength and appeal of alcohol products diminished the more the verbal descriptors implied a deviation fromRegular. The implications of these findings are discussed in terms of policy implications for lower strength alcohol labelling and associated public health outcomes.

Statement of contribution

What is already known about this subject?

Current UK and EU legislation limits the number of low strength verbal descriptors and the associated alcohol by volume (ABV) to 1.2% ABV and lower.

There is growing interest from policymakers and producers to extend the range of lower strength alcohol products above the current cap of 1.2% ABV set out in national legislation.

There is a lack of evidence on how the general population perceives verbal descriptors of alcohol product strength (both low and high).

What does this study add?

Verbal descriptors of lower strength wine and beer form two clusters and effectively communicate reduced alcohol content.

Low, Lower, Light, Lighter,andReducedwere considered lower in strength thanRegular(average %ABV).

Descriptors using intensifiers (Extra Low, Super Low, Extra Light,andSuper Light) were considered lowest in strength.

Similar clustering in perceived strength was observed amongst the high verbal descriptors.

The appeal of alcohol products reduced the more the verbal descriptors implied a deviation fromRegular.
Multiple growth periods predict unfavourable pathology in patients with small renal masses
Authors: Jang Alex , Patel Hiten D. , Riffon Mark , Gorin Michael A. , Semerjian Alice , Johnson Michael H. , Allaf Mohamad E. , Pierorazio Phillip M.
Published: October 2017

Objective

To use the number of positive growth periods as a characterization of the growth of small renal masses in order to determine potential predictors of malignancy.

Patients and Methods

Patients who underwent axial imaging at multiple time points prior to surgical resection for a small renal mass were queried. Patients were categorized based on their pathological tumour grade and stage: favourable (benign, chromophobe and low‐grade pT1–2 renal cell carcinoma [RCC]) vs unfavourable (high‐grade of any stage and low‐grade pT3–4 RCC). A positive growth period was counted each time the difference in greatest tumour diameters between two images was positive. The Cochran–Armitage trend test and Somers' D association were used to determine if the number of positive growth periods was correlated with unfavourable pathology.

Results

Of the 124 patients, 86 (69.4%) had favourable pathology and 38 (30.6%) had unfavourable pathology. Those who had favourable pathology were younger than those who had unfavourable pathology: median (interquartile range [IQR]) 61.0 (52.2–66.0) vs 68.5 (61.5–77.0); P < 0.001. The overall growth rate was higher in the unfavourable group, but was not statistically significant: mean (sd) 0.7 (1.7) vs 1.6 (2.8) cm/year; P = 0.07. There was a significant trend difference in the number of positive growth periods between favourability groups (P = 0.02). An association between increased number of positive growth periods and unfavourable pathology was observed: 0.15 (95% confidence interval 0.02, 0.29). The ratios of favourable to unfavourable pathology were 1.8, 1.0, 0.66, 0.59 and 0 as the number of positive growth periods increased from 0 to 4, respectively.

Conclusion

While overall growth rate was not predictive of pathology favourability, there was a positive association between the number of positive growth periods and unfavourable pathology. The number of positive growth periods may be a potential parameter for malignant potential in patients undergoing active surveillance for small renal masses.
Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement
Authors: Hirose Takanori , Nobusawa Sumihito , Sugiyama Kazuhiko , Amatya Vishwa J. , Fujimoto Naomi , Sasaki Atsushi , Mikami Yoshiki , Kakita Akiyoshi , Tanaka Shinya , Yokoo Hideaki
Published: October 2017

Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well‐bordered, nodular tumors often associated with cystic areas and contrast‐enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow‐up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by “astroblastic” pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S‐100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break‐apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma.
Epithelioid glioblastomas stratify into established diagnostic subsets upon integrated molecular analysis
Authors: Korshunov Andrey , Chavez Lukas , Sharma Tanvi , Ryzhova Marina , Schrimpf Daniel , Stichel Damian , Capper David , Sturm Dominik , Kool Marcel , Habel Antje , Kleinschmidt‐DeMasters Bette K. , Rosenblum Marc , Absalyamova Oksana , Golanov Andrey , Lichter Peter , Pfister Stefan M. , Jones David T.W. , Perry Arie , von Deimling Andreas
Published: October 2017

Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as “eGBM.” Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort. Methylation patterns, copy number alterations, and mutational analysis data, in combination with clinical findings disclosed three different, well established tumor subtypes: (i) PXA‐like tumors with favorable prognosis, predominantly in children and young adults (38), (ii) IDHwt GBM‐like tumors with poor prognosis, mainly occurring in older adults, albeit with more frequent BRAF mutations (17), and (iii) RTK1 pediatric GBM‐like neoplasms of intermediate prognosis in children and young adults, associated with chromothripsis and frequent PDGFRA amplifications (9). We conclude that the histopathologically defined eGBM do not represent a single diagnostic entity, but rather at least three molecularly and biologically distinct categories. Therefore, additional molecular testing through genome‐wide molecular profiling is recommended to further stratify these rare cases.
Mauritius on fire: Tracking historical human impacts on biodiversity loss
Authors: Gosling William D. , de Kruif Jona , Norder Sietze J. , de Boer Erik J. , Hooghiemstra Henry , Rijsdijk Kenneth F. , McMichael Crystal N. H.
Published: October 2017

Fire was rare on Mauritius prior to human arrival (AD 1598); subsequently three phases of elevated fire activity occurred: ca 1630–1747, 1787–1833, and 1950–modern. Elevated fire frequency coincided with periods of high human impact evidenced from the historical record, and is linked to the extinction of island endemics.
Are Brazil nut populations threatened by fruit harvest?
Authors: Bertwell Todd D. , Kainer Karen A. , Cropper Wendell P. , Staudhammer Christina L. , de Oliveira Wadt Lúcia H.
Published: October 2017

Harvest of Brazil nuts from the large, iconic tree Bertholletia excelsa generates substantial income for smallholders, providing a strong incentive to conserve the mature forests where it grows. Although much previous work has focused on the impact of nut harvest on new seedling recruits into B. excelsa populations, the connection between harvest rates and long‐term population stability is still unclear. Moreover, there is additional uncertainty for Brazil nut management in terms of population response to climate change and other anthropogenic influences. We drew on 14 years of research in two sites in Acre, Brazil with different B. excelsa nut harvest intensities (39% and 81%), to produce stochastic and deterministic matrix population models which incorporated parameter uncertainty in vital rates. Adult abundance was projected to remain close to the current observed abundance or higher through the next 50 years. Elasticity analyses revealed that the asymptotic population growth rate (λ) was most sensitive to stasis vital rates in sapling, juvenile, and adult stages. Deterministic transition matrices calculated using diameter growth rates dependent on rainfall yielded average λ values around 1.0 under extreme high, extreme low, and average annual rainfall. While sustained high rates of Brazil nut harvest and climate change could potentially negatively impact B. excelsa populations, changes in human use of the forested landscape are more immediate concern. To reduce the risk of population decline, smallholders and managers of B. excelsa rich forests should focus on conservation of pre‐mature and mature individuals.
An Expanded View of Joint Attention: Skill, Engagement, and Language in Typical Development and Autism
Authors: Adamson Lauren B. , Bakeman Roger , Suma Katharine , Robins Diana L.
Published: October 2017

This study provides an expanded view of joint attention and its relation to expressive language development. A total of 144 toddlers (40 typically developing, 58 with autism spectrum disorder [ASD], 46 with developmental delay [DD]) participated at 24 and 31 months. Toddlers who screened positive for ASD risk, especially those subsequently diagnosed with ASD, had poorer joint attention skills, joint engagement during parent–toddler interaction, and expressive language. Findings highlight the dynamic relation between joint attention and language development. In the ASD and DD groups, joint engagement predicted later expressive vocabulary, significantly more than predictions based on joint attention skills. Joint engagement was most severely impacted when toddlers did not talk initially and improved markedly if they subsequently began to speak.
Bronchiectasis and deteriorating lung function in agammaglobulinaemia despite immunoglobulin replacement therapy
Authors: Stubbs A , Bangs C , Shillitoe B , Edgar J D , Burns S O , Thomas M , Alachkar H , Buckland M , McDermott E , Arumugakani G , Jolles M S , Herriot R , Arkwright P D
Published: October 2017

