bluuebunny/crossref_metadata_2025 huggingface dataset:
Forkhead box C1 boosts triple‐negative breast cancer metastasis through activating the transcription of chemokine receptor‐4
Authors: Pan Hongchao , Peng Zhilan , Lin Jiediao , Ren Xiaosha , Zhang Guojun , Cui Yukun
Published: October 2018

The transcription factor forkhead box C1 (FOXC1) has recently been proposed as a crucial regulator of triple‐negative breast cancer (TNBC) and associated with TNBC metastasis. However, the mechanism of FOXC1 in TNBC development and metastasis is elusive. In this study, overexpression of FOXC1 in MDA‐MB‐231 cells significantly enhanced, whereas knockdown of FOXC1 in BT549 cells significantly reduced, the capabilities of TNBC cell invasion and motility in vitro and metastasis to the lung in vivo, when compared to their respective control cells. Mechanistic studies revealed that FOXC1 increased the expression of CXC chemokine receptor‐4 (CXCR4), probably through transcriptional activation. AMD3100, an inhibitor of CXCR4, could block cell migration. In a zebrafish tumor model, AMD3100 could suppress cell invasion and metastasis. In addition, overexpressing CXCR4 in FOXC1‐knockdown BT549 cells increased the capabilities of TNBC cell invasion and motility. In contrast, inhibition of CXCR4 with either AMD3100 or siRNA in MDA‐MB‐231 cells overexpressing FOXC1 reduced the capabilities of invasion and motility. Taken together, our results reveal a potential mechanism for FOXC1‐induced TNBC metastasis.
Urea transport B gene induces melanoma B16 cell death via activation of p53 and mitochondrial apoptosis
Authors: Liu Lianqin , Sun Yuxin , Zhao Yunxia , Wang Qian , Guo Hua , Guo Rui , Liu Yanan , Fu Shuang , Zhang Ling , Li Yang , Meng Yan
Published: October 2018

Urea Transporter B (UT‐B) is a membrane channel protein that mediates the rapid transmembrane transport of urea and participates in urine concentration. Urea Transporter B is expressed in skin, but we found that there is little expression in human melanoma tissue. In this study, we examined the effects of UT‐B overexpression in melanoma. The results indicated that there is no UT‐B mRNA expression in B16 cells, and UT‐B overexpression repressed B16 cell proliferation and induced apoptosis in vitro. We show that UT‐B overexpression causes increased reactive oxygen species production, which may be caused by mitochondria dysfunction. The mitochondrial membrane potential (ΨΔm) was lower in UT‐B‐overexpressing B16 cells. The proteins involved in complexes I, III, IV and V of the respiratory chain were clearly downregulated in UT‐B‐overexpressing B16 cells, which would strongly reduce the activity of the electron transport chain. We found that mitochondrial release of cytochrome C into the cytoplasm also increased, indicating that apoptosis had been activated. In addition, UT‐B overexpression reduced AKT phosphorylation and MDM2 expression and increased p53 expression; p53 activation may be involved in the anticancer effects of UT‐B overexpression. Urea Transporter B overexpression also inhibited tumor growth in vivo. In conclusion, we demonstrated that UT‐B may be related to the occurrence of melanoma and play a role in tumor development.
Reduced Autobiographical Memory Specificity Among Maltreated Preschoolers: The Indirect Effect of Neglect Through Maternal Reminiscing
Authors: Lawson Monica , Valentino Kristin , Speidel Ruth , McDonnell Christina G. , Cummings E. Mark
Published: October 2018

Maternal reminiscing and preschoolers’ (M = 5.00 years,SD = 1.11) autobiographical memory specificity (AMS) were examined among abusive (n = 24), neglecting (n = 78), emotionally maltreating (n = 32), and demographically similar nonmaltreating families (n = 74). Neglect was negatively associated with child AMS and the quantity of maternal elaborations. In a moderated mediation model, neglect was negatively associated with the quantity of maternal elaborations, which was positively associated with AMS when mothers reminisced in a coherent and sensitive manner (i.e., affective quality). In the context of high maternal affective quality, maternal elaborative quantity accounted for reduced AMS among neglected preschoolers. The findings extend observations of reduced AMS to neglected preschoolers and inform theoretical models of autobiographical memory development.
Early‐life exposure to sibling modifies the relationship between CD14 polymorphisms and allergic sensitization
Authors: Lau Melisa Y. Z. , Dharmage Shyamali C. , Burgess John A. , Win Aung K. , Lowe Adrian J. , Lodge Caroline J. , Perret Jennifer , Hui Jennie , Thomas Paul S. , Giles Graham , Thompson Bruce R. , Abramson Michael J. , Walters E. Haydn , Matheson Melanie C. ,   the investigators of the TAHS and MACS
Published: October 2018

Background

Markers of microbial exposure are thought to be associated with risk of allergic sensitization; however, the associations are inconsistent and may be related to gene‐environment interactions.

Objective

To examine the relationship between polymorphisms in the CD14 gene and allergic sensitization and whether sibling exposure, as a marker of microbial exposure, modified this relationship.

Methods

We used data from the Tasmanian Longitudinal Health Study and the Melbourne Atopy Cohort Study. Two CD14 polymorphisms were genotyped. Allergic sensitization was defined by a positive response to a skin prick test. Sibling exposure was measured as cumulative exposure to siblings before age 6 months, 2 and 4 years. Logistic regression and multi‐level mixed‐effects logistic regression were used to examine the associations. Effect estimates across the cohorts were pooled using random‐effects meta‐analysis.

