bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does Transfer Pricing Risk Affect Premiums in Cross‐Border Mergers and Acquisitions?
Authors: Mescall Devan , Klassen Kenneth J.
Published: February 2018

This study investigates how transfer pricing risk affects the premiums in cross‐border mergers and acquisitions (M&A). Differences in the rigor of transfer pricing enforcement and the severity and clarity of rules across countries create differential risk of material costs for multinationals as they expand globally. We use 448 country‐level transfer pricing risk assessments by global transfer pricing partners and managers from two firms in 33 countries to develop a metric of country‐year transfer pricing risks. The resulting measure of transfer pricing risk is used to analyze the premiums of 3,103 cross‐border M&A from 2000 to 2012. We find that lower bid premiums are associated with higher transfer pricing risk in the target's country. We find the relation is stronger when expected future transfer pricing benefits are larger. Our results, consistent with the views of experts in the field, provide the first archival evidence that acquirers consider synergies created by future tax planning when estimating the value of a target.
Auditor Experience and the Timeliness of Litigation Loss Contingency Disclosures*
Authors: Chen Feng , Hou Yu , Richardson Gordon , Ye Minlei
Published: February 2018

This paper hypothesizes and finds that firms audited by city‐industry specialists have more timely disclosures of contingent losses from litigation when there is no news coverage relating to the legal case prior to management disclosures. A closer examination reveals that this result is explained by the specialist auditors’ prior experience auditing clients in the same office and industry who are involved with litigation. In our setting, disclosures of litigation‐related contingent losses, we identify two kinds of knowledge generated from experience: industry knowledge and litigation knowledge. Industry knowledge helps auditors detect and correct poor implementation of guidance for litigation loss contingency disclosures. Auditors gain litigation knowledge from auditing clients in a given office and industry with previous involvement as defendants. Thus, the two types of knowledge interact in their effects on reporting outcomes.
How to measure capital investment efficiency: a literature synthesis
Authors: Gao Ru , Yu Xin
Published: February 2018

This article reviews and integrates the empirical literature on the measurement of investment efficiency in the areas of accounting and finance. We identify the theories behind the measures and provide a framework which organises the measures of investment efficiency into three groups: those based on neoclassical theories, agency theory and real options theory. Furthermore, the advantages and disadvantages of each type of measure are discussed, allowing researchers to compare and then ascertain the most appropriate measure for their research purpose and research context.
Psychotic experiences and religiosity: data from the WHO World Mental Health Surveys
Authors: Kovess‐Masfety V. , Saha S. , Lim C. C. W. , Aguilar‐Gaxiola S. , Al‐Hamzawi A. , Alonso J. , Borges G. , de Girolamo G. , de Jonge P. , Demyttenaere K. , Florescu S. , Haro J. M. , Hu C. , Karam E. G. , Kawakami N. , Lee S. , Lepine J. P. , Navarro‐Mateu F. , Stagnaro J. C. , ten Have M. , Viana M. C. , Kessler R. C. , McGrath J. J. ,   the WHO World Mental Health Survey Collaborators
Published: February 2018

Objectives

Religiosity is often associated with better health outcomes. The aim of the study was to examine associations between psychotic experiences (PEs) and religiosity in a large, cross‐national sample.

Methods

A total of 25 542 adult respondents across 18 countries from the WHO World Mental Health Surveys were assessed for PEs, religious affiliation and indices of religiosity, DSM‐IV mental disorders and general medical conditions. Logistic regression models were used to estimate the association between PEs and religiosity with various adjustments.

Results

Of 25 542 included respondents, 85.6% (SE = 0.3) (n = 21 860) respondents reported having a religious affiliation. Overall, there was no association between religious affiliation status and PEs. Within the subgroup having a religious affiliation, four of five indices of religiosity were significantly associated with increased odds of PEs (odds ratios ranged from 1.3 to 1.9). The findings persisted after adjustments for mental disorders and/or general medical conditions, as well as religious denomination type. There was a significant association between increased religiosity and reporting more types of PEs.

Conclusions

Among individuals with religious affiliations, those who reported more religiosity on four of five indices had increased odds of PEs. Focussed and more qualitative research will be required to unravel the interrelationship between religiosity and PEs.
An investigation of an open‐access model for scaling up methadone maintenance treatment
Authors: Madden Lynn M. , Farnum Scott O. , Eggert Kathryn F. , Quanbeck Andrew R. , Freeman Robert M. , Ball Samuel A. , Schottenfeld Richard S. , Shi Julia M. , Savage Mary Ellen , Barry Declan T.
Published: February 2018

Aims

To examine retrospectively patient and programmatic outcomes following the development and implementation of an ‘open‐access’ model in which prospective patients were enrolled rapidly in methadone maintenance treatment, irrespective of ability to pay, and provided real‐time access to multiple voluntary treatment options.

Design

Medical and administrative records were abstracted to compare data for 1 year before and 9 years after initiating the implementation of an open‐access treatment model in May 2007.

Setting

Methadone maintenance treatment center in Connecticut, USA.

Participants

Individuals with opioid use disorder entering treatment between July 2006 and June 2015. In June 2015, 64% (n = 2594) of the sample were men and 80% (n = 3133) reported that they were white.

