bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed connective tissue disease: state of the art on clinical practice guidelines
Authors: Chaigne Benjamin , Scirè Carlo Alberto , Talarico Rosaria , Alexander Tobias , Amoura Zahir , Avcin Tadej , Beretta Lorenzo , Doria Andrea , Guffroy Aurelien , Guimarães Vera , Hachulla Éric , Krieg Thomas , Launay David , Lepri Gemma , Moinzadeh Pia , Müller-Ladner Ulf , Rednic Simona , Rodrigues Ana , Tas Sander W , Van Vollenhoven Ronald F , Vieira Ana , Bombardieri Stefano , Fonseca João Eurico , Galetti Ilaria , Schneider Matthias , Smith Vanessa , Cutolo Maurizio , Mosca Marta , Fischer-Betz Rebecca
Published: October 2018

Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with antibodies targeting the U1 small nuclear ribonucleoprotein particle. In this narrative review, we summarise the results of a systematic literature research which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines (CPGs) or recommendations. Since no specific CPGs on MCTD were found, other CPGs developed for other CTDs were taken into consideration in order to discuss what can be applied to MCTD even if designed for other diseases. Three major objectives were proposed for the future development of CPGs: MCTD diagnosis (diagnostic criteria), MCTD initial and follow-up evaluations, MCTD treatment. Early diagnosis, epidemiological data, assessment of burden of disease and QOL aspects are among the unmet needs identified by patients.
Sjögren’s syndrome: state of the art on clinical practice guidelines
Authors: Romão Vasco C , Talarico Rosaria , Scirè Carlo Alberto , Vieira Ana , Alexander Tobias , Baldini Chiara , Gottenberg Jacques-Eric , Gruner Heidi , Hachulla Eric , Mouthon Luc , Orlandi Martina , Pamfil Cristina , Pineton de Chambrun Marc , Taglietti Marco , Toplak Natasa , van Daele Paul , van Laar Jacob M , Bombardieri Stefano , Schneider Matthias , Smith Vanessa , Cutolo Maurizio , Mosca Marta , Mariette Xavier
Published: October 2018

Sjögren’s syndrome (SS) is a complex autoimmune rheumatic disease that specifically targets salivary and lachrymal glands. As such, patients typically had ocular and oral dryness and salivary gland swelling. Moreover, skin, nasal and vaginal dryness are frequently present. In addition to dryness, musculoskeletal pain and fatigue are the hallmarks of this disease and constitute the classic symptom triad presented by the vast majority of patients. Up to 30% to 50 % of patients with SS may present systemic disease; moreover, there is an increased risk for the development of non-Hodgkin’s lymphoma that occurs in a minority of patients. The present work was developed in the framework of the European Reference Network (ERN) dedicated to Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET). In line with its goals of aiming to improve early diagnosis, treatment and care of rare connective and musculoskeletal diseases, ERN-ReCONNET set to review the current state of clinical practice guidelines (CPGs) in the rare and complex connective tissue diseases of interest of the network. Therefore, the present work was aimed at providing a state of the art of CPGs for SS.
Association of interleukin-10 promoter polymorphisms with serofast state after syphilis treatment
Authors: Pastuszczak Maciej , Jakiela Bogdan , Wojas-Pelc Anna
Published: October 2018

Objectives

Recent studies suggested that upregulation of anti-inflammatory immune response during early syphilis may be associated with persistence ofTreponema palliduminfection despite adequate treatment, resulting in a serofast state. The objective of this study was to determine whether enhanced interleukin (IL)-10-related response during earlyT. palliduminfection increased the risk of serofast syphilis.

Methods

TwoIL10gene promoter polymorphisms affecting IL-10 production (−1082A>G [rs1800896], −592C>A [rs1800872]) and serum levels of IL-10 were measured in 80 patients with early syphilis before and 6 months after penicillin treatment and in 24 healthy volunteers (control group).

Results

After 6 months, patients were stratified based on serological response into two groups: (1) serofast state (n = 28) and (2) serologically cured (n = 52). Pretreatment and post-treatment serum IL-10 levels were significantly higher in patients who remained serofast compared with those who had a serological cure (p<0.001). The GG genotype of the −1082A>G (rs1800896) polymorphism and the CC genotype of the −592C>A (rs1800872) polymorphism were significantly correlated with higher serum IL-10 levels. Moreover, the OR for remaining serofast for carriers of these genotypes was 16.2 (95% CI: 4.1 to 65.0, p<0.0001) and 2.9 (95% CI: 1.4 to 5.9, p=0.002), respectively.