Results

CD14 SNPs were not individually associated with allergic sensitization in either cohort. In TAHS, cumulative sibling exposure before age 6 months, 2 and 4 years was each associated with a reduced risk of allergic sensitization at age 45 years. A similar effect was observed in MACS. Meta‐analysis across the two cohorts showed consistent evidence of an interaction between cumulative sibling exposure before 6 months and the rs5744455‐SNP (P = 0.001) but not with the rs2569190‐SNP (P = 0.60). The pooled meta‐analysis showed that the odds of sensitization with increasing cumulative exposure to sibling before 6 months of age was 20.9% smaller in those with the rs5744455‐C‐allele than the T‐allele (OR = 0.83 vs 1.05, respectively).

Conclusion and Clinical Relevance

Cumulative sibling exposure reduced the risk of sensitization from childhood to middle age in genetically susceptible individuals.
Radiosurgery as primary management for acromegaly
Authors: Sims‐Williams Hugh P. , Rajapaksa Kaveesha , Sinha Saurabh , Radatz Matthias , Walton Lee , Yianni John , Newell‐Price John
Published: October 2018

Objective

Transsphenoidal surgery (TSS) remains the recommended primary treatment for acromegaly. Long‐term outcome data are not available for patients treated with gamma knife radiosurgery (STRS) as a primary treatment.

Design

Retrospective cohort study. Data collection: notes review, laboratory results, general physician notes, patient questionnaire and death certification.

Patients

Twenty acromegaly patients underwent primary STRS at the National Centre for Radiosurgery, Sheffield, UK, between 1985 and 2015.

Measurements

Biochemical control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded.

Results

At 20 years of follow‐up, control was seen in all on acromegaly‐specific medication (n = 12) and 75% of those off medication (3/4). Time for 50% to achieve control on medication was 3 years, and 7.4 years off medication. Median marginal radiation dose was 27.5 Gy, and median follow‐up was 166.5 months. 53% of patients developed new hypopituitarism at a median follow‐up of 146 months, and the development of first onset of hypopituitarism occurred as late as 20 years after treatment. With MRI planning, no other complications were noted. Three patients underwent subsequent TSS due to poor biochemical control. During follow‐up, 7 patients died at a median age of 65 years. There were no STRS‐related deaths.

Conclusion

This is the longest follow‐up of patients who have undergone primary STRS for acromegaly. It shows low morbidity, but significant latency to biochemical control and new‐onset hypopituitarism. This mandates very long‐term follow‐up for these patients. STRS has shown good long‐term efficacy providing initial control can be afforded by optimal medical management. While TSS remains best practice, STRS offers an alternative for those in whom surgery is not an option.
Predicting outcomes and complications following radioiodine therapy in Graves’ thyrotoxicosis
Authors: Aung Ei Thuzar , Zammitt Nicola N. , Dover Anna R. , Strachan Mark W. J. , Seckl Jonathan R. , Gibb Fraser W.
Published: October 2018

Objective

Radioiodine (RAI) is an effective treatment for Graves’ thyrotoxicosis but is associated with a failure rate of 15% and may be a risk factor for thyroid eye disease (TED) and weight gain. We sought to examine predictors of RAI failure, weight gain, TED and patient satisfaction.

Design

Retrospective cohort study.

Patients

A total of 655 episodes of RAI in Graves’ thyrotoxicosis patients (2006‐2015).

Measurements

Biochemical assessment, including TFTs and thyrotropin receptor antibodies (TRAb), clinical features (eg, TED, weight and thionamide use) and patient questionnaire.

Results

The treatment failure rate was 17%. Failure was greater with higher fT4 (P = 0.002) and higher TRAb (P = 0.004). Failure rate was 42.2% when TRAb >40 U/L. Median weight gain was 3.2 kg in those with normal fT4 prior to RAI and 5.8 kg when fT4 was elevated (P < 0.001). New TED developed in 7.6% but was not associated with post‐RAI dysthyroidism. Treatment satisfaction was generally high (median response 8/10).

Conclusions

Treatment failure after RAI occurs in predictable groups and this should be reflected in the information provided to patients. Weight gain is common and may not entirely be explained by a return to pre‐thyrotoxic baseline. We were unable to detect any significant impact of post‐RAI dysthyroidism on weight gain, TED or thyroid symptoms in this large cohort.
Protective role of skeletal muscle mass against progression from metabolically healthy to unhealthy phenotype
Authors: Lee Min Jung , Kim Eun‐Hee , Bae Sung‐Jin , Choe Jaewon , Jung Chang Hee , Lee Woo Je , Kim Hong‐Kyu
Published: October 2018

Objective

Metabolically healthy individuals are known to be resistant to cardiovascular disease development. However, a considerable fraction of those individuals shows deteriorated metabolic health over time. Although skeletal muscle is the primary insulin‐responsive target organ, a longitudinal investigation of the skeletal muscle mass in relation to the development of metabolically unhealthy phenotype has not been performed. We aimed to evaluate whether greater skeletal muscle mass is an independent protective factor for the development of metabolically unhealthy phenotype.