Immunoglobulin replacement therapy enhances survival and reduces infection risk in patients with agammaglobulinaemia. We hypothesized that despite regular immunoglobulin therapy, some patients will experience ongoing respiratory infections and develop progressive bronchiectasis with deteriorating lung function. One hundred and thirty-nine (70%) of 199 patients aged 1–80 years from nine cities in the United Kingdom with agammaglobulinaemia currently listed on the UK Primary Immune Deficiency (UKPID) registry were recruited into this retrospective case study and their clinical and laboratory features analysed; 94% were male, 78% of whom had Bruton tyrosine kinase (BTK) gene mutations. All patients were on immunoglobulin replacement therapy and 52% had commenced therapy by the time they were 2 years old. Sixty per cent were also taking prophylactic oral antibiotics; 56% of patients had radiological evidence of bronchiectasis, which developed between the ages of 7 and 45 years. Multivariate analysis showed that three factors were associated significantly with bronchiectasis: reaching 18 years old [relative risk (RR) = 14·2, 95% confidence interval (CI) = 2·7–74·6], history of pneumonia (RR = 3·9, 95% CI = 1·1–13·8) and intravenous immunoglobulin (IVIG) rather than subcutaneous immunoglobulin (SCIG) = (RR = 3·5, 95% CI = 1·2–10·1), while starting immunoglobulin replacement after reaching 2 years of age, gender and recent serum IgG concentration were not associated significantly. Independent of age, patients with bronchiectasis had significantly poorer lung function [predicted forced expiratory volume in 1 s 74% (50–91)] than those without this complication [92% (84–101)] (P < 0·001). We conclude that despite immunoglobulin replacement therapy, many patients with agammaglobulinaemia can develop chronic lung disease and progressive impairment of lung function.
Case of neuromyelitis optica with recurrent stomach carcinoma
Authors: Takewaki Daiki , Kasai Takashi , Itoh Kyoko , Shiga Kensuke , Tokui Masafumi , Tanaka Akihiro , Noto Yu‐ichi , Ohara Tomoyuki , Mizuno Toshiki
Published: October 2017

Background

Neuromyelitis optica (NMO) is an autoimmune astrocytopathy associated with anti‐aquaporin‐4 (AQP4). The development of NMO in the setting of cancer suggests that AQP4 autoimmunity might in some cases be paraneoplastic.

Case presentation

We report an 85‐year‐old woman who developed a right optic neuritis and a longitudinally extensive transverse myelitis associated with AQP4 autoantibodies after the relapse of stomach cancer. Histopathological observations in several case reports have led to the hypothesis that the NMO associated with the malignancy is caused by an autoimmunity against abnormally expressed AQP4 on tumor cells. However, we found no AQP4 antigen on the cancer cells in our resected tissues. Our findings did not support the concept of a paraneoplastic process in the narrow sense.

Conclusions

The exact mechanisms of cancer‐related NMO, which might be multifactorial, remain controversial.
Effectiveness of terrestrial protected areas for conservation of lake fish communities
Authors: Chu Cindy , Ellis Lucy , de Kerckhove Derrick T.
Published: October 2017

Freshwater protected areas are rare even though freshwater ecosystems are among the most imperiled in the world. Conservation actions within terrestrial protected areas (TPAs) such as development or resource extraction regulations may spill over to benefit freshwater ecosystems within their boundaries. Using data from 175 lakes across Ontario, Canada, we compared common indicators of fish‐assemblage status (i.e., species richness, Shannon diversity index, catch per unit effort, and normalized‐length size spectrum slopes) to evaluate whether TPAs benefit lake fish assemblages. Nearest neighbor cluster analysis was used to generate pairs of lakes: inside versus outside, inside versus bordering, and bordering versus outside TPAs based on lake characteristics. The diversity and abundance indicators did not differ significantly across comparisons, but normalized‐length size spectrum slopes (NLSS) were significantly steeper in lakes outside parks. The latter indicated assemblage differences (greater abundances of small‐bodied species) and less‐efficient energy transfer through the trophic levels of assemblages outside parks. Although not significantly different, pollution‐ and turbidity‐tolerant species were more abundant outside parks, whereas 3 of the 4 pollution‐intolerant species were more abundant within parks. Twenty‐one percent of the difference in slopes was related to higher total dissolved solids concentrations and angling pressure. Our results support the hypothesis that TPAs benefit lake fish assemblages and suggest that NLSS slopes are informative indicators for aquatic protected area evaluations because they represent compositional and functional aspects of communities.
Mesenchymal‐like stem cells in canine ovary show high differentiation potential
Authors: Trindade Hill A. B. , Therrien J. , Garcia J. M. , Smith L. C.
Published: October 2017