Intervention

The Network for the Improvement of Addiction Treatment‐informed open‐access treatment model uses process improvement strategies to improve treatment access and capacity.

Measurements

Census, waiting time, retention, non‐medical opioid use, patient mortality and financial sustainability (net income and state‐block grants as proportions of revenue).

Findings

In the 9 years following the initial implementation of the open‐access model, patient census increased by 183% from 1431 to 4051, and average waiting‐time days decreased from 21 to 0.3 (same day) without apparent deleterious effects on rates of retention, non‐medical opioid use or mortality. Between fiscal years (FY) 06 and FY 15, net operating margin rose from 2 to 10%, while state‐block grant revenues declined 14% and the proportion of total revenue from state‐block grant revenue decreased from 49 to 24%.

Conclusions

An open‐access model for rapid enrolment of people with opioid use disorder in methadone treatment appears to improve treatment access, capacity, and financial sustainability without evidence of deleterious effects on treatment outcomes.
Trajectory classes of cannabis use and heavy drinking among rural African American adolescents: multi‐level predictors of class membership
Authors: Barton Allen W. , Brody Gene H. , Zapolski Tamika C. B. , Goings Trenette C. , Kogan Steven M. , Windle Michael , Yu Tianyi
Published: February 2018

Aims

To inform research on the etiology and prevention of substance use among rural African American youth by (a) identifying developmental trajectory classes of cannabis use and heavy drinking across adolescence and young adulthood and (b) examining associations between trajectory class membership and multi‐level assessments of risk factors.

Design

A prospective study spanning 9 years with assessments of cannabis use and heavy drinking, the catecholamines epinephrine and norepinephrine, perceived stress and psychosocial risk factors.

Setting

Rural communities in the southeastern United States.

Participants

African American youth (n = 518).

Measurements

Participants were assessed for cannabis use and heavy drinking at seven assessments beginning at 16 years of age and continuing to 25 years of age. At age 19, participants provided overnight urine voids that were assayed for catecholamines, a biological marker of life stress resulting from sympathetic nervous system activation. At ages 16 and 19, participants provided information on malleable psychosocial risk factors.

Findings

Latent class growth models revealed three distinct trajectory classes for cannabis use and for heavy drinking. Higher levels of circulating stress hormones and perceived stress were associated with classes reporting greater substance use over time (all Ps < 0.05). A composite of selected risk factors discriminated class membership (all Ps < 0.05). Trajectory classes characterized by rapid usage increases in early adulthood exhibited the greatest increase in deviant peer affiliations between ages 16 and 19 years.

Conclusions

Rural African American youth's cannabis use and heavy drinking across adolescence and young adulthood demonstrate distinct developmental courses; a small number of risk factors and measures of biological and perceived stress differentiate class membership prognostically. Variability over time in these measures, specifically an increase in deviant peer affiliation, may help to account for steep increases in young adulthood.
Diversity of terrestrial isopod species in the Chambi National Park (Kasserine, Tunisia)
Authors: Khila Mouna , Zaabar Wahiba , Achouri Mohamed Sghaier
Published: February 2018

Diversity of terrestrial isopods across habitats and altitude was studied in the National Park of Chambi (central Tunisia). Samples were collected over five years in seven sites (S1–S7), within an altitudinal range from 750 to 1,500 m a.s.l. Twelve species belonging to five families were identified, with one endemic species (Porcellio djahizi) to this area, and three species were present in all sites (P. djahizi, Leptotrichus panzerii and Armadillidium tunisiense). Agnaridae represented by Hemilepistus reaumurii species was the most abundant family (58.77%) and found in only one site. Our results showed differences in species richness between sites. Indeed, S2 and S3 (900 and 1,050 m) showed the highest species richness with 11 species each. This result validates the hypothesis of mid‐elevational richness peak and contradicts the theory of large sampling regimes in determining the relationship between species richness and elevation. Terrestrial isopod species richness in the Chambi Mountain tends to decrease with altitude: 11 species in S2 and S3 to four species in S7. The highest Shannon–Wiener diversity index value was observed in S2 (H′ = 3.21 bits). Canonical correspondence analysis revealed that H. reaumurii was positively correlated with temperature whereas A. tunisiense and P. djahizi were the only species positively correlated with altitude.
Cross‐sectional studies – what are they good for?
Authors: Kesmodel Ulrik S.
Published: February 2018

Cross‐sectional studies serve many purposes, and the cross‐sectional design is the most relevant design when assessing the prevalence of disease, attitudes and knowledge among patients and health personnel, in validation studies comparing, for example, different measurement instruments, and in reliability studies. This paper describes the use of cross‐sectional studies and provides examples within obstetrics and gynecology. Caveats are also described; for example, when cross‐sectional data is used for analytical purposes of associations between an exposure and an outcome, authors and readers should be careful not to make causal inferences, unless the exposure may safely be assumed to be stable over time and not influenced by experiencing the outcome. In such cases, analyses are also subject to selection and information bias as well as confounding.
Better educational inclusion of migrant children in urban schools? Exploring the influences of the population control policy in large Chinese cities
Authors: Liu Ting , Holmes Kathryn , Zhang Minghong
Published: February 2018