Design, Participants and Measurements

We conducted a retrospective cohort study with 9033 metabolically healthy volunteers who underwent routine health examinations in 2012 and a follow‐up examination in 2016. Obesity was defined as Asian‐Pacific body mass index criterion ≥25 kg/m2. Subjects with fewer than two risk factors (elevated blood pressure, triglyceride, glucose, high‐sensitivity C‐reactive protein, insulin resistance and decreased high‐density lipoprotein cholesterol levels) were characterized as metabolically healthy using Wildman criteria.

Results

At the 4‐year follow‐up, approximately one‐fourth of the nonobese participants and half of the participants with obesity showed metabolic deterioration. In nonobese men and women, higher appendicular skeletal muscle mass (ASM)/weight at baseline was significantly associated with decreased risk of metabolic deterioration. Compared to the lowest quartile of ASM/weight, the adjusted odds ratios (95% confidence intervals) of the highest quartile were 0.68 (0.52‐0.89) in nonobese men and 0.64 (0.46‐0.90) in nonobese women. However, this association was not observed in obese subjects.

Conclusions

Greater skeletal muscle mass at baseline is significantly associated with maintenance of metabolically healthy status, especially in nonobese individuals.
Novel exostosin‐2 missense variants in a family with autosomal recessive exostosin‐2‐related syndrome: further evidences on the phenotype
Authors: Gentile Mattia , Agolini Emanuele , Cocciadiferro Dario , Ficarella Romina , Ponzi Emanuela , Bellacchio Emanuele , Antonucci Maria F. , Novelli Antonio
Published: October 2018

Biallelic exostosin‐2 (EXT2) pathogenic variants have been described as the cause of the Seizures‐Scoliosis‐Macrocephaly syndrome (OMIM 616682) characterized by intellectual disability, facial dysmorphisms and seizures. More recently, it has been proposed to rename this disorder with the acronym AREXT2 (autosomal recessive EXT2‐related syndrome). Here, we report the third family affected by AREXT2 syndrome, harboring compound missense variants in EXT2, p.Asp227Asn, and p.Tyr608Cys. In addition, our patients developed multiple exostoses, which were not observed in the previously described families. AREXT2 syndrome can be considered as a multiorgan Congenital Disorder of Glycosylation caused by a significant, but non‐lethal, decrease in EXT2 expression, thereby affecting the synthesis of the heparan sulfate proteoglycans, which is relevant in many physiological processes. Our finding expands the clinical and molecular spectrum of the AREXT2 syndrome and suggests a possible genotype/phenotype correlation in the development of the exostoses.
The Outcome‐Representation Learning Model: A Novel Reinforcement Learning Model of the Iowa Gambling Task
Authors: Haines Nathaniel , Vassileva Jasmin , Ahn Woo‐Young
Published: October 2018

The Iowa Gambling Task (IGT) is widely used to study decision‐making within healthy and psychiatric populations. However, the complexity of the IGT makes it difficult to attribute variation in performance to specific cognitive processes. Several cognitive models have been proposed for the IGT in an effort to address this problem, but currently no single model shows optimal performance for both short‐ and long‐term prediction accuracy and parameter recovery. Here, we propose the Outcome‐Representation Learning (ORL) model, a novel model that provides the best compromise between competing models. We test the performance of the ORL model on 393 subjects' data collected across multiple research sites, and we show that the ORL reveals distinct patterns of decision‐making in substance‐using populations. Our work highlights the importance of using multiple model comparison metrics to make valid inference with cognitive models and sheds light on learning mechanisms that play a role in underweighting of rare events.
Insulinoma‐associated protein 1 expression in pancreatic neuroendocrine tumours in endoscopic ultrasound‐guided fine‐needle aspiration cytology: An analysis of 14 patients
Authors: Takase Yorihiko , Naito Yoshiki , Okabe Yoshinobu , Ishida Yusuke , Yamaguchi Tomohiko , Abe Hideyuki , Murata Kazuya , Ito Takaaki , Tanigawa Masahiko , Kawahara Akihiko , Yano Hirohisa , Akiba Jun
Published: October 2018

Background

Insulinoma‐associated protein 1 (INSM1) has been reported to be a useful marker for diagnosing pancreatic neuroendocrine tumours (PNETs). However, INSM1 expression in endoscopic ultrasound‐guided fine needle aspiration cytology has not been examined. We evaluated INSM1 expression in the cytology of cases diagnosed with PNETs.

Methods

We immunocytochemically stained INSM1 and Ki‐67 in 14 PNET cases, and according to the 2017 World Health Organisation criteria, seven PNET Grade 1 cases, four Grade 2 cases and three Grade 3/neuroendocrine carcinoma cases were identified. As a control for INSM1 and Ki‐67 expression, we used cytological specimens from 15 cases of pancreatic ductal adenocarcinoma.

Results

In PNET cases, INSM1‐expressing tumour cells were identified in all cytological specimens of PNET. The median INSM1 expression rate in Grade 1 cases was 49.8% (mean ± standard deviation: 55.1 ± 12.5%, min: 39.3%, max: 74.1%), and in Grade 2 and Grade 3/neuroendocrine carcinoma cases was 81.1% (mean ± standard deviation: 77.6 ± 18.6%, min: 50.3%, max: 100%). However, there was no correlation between INSM1 and Ki‐67 expression (r = −0.15). The median expression rate in PNET cases was 64.3%, which was significantly higher than that in pancreatic ductal adenocarcinoma cases (P < 0.0001).