Objectives

Recent studies have reported the existence of stem cells in ovarian tissue that show enhanced proliferative and differentiation potential compared to other adult tissues. Based on this evidence, we hypothesized that ovarian tissue contained mesenchymal‐like stem cells (MSC) that could be isolated using a novel rapid plastic adhesion technique.

Materials and methods

We established MSC lines derived from ovarian and adipose tissue based on their ability to rapidly adhere to plastic culture dishes in the first 3 hours after plating and studied their potentiality in terms of molecular markers and differentiation capacity.

Results

Morphological and kinetic properties of in vitro cultured ovarian MSC were similar to adipose‐derived MSC, and both reached senescence after similar passage numbers. Ovarian‐derived MSC expressed mesenchymal (CD90 and CD44) but not haematopoietic markers (CD34 and CD45), indicating similarity to adipose‐derived MSC. Moreover, ovarian‐derived MSC expressed NANOG, TERT, SOX2, OCT4 and showed extensive capacity to differentiate not only into adipogenic, osteogenic and chondrogenic tissue but also towards neurogenic and endodermal lineages and even precursors of primordial germ cells.

Conclusion

These results show for the first time the derivation of ovarian cells with the molecular properties of MSC as well as wide differentiation potential. Canine ovarian tissue is accessible, expandable, multipotent and has high plasticity, holding promise for applications in regenerative medicine.
IFI16 restoration in hepatocellular carcinoma induces tumour inhibition via activation of p53 signals and inflammasome
Authors: Lin Wei , Zhao Zhiguang , Ni Zhonglin , Zhao Yaxin , Du Wenjun , Chen Shijun
Published: October 2017

Objective

Interferon‐inducible 16 (IFI16) is known to involve in p53‐dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death‐derived free DNA. In this study, we investigated the anti‐tumour role of IFI16 in hepatocellular carcinoma (HCC).

Materials and methods

Hepatocellular carcinoma tissues (n = 20) and corresponding non‐neoplastic tissues (n = 20) were collected to determine the expression of IFI16. After the transfection of pcDNA3.1‐IFI16 into Huh7 and SMMC7721 cells in vitro, the influence of IFI16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI16 in vivo was further investigated.

Results

The expression of IFI16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI16 could activate p53 at Ser15 to up‐regulate the p21WAF1/CIP1 level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin‐α (20 μmol/L). Moreover, IFI16‐induced tumour cell death promoted the recruitment of inflammasome complex to enhance tumour inhibition, but the caspase‐1 inhibitor Ac‐YVAD‐CMK (50 μmol/L) could suppress this process in HCC. The results in vivo indicated that restored expression of IFI16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome.

Conclusion

IFI16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome.
Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long‐term follow‐up
Authors: Peled Yael , Lavee Jacob , Raichlin Eugenia , Katz Moshe , Arad Michael , Kassif Yigal , Peled Amir , Asher Elad , Elian Dan , Har‐Zahav Yedael , Shlomo Nir , Freimark Dov , Goldenberg Ilan , Klempfner Robert
Published: October 2017

Aim

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality after heart transplantation (HT). Enhanced platelet reactivity is a contributing factor. We aimed to investigate the association between early initiation of aspirin therapy post‐HT and the 15‐year risk of the development of CAV.

Methods

We studied 206 patients who underwent HT between 1991 and 2016. Multivariate Cox proportional hazards regression modeling was employed to evaluate the association between early aspirin initiation and the long‐term risk of CAV.

Results

Ninety‐seven patients (47%) received aspirin therapy. At 15 years of follow‐up, the rate of CAV was lowered by sixfold in patients treated with aspirin compared with the non‐treated patients: 7% vs 37% (log‐rank P‐value<.001). The corresponding rates of the combined end‐point of CAV or death were also lower in patients treated with aspirin, compared with the non‐treated patients: 42% vs 78% (log‐rank P < .001). Consistently, multivariate analysis showed that early aspirin therapy was associated with a significant 84% (P < .001) reduction in CAV risk, and with a corresponding 68% (P < .0001) reduction in the risk of the combined end‐point of CAV or death. We further validated these results using a propensity score‐adjusted Cox model.

