bluuebunny/crossref_metadata_2025 huggingface dataset:
An immunoevasive strategy through clinically-relevant pan-cancer genomic and transcriptomic alterations of JAK-STAT signaling components
Authors: Chang Wai Hoong , Lai Alvina G.
Published: March 2019

Since its discovery almost three decades ago, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has paved the road for understanding inflammatory and immunity processes related to a wide range of human pathologies including cancer. Several studies have demonstrated the importance of JAK-STAT pathway components in regulating tumor initiation and metastatic progression, yet, the extent of how genetic alterations influence patient outcome is far from being understood. Focusing on 133 genes involved in JAK-STAT signaling, we found that copy number alterations underpin transcriptional dysregulation that differs within and between cancer types. Integrated analyses on over 18,000 tumors representing 21 cancer types revealed a core set of 28 JAK-STAT pathway genes that correlated with survival outcomes in brain, renal, lung and endometrial cancers. High JAK-STAT scores were associated with increased mortality rates in brain and renal cancers, but not in lung and endometrial cancers where hyperactive JAK-STAT signaling is a positive prognostic factor. Patients with aberrant JAK-STAT signaling demon-strated pan-cancer molecular features associated with misex-pression of genes in other oncogenic pathways (Wnt, MAPK, TGF-β, PPAR and VEGF). Brain and renal tumors with hyperactive JAK-STAT signaling had increased regulatory T cell gene (Treg) expression. A combined model uniting JAK-STAT and Tregs allowed further delineation of risk groups where patients with high JAK-STAT and Treg scores consistently performed the worst. Providing a pan-cancer perspective of clinically-relevant JAK-STAT alterations, this study could serve as a framework for future research investigating anti-tumor immunity using combination therapy involving JAK-STAT and immune checkpoint inhibitors.
Age-related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields
Authors: Stark Shauna M. , Frithsen Amy , Stark Craig E.L.
Published: March 2019

Aging causes hippocampal circuit alterations that differentially affect hippocampal subfields and are associated with age-related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A-P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high-resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and PHC and PRC. This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra-hippocampal connectivity also reflected an age-related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior-posterior shift in older adults between hippocampus and PHC was predictive of lure discrimination performance on the MST, suggesting that this shift may reflect a compensation mechanism that preserves memory performance. While age-related dysfunction within the hippocampal subfields has been well-documented, these results suggest that the age-related A-P shift in hippocampal connectivity may also contribute significantly to memory decline in older adults.
Antibody-mediated cross-linking of gut bacteria hinders the spread of antibiotic resistance
Authors: Bansept Florence , Marrec Loïc , Anne-Florence Bitbol , Loverdo Claude
Published: March 2019

The body is home to a diverse microbiota, mainly in the gut. Resistant bacteria are selected for by antibiotic treatments, and once resistance becomes widespread in a population of hosts, antibiotics become useless. Here, we develop a multiscale model of the interaction between antibiotic use and resistance spread in a host population, focusing on an important aspect of within-host immunity. Antibodies secreted in the gut enchain bacteria upon division, yielding clonal clusters of bacteria. We demonstrate that immunity-driven bacteria clustering can hinder the spread of a novel resistant bacterial strain in a host population. We quantify this effect both in the case where resistance pre-exists and in the case where acquiring a new resistance mutation is necessary for the bacteria to spread. We further show that the reduction of spread by clustering can be countered when immune hosts are silent carriers, and are less likely to get treated, and/or have more contacts. We demonstrate the robustness of our findings to including stochastic within-host bacterial growth, a fitness cost of resistance, and its compensation. Our results highlight the importance of interactions between immunity and the spread of antibiotic resistance, and argue in the favor of vaccine-based strategies to combat antibiotic resistance.
Cell type-specific monoclonal antibody cross-reactivity screening in non-human primates and development of comparative immunophenotyping panels for CyTOF
Authors: Bjornson-Hooper Zachary B , Fragiadakis Gabriela K , Spitzer Matthew H , Madhireddy Deepthi , Hu Kevin , Lundsten Kelly , Nolan Garry P
Published: March 2019

Monoclonal antibodies are a critical tool for immunologists, with applications including immunomicroscopy and cytometry, and non-human primates are essential models for drug development. Very few antibodies are raised against non-human primate antigens; instead, researchers typically use anti-human antibodies that are found to be cross-reactive with non-human primates. The NIH maintains a valuable database of cross-reactivity, but its coverage is not complete, especially for less common species. Furthermore, the database only indicates the presence or absence of staining and does not indicate if a different cell population is stained in the NHP species than in humans. We screened 332 antibodies in five immune cell populations in blood from cynomologus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), African green monkeys (Chlorocebus aethiops) and olive/yellow baboons (Papio hamadryas anubis × Papio hamadryas cynocephalus), thereby generating a comprehensive cross-reactivity catalog that includes cell type-specificity. We subsequently used this catalog to help create large CyTOF mass cytometry panels for three of those species and humans. The curated dataset containing the primary data for each antibody has been deposited as a browsable resource at https://immuneatlas.org and https://flowrepository.org/id/FR-FCM-Z2Z7.
Relationship between ocean area and incidence of anthropogenic debris ingested by longnose lancetfish (Alepisaurus ferox)
Authors: Kuroda Mao , Uchida Keichi , Miyamoto Yoshinori , Hagita Ryuiti , Shiode Daisuke , Joshima Hiroki , Nemoto Masaki , Hamada Hiroaki , Yamada Yuta , Takada Hideshige , Yamashita Rei , Fukunaga Kohei
Published: March 2019