The educational inclusion of rural–urban migrant children in Chinese urban schools has been promoted in the past decades. This paper provides a contextualized interpretation of recent policy developments governing large Chinese cities and evaluates its impact upon the status of migrant children's education. Drawing on data collected from 1,331 migrant children in urban inclusive schools, this study compared current migrant children's family backgrounds and psychological sense of belonging at school in relation to educational outcomes at the primary education level. Results showed that migrant children's socioeconomic status (SES) levels were slightly higher than their counterparts in inclusive schools and a salient SES stratification of migrant students was found. This correlates with students’ reports of fewer incidences of discrimination than hypothesized. Furthermore, capital in migrant families was positively associated with the psychological sense of belonging and academic achievement. These results reveal a significant change to migrant students’ SES as a result of the recent population control policy pertaining to China's large cities since 2014. Implications for research and educational practice, especially with at‐risk migrant students of low‐SES, are discussed.
Impact of postdiagnostic statin use on ovarian cancer mortality: A systematic review and meta‐analysis of observational studies
Authors: Li Xia , Zhou Jing
Published: February 2018

Aims

To comprehensively evaluate the association between postdiagnostic statin use and mortality of ovarian cancer (OC) patients.

Methods

Using a comprehensive strategy, multiple databases (Medline, Embase and Web of Science) were systematically searched to identify observational studies that examined the correlation between statin use and OC mortality up to 31 December 2017. The studies were independently reviewed and selected based on predetermined selection criteria. Data were extracted independently and in duplicate. The risk of bias was evaluated with the Newcastle–Ottawa scale. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were summarized with a profile likelihood random effects model.

Results

Of 269 studies, eight cohort studies of 19 904 OC patients met the inclusion criteria. Postdiagnostic statin use was inversely associated with all‐cause mortality/overall survival (summarized HR = 0.74; 95%CI = 0.63–0.87; I2 = 55%; n = 7) and cancer‐specific mortality (summarized HR = 0.87; 95%CI = 0.80–0.95; I2 = 0%; n = 3) of OC patients. These findings were consistent by subgroup analyses stratified by study and patient characteristics as well as adjustments made for potential confounders. A meta‐regression analysis found no effect of modification by these variables. Of note, similar significant inverse effects were also observed when increasing the intensity (highest vs. lowest) of postdiagnostic statin use (summarized HR = 0.84; 95%CI = 0.74–0.96; I2 = 0%; n = 3).

Conclusion

Postdiagnostic statin use can improve the survival of patients with OC. Further prospective cohort and randomized controlled trials are warranted to confirm the therapeutic role of statin use on the outcome of OC.
Trends and predictors of cesarean birth in Singapore, 2005‐2014: A population‐based cohort study
Authors: Chi Claudia , Pang Deanette , Aris Izzuddin M. , Teo Wei Ting , Li Sarah Weiling , Biswas Arijit , Yong Eu Leong , Chong Yap Seng , Tan Kelvin , Kramer Michael S.
Published: February 2018

Background

Rates of cesarean birth have continued to rise in many high‐income countries. We examined the temporal trends and predictors of cesarean birth in Singapore.

Methods

Linked hospitalization and Birth Registry data were used to examine all live births to Singaporean citizens and permanent residents between January 1, 2005 and December 31, 2014 (n = 342 932 births). We calculated cesarean rates and age‐adjusted average annual percent change (AAPC) in those rates and used sequential multivariable regression modeling to assess the contribution of changes in predictors to the change in cesarean rates over time.

Results

The overall cesarean rate in Singapore rose from 32.2% in 2005 to 37.4% in 2014. Among singleton, cephalic, term pregnancies, the two major predictions of cesarean were nulliparity and previous cesarean, each accounting for just over one‐third of all cesareans.

Higher AAPC was observed in nulliparous women of Indian ethnicity (0.74% [95% confidence interval 0.68‐0.80]) compared with Chinese (0.62% [0.60‐0.65]) or Malay women (0.63% [0.59‐0.68]), and in women who delivered in private hospitals (0.62% [0.60‐0.64]) compared with those delivered under subsidized care in public hospitals (0.58% [0.52‐0.63]). Parity and education had the largest influences on cesarean birth trend (attenuation of AAPC from 0.62% [0.59‐0.66] to 0.39% [0.38‐0.40] after adjustment).