Conclusions

Early aspirin initiation is independently associated with a significant reduction in the risk of CAV.
The plans they are a‐changin’: More frequent iterative adjustment of regional priorities in the transition to local actions can benefit implementation
Authors: Cheok Jessica , Pressey Robert L. , Weeks Rebecca , VanDerWal Jeremy , Storlie Collin
Published: October 2017

Aim

Regional‐scale assessments are frequently conceived to guide the strategic application of conservation actions. Although changes to priority areas from initial assessments are inevitable, the transition from regional‐scale assessment to implementing local actions is poorly understood. An outstanding question concerns the frequency with which regionally assessed priorities should be updated as actions are implemented. We address this gap by simulating the incremental implementation of local actions guided by regional conservation assessments, exploring how update frequency can influence aspects of translating regional assessments to local actions.

Location

Fiji coral reefs.

Methods

Our simulations were designed within the framework of systematic conservation planning, with implemented actions simulated based on conservation value in achieving objectives and feature rarity. Other decision rule‐sets were put in place to simulate on‐the‐ground negotiations that are often necessary when transitioning from regional‐scale conservation assessments to local actions. We use our simulations to evaluate how the frequency of updating regional priorities influences (1) total time taken to achieve objectives represented by numbers of planning units investigated, (2) total extent of final reserve systems and (3) spatial overlap between initial regional priorities and final implemented reserves.

Results

Changes in the frequencies of updating did not influence the time taken to achieve conservation objectives, nor the total extent of final reserve systems. However, there was a significant difference in the number of times planning units were re‐investigated for implementing actions within in scenarios that involved more frequent updates. Spatial overlap between initial regional priorities and final implemented reserves increased with decreases in update frequency.

Main conclusions

We find two potential benefits to updating priorities more frequently: (1) faster achievement of objectives for high‐priority features and (2) greater potential to capitalize on areas previously investigated. Our findings provide insights into trade‐offs to consider regarding the frequency of updating regional assessments, which varies depending on the planning context.
Niche centrality and human influence predict rangewide variation in population abundance of a widespread mammal: The collared peccary (Pecari tajacu)
Authors: Martínez‐Gutiérrez P. G. , Martínez‐Meyer E. , Palomares F. , Fernández N.
Published: October 2017

Aim

(1) To evaluate whether geographic variation in population abundance of a widespread mammal (Pecari tajacu) is related to its location with respect to the centroid of its ecological niche or to the centroid of its geographic range. (2) To assess whether the abundance–niche centrality relationship defines the maximum expected abundance at any location, rather than the realized abundance. (3) To test whether including human impacts improves the abundance–niche centrality relationship, and therefore the prediction of geographic variation in population abundance.

Location

The Americas.

Methods

We modelled the ecological niche of the species using occurrence and environmental data and created spatial models of distance to the niche centroid (DNC) and to the geographic centroid (DGC). We tested the relationships between population abundance andDNCand between abundance andDGC. We evaluated whether the rate of change in the abundance–DNCrelationship was steeper near the upper boundary of quantile regressions. We tested whether the human influence index (HII) contributed to improve niche‐based predictions of population abundance. Finally, we generated broad‐scale predictions of collared peccary population abundances.

Results

We found a negative relationship between abundance andDNCand a non‐significant relationship between abundance andDGC. The abundance–DNCrelationship was wedge‐shaped, steeper in the upper quantile boundary than in the median.HIIalso had a negative effect on abundance. The model includingDNCandHIIwas best supported for predicting the median abundance, whileDNCalone was the best to predict the upper boundary of population abundances.