Conclusion

INSM1 immunocytochemistry of cytological specimens obtained from endoscopic ultrasound‐guided fine needle aspiration cytology can accurately diagnose PNETs; therefore, INSM1 could be an important diagnostic tool in assessing therapeutic strategies, including molecular‐targeted therapy.
Clinicopathological features of immunoglobulin G4‐related pleural lesions and diagnostic utility of pleural effusion cytology
Authors: Kasashima Satomi , Kawashima Atsuhiro , Ozaki Satoru , Kita Toshiyuki , Araya Tomoyuki , Ohta Yasuhiko , Suzuki Mitsutaka
Published: October 2018

Objective

Immunoglobulin (Ig)G4‐related disease is a recently described systemic immune‐mediated fibro‐inflammatory disease that frequently occurs in tumorous form. Herein, we elucidated the clinicopathological and cytological characteristics of IgG4‐related pleural lesions (PLs).

Patients and methods

Among 22 patients with fibro‐inflammatory PLs of idiopathic aetiology, eight cases were diagnosed as IgG4‐PL and the remaining 14 as non‐IgG4‐PL according to comprehensive diagnostic criteria for IgG4‐related disease. Cell block examination of pleural effusion (CBPE) was performed in five patients with IgG4‐PL and in six with non‐IgG4‐PL. Both groups were compared in terms of clinical presentation, laboratory data, histopathological features of resected pleura, and cytological features of pleural effusion (PE).

Results

PE was the most common (six patients, 75%) clinical presentation of IgG4‐PL. IgG4‐PL comparatively showed significantly more frequent concomitant allergic disease (P = .021), higher serum IgE levels (P = .012), higher adenosine deaminase levels in pleural fluid (P = .005), and rare spontaneous recovery without treatment (P = .046). The IgG4‐PL group was histologically characterised by thicker fibrous pleura, storiform fibrosis, and infiltration of regulatory T cells, eosinophils and basophils. Using CBPE, IgG4‐PL was cytologically distinct with numerous IgG4+ cells and eosinophils. The cytology of CBPE positively correlated with the histology of pleural tissue in the number of IgG4+ cells and eosinophils (R = .769 and .803, respectively).

Conclusion

IgG4‐PL frequently presents with PE and is histologically and cytologically characterised by abundant infiltration of IgG4+ cells and eosinophils. We believe that CBPE with immunohistochemistry/special staining could assist in the auxiliary diagnosis of IgG4‐PL.
Urine drug screening for early detection of unwitting use of fentanyl and its analogues among people who inject heroin in Sydney, Australia
Authors: Barratt Monica J. , Latimer Julie , Jauncey Marianne , Tay Emma , Nielsen Suzanne
Published: October 2018

Introduction and Aims

North America has witnessed a dramatic rise in fatal opioid overdoses due to the unwitting consumption of non‐pharmaceutical fentanyl and its analogues. While some of the drivers of this crisis—including profitability and access to high‐potency opioids through internet sources—also apply in Australia, to our knowledge, there have been no ongoing surveillance studies of local populations. Therefore, this pilot study aimed to detect unintentional fentanyl consumption among people who inject heroin through instant urine screening, and determine the feasibility and acceptability of voluntary urinalysis of clients at the Medically Supervised Injecting Centre, Kings Cross, Sydney.

Design and Methods

Brief surveys and urine drug screens were conducted with 67 participants in Wave 1 (October 2017) and 51 participants in Wave 2 (March 2018). Urine samples were tested with BTNX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/mL norfentanyl. These strips also cross‐react to numerous fentanyl analogues.

Results

There were no cases where positive urine tests suggested unwitting fentanyl use detected in this study.

Discussion and Conclusions

These negative findings contrast sharply with similar Canadian studies. While no cases of fentanyl‐laced heroin use have been detected so far, we have demonstrated that this surveillance design is low‐cost, feasible and scalable approach to monitoring the considerable public‐health threat of undetected fentanyl and its analogues in Australia. Further validation of cross‐reactivity of test strips would strengthen this method.
The relationship between cannabis use and diabetes: Results from the National Epidemiologic Survey on Alcohol and Related Conditions III
Authors: Imtiaz Sameer , Rehm Jürgen
Published: October 2018

Introduction and Aims

The relationship between cannabis use and diabetes is puzzling. Although cannabis users versus non‐users should theoretically have a higher likelihood of diabetes, epidemiological studies suggest otherwise. However, previous epidemiological studies have not considered the potential confounding effects of mental health disorders. As such, the relationship between cannabis use and diabetes was examined while accounting for a range of potential confounders, including mental health disorders.

Design and Methods

Data were obtained from the National Epidemiologic Survey on Alcohol and Related Conditions III. Chi‐square tests were used to compare socio‐demographics, lifestyle behaviours, physical health disorders and mental health disorders between diabetics and non‐diabetics. Measures that exhibited statistical significance in these tests were subsequently included in multiple logistic regression analyses to quantify the relationships between lifetime and 12‐month cannabis use and diabetes.

Results

Although there was a considerable attenuation in the magnitude of the odds ratios after adjustment for confounders, there was still a decreased likelihood of diabetes for cannabis users versus non‐users. The corresponding odds ratios of diabetes were 0.81 (95% confidence interval 0.70, 0.94) and 0.51 (95% confidence interval 0.41, 0.63) for lifetime and 12‐month cannabis use, respectively.