Longnose lancetfish (Alepisaurus ferox) may has been studied as an indicator of marine pollution caused by marine litter. The objectives of this study were to determine the difference in frequency of occurrence of plastics ingested by longnose lancetfish in different ocean area. In this study, we compared the incidence and characteristics of anthropogenic debris in the stomachs of longnose lancetfish. We examined 91 longnose lancetfish caught by pelagic longline fishing in Sagami Bay, the North Pacific Ocean, approximately 200 km south of Shikoku, and in the Indian Ocean. Broken down by ocean area, the incidence of anthropogenic debris ingestion was highest in Sagami Bay (23 of 34 specimens, 68%), followed by the North Pacific Ocean (1 of 9, 11%), and the Indian Ocean (8 of 48, 17%). The frequency of occurrence increased in area close to the sphere of human habitation. The anthropogenic debris collected in this study were more than 70% classified as plastic sheeting. Stomach content analysis revealed that more than 90% of the plastic fragments were composed of PP and PE, which have specific gravities that are less than that of seawater. The results of this study show that some of the plastics flowing from the land into the sea are spreading through under the water surface of the ocean.
China’s quarter-century struggle with a nuclear North Korea with a focus on its strategic calculation
Authors: Kim Jih-Un
Published: March 2019

Purpose

The purpose of this paper is to describe how China’s approach to a nuclear North Korea has changed and find key variables that explain the changes.

Design/methodology/approach

This paper adopts the traditional qualitative method, referring to different types of reliable and authoritative Chinese and English scholars, books and articles.

Findings

Although China has accumulated distrust of North Korea and reprimanded the regime for its nuclear program, it has never ignored the strategic value or balance – especially vis-à-vis the USA – the neighboring country provides for it. And for that matter, it has been keen to prevent North Korea from bypassing it and getting closer to the USA. With this strategic calculation in mind, China has mostly made gestures in implementing the UN sanctions against North Korea, though not always.

Originality/value

This paper proves that China’s strategic calculation has been a constant key variable that explains its approach toward a nuclear North Korea since the inception of the issue in the early 1990s.
Do embedded employees voice more?
Authors: Tan Alice J.M. , Loi Raymond , Lam Long W. , Zhang Lida L.
Published: March 2019

Purpose

The purpose of this paper is to investigate whether embedded employees proactively provide voice for future improvement, and how interactional justice moderates this relationship.

Design/methodology/approach

Survey data were collected from the administrative staff and their immediate supervisors of a major university located in Southern China. The data were analyzed using hierarchical linear modeling.

Findings

Job embeddedness was positively related to voice behavior toward organization (VBO) but not to voice behavior toward work unit. Interactional justice was positively related to both types of voice behavior. The relationship between job embeddedness and VBO was stronger among employees who perceived lower interactional justice.

Practical implications

To encourage voice behavior, organizations should attempt to enhance employees’ job embeddedness by adopting human resource strategies such as providing training that helps employees to meet their long-term career goals. This is particularly important when supervisors fail to treat their employees with fairness. When employees are treated with fairness by supervisors, they are also motivated to speak up. Thus, supervisors should pay attention to the ways in which they interact with employees.

Originality/value

This paper adds to the existing knowledge of the consequences of job embeddedness by examining its relationship with voice, a proactive behavior which can benefit the organization but is considered as risky by the employees. Additionally, studying the moderating effect of interactional justice enriches the understanding of the conditions under which the relationship between job embeddedness and voice may vary. It also reveals the uncertainty management process underlying the influences of job embeddedness and interactional justice on voice behavior.
Perceptions of supervisor competence, perceived employee mobility, and abusive supervision
Authors: Meglich Patricia , Valentine Sean , Eesley Dale
Published: March 2019

Purpose

In response to the call for deeper investigation of abusive supervision (Martinko et al., 2013), the purpose of this paper is to examine perceived supervisor competence and perceived employee mobility (an individual’s perception of his/her ability to obtain new employment) to better understand contextual and individual factors that potentially influence the degree of harmful supervisory behaviors experienced by employees.

Design/methodology/approach

Responses from 749 survey participants were analyzed to determine the impact of perceived supervisor competence and perceived employee mobility on perceptions of abusive supervisory conduct. A bootstrapping-based mediation analysis (Hayes, 2012) was used to test for mediation by the variables of interest.

Findings

The authors found that perceived supervisor competence is associated with weakened perceptions of abusive supervision, and that this relationship is partially mediated by respondents’ perceived occupational mobility.

Research limitations/implications

The data are cross-sectional and were collected with a self-report questionnaire and compiled utilizing student-enumerators. The sample was also regional in scope and lacked information that would indicate if respondents were also supervisors.

Practical implications

These results imply that perceptions of abusive supervision can be mitigated by building stronger competencies in supervisors, which translates into greater individual employee perceived mobility. Human resource (HR) professionals can implement practices to decrease the likelihood of abusive supervisory conduct by ensuring that supervisors are competent in their jobs, facilitating a coaching/mentoring process between supervisors and subordinates and establishing/maintaining an effective developmental performance feedback process for supervisors.