Conclusion

Cesarean birth has continued to rise at a steady rate in Singapore. Strategies to curb this temporal increase include avoidance of medically unnecessary primary cesarean and attempts at trial of labor and vaginal delivery among women with a history of prior cesarean.
‘I'm happy to own my implicit biases’: Public encounters with the implicit association test
Authors: Yen Jeffery , Durrheim Kevin , Tafarodi Romin W.
Published: February 2018

The implicit association test (IAT) and concept of implicit bias have significantly influenced the scientific, institutional, and public discourse on racial prejudice. In spite of this, there has been little investigation of how ordinary people make sense of the IAT and the bias it claims to measure. This article examines the public understanding of this research through a discourse analysis of reactions to the IAT and implicit bias in the news media. It demonstrates the ways in which readers interpreted, related to, and negotiated the claims of IAT science in relation to socially shared and historically embedded concerns and identities. IAT science was discredited in accounts that evoked discourses about the marginality of academic preoccupations, and helped to position test‐takers as targets of an oppressive political correctness and psychologists as liberally biased. Alternatively, the IAT was understood to have revealed widely and deeply held biases towards racialized others, eliciting accounts that took the form of psychomoral confessionals. Such admissions of bias helped to constitute moral identities for readers that were firmly positioned against racial bias. Our findings are discussed in terms of their implications for using the IAT in prejudice reduction interventions, and communicating to the public about implicit bias.
Diminished CXCR5 expression in peripheral blood of patients with Sjögren's syndrome may relate to both genotype and salivary gland homing
Authors: Aqrawi L A , Ivanchenko M , Björk A , Ramírez Sepúlveda J I , Imgenberg-Kreuz J , Kvarnström M , Haselmayer P , Jensen J L , Nordmark G , Chemin K , Skarstein K , Wahren-Herlenius M
Published: February 2018

Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. C-X-C motif chemokine receptor 5 (CXCR5) is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand C-X-C motif chemokine ligand 13 (CXCL13). In this study we aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay. CXCR5+ and CXCL13+ cells in minor salivary glands were detected using immunohistochemistry. Our results demonstrated that SS-associated genetic polymorphisms affected the expression of CXCR5 (P < 0·01). Notably, a decreased percentage of CXCR5+ cells, with lower CXCR5 expression, was observed for most circulating B and T cell subsets in SS patients, reaching statistical significance in CD19+CD27+immunoglobulin (Ig)D+ marginal zone (P < 0·001), CD19+CD27+IgD– memory (P < 0·05) and CD27-IgD double-negative (P < 0·01) B cells and CD4+CXCR3–CCR6+ Th17 cells (P < 0·05). CXCL13 levels were increased in patient plasma (P < 0·001), and immunohistochemical staining revealed expression of CXCL13 and higher numbers of CXCR5+ cells (P < 0·0001) within focal infiltrates and interstitially in salivary glands of SS patients. In conclusion, we link a genetic susceptibility allele for SS to a functional phenotype in terms of decreased CXCR5 expression. The decrease of CXCR5+ cells in circulation was also related to homing of B and T cells to the autoimmune target organ. Therapeutic drugs targeting the CXCR5/CXCL13 axis may be useful in SS.
Impact of TSH during the first trimester of pregnancy on obstetric and foetal complications: Usefulness of 2.5 mIU/L cut‐off value
Authors: Hernández Marta , López Carolina , Soldevila Berta , Cecenarro Laura , Martínez‐Barahona María , Palomera Elisabet , Rius Ferran , Lecube Albert , Pelegay Maria José , García Jordi , Mauricio Dídac , Puig Domingo Manel
Published: February 2018

Objective

An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal‐maternal complications with first trimester maternal Thyrotropin (TSH) values.

Design

A retrospective study in a single tertiary care hospital was performed.

Patients

A total of 1981 pregnant women were studied during 2012.

Measurements

Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal‐maternal complications and newborn health parameters.

Results

Median TSH was 1.72 (0.99‐2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29‐3.28) vs 1.71 (0.96‐2.58) mIU/L (P = .009). Incidence of pre‐eclampsia was 3.2%; TSH in these women was 2.10 (1.40‐2.74) vs 1.71 (0.98‐2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00‐2.53) vs 1.68 (0.94‐2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5‐5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085‐2.329)], miscarriage [OR 1.702 (1.126‐2.572)] and premature birth [OR 1.39 (1.013‐1.876)], adjusted by mother's age. There was no association with the other outcomes analysed.

Conclusions

There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut‐off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.
The association between thyroid function and incidence of metabolic syndrome in euthyroid subjects: Tianjin chronic low‐grade systemic inflammation and health cohort study
Authors: Gu Yeqing , Wang Yanyan , Zhang Qing , Liu Li , Meng Ge , Yao Zhanxin , Wu Hongmei , Xia Yang , Bao Xue , Shi Hongbin , Wang Honglei , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Niu Kaijun
Published: February 2018

Objective

Thyroid hormones (THs) are primarily responsible for the regulation of energy homeostasis and metabolism. However, few prospective studies have assessed the association between THs and metabolic syndrome (MetS) in a general population. We therefore designed a cohort study to examine whether serum TH levels within the reference range are predictive factors for developing MetS in adults.

Design

Prospective cohort study.

Participants

A prospective study (n = 6119) was performed in Tianjin, China. Participants without a history of MetS were followed up for 1 to 3 years with a median follow‐up duration of 2 years.

Measurements

Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid‐stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay. MetS was defined in accordance with the criteria of the American Heart Association scientific statements of 2009. THs, TSH levels and MetS were assessed yearly during the follow‐up. Adjusted Cox proportional hazards regression models were used to assess the associations between FT3, FT4 and TSH quintiles and MetS.