Discussion and Conclusions

A decreased likelihood of diabetes for cannabis users versus non‐users was indicated after accounting for a range of potential confounders, including mental health disorders. Before the protective effects of cannabis use for diabetes can be suggested, further epidemiological studies are needed that incorporate prospective designs, as well as feature innovative exposure measurements and statistical analyses.
Niche shift and resource supplementation facilitate an amphibian range expansion
Authors: Davies Sarah J. , Hill Matthew P. , McGeoch Melodie A. , Clusella‐Trullas Susana
Published: October 2018

Aim

To determine whether recent range expansion of small‐bodied arboreal frogs, Hyperolius marmoratus Rapp, is accompanied by changes in species–environment relationships and whether its historical range was constrained by climate, availability of water bodies or topographic variables. We test if artificial water bodies in the novel range have facilitated niche shift by increasing available habitats for frog establishment.

Location

Western Cape Province, South Africa, with reference to the broader species range in southeastern Africa.

Methods

We build species distribution models using occurrence data from the historical and novel ranges and reciprocally project them to highlight areas of putative niche change. We test for niche shift through ordination‐based approaches to disentangle how species–environment relationships may have altered and whether climate or landscape features (artificial water bodies and topography) are more strongly associated with the identified change. We further decompose niche change into areas of expansion and unfilling to quantify niche shift and describe potential future spread.

Results

We observed niche expansion into novel environmental space, with 21% of niche space in the invaded range composed of environments that were not occupied in the native range. We also observed 16% niche unfilling, signifying range disequilibrium and potential for further spread. Mean annual precipitation and proximity to water bodies were more influential in models constructed in the novel range than in historical or combined range models, suggesting that presence of artificial water bodies in the landscape ameliorates novel range conditions. Together, these metrics suggest that range expansion may be ongoing based on climate and water body availability.

Main conclusions

Our analyses identify a realised niche shift that has allowed painted reed frogs to occupy drier and more thermally variable habitats in their novel (invaded) range. This shift may be mediated by artificial water bodies that provide additional buffered habitats, a key resource supplement for these small‐bodied tropical frogs.
Direct recanalization of pancreaticogastrostomy obstruction with a forward‐viewing echoendoscope
Authors: Kuwatani Masaki , Kato Shin , Sakamoto Naoya
Published: October 2018

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Payment by results in international development: Evidence from the first decade
Authors: Clist Paul
Published: October 2018

Payment by results is a relatively new way of giving development aid, where a recipient's performance against pre‐agreed measures determines the amount of aid they receive. Advocates for the mechanism argue it provides donors with both a ready justification for maintaining aid budgets and better results through innovation and autonomy. It has proved popular, with most bilateral aid donors having at least experimented with the mechanism and the variety of measures stretching from individual health workers being paid for each procedure, to national governments being paid for students' test scores. However, there has not been a robust assessment of whether Payment By Results (PbR) achieves its aims for greater effectiveness. I synthesize the evidence from eight projects fully or partially funded by DFID, the recognized world leader on PbR. This represents the best evidence currently available, and is critically analysed using the leading theoretical framework that breaks each agreement into its constituent parts. I find no evidence that PbR leads to fundamentally more innovation or autonomy, with the overall range of success and failure broadly similar to other aid projects. This may partly be due to the current use of Payment by Results, with no readily identifiable examples of projects that truly meet the idealized PbR designs. Advocates of PbR may thus conclude the idea is yet to be tested. I argue PbR does not deal with the fundamental constraints that donors face, and so it is unsurprising that PbR is subject to the normal pressures that affect all aid spending.
Functional and phenotypic heterogeneity of Th17 cells in health and disease
Authors: Bystrom Jonas , Clanchy Felix I. L. , Taher Taher E. , Al‐Bogami Mohammed , Ong Voon H. , Abraham David J. , Williams Richard O. , Mageed Rizgar A.
Published: October 2018

Background

Th17 cells have nonredundant roles in maintaining immunity, particularly at mucosal surfaces. These roles are achieved principally through the production of cytokines and the recruitment of other immune cells to maintain the integrity of mucosal barriers and prevent the dissemination of microorganisms. Th17 cells are heterogeneous and exhibit a considerable degree of plasticity. This allows these cells to respond to changing environmental challenges. However, Th17 cells also play pro‐inflammatory roles in chronic autoimmune diseases. The trigger(s) that initiate these Th17 responses in chronic autoimmune diseases remain unclear.

Design

In this report, we provide an overview of studies involving animal models, patient data, genome wide association studies and clinical trials targeting IL‐17 for treatment of patients to gain a better understanding of the pathogenic roles of Th17 cells play in a range of autoimmune diseases.

Results

The report sheds light on likely triggers that initiate or perpetuate Th17 responses that promote chronic inflammation and autoimmunity. The divergent effects of tumour necrosis factor alpha blockade on Th17 cells in patients, is explored. Furthermore, we highlight the role of Th17 cells in inducing autoreactive B cells, leading to autoantibody production. Pathogenic bacterial species can change Th17 cell phenotype and responses. These findings provide insights into how Th17 cells could be induced to promoting autoimmune disease pathogenesis.