Social implications

Since perceived supervisor competence is one element of reducing abusive conduct, while also enhancing subordinate perceived mobility, selection and training efforts should focus on hiring and preparing individuals to be effective work supervisors. Enhancing worker capabilities and marketability may result in greater perceived occupational mobility and reduced perceptions of abuse by supervisors.

Originality/value

These results lend support to the argument that perceptions of abusive supervision can be mitigated by building stronger competencies in supervisors, which translates into greater perceived mobility among employees. Organizations may benefit through lowered employee turnover, employees may enjoy more harmonious, supportive relationships with their supervisors and HR staff may benefit by having competent supervisors who do not generate employee complaints and intentions to quit.
Outcome of pregnancies in women with pulmonary hypertension: a single‐centre experience from South India
Authors: Keepanasseril A , Pillai AA , Yavanasuriya J , Raj A , Satheesh S , Kundra P
Published: March 2019

Objective

To study maternal complications and pregnancy outcome in women with pulmonary hypertension, attending a tertiary centre in south India.

Study design

Retrospective observational study.

Setting

Tertiary centre in south India.

Population

Pregnant women with pulmonary hypertension.

Method

Data regarding demographics, clinical course, medication received, and echocardiographic diagnosis regarding pulmonary hypertension and antenatal care received were collected from the records. Details of labour and delivery, and postpartum follow up were retrieved. We compared the outcome based on the presence or absence of cyanosis and right ventricular systolic pressure levels.

Main outcome measures

Maternal mortality, occurrence of complications such as heart failure, fetal growth restriction.

Results

There were 81 pregnancies in 73 women with pulmonary hypertension. The majority of them had pulmonary hypertension secondary to congenital heart disease (80.8%); 17.8% had Eisenmenger syndrome. An advanced pulmonary artery hypertension (PAH) medication, sildenafil, was administered in 25 (31.3%) pregnancies. There were four maternal deaths, of which three had Eisenmenger syndrome. Heart failure complicated 6.3% and fetal growth restriction 26.3% of pregnancies. Morbidity was significantly increased in women with pulmonary hypertension associated with a cyanotic cardiac lesion or with right ventricular systolic pressure >70 mmHg.

Conclusion

Despite advances in care, mortality in pregnant women with pulmonary hypertension is a matter of concern, especially in those with Eisenmenger syndrome. Multidisciplinary team management in tertiary centres and the use of advanced PAH medications even in low‐ to middle‐income countries with limited resources, could lead to a reduction in morbidity and mortality related to pulmonary hypertension.

Tweetable abstract

Multidisciplinary care and use of new medication may improve outcomes in pregnant women with pulmonary hypertension.
Post‐renal transplant ureterocutaneous fistula: Management of complications and literature review
Authors: Lam Wilson Wing‐Chung , Chan Tsz‐Yeung , Cheng Cheung‐Hing , Lee Yue‐Kit , Chau Lysander Hin , Man Chi‐Wai , Chu Sau‐Kwan
Published: March 2019

Ureterocutaneous fistula is a major complication following renal transplantation. Timely management can minimise patient and graft comorbidities. We reported three cases of post‐renal transplant ureterocutaneous fistula. Two of them were successfully repaired with Boari flap and one of them were repaired with ileal interposition. Literature review revealed that double‐J stent insertion during renal transplant can significantly reduce post‐transplant major ureteric complications (MUC). Evidence did not show any difference in MUC between early removal of stent (≤14 days) and late removal (>14 days). Yet incidence of UTI could be reduced in early stent removal.
Persistence of smoking induced non‐small cell lung carcinogenesis by decreasing ERBB pathway‐related microRNA expression
Authors: Zhang Lianmin , Wang Hailong , Wang Changli
Published: March 2019

Background

Tobacco use is responsible for approximately 80–90% of non‐small cell lung cancer cases. A large evidence base has shown that the ERBB pathway is associated with the occurrence of lung cancer. However, the mechanisms of how smoking activates the ERBB pathway have yet to be explained. We hypothesized that microRNAs may induce ERBB pathway activity during the process of lung cancer carcinogenesis.

Methods

We analyzed microRNA array data from the Gene Expression Omnibus and the Kyoto Encyclopedia of Genes and Genomes to determine any associations between genes and smoking in three groups of patients with NSCLC: smokers, former smokers, and non‐smokers.

Results

The interaction network among miRNAs, including hsa‐mir‐185‐3p, hsa‐mir‐4295, hsa‐mir‐4288, and hsa‐mir‐613, promotes lung cancer development by affecting the ERBB pathway.

Conclusion

Our findings provide evidence to explain the mechanism of lung cancer development in smokers.
Range expansion of the small spruce bark beetle Ips amitinus: a newcomer in northern Europe
Authors: Økland Bjørn , Flø Daniel , Schroeder Martin , Zach Peter , Cocos Dragos , Martikainen Petri , Siitonen Juha , Mandelshtam Michail Y. , Musolin Dmitry L. , Neuvonen Seppo , Vakula Jozef , Nikolov Christo , Lindelöw Åke , Voolma Kaljo
Published: March 2019

Ips amitinus arrived in Northern Europe at the beginning of 1900s, although its recent expansions to the northernmost conifers have been rapid.