Results

The incidence of MetS was 17.7% (96 per 1000 person‐years). In the final multivariate models, the hazard ratios (95% confidence interval) for MetS across serum FT3 quintiles were 1.00 (reference), 1.03 (0.84, 1.25), 1.14 (0.94, 1.38), 1.09 (0.90, 1.32) and 1.33 (1.11, 1.61), respectively (P for trend <.01). However, no significant associations between FT4, TSH and MetS were observed.

Conclusions

This population‐based prospective cohort study suggests that increased serum FT3 level, rather than FT4 and TSH, is an independent predictor for developing MetS in euthyroid subjects.
Clinical and aesthetic outcomes of immediately placed single‐tooth implants with immediate vs. delayed restoration in the anterior maxilla: A retrospective cohort study
Authors: Arora Himanshu , Ivanovski Saso
Published: February 2018

Objective

To evaluate the impact of the timing of restoration on clinical and aesthetic outcomes following immediate implant placement in the maxillary aesthetic zone.

Material and Methods

Forty patients (16 males, 24 females) with a mean age of 50.55 ± 12.79 years (range 19–74) who had a single maxillary anterior tooth replaced by an immediate implant were included in this study. Twenty patients had their implant restored immediately with a provisional restoration (Group A), while the other 20 patients had a delayed restoration placed after 3–4 months of non‐submerged healing (Group B). Clinical parameters and hard‐tissue changes were evaluated after a mean follow‐up period of 3 years. Aesthetic evaluation was carried out using the Pink Esthetic Score (PES) and the White Esthetic Score (WES).

Results

No significant differences were observed in the bone level changes between the two groups: 0.05 ± 0.65 mm mesially and 0.06 ± 0.52 mm distally for the immediate group and 0.30 ± 0.54 mm mesially and 0.21 ± 0.60 mm distally for the delayed group, respectively. The medianPESscores were 11.5 for Group A and 10 for Group B. MeanPESandWESscores did not differ significantly between Groups A and B:PES(11.1 vs. 10.3;p = .16) andWES(8.4 vs. 7.8;p = .16). In terms of individualPESvariables, the distal papillae were significantly better in Group A as compared to Group B (p = .006).

Conclusions

Within the limits of this study, timing of restoration seemed to positively affect the aesthetic outcomes of immediately placed implants as evidenced by higher medianPESvalues for the immediate restoration group when compared to the delayed restoration group. Restoration timing had no impact on the individualPESvariables, except for the distal papillary height which was superior in the immediate restoration group.
Myt1l induced direct reprogramming of pericytes into cholinergic neurons
Authors: Liang Xing‐Guang , Tan Chao , Wang Cheng‐Kun , Tao Rong‐Rong , Huang Yu‐Jie , Ma Kui‐Fen , Fukunaga Kohji , Huang Ming‐Zhu , Han Feng
Published: February 2018

Objective

The cholinergic deficit is thought to underlie progressed cognitive decline in Alzheimer Disease. The lineage reprogramming of somatic cells into cholinergic neurons may provide strategies toward cell‐based therapy of neurodegenerative diseases.

Methods and results

Here, we found that a combination of neuronal transcription factors, including Ascl1, Myt1l, Brn2, Tlx3, and miR124 (5Fs) were capable of directly converting human brain vascular pericytes (HBVPs) into cholinergic neuronal cells. Intriguingly, the inducible effect screening of reprogramming factors showed that a single reprogramming factor, Myt1l, induced cells to exhibit similarly positive staining for Tuj1, MAP2, ChAT, and VAChT upon lentivirus infection with the 5Fs after 30 days. HBVP‐converted neurons were rarely labeled even after long‐term incubation with BrdU staining, suggesting that induced neurons were directly converted from HBVPs rather than passing through a proliferative state. In addition, the overexpression of Myt1l induced the elevation of Ascl1, Brn2, and Ngn2 levels that contributed to reprogramming.

Conclusions

Our findings provided proof of the principle that cholinergic neurons could be produced from HBVPs by reprogramming factor‐mediated fate instruction. Myt1l was a critical mediator of induced neuron cell reprogramming. HBVPs represent another excellent alternative cell resource for cell‐based therapy to treat neurodegenerative disease.
Neurotrophin‐3 restores synaptic plasticity in the striatum of a mouse model of Huntington's disease
Authors: Gómez‐Pineda Victor G. , Torres‐Cruz Francisco M. , Vivar‐Cortés César I. , Hernández‐Echeagaray Elizabeth
Published: February 2018

Aims

Neurotrophin‐3 (NT‐3) is expressed in the mouse striatum; however, it is not clear the NT‐3 role in striatal physiology. The expression levels of mRNAs and immune localization of the NT‐3 protein and its receptor TrkC are altered in the striatum following damage induced by an in vivo treatment with 3‐nitropropionic acid (3‐NP), a mitochondrial toxin used to mimic the histopathological hallmarks of Huntington's disease (HD). The aim of this study was to evaluate the role of NT‐3 on corticostriatal synaptic transmission and its plasticity in both the control and damaged striatum.

Methods

Corticostriatal population spikes were electrophysiologically recorded and striatal synaptic plasticity was induced by high‐frequency stimulation. Further, the phosphorylation status of Trk receptors was tested under conditions that imitated electrophysiological experiments.