Conclusion

This article provides an overview of the distinct roles Th17 cells play in maintaining immunity at mucosal surfaces and in skin mucosa and how their functional flexibility could be linked with chronic inflammation in autoimmune rheumatic diseases.
Testing the role of the posterior cingulate cortex in processing salient stimuli in cannabis users: an rTMS study
Authors: Prashad Shikha , Dedrick Elizabeth S. , To Wing Ting , Vanneste Sven , Filbey Francesca M.
Published: October 2018

The posterior cingulate cortex (PCC) and precuneus are hubs in the default mode network and play a role in processing external salient stimuli. Accordingly, activation in these regions has been associated with response to salient stimuli using drug cue‐reactivity paradigms in substance using populations. These studies suggest that the PCC and precuneus may underlie deficits in processing salient stimuli that contribute toward the development of substance use disorders. The goal of this study was to directly test this hypothesis using repetitive transcranial magnetic stimulation (rTMS). Using a double‐blind, placebo‐controlled design, we used rTMS to target the PCC and precuneus with a double‐cone coil at 10 Hz (high frequency) and 1 Hz (low frequency) in 10 adult cannabis users and 10 age‐ and sex‐matched non‐using controls. Electroencephalography data were collected before and after rTMS during a modified oddball paradigm with neutral, oddball, self‐relevant, and cannabis‐related stimuli. Cannabis users exhibited increased amplitude in P3 and faster latencies in the P3, N2, and P2 components in response to self‐relevant stimuli compared to controls during baseline that normalized after rTMS. These results suggest that cannabis users exhibited heightened salience to external self‐relevant stimuli that were modulated after rTMS. PCC dysfunction in cannabis users may be related to abnormalities in processing salient stimuli, such those during cue‐reactivity, and provides a potential target for cannabis use disorder intervention.
Response anisocoria in the pupillary light and darkness reflex
Authors: Wang Chin‐An , Tworzyanski Leanne , Huang Jeff , Munoz Douglas P.
Published: October 2018

The pupil constricts or dilates in response to a luminance increase or decrease, and these transient pupillary responses are controlled by the parasympathetic and sympathetic pathways. Although pupillary responses of the two eyes are highly correlated, they are not always identical (referred to as anisocoria). For example, there are unequal direct and consensual pupillary constriction responses after an increase in luminance to one eye. While contraction anisocoria (i.e. constriction) has been demonstrated in the pupillary light reflex, it is not yet known if there is also dilation anisocoria in the pupillary darkness reflex. Unlike previous studies that focused on the pupillary light reflex, we examined response anisocoria in both pupillary light and darkness reflexes. While requiring participants to maintain central fixation, we presented a light or dark stimulus to either the right or left visual field to induce transient pupillary constriction or dilation. Both the pupillary light and darkness reflexes had significantly larger ipsilateral responses compared to the contralateral responses relative to the stimulated visual field. The observed ipsilateral effects occurred significantly faster in the light than darkness reflex, suggesting that larger ipsilateral pupillary dilation after a luminance decrease cannot be only attributed to the inhibition of the parasympathetic system, but is also mediated by the excitation of the sympathetic system. Together, our results demonstrated a larger ipsilateral pupil response in both the pupillary light and darkness reflex, indicating an asymmetry in ipsilateral and contralateral neural circuitry of the pupillary darkness reflex.
Neural basis of goal‐driven changes in knowledge activation
Authors: Wang Wei‐Chun , Brashier Nadia M. , Wing Erik A. , Marsh Elizabeth J. , Cabeza Roberto
Published: October 2018

Depending on a person's goals, different aspects of stored knowledge are accessed. Decades of behavioral work document the flexible use of knowledge, but little neuroimaging work speaks to these questions. We used representational similarity analysis to investigate whether the relationship between brain activity and semantic structure of statements varied in two tasks hypothesized to differ in the degree to which knowledge is accessed: judging truth (semantic task) and judging oldness (episodic task). During truth judgments, but not old/new recognition judgments, a left‐lateralized network previously associated with semantic memory exhibited correlations with semantic structure. At a neural level, people activate knowledge representations in different ways when focused on different goals. The present results demonstrate the potential of multivariate approaches in characterizing knowledge storage and retrieval, as well as the ways that it shapes our understanding and long‐term memory.
Investigation of soil properties using different techniques of mid‐infrared spectroscopy
Authors: Ma F. , Du C. W. , Zhou J. M. , Shen Y. Z.
Published: October 2018

Diffuse reflectance spectroscopy (DRF), attenuated total reflectance spectroscopy (ATR) and Fourier transform infrared photoacoustic spectroscopy (PAS) are useful techniques that are commonly used to characterize soil properties. Here, these techniques were used to evaluate individual properties of 1456 paddy soil samples from Nanjing, China, to explore their features in the mid‐infrared range. The diffuse reflectance spectroscopy showed broad and shouldered peaks that ranged from 4000 to 500 cm−1. Attenuated total reflectance spectroscopy produced main peaks around 1000 cm−1. Fourier transform infrared photoacoustic spectroscopy spectra showed several moderate intensity peaks in the regions of 4000–2600 and 2500–500 cm−1. The effective variables (wavenumbers) were selected using an uninformative variable elimination (UVE) algorithm to predict soil pH, and soil organic matter (SOM), total nitrogen (TN) and available phosphorus (AP) contents; it used a self‐adaptive partial least squares model (SAM–PLS). The results showed that selected wavenumbers improved the accuracy of prediction for pH, and SOM, TN and AP contents. For the prediction of pH, ATR spectra showed marginally better performance than the other spectra. The DRF spectroscopy was the optimal method for SOM and TN prediction. Available phosphorus contents were predicted poorly by all three spectra. Furthermore, mid‐infrared incident light paths, absorption modes, sensing styles, as well as peak interference and the prediction model, were the main factors that affected the assessment of soil properties in the three types of spectroscopy.