Analyses of recent records, MaxEnt models and regional population size estimates are used to discuss its peculiar range shifts and potential as a forest pest in Northern Europe.

Ips amitinus was probably absent in northern glacial refugia for Norway spruce in the Russian plain and northward expansions from its glacial refugia in the Central European mountains may have been slowed down by: (i) ecological barriers of post‐glacial dry plains and bogs in Central Europe; (ii) heavy utilization of conifers; and (iii) Allee effects as a result of fragmented forests and an unfavourable climate for a cold‐adapted species in the continental lowlands.

MaxEnt models predict that I. amitinus may become widespread in the Northern European forests, whereas its populations in the southernmost mountain ranges of Europe may decline in the future.

The population levels of I. amitinus in recently invaded northern areas are still lower than those in core areas of Central Europe, although the population development in Central Europe indicates that future bark beetle outbreak periods may boost the I. amitinus populations in Northern Europe as well.
Hysterectomy‐corrected cervical cancer mortality rates in Denmark during 2002‐2015: A registry‐based cohort study
Authors: Hammer Anne , Kahlert Johnny , Gravitt Patti E. , Rositch Anne F.
Published: March 2019

Introduction

We aimed to describe the cervical cancer mortality rates after correcting for hysterectomy and to evaluate trends over calendar time and by age.

Material and methods

Using data from nationwide registries, we calculated uncorrected and hysterectomy‐corrected cervical cancer mortality rates among women age ≥20 years in Denmark during 2002‐2015. We calculated hysterectomy‐corrected rates by subtracting post‐hysterectomy person‐years from the denominator, unless hysterectomy was performed due to cervical cancer.

Results

The age‐standardized hysterectomy‐corrected cervical cancer mortality rate of 5.8/100 000 was 18.4% higher than the corresponding uncorrected rate. The hysterectomy‐corrected cervical cancer mortality rate increased significantly with age, particularly in women aged 65+ (annual percent change +4.57), peaking at 26.1/100 000 person‐years in women aged ≥85. The hysterectomy‐corrected cervical cancer mortality declined significantly over calendar time, from 6.3/100 000 person‐years in 2002 to 4.5/100 000 person‐years in 2015 (annual percent change −0.22). This was mainly due to a significant decline in women aged 60 years and older, from 20.4/100 000 person‐years in 2003 to 9.3/100 000 person‐years in 2015 (annual percent change −0.75).

Conclusions

The mortality of cervical cancer increased significantly by age, particularly among women aged 65 years and older for whom routine cervical cancer screening is not recommended. Understanding reasons for the high mortality rate in older women is critical, as this may help identify interventions needed to ensure a continued decline in cervical cancer mortality in older Danish women.
Cancer‐associated fibroblasts contribute to cisplatin resistance by modulating ANXA3 in lung cancer cells
Authors: Wang Limin , Li Xueqin , Ren Yinghui , Geng Hua , Zhang Qicheng , Cao Limin , Meng Zhaowei , Wu Xiang , Xu Meilin , Xu Ke
Published: March 2019

Cancer tissues consist of cancer cells, surrounding stromal cells and the extracellular matrix. Cancer‐associated fibroblasts (CAF) are one of the key components of stromal cells. CAF have a great impact on the behavior of cancer cells, including proliferation, invasion, metastasis and chemoresistance in many ways. However, the underlying mechanism had not been fully elucidated. In this study, we investigated the role of CAF in cisplatin resistance of lung cancer cells. By using conditioned medium from CAF (CAF‐CM), we found that CAF decreased the sensitivity of lung cancer cells to cisplatin. RNA sequencing results showed that CAF expressed a higher level of Annexin A3 (ANXA3) than normal fibroblasts (NF), and CAF‐CM incubation increased the ANXA3 level in lung cancer cells. Overexpression of ANXA3 in lung cancer cells increased cisplatin resistance and activated c‐jun N‐terminal kinase (JNK), whereas knockdown of ANXA3 increased cisplatin sensitivity. Further study showed that CAF‐CM enhanced cisplatin resistance by inhibiting cisplatin‐induced apoptosis, determined by repression of caspase‐3 and caspase‐8, through activation of the ANXA3/JNK pathway. Conversely, suppression of JNK activation by specific inhibitor retarded the effect of CAF‐CM and ANXA3 on cisplatin sensitivity. Taken together, our study demonstrated that CAF potentiated chemoresistance of lung cancer cells through a novel ANXA3/JNK pathway both in vitro and in vivo, suggesting ANXA3 could be a potential therapeutic target for the treatment of chemoresistant cancer.
Bilateral anterior capsulotomy enhances medication compliance in patients with epilepsy and psychiatric comorbidities
Authors: Huang Peng , Zheng‐Dao Deng , Sun Bo‐Min , Pan Yi‐Xin , Zhang Jing , Wang Tao , Liu Wei , Jin Hai‐Yan , Zhan Shi‐Kun
Published: March 2019

Objectives

Patients with epilepsy and refractory comorbid psychiatric disorders often experience functional impairments and a lower quality of life as well as showing a lack of compliance with anti‐epileptic medication regimens. We reasoned that widespread clinical benefits could be gained if the psychiatric comorbidities among these patients were reduced. In this study, we assessed the utility of anterior capsulotomy in managing medication‐refractory comorbid psychotic symptoms and aggression in patients with epilepsy.