Main conclusions

Population abundances are associated with the structure of the ecological niche, especially the maximum abundance expected in an area. Thus, theDNCapproach can be useful in obtaining a spatial approximation of potential abundance patterns at biogeographic extents. To achieve a better prediction of realized abundances, it is critical to consider the human influence.
Habitat disturbance selects against both small and large species across varying climates
Authors: Gibb H. , Sanders N. J. , Dunn R. R. , Arnan X. , Vasconcelos H. L. , Donoso D. A. , Andersen A. N. , Silva R. R. , Bishop T. R. , Gomez C. , Grossman B. F. , Yusah K. M. , Luke S. H. , Pacheco R. , Pearce‐Duvet J. , Retana J. , Tista M. , Parr C. L.
Published: October 2017

Global extinction drivers, including habitat disturbance and climate change, are thought to affect larger species more than smaller species. However, it is unclear if such drivers interact to affect assemblage body size distributions. We asked how these two key global change drivers differentially affect the interspecific size distributions of ants, one of the most abundant and ubiquitous animal groups on earth. We also asked whether there is evidence of synergistic interactions and whether effects are related to species’ trophic roles. We generated a global dataset on ant body size from 333 local ant assemblages collected by the authors across a broad range of climates and in disturbed and undisturbed habitats. We used head length (range: 0.22–4.55 mm) as a surrogate of body size and classified species to trophic groups. We used generalized linear models to test whether body size distributions changed with climate and disturbance, independent of species richness. Our analysis yielded three key results: 1) climate and disturbance showed independent associations with body size; 2) assemblages included more small species in warmer climates and fewer large species in wet climates; and 3) both the largest and smallest species were absent from disturbed ecosystems, with predators most affected in both cases. Our results indicate that temperature, precipitation and disturbance have differing effects on the body size distributions of local communities, with no evidence of synergistic interactions. Further, both large and small predators may be vulnerable to global change, particularly through habitat disturbance.
Automated analysis of seizure semiology and brain electrical activity in presurgery evaluation of epilepsy: A focused survey
Authors: Ahmedt‐Aristizabal David , Fookes Clinton , Dionisio Sasha , Nguyen Kien , Cunha João Paulo S. , Sridharan Sridha
Published: October 2017

Epilepsy being one of the most prevalent neurological disorders, affecting approximately 50 million people worldwide, and with almost 30–40% of patients experiencing partial epilepsy being nonresponsive to medication, epilepsy surgery is widely accepted as an effective therapeutic option. Presurgical evaluation has advanced significantly using noninvasive techniques based on video monitoring, neuroimaging, and electrophysiological and neuropsychological tests; however, certain clinical settings call for invasive intracranial recordings such as stereoelectroencephalography (SEEG), aiming to accurately map the eloquent brain networks involved during a seizure. Most of the current presurgical evaluation procedures focus on semiautomatic techniques, where surgery diagnosis relies immensely on neurologists’ experience and their time‐consuming subjective interpretation of semiology or the manifestations of epilepsy and their correlation with the brain's electrical activity. Because surgery misdiagnosis reaches a rate of 30%, and more than one‐third of all epilepsies are poorly understood, there is an evident keen interest in improving diagnostic precision using computer‐based methodologies that in the past few years have shown near‐human performance. Among them, deep learning has excelled in many biological and medical applications, but has advanced insufficiently in epilepsy evaluation and automated understanding of neural bases of semiology. In this paper, we systematically review the automatic applications in epilepsy for human motion analysis, brain electrical activity, and the anatomoelectroclinical correlation to attribute anatomical localization of the epileptogenic network to distinctive epilepsy patterns. Notably, recent advances in deep learning techniques will be investigated in the contexts of epilepsy to address the challenges exhibited by traditional machine learning techniques. Finally, we discuss and propose future research on epilepsy surgery assessment that can jointly learn across visually observed semiologic patterns and recorded brain electrical activity.
What Style Liquidity Timing Skills Do Mutual Fund Managers Possess?
Authors: Bazgour Tarik , Bodson Laurent , Sougné Danielle
Published: October 2017

Recent studies claim that mutual fund managers demonstrate strong MARKET liquidity timing skills. We extend their liquidity timing tests to the four‐factor case and investigate liquidity timing skills with respect to the MARKET, SIZE, VALUE and MOMENTUM factors. Contrary to these claims, we find no evidence that fund managers adjust market exposure in anticipation of market liquidity changes. We find rather strong evidence that fund managers successfully overweight small stocks as market liquidity increases. Our study also demonstrates that it is easy to misidentify SIZE liquidity timing as MARKET liquidity timing in models that focus only on MARKET liquidity timing.