Conclusions

We showed that a pronounced anti-inflammatory immune response may be an important predictor for the serofast state. Additionally, host-related factors such as polymorphisms of immune regulatory genes may influence the risk of remaining serofast after syphilis therapy.
Joint management format at the mixed-surgical intermediate care unit: an interrupted time series analysis
Authors: Plate Joost D J , Peelen Linda M , Leenen Luke P H , Houwert R Marijn , Hietbrink Falco
Published: October 2018

Background

The management format of the mixed-surgical intermediate care unit (IMCU) affects its performance. A format of combined supervision of surgeons with additional critical care certifications and admitting specialists, named the “joint format”, may herein be a promising new model of specialized critical care. This study aims to assess the performance of the joint management format.

Methods

This observational cohort study compared three IMCU management formats at the stand-alone, mixed-surgical IMCU of a tertiary referral hospital using interrupted time series analyses. All admissions from 2001 until 2015 were included. Predetermined criteria for performance (utilization, efficiency, and safety) were applied to three different management format periods: open (2001–2006), closed (2006–2011), and joint (2011–2015) formats.

Results

A total of 8894 admissions were analyzed. In terms of case load (utilization), there was an overall increase in the number of surgical patients (0.25%/year) (p<0.001), age (0.38/year) (p<0.001), and readmissions from the ward (0.16%/year) (p<0.001) and from the intensive care unit (ICU) (0.17%/year) (p=0.014). In terms of efficiency, the admission duration decreased (1.58 hours/year) (p<0.001). Transfer to the ICU within 24  hours, readmission within 24  hours from the ward, and unplanned mortality (eg, safety) did not change over time.

Discussion

At a time of increasingly complex case load, the joint format at the mixed-surgical IMCU is an efficient and safe management format in which the admitting specialist continues to provide specialized care. Specialty-specific supervision at IMCUs is a safe option which should be considered in healthcare policy decisions.

Level of evidence

Level IV.
Unilateral otitis externa induced by a plastic foreign body
Authors: May Elizabeth
Published: October 2018

A nine‐year‐old, male, neutered Tibetan terrier was evaluated for unilateral otitis externa associated with the history of a dog bite injury to the pinna five years prior. Examination findings of the left ear included severe inflammation, abundant purulent exudate and a polypoid mass, obscuring view of the horizontal ear canal and tympanic membrane. CT scan confirmed the visualised mass location and confinement to the ear canal. Aerobic otic culture revealed abundant colonies of Staphylococcus pseudintermedius and Corynebacterium species. Histopathology was consistent with a fibrous polyp. Otitis externa treatment provided minimal relief following mass removal, and the patient was re‐examined. A transparent plastic foreign body lodged within the horizontal canal was identified and removed. The item was recognised as a cap used for packaging of topical treatments prescribed at the time of the original traumatic injury. All clinical signs resolved following removal of the foreign body and oral anti‐inflammatory therapy.
Zinc supplementation reduces diet-induced obesity and improves insulin sensitivity in rats
Authors: Thoen Rutiane Ullmann , Barther Nathaniele Nebel , Schemitt Elizângela , Bona Sílvia , Fernandes Sabrina , Coral Gabriela , Marroni Norma Possa , Tovo Cristiane , Guedes Renata Padilha , Porawski Marilene
Published: October 2018

Rates of obesity have been growing at alarming rates, compromising the health of the world population. Thus, the search for interventions that address the metabolic repercussions of obesity are necessary. Here we evaluated the metabolic and antioxidant effects of zinc and branched-chain amino acids (BCAA) supplementation on obese rats. Male Wistar rats were fed either a high-fat/high-fructose diet (HFD) or a standard diet (SD) for 19 weeks. From the fifteenth week until the end of the experiment, HFD- and SD-fed rats received zinc (6 mg/kg) or BCAA (750 mg/kg) supplementation. Body weight, abdominal fat, lipid profile, blood glucose, insulin, leptin, and hepatic transaminases were evaluated. In the liver, superoxide dismutase and catalase activities and lipid peroxidation were also analyzed. HFD-fed animals showed increased weight gain, abdominal fat pad, plasma insulin, leptin, and triglycerides levels in comparison with SD-fed rats. Zinc supplementation reduced all these parameters, suggesting a beneficial role for the treatment of obesity. BCAA, on the other hand, did not show any beneficial effect. Liver antioxidant enzymes and hepatic transaminases plasma levels did not change among groups. Lipid peroxidation was higher in HFD-fed rats and was not reverted by zinc or BCAA supplementation. In conclusion, zinc supplementation may be a useful strategy for the treatment of the metabolic dysfunction associated with obesity.
Description of a partialDromiceiomimus(Dinosauria: Theropoda) skeleton with comments on the validity of the genus
Authors: Macdonald Ian , Currie Philip J.
Published: October 2018