Methods

In this retrospective case series, we evaluated the clinical outcomes of 13 epilepsy patients with severe psychiatric comorbidities who had received bilateral anterior capsulotomy. Clinical outcome assessments were performed at 1 week, 6 months, 1 year, and several years after surgery focusing on: (a) severity of psychotic symptoms, as assessed by the 18‐item Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale; (b) severity of impulsivity and aggression, measured by the Barratt Impulsiveness Scale‐11 and the Buss‐Perry Aggression Scale; and (c) social function and quality of life, assessed by the Social Disability Screening Scale and the Quality of Life in Epilepsy.

Results

After anterior capsulotomy, patients displayed significant improvements of psychotic symptoms, as well as of impulsivity and aggression, along with improvements of social function and quality of life. The clinical benefits to patients were evident within 6 months after surgery and remained stable or continued to improve at a much slower rate thereafter. Furthermore, after anterior capsulotomy all patients complied with epilepsy interventions that they did not comply with prior to surgery. No significant side effects or complications occurred during the study.

Conclusion

Anterior capsulotomy seems to be a safe and effective treatment for epilepsy patients with otherwise intractable comorbid psychotic symptoms and aggression. Moreover, this neurosurgical treatment may improve the patients' social function, quality of life, and compliance with anti‐epilepsy medication regimens.
Diagnostic utility of two‐dimensional speckle tracking echocardiography to identify ischemic etiology of left ventricular systolic dysfunction
Authors: Kowalczyk Ewelina , Kasprzak Jarosław D. , Wejner‐Mik Paulina , Wdowiak‐Okrojek Katarzyna , Lipiec Piotr
Published: March 2019

Background

The differentiation between dilated cardiomyopathy (DCM) and systolic dysfunction caused by coronary artery disease (CAD) based on clinical and echocardiographic presentation can be difficult in some cases.

Aim

Our study aimed to define differences in myocardial function between patients with ischemic and nonischemic etiology of reduced left ventricular ejection fraction using 2D speckle tracking echocardiography (STE).

Material and methods

We retrospectively analyzed 90 patients (mean age 65 ± 11 years, 70% male) with de novo diagnosed reduced left ventricular ejection fraction (≤45% as determined by the transthoracic echocardiography), who were referred for coronary angiography to determine the presence of significant CAD. On the basis of coronary angiography results, patients were divided into two subgroups as follows: 45 subjects with significant CAD (group A) and 45 subjects without CAD (group B). Acquired transthoracic echocardiographic images were assessed off‐line using 2DSTE. In each patient, we calculated arithmetic mean, median value, and standard deviation of regional longitudinal strain and strain rate of 18 left ventricular segments.

Results

Standard deviation of the regional peak early diastolic strain rate was significantly higher in group A than in group B (P = 0.01). The cutoff value with the highest diagnostic value was >0.37/s—its sensitivity and specificity for the diagnosis of CAD were 73% and 53%, respectively. The remaining parameters did not differ significantly between the study groups.

Conclusions

Patients with systolic dysfunction resulting from CAD have significantly more heterogeneous regional longitudinal early diastolic strain rate assessed by 2DSTE than patients with DCM.
Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo
Authors: Roche Eric D. , Woodmansey Emma J. , Yang Qingping , Gibson Daniel J. , Zhang Hongen , Schultz Gregory S.
Published: March 2019

Biofilms are prevalent in non‐healing chronic wounds and implicated in delayed healing. Tolerance to antimicrobial treatments and the host's immune system leave clinicians with limited interventions against biofilm populations. It is therefore essential that effective treatments be rigorously tested and demonstrate an impact on biofilm across multiple experimental models to guide clinical investigations and protocols. Cadexomer iodine has previously been shown to be effective against biofilm in various in vitro models, against methicillin‐resistant Staphylococcus aureus biofilm in mouse wounds, and clinically in diabetic foot ulcers complicated by biofilm. Similarities between porcine and human skin make the pig a favoured model for cutaneous wound studies. Two antiseptic dressings and a gauze control were assessed against mature biofilm grown on ex vivo pig skin and in a pig wound model. Significant reductions in biofilm were observed following treatment with cadexomer iodine across both biofilm models. In contrast, silver carboxymethylcellulose dressings had minimal impact on biofilm in the models, with similar results to the control in the ex vivo model. Microscopy and histopathology indicate that the depth of organisms in wound tissue may impact treatment effectiveness. Further work on the promising biofilm efficacy of cadexomer iodine is needed to determine optimal treatment durations against biofilm.
An association study using imputed whole‐genome sequence data identifies novel significant loci for growth‐related traits in a Duroc × Erhualian F2 population
Authors: Ji Jiuxiu , Yan Guorong , Chen Dong , Xiao Shijun , Gao Jun , Zhang Zhiyan
Published: March 2019