Results

NT‐3 modulates both synaptic transmission and plasticity in the striatum; nonetheless, synaptic plasticity was modified by the 3‐NP treatment, where instead of producing striatal long‐term depression (LTD), long‐term potentiation (LTP) was obtained. Moreover, the administration of NT‐3 in the recording bath restored the plasticity observed under control conditions (LTD) in this model of striatal degeneration.

Conclusion

NT‐3 modulates corticostriatal transmission through TrkB stimulation and restores striatal LTD by signaling through its TrkC receptor.
Iatrogenic hepatic portal venous gas following balloon endoscopy in a patient with hepaticojejunostomy stricture
Authors: Kawakami Hiroshi , Ban Tesshin , Kubota Yoshimasa
Published: February 2018

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Cognitive outcomes in children and adolescents born very preterm: a meta‐analysis
Authors: Brydges Christopher R , Landes Jasmin K , Reid Corinne L , Campbell Catherine , French Noel , Anderson Mike
Published: February 2018

Aim

To estimate the association between very preterm birth (<32wks' gestation) and intelligence, executive functioning, and processing speed throughout childhood and adolescence, and to examine the effects of gestational age, birthweight, and age at assessment.

Method

Studies were included if children were born at earlier than 32 weeks’ gestation, aged 4 to 17 years, had an age‐matched term control group, and if the studies used standardized measures, were published in an English‐language peer‐reviewed journal, and placed no restrictions on participants based on task performance.

Results

We evaluated 6163 children born very preterm and 5471 term‐born controls from 60 studies. Children born very preterm scored 0.82 SDs (95% confidence interval [CI] 0.74–0.90; p<0.001) lower on intelligence tests, 0.51 SDs (95% CI 0.44–0.58; p<0.001) lower on measures of executive functioning, and 0.49 SDs (95% CI 0.39–0.60; p<0.001) lower on measures of processing speed than term‐born controls. Gestational age and birthweight were associated with study effect size in intelligence and executive functioning of younger children only. Age at assessment was not associated with study effect size.

Interpretation

Children born very preterm have medium to large deficits in these cognitive domains.

What this paper adds

This meta‐analysis is centred on very preterm birth and three cognitive domains.

The three critical cognitive domains are intelligence, executive functioning, and processing speed.
Bacterial neuraminidase‐mediated erythrocyte desialylation provokes cell surface aminophospholipid exposure
Authors: Qadri Syed M. , Donkor David A. , Nazy Ishac , Branch Donald R. , Sheffield William P.
Published: February 2018

Background

Surface desialylation is associated with erythrocyte aging and mediates phagocytic recognition and clearance of senescent erythrocytes. Neuraminidases, a family of glycohydrolytic enzymes, cleave the glycosidic linkages between sialic acid and mucopolysaccharides and have previously been implicated in erythrocyte dysfunction associated with sepsis. Erythrocytes in septic patients further display a phenotype of accelerated eryptosis characterized by membrane phospholipid scrambling resulting in phosphatidylserine (PS) externalization. Herein, we examined the impact of artificial erythrocyte desialylation on eryptosis.

Methods

Using flow cytometry and/or fluorescence microscopy, we analyzed desialylation patterns and eryptotic alterations in erythrocytes exposed to Clostridium perfringens‐derived neuraminidase.

Results

Exogenous bacterial neuraminidase significantly augmented membrane PS exposure and cytosolic Ca2+ levels in a dose‐ and time‐dependent manner. Neuraminidase treatment significantly reduced fluorescence‐tagged agglutinin binding, an effect temporally preceding the increase in PS externalization. Neuraminidase‐induced PS exposure was significantly curtailed by pretreatment with the pan‐sialidase inhibitor N‐acetyl‐2,3‐dehydro‐2‐deoxyneuraminic acid. Neuraminidase treatment further induced hemolysis but did not significantly impact erythrocyte volume, ceramide abundance, or the generation of reactive oxygen species.

Conclusion

Collectively, our data reveal that alteration of erythrocyte sialylation status by bacterial neuraminidase favors eryptotic cell death, an effect potentially contributing to reduced erythrocyte lifespan and anemia in sepsis.
Intramuscular allopregnanolone and ganaxolone in a mouse model of treatment‐resistant status epilepticus
Authors: Zolkowska Dorota , Wu Chun‐Yi , Rogawski Michael A.
Published: February 2018