Dromiceiomimus brevitertius is a North American ornithomimid diagnosed primarily by the ratio of tibia length to femur length. It has recently, and perhaps incorrectly, been considered synonymous with Ornithomimus edmontonicus, with several authors questioning the utility of limb ratios in diagnosing taxa. While isolated ornithomimosaur material is common, specimens with sufficient diagnostic material to explore the question of synonymy are comparatively rare. The putative Dromiceiomimus specimen UALVP 16182 represents one of the few specimens in which diagnostic elements are available. It is therefore an important specimen for assessing the validity of Dromiceiomimus and for examining the utility of using limb proportions to diagnose ornithomimid taxa. In this paper, UALVP 16182 is described, the tibia/femur ratio is examined in closely related ornithomimid taxa, and the ratio is found to distinguish Dromiceiomimus from Gallimimus, Ornithomimus, and Struthiomimus. A phylogenetic analysis recovered Anserimimus and Ornithomimus as sister taxa with Dromiceiomimus as an outgroup. Comparison of the manus revealed differences in the morphology of metacarpal I and the flexor tubercle of manual ungual II-3. Differences also appear in the surangular and scapula. An examination of stratigraphic positions of various specimens indicates that Dromiceiomimus is generally higher in section than Ornithomimus, although there are too few specimens to be statistically significant. This study agrees with other studies in concluding that limb proportions are roughly isometric in small theropods like ornithomimids and that the tibia/femur ratio may therefore be useful for diagnosing certain small taxa. These findings suggest that Dromiceiomimus may indeed be a valid taxon.
Loss of ash trees in riparian forests from emerald ash borer infestations has implications for aquatic invertebrate leaf-litter consumers
Authors: Kreutzweiser David , Nisbet David , Sibley Paul , Scarr Taylor
Published: October 2018

Rapid loss of ash (Fraxinus spp.) trees in riparian forests from an invasive insect, the emerald ash borer (EAB; Agrilus planipennis Fairmaire, 1888), could pose risk of altering organic matter inputs to water bodies that underpin many aquatic ecosystem processes. We measured the composition of riparian forests and their leaf-litter contributions to headwater streams and determined the relative palatability of ash leaves and leaves of three other common riparian trees to aquatic invertebrate leaf-litter consumers (the stonefly (Pteronarcys sp.) and the cranefly (Tipula sp.)) in laboratory microcosms and whole invertebrate communities in forest streams. Ash trees contributed, on average, 24% to riparian tree density and 20% to total litterfall. Among the four common streamside trees accounting for 65% of total litterfall, ash was the first or second most preferred food source for consumers. Leaf packs without ash decomposed at slower rates than packs containing 25%–100% ash leaves. Preferential feeding on ash leaves infers a high-quality food source selected by consumers, and this concurred with comparatively high N content and low C–N ratio of ash leaves. Aquatic invertebrate communities on leaf packs in streams differed among leaf mixtures with or without ash, although community dissimilarity was low. The loss of ash in riparian forests represents an EAB-induced reduction in a high-quality resource subsidy to organic matter consumers in streams. We discuss how this has implications for risk predictions and management response strategies.
Prediction for the cosmological constant and constraints on SUSY GUTs in resummed quantum gravity
Authors: Ward B. F. L.
Published: October 2018

Working in the context of the Planck scale cosmology formulation of Bonanno and Reuter, we use our resummed quantum gravity approach to Einstein’s general theory of relativity to estimate the value of the cosmological constant as [Formula: see text]. We show that SUSY GUT models are constrained by the closeness of this estimate to experiment. We also address various consistency checks on the calculation. In particular, we use the Heisenberg uncertainty principle to remove a large part of the remaining uncertainty in our estimate of [Formula: see text].
E6 inspired SUSY models with custodial symmetry
Authors: Nevzorov R.
Published: October 2018

The breakdown of [Formula: see text] within the supersymmetric (SUSY) Grand Unified Theories (GUTs) can result in SUSY extensions of the standard model (SM) based on the SM gauge group together with extra [Formula: see text] gauge symmetry under