The average daily gain (ADG) and body weight (BW) are very important traits for breeding programs and for the meat production industry, which have attracted many researchers to delineate the genetic architecture behind these traits. In the present study, single‐ and multi‐trait genome‐wide association studies (GWAS) were performed between imputed whole‐genome sequence data and the traits of the ADG and BW at different stages in a large‐scale White Duroc × Erhualian F2 population. A bioinformatics annotation analysis was used to assist in the identification of candidate genes that are associated with these traits. Five and seven genome‐wide significant quantitative trait loci (QTLs) were identified by single‐ and multi‐trait GWAS, respectively. Furthermore, more than 40 genome‐wide suggestive loci were detected. On the basis of the whole‐genome sequence association study and the bioinformatics analysis, NDUFAF6, TNS1 and HMGA1 stood out as the strongest candidate genes. The presented single‐ and multi‐trait GWAS analysis using imputed whole‐genome sequence data identified several novel QTLs for pig growth‐related traits. Integrating the GWAS with bioinformatics analysis can facilitate the more accurate identification of candidate genes. Higher imputation accuracy, time‐saving algorithms, improved models and comprehensive databases will accelerate the identification of causal genes or mutations, which will contribute to genomic selection and pig breeding in the future.
Cutaneous granulomas with primary immunodeficiency in children: a report of 17 new patients and a review of the literature
Authors: Leclerc‐Mercier S. , Moshous D. , Neven B. , Mahlaoui N. , Martin L. , Pellier I , Blanche S. , Picard C. , Fischer A. , Perot P. , Eloit M. , Fraitag S. , Bodemer C.
Published: March 2019

Background

Paediatric cutaneous granuloma with primary immunodeficiency (PID) is a rare condition. The physiopathology is unclear, and treatment is challenging. We report on 17 paediatric cases and review the literature.

Objectives

To make dermatologists and dermatopathologists aware of the diagnostic value of skin granulomas in paediatric PID.

Methods

We collected data on 17 patients with cutaneous granulomas and PID registered with us and also reviewed 33 cases from the literature.

Results

Cutaneous granuloma was the presenting feature of the PID in 15 of the 50 collated cases. The lesions presented as red‐brownish nodules and infiltrated ulcerative plaques, predominantly on the face and limbs. Scleroderma‐like infiltration on a single limb was observed in 10% of the cases. The associated PID was ataxia‐telangiectasia (52%), combined immunodeficiency (24%), cartilage‐hair hypoplasia (6%) and other subtypes (18%). The granulomas were mostly sarcoidal, tuberculoid, palisaded or undefined subtypes. In some patients, several different histopathologic granulomatous patterns were found in the same biopsy. Some granulomas were associated with the presence of a vaccine strain of rubella virus.

Conclusion

Cutaneous granulomas associated with a PID have a variable clinical presentation. A PID can be suspected when crusty, brownish lesions are found on the face or limbs. The concomitant presence of several histological subtypes in a single patient is suggestive of a PID.
Bayesian Model Selection Methods for Multilevel IRT Models: A Comparison of Five DIC‐Based Indices
Authors: Zhang Xue , Tao Jian , Wang Chun , Shi Ning‐Zhong
Published: March 2019

Model selection is important in any statistical analysis, and the primary goal is to find the preferred (or most parsimonious) model, based on certain criteria, from a set of candidate models given data. Several recent publications have employed the deviance information criterion (DIC) to do model selection among different forms of multilevel item response theory models (MLIRT). The majority of the practitioners use WinBUGS for implementing MCMC algorithms for MLIRT models, and the default version of DIC provided by WinBUGS focused on the measurement‐level parameters only. The results herein show that this version of DIC is inappropriate. This study introduces five variants of DIC as a model selection index for MLIRT models with dichotomous outcomes. Considering a multilevel IRT model with three levels, five forms of DIC are formed: first‐level conditional DIC computed from the measurement model only, which is the index given by many software packages such as WinBUGS; second‐level marginalized DIC and second‐level joint DIC computed from the second‐level model; and top‐level marginalized DIC and top‐level joint DIC computed from the entire model. We evaluate the performance of the five model selection indices via simulation studies. The manipulated factors include the number of groups, the number of second‐level covariates, the number of top‐level covariates, and the types of measurement models (one‐parameter vs. two‐parameter). Considering the computational viability and interpretability, the second‐level joint DIC is recommended for MLIRT models under our simulated conditions.
Routing Strategies and Optimizing Design for Multistage Testing in International Large‐Scale Assessments
Authors: Svetina Dubravka , Liaw Yuan‐Ling , Rutkowski Leslie , Rutkowski David
Published: March 2019

This study investigates the effect of several design and administration choices on item exposure and person/item parameter recovery under a multistage test (MST) design. In a simulation study, we examine whether number‐correct (NC) or item response theory (IRT) methods are differentially effective at routing students to the correct next stage(s) and whether routing choices (optimal versus suboptimal routing) have an impact on achievement precision. Additionally, we examine the impact of testlet length on both person and item recovery. Overall, our results suggest that no single approach works best across the studied conditions. With respect to the mean person parameter recovery, IRT scoring (via either Fisher information or preliminary EAP estimates) outperformed classical NC methods, although differences in bias and root mean squared error were generally small. Item exposure rates were found to be more evenly distributed when suboptimal routing methods were used, and item recovery (both difficulty and discrimination) was most precisely observed for items with moderate difficulties. Based on the results of the simulation study, we draw conclusions and discuss implications for practice in the context of international large‐scale assessments that recently introduced adaptive assessment in the form of MST. Future research directions are also discussed.
Survival of a grey reef shark Carcharhinus amblyrhynchos without a dorsal fin
Authors: Mumby Peter J.
Published: March 2019