Allopregnanolone (5α‐pregnan‐3α‐ol‐20‐one) and its synthetic 3β‐methyl analog, ganaxolone, are positive allosteric modulators of synaptic and extrasynaptic γ‐aminobutyric acid (GABA)A receptors that exhibit antiseizure activity in diverse animal seizure models, including models of status epilepticus (SE). The 2 neuroactive steroids are being investigated as treatments for SE, including as a treatment for SE induced by chemical threat agents. Intramuscular injection is the preferred route of administration in the prehospital treatment of SE. The objective of this study was to assess the efficacy of intramuscular allopregnanolone and ganaxolone in the treatment of SE induced by the chemical threat agent tetramethylenedisulfotetramine (TETS). The test agents were administered 40 minutes after the onset of SE when mice are refractory to treatment. Allopregnanolone and ganaxolone (each at 3 mg/kg) terminated SE in, respectively, 92% and 75% of animals, and prevented mortality in 85% and 50% of animals; the mean times to termination of behavioral seizures were, respectively, 172 ± 16 and 447 ± 52 seconds. In a separate series of experiments, mice were dosed with the neuroactive steroids by intramuscular injection, and plasma and brain levels were sampled at various time points following injection to estimate pharmacokinetic parameters. Plasma Cmax (maximum concentration) values for allopregnanolone and ganaxolone were 645 and 550 ng/mL, respectively. Brain exposure of both steroids was approximately 3‐fold the plasma exposure. Two‐compartment pharmacokinetic analysis revealed that the central compartment Vd (volume of distribution), CL (clearance), t½ (terminal half‐life), and F (intramuscular bioavailability) values for allopregnanolone and ganaxolone were, respectively, 4.95 L/kg 12.88 L/kg/h,16 minutes, 97%, and 5.07 L/kg, 8.35 L/kg/h, 25 minutes, 95%. Allopregnanolone and ganaxolone are effective in the treatment of TETS‐induced SE when administered by the intramuscular route. Allopregnanolone is more rapidly acting and modestly more effective, possibly because it has greater potency on GABAA receptors.
Shedding light on aberrant interactions – a review of modern tools for studying protein aggregates
Authors: Kundel Franziska , Tosatto Laura , Whiten Daniel R. , Wirthensohn David C. , Horrocks Mathew H. , Klenerman David
Published: February 2018

The link between protein aggregation and neurodegenerative disease is well established. However, given the heterogeneity of species formed during the aggregation process, it is difficult to delineate details of the molecular events involved in generating pathological aggregates from those producing soluble monomers. As aberrant aggregates are possible pharmacological targets for the treatment of neurodegenerative diseases, the need to observe and characterise soluble oligomers has pushed traditional biophysical techniques to their limits, leading to the development of a plethora of new tools capable of detecting soluble oligomers with high precision and specificity. In this review, we discuss a range of modern biophysical techniques that have been developed to study protein aggregation, and give an overview of how they have been used to understand, in detail, the aberrant aggregation of amyloidogenic proteins associated with the two most common neurodegenerative disorders, Alzheimer's disease and Parkinson's disease.
Organisation of lymphocytic infiltrates in ANCA‐associated glomerulonephritis
Authors: Brix Silke R , Noriega Mercedes , Herden Elisabeth M , Goldmann Birgit , Langbehn Ulrike , Busch Martin , Jabs Wolfram J , Steinmetz Oliver M , Panzer Ulf , Huber Tobias B , Stahl Rolf A K , Wiech Thorsten
Published: February 2018

Aims

Renal involvement in anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis contributes to significant morbidity and mortality in patients. In chronic inflammation, B cells are recruited to the inflamed tissue and organised lymphoid structures have been described in several autoimmune diseases. The aim of this study was to correlate the lymphoid organisation in renal biopsies with renal outcome in ANCA‐associated glomerulonephritis (GN).

Methods and results

We investigated 112 renal biopsies from patients with newly diagnosed ANCA‐associated necrotising GN. We identified four different levels of the intrarenal organisation of lymphocytes: T cells without B cells, scattered B and T cells, clustered lymphocytic infiltrates and nodular compartmentally arranged B and T cell aggregates. Almost half the patients showed clusters of B and T lymphocytes in their biopsies. In 15 of these biopsies, a higher degree of organisation with lymphocytic compartments was detected. Inflammatory cell organisation was associated with renal failure, but not with tubular atrophy and interstitial fibrosis. Patients with organised lymphocytic infiltrates in their biopsy had worse renal function during follow‐up and were more likely to develop end stage renal disease.

Conclusions

In the present study, we show that the renal lymphocytic organisation is associated with renal outcome in ANCA‐associated GN. The organisation of the lymphocytic infiltrate may be a morphological correlate of a perpetual and exaggerated inflammation in renal ANCA disease. Classifying the lymphocytic infiltrate could help to predict renal outcome, and might therefore be used for individualised adjustments in the intensity and duration of immunosuppressive therapy.
Syndromic sebaceous nevus: current findings
Authors: El Ezzi Oumama , de Buys Roessingh Anthony S. , Bigorre Michèle , Captier Guillaume
Published: February 2018

Background

Sebaceous nevus is a congenital malformation of the skin that usually occurs on the scalp or face. Syndromic forms do rarely exist with associated cerebral and ocular malformations. The skin lesions are pale at birth and become irregular by puberty. In the adult patient, tumors (usually benign) develop from sebaceous nevus. Their surgical excision during childhood can give a better result in terms of the definitive scar.

Objectives

The aim of this study is to analyze our cases of syndromic sebaceous hamartoma, perform a review of the existing literature, and propose guidelines for the therapeutic plan.

Methods

This is a retrospective study reviewing the cases of syndromic sebaceous nevus treated in the Department of Orthopedic Plastic Pediatric Surgery in Montpellier, France, and the Department of Pediatric Surgery in Lausanne, Switzerland, between 1994 and 2016.