Highlights

Soil spectra data were measured with DRF, ATR and PAS spectrometers over the range 4000–500 cm−1.

A UVE algorithm was used to select effective wavenumbers from the full spectrum.

The pH, SOM, TN and AP were estimated using three techniques based on a SAM–PLS model.

Mid‐infrared incident light paths and absorption modes affected prediction performance of the three techniques.
Combining two national‐scale datasets to map soil properties, the case of available magnesium in England and Wales
Authors: Lark R. M. , Ander E. L. , Broadley M. R.
Published: October 2018

Given the costs of soil survey it is necessary to make the best use of available datasets, but data that differ with respect to some aspect of the sampling or analytical protocol cannot be combined simply. In this paper we consider a case where two datasets were available on the concentration of plant‐available magnesium in the topsoil. The datasets were the Representative Soil Sampling Scheme (RSSS) and the National Soil Inventory (NSI) of England and Wales. The variable was measured over the same depth interval and with the same laboratory method, but the sample supports were different and so the datasets differ in their variance. We used a multivariate geostatistical model, the linear model of coregionalization (LMCR), to model the joint spatial distribution of the two datasets. The model allowed us to elucidate the effects of the sample support on the two datasets, and to show that there was a strong correlation between the underlying variables. The LMCR allowed us to make spatial predictions of the variable on the RSSS support by cokriging the RSSS data with the NSI data. We used cross‐validation to test the validity of the LMCR and showed how incorporating the NSI data restricted the range of prediction error variances relative to univariate ordinary kriging predictions from the RSSS data alone. The standardized squared prediction errors were computed and the coverage of prediction intervals (i.e. the proportion of sites at which the prediction interval included the observed value of the variable). Both these statistics suggested that the prediction error variances were consistent for the cokriging predictions but not for the ordinary kriging predictions from the simple combination of the RSSS and NSI data, which might be proposed on the basis of their very similar mean values. The LMCR is therefore proposed as a general tool for the combined analysis of different datasets on soil properties.

Highlights

Differences in sample support mean that two datasets on a soil property cannot be combined simply.

We showed how a multivariate geostatistical model can be used to elucidate the relationships between two such datasets.

The same model allows soil properties to be mapped jointly from such data.

This offers a general basis for combining soil datasets from diverse sources
How do speculators in agricultural commodity markets impact production decisions and commodity prices? A theoretical analysis
Authors: Koziol Christian , Treuter Tilo
Published: October 2018

We analyze the impact of speculative trading in agricultural commodity markets on major economic quantities. We consider a theoretical model with production shocks, in which a farmer interacts with a retailer in both the spot and the forward market. The contribution of the paper is twofold. First, we show that the current forward price drives agricultural production decisions. Since the forward trading of speculators influences the forward price, they indirectly affect production decisions. Second, we identify crucial variables determining whether speculative trading is beneficial or dangerous, such as the correlation between the speculators’ portfolio and the commodity prices, the risk premium of the forward, and the producer's gains.
Distinguishing the victim from the threat: SNP‐based methods reveal the extent of introgressive hybridization between wildcats and domestic cats in Scotland and inform future in situ and ex situ management options for species restoration
Authors: Senn Helen V. , Ghazali Muhammad , Kaden Jennifer , Barclay David , Harrower Ben , Campbell Ruairidh D. , Macdonald David W. , Kitchener Andrew C.
Published: October 2018

The degree of introgressive hybridization between the Scottish wildcat and domestic cat has long been suspected to be advanced. Here, we use a 35‐SNP‐marker test, designed to assess hybridization between wildcat and domestic cat populations in Scotland, to assess a database of 295 wild‐living and captive cat samples, and test the assumptions of the test using 3,097 SNP markers generated independently in a subset of the data using ddRAD. We discovered that despite increased genetic resolution provided by these methods, wild‐living cats in Scotland show a complete genetic continuum or hybrid swarm structure when judged against reference data. The historical population of wildcats, although hybridized, clearly groups at one end of this continuum, as does the captive population of wildcats. The interpretation of pelage scores against nuclear genetic data continues to be problematic. This is probably because of a breakdown in linkage equilibrium between wildcat pelage genes as the two populations have become increasingly mixed, meaning that pelage score or SNP score alone is poor diagnostic predictors of hybrid status. Until better tools become available, both should be used jointly, where possible, when making management decisions about individual cats. We recommend that the conservation community in Scotland must now define clearly what measures are to be used to diagnose a wildcat in the wild in Scotland, if future conservation action is to be effective.
Brimonidine displays anti‐inflammatory properties in the skin through the modulation of the vascular barrier function
Authors: Bertino Béatrice , Blanchet‐Réthoré Sandrine , Thibaut de Ménonville Séverine , Reynier Philippe , Méhul Bruno , Bogouch Audrey , Gamboa Bastien , Dugaret Anne Sophie , Zugaj Didier , Petit Laurent , Roquet Manon , Piwnica David , Vial Emmanuel , Bourdès Valerie , Voegel Johannes J. , Nonne Christelle
Published: October 2018

Background

Rosacea is a chronic inflammatory skin disease. Characteristic vascular changes in rosacea skin include enlarged, dilated vessels of the upper dermis and blood flow increase.