An adult, female grey reef shark Carcharhinus amblyrhnchos was observed missing its first dorsal fin in 2014. The same individual was re‐photographed 4 years later indicating that this numerically dominant reef shark can survive total loss of its first dorsal fin. While this disability may impair the shark's ability to undertake pursuit predation, the species has a diversity of foraging modes that probably facilitates survival.
Association between echo intensity of the tongue and its thickness and function in elderly subjects
Authors: Chantaramanee Ariya , Tohara Haruka , Nakagawa Kazuharu , Hara Koji , Nakane Ayako , Yamaguchi Kohei , Yoshimi Kanako , Junichi Furuya , Minakuchi Shunsuke
Published: March 2019

Background

The tongue plays an important role during the oropharyngeal phase of swallowing. Each part of the tongue has a different function during swallowing. Ageing causes changes in muscle quantity and quality. Qualitative changes, such as an increase in intramuscular adipose tissue, can be determined by the echo intensity (EI) of the tongue on ultrasonography (US).

Objective

To clarify the relationship between EI and thickness and function of the tongue.

Methods

Ninety‐four healthy elderly individuals (30 male, 64 female) aged >65 years (mean 71.10 ± 4.13 years) were enrolled. Tongue thickness (TT) and EI were determined by US. Tongue function was evaluated by measurement of tongue pressure and oral diadochokinesis (OD). Multiple regression analysis was used to identify the factor with the strongest influence on EI of the tongue.

Results

The mean thickness of the middle of the tongue was 40.42 ± 4.24 mm and that of the base was 23.35 ± 3.32 mm; the respective EI values were 46.54 ± 9.33 and 49.33 ± 9.83. The average OD rates for /ta/ and /ka/ were 5.73 ± 1.09 and 5.40 ± 1.00 times/s, respectively. Multiple regression analysis for EI showed that /ta/ (β = −2.518,P = 0.042) and thickness of the middle of the tongue (β = −1.278,P < 0.001) were significant independent variables. Similarly, the EI at the base of the tongue showed that /ka/ (β = −4.038,P = 0.021) and base of TT (β = −0.913,P = 0.004) were significant independent variables.

Conclusion

EI may be an indicator of TT and OD in both the middle and base of the tongue. Ultrasound is beneficial for evaluating TT and function.
Long‐term survival analysis of standard‐length and short implants with multifunctional abutments
Authors: Martinolli Matteo , Bortolini Sergio , Natali Alfredo , Pereira Luciano José , Castelo Paula Midori , Rodrigues Garcia Renata Cunha Matheus , Gonçalves Thais Marques Simek Vega
Published: March 2019

Background

Spherical shape and connecting bypass screw of the OT Equator abutment (Rhein83, Italy) provides several retentive possibilities, even in non‐parallel implants.

Objective

This study assessed the long‐term survival of standard‐length and short implants receiving this multifunctional abutment.

Methods

Partially, edentulous patients (44 males and 64 females) (mean age 58.2 ± 10.5 years) rehabilitated with a fixed implant‐supported prosthesis where the OT Equator abutments (Rhein83) were applied. Follow‐up evaluations were performed up to 5 years following prosthesis delivery. Kaplan‐Meier survival analysis and Cox regression analysis were used to determine whether the distribution of time to failure differed based on implant characteristics (length and region), adjusting for sex (α = 0.05).

Results

In total, 216 implants (5 × 8 mm, n = 126; 5 × 6 mm, n = 90) (Betwice, Mech & Human, Italy) were installed. The average follow‐up period was 25.3 months (±19.3 months). Eight failures occurred, with most observed before loading (n = 6). Cumulative survival rates (CSR) at implant and abutment levels were 94.3% and 97.1%, respectively. Regarding implant length, CSRs were 97.8% and 90.6% for short and standard‐length implants, respectively, with no difference between subgroups (logrank: χ2 = 1.34, df = 1, P = 0.25). No significant difference was also found between implants of maxilla (CSR = 92.2%) and mandible (CSR = 95.5%; logrank: χ2 = 0.08, df = 1, P = 0.78).

Conclusion

The OT Equator abutment (Rhein83) showed a stable clinical performance, with continuous and predictable survival.
Puberty in the Last 25 Years: A Retrospective Bibliometric Analysis
Authors: Marceau Kristine , Hottle Savannah , Yatcilla Jane Kinkus
Published: March 2019

Puberty research has been highly productive in the past few decades and is gaining momentum. We conducted an analysis of bibliographic data, including titles, abstracts, keywords, indexing terms, and citation data to assess the sheer numbers, audience and reach, publication types, and impact of puberty‐related publications. Findings suggest that puberty‐related publications are increasing in sheer numbers, and have reach in many fields as befits an interdisciplinary science. Puberty‐related publications typically have higher impact in terms of citations than the journal averages, among the journals that published the most studies on puberty. Limitations of the field and recommendations for researchers to improve the impact and reach of puberty‐related publications (e.g., clear conclusions in abstracts, highlighting the importance of puberty) are discussed.
Manufacturing (co)agglomeration in a transition country: Evidence from Russia
Authors: Aleksandrova Ekaterina , Behrens Kristian , Kuznetsova Maria
Published: March 2019

We document the geographic concentration patterns of Russian manufacturing using detailed microgeographic data. About 80% of three‐digit industries are significantly agglomerated, and a similar share of three‐digit industry pairs is significantly coagglomerated. Industry pairs with stronger buyer–supplier links—as measured using Russian input–output tables—tend to be slightly more coagglomerated. This result is robust to instrumental variable estimation using either Canadian or US instruments. Using Canadian ad valorem transport costs as a proxy for transport costs in Russia, we further find that industries with higher transport costs are more dispersed, and industry pairs with higher transport costs are less coagglomerated.
Cervical hyperaesthesia in dogs: an epidemiological retrospective study of 185 cases
Authors: De Strobel F. , Paluš V. , Vettorato E. , Cherubini G. B.
Published: March 2019

Objectives

To describe the prevalence, clinical findings and predictors of disease in dogs with cervical hyperaesthesia.

Materials and Methods

Medical records of dogs referred for neurological investigation of cervical hyperaesthesia between 2009 and 2013 were retrospectively reviewed. Dogs were assigned to one of the following groups according to the final diagnosis: Non‐Neurologic, Brain, Cervical Spine, Multifocal, and Chiari‐like Malformation/Syringomyelia. Demographic data, clinical and neurological signs and laboratory findings were compared between groups using univariate analysis; predictors of disease location were assessed by multivariate analysis.

Results

Final diagnostic allocations of the 185 records included in the study were as follows: 2.7%Non‐Neurologic, 2.2%Brain, 63.2%Cervical Spine, 22.2%Multifocaland 9.7%Chiari Malformation/Syringomyelia. Intervertebral disc extrusion and steroid‐responsive meningitis arteritis were the most common diseases. Compared toMultifocaldogs, those allocated aCervical Spinediagnosis were older, heavier, more frequently ataxic and lame on a thoracic limb; furthermore, they were less frequently depressed or hyperthermic at presentation. Leucocytosis, neutrophilia and monocytosis were more frequent in dogs allocated aMultifocaldiagnosis. Dogs with cervical hyperaesthesia older than 36 months and non‐hyperthermic at presentation were more likely to have a lesion of the cervical region rather than a multi‐focal disease.

Clinical Significance

Although non‐specific, these results may be useful to guide clinicians in management of dogs presenting with cervical hyperaesthesia. Animal age and body temperature may support the suspicion of either focal or multi‐focal cervical spinal disease.
Equine platelet concentrate preparation and validation
Authors: Bozorgmanesh Rana , Magdesian K. Gary , Sutton‐Burges Julie W. , Owens Sean D. , Tablin Fern
Published: March 2019

Background

Development of equine platelet concentrate (PC) would aid management of cases requiring transfused platelets (PLTs), where adminstration of whole‐blood or platelet‐rich plasma (PRP) might be contraindicated.

Objectives

To test and validate a method for production of an equine PRP‐PC product.

Animals

Six healthy Thoroughbred geldings from a research herd.

Methods

In this prospective experimental study, whole blood was collected and processed through multiple centrifugation steps to yield 120 mL of PC. The PC was stored at 22°C and gently and continuously agitated. Measurements of PLT count, pH, and concentrations of glucose, lactate, electrolytes, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST), as well as partial pressures of oxygen and carbon dioxide were performed on days 0, 1, 2, 3, 5, and 7. Platelet aggregometry and bacterial culture were also performed.

Results

The PC always had a PLT count of ≥550 × 103cells/μL. Aggregometry graph amplitude (P < .0001) and area under the curve (P < .05) significantly decreased over time. Sodium, chloride, lactate (P < .0001), and oxygen (P < .01) concentrations significantly increased over time. pH (P < .001), glucose and bicarbonate concentrations (P < .0001) significantly decreased over time. There was no significant difference in potassium concentration, PLT count, LDH and AST activities and no bacterial growth from culture.

Conclusions and Clinical Importance

The described technique yielded a PC that meets the standards of the American Association of Blood Banks for human PC.
How Borrowing Constraints Hinder Migration: Theoretical Insights from a Random Utility Maximization Model*
Authors: Marchal Léa , Naiditch Claire
Published: March 2019

We provide a theoretical framework to analyze how financial constraints hinder migration. Introducing wealth heterogeneity and borrowing constraints into a random utility maximization model of migration, we find evidence of multilateral resistance to migration stemming from borrowing constraints. We calibrate the model on 22 European countries, and we show that omitting the constraints biases upward the estimation of bilateral migration rates. We then simulate an increase in the bilateral cost of migration to the United Kingdom. We find that omitting the constraints biases downward the change entailed by the cost increase in the bilateral rates of migration to all destinations.
Identification of the novel HLA‐B*40:357 allele by polymerase chain reaction sequence‐based typing
Authors: Zhao Shuoxian , Wang Wei , Zhang Wei , He Ji , Zhu Faming
Published: March 2019

HLA‐B*40:357 shows a substitution C to G at position 263 when compared to HLA‐B*40:01:01.