Results

The files of six patients with syndromic sebaceous nevus were analyzed. The average age at the first consultation was 4 months. The location was craniofacial in all cases. Cerebral radiological imaging was performed on all patients; two showed abnormal findings. Four patients underwent ophthalmic examination, which all revealed abnormalities. Three patients had other associated malformations. Three patients presented with epilepsy or learning difficulties in the course of follow‐up.

Conclusion

All patients presenting with extensive sebaceous nevus of the craniofacial region should benefit from cerebral imagery and ophthalmic examination since there is a very high probability of associated abnormalities. The developmental problems encountered could not be definitively associated with the skin malformations.
Cranberry seed fibre: a promising prebiotic fibre and its fermentation by the probiotic Bacillus coagulans MTCC 5856
Authors: Majeed Muhammed , Nagabhushanam Kalyanam , Arumugam Sivakumar , Natarajan Sankaran , Majeed Shaheen , Pande Anurag , Beede Kirankumar , Ali Furqan
Published: February 2018

Cranberry, a versatile fruit, is known for nutritional as well as medicinal properties due to the presence of bioactive compounds. However, cranberry fruit has not been fully explored for its prebiotic potential. Therefore, this study was conducted to evaluate prebiotic potential of cranberry seed fibre (CSF) and also evaluate its fermentability by the probiotic strain Bacillus coagulans MTCC 5856. The resistance to gastric acid and porcine pancreatic enzymatic (PPE) hydrolysis of CSF was investigated using an in vitro model. It was found that CSF was resistant to gastric acid and also nondigestible to PPE hydrolysis. CSF as sole nutrition source was evaluated for the fermentability by B. coagulans MTCC 5856. A significant amount of short‐chain fatty acids was produced by the B. coagulans MTCC 5856 while fermenting cranberry fibres anaerobically. CSF supported the growth of B. coagulans MTCC 5856 and also inhibited the growth of E. coli ATCC 25922 when cocultured in an anaerobic environment. CSF from the cranberry fruit exhibited prebiotic potential and also found to be fermentable by B. coagulans MTCC 5856. This study provided the scientific evidence of CSF as a prebiotic fibre and also its suitability with the probiotic B. coagulans MTCC 5856 for an ideal synbiotic preparation.
White tea intake interferes with the expression of angiogenic factors in the corpora lutea of superovulated rats
Authors: Garcia Santos Francislaine Anelize , Freire Samuel Aparecido , Vieira Deyvid Parreira , Papa Paula de Carvalho , de Barros Gabriela Fernandes , Castilho Caliê , Guaberto Luciana Machado , Souza Lilian Francisco Arantes de , Laposy Cecília Braga , Nogueira Rosa Maria Barilli , Santos Aline de Oliveira , Giometti Ines Cristina
Published: February 2018

White tea derived from the Camellia sinensis (L.) plant has anticancer effects. Its main catechin decreases the gene expression of Vegf in tumours. However, VEGF is also the angiogenic factor of the reproductive organs. In this study, Wistar rats were divided into the following groups (n = 30): the control group (CT), which received water, and the white tea intake group (WT), for 3 months. At the end of every month, the corpora lutea (CL) of ten rats were removed to evaluate the gene expression of Vegf and its receptors (Flt‐1 and Kdr). White tea increased the relative mRNA abundance of Vegf (CT = 0.95 ± 0.06 and WT = 2.13 ± 0.19), Kdr (CT = 0.88 ± 0.06 and WT = 1.94 ± 0.32) and Flt‐1 (CT = 0.94 ± 0.06 and WT = 2.11 ± 0.22) in CL (P < 0.05). White tea increased angiogenic‐related genes in rat CL but did not alter the number of rat CL.
Paeoniflorin ameliorates collagen‐induced arthritis via suppressing nuclear factor‐κB signalling pathway in osteoclast differentiation
Authors: Xu Haiyan , Cai Li , Zhang Lili , Wang Guojue , Xie Rongli , Jiang Yongshuai , Yuan Yuanyang , Nie Hong
Published: February 2018

Paeoniflorin (PF), extracted from the root of Paeonia lactiflora Pall, exhibits anti‐inflammatory properties in several autoimmune diseases. Osteoclast, the only somatic cell with bone resorbing capacity, was the direct cause of bone destruction in rheumatoid arthritis (RA) and its mouse model, collagen‐induced arthritis (CIA). The objective of this study was to estimate the effect of PF on CIA mice, and explore the mechanism of PF in bone destruction. We demonstrated that PF treatment significantly ameliorated CIA through inflammatory response inhibition and bone destruction suppression. Furthermore, PF treatment markedly decreased osteoclast number through the altered RANKL/RANK/OPG ratio and inflammatory cytokines profile. Consistently, we found that osteoclast differentiation was significantly inhibited by PF through down‐regulation of nuclear factor‐κB activation in vitro. Moreover, we found that PF suppressed nuclear factor‐κB activation by decreasing its translocation to the nucleus in osteoclast precursor cells. Taken together, our new findings provide insights into a novel function of PF in osteoclastogenesis and demonstrate that PF would be a new therapeutic modality as a natural agent for RA treatment and other autoimmune conditions with bone erosion.