Brimonidine is approved for symptomatic relief of the erythema of rosacea. It acts by selectively binding to α2‐adrenergic receptors present on smooth muscle in the peripheral vasculature, resulting in transient local vasoconstriction.

Objectives

To provide further evidence of the anti‐inflammatory potential of brimonidine across preclinical models of skin inflammation and its ability to decrease the neutrophil infiltration in human skin after ultraviolet light exposure.

Methods

The anti‐inflammatory properties of brimonidine through modulation of the vascular barrier function were assessed using in vivo neurogenic vasodilation and acute inflammatory models and a well‐described in vitro transmigration assay. A clinical study assessed the neutrophil infiltration in human skin after exposure to UV in 37 healthy Caucasian male subjects.

Results

In vitro, brimonidine affects the transmigration of human neutrophils through the endothelial barrier by modulating adhesion molecules.

In vivo, in the mouse, topical treatment with brimonidine, used at a vasoconstrictive dose, confirmed its anti‐inflammatory properties and prevented leucocyte recruitment (rolling and adhesion) mediated by endothelial cells.

Topical pretreatment with brimonidine tartrate 0.33% gel once a day for 4 days significantly prevented neutrophil infiltration by 53.9% in human skin after exposure to UV light.

Conclusion

Results from in vitro, in vivo and from a clinical study indicate that brimonidine impacts acute inflammation of the skin by interfering with neurogenic activation and/or recruitment of neutrophils.
Beta‐lactam‐induced severe neutropaenia: a descriptive study
Authors: Vial Thierry , Bailly Henry , Perault‐Pochat Marie‐Christine , Default Anne , Boulay Charlène , Chouchana Laurent , Kassai Behrouz ,   the French Network of Pharmacovigilance Centres
Published: October 2018

The objectives of this study were to describe the characteristics and natural history of beta‐lactam‐induced severe neutropaenia and to evaluate the risk of recurrences after another beta‐lactam readministration. Reports of pure agranulocytosis associated with a beta‐lactam exposure within the 10 days preceding the neutropaenia were extracted from the French Pharmacovigilance Database over the year 2010. Cases with another evident cause or more likely attributable to another drug were excluded. Data were analyzed for demographics, clinical and biological features, prognosis factors, granulocyte colony stimulating factors administration and outcome. Sixty‐two cases were included (median age: 65 years). The median duration of treatment before neutropaenia was 16 days. In 47% of cases, the diagnosis was made on a systematic blood cell count. The median neutrophil count at nadir was 0.125 × 109/L, and bone marrow examination evidenced features of neutrophilic maturation arrest or aplasia in 21 patients, hyperplasia of granulopoietic cells in three and normal findings in five. Three patients developed severe sepsis. All but one recovered a normal blood cell count within 2–56 days after beta‐lactam discontinuation. The last patient died from recurrent severe septic shock. No significant effect of granulocyte colony stimulating factor on the mean duration of haematological recovery was found. Among the 21 patients who later received another beta‐lactam, two experienced recurrence of the neutropaenia after receiving a beta‐lactam from another subfamily. Beta‐lactam‐induced agranulocytosis was usually observed after prolonged treatment, and severe complications are uncommon. In most patients, a subsequent treatment with another beta‐lactam was well tolerated.
Medicated or not medicated hypnotic substance use: strategies in sleep disorders among patients of community pharmacy
Authors: Lauzeille Delphine , Guerlais Marylène , Sallenave‐Namont Claire , Etcheverrigaray François , Broccato Luciano , Poisblaud Quentin , Jolliet Pascale , Victorri‐Vigneau Caroline
Published: October 2018

The principal outcome was to identify which hypnotics substances, medicated (benzodiazepines, antihistamine, antidepressant…) or not medicated (herbal medicine, homeopathy, melatonin…), were consumed by community pharmacy patients who reported taking something for sleep disorder, and which factors can influence the consumption of medicated substance rather than nonmedicated substance. Data were collected via a network of 73 partner pharmacies around Nantes, France. Patients who reported taking a substance to sleep completed a questionnaire that collected data relative to the different substances consumed by that person for sleep, and the desired effect. Substances were classified in Hypnotic Drug Substances and nonmedicated hypnotic substances. A logistical regression was done in order to highlight the factors associated with the consumption of Hypnotic Drug Substance rather than nonmedicated hypnotic substances. Six hundred and forty‐seven patients were included, with an average age of 58 years and 74% female. The principal strategy employed to combat sleep disorder was the consumption of Hypnotic Drug Substance (54%), followed by herbal medicine (32%) and homeopathy (19%). The factors positively associated with the consumption of a Hypnotic Drug Substance are age, living alone, being out of work, or in the process of looking for a job and being a parent. In our survey, the use of Hypnotic Drug Substance to help patients with sleep is far from systematic. On the other hand, among patients who consume HDS, misuse is still significant, particularly in terms of the duration of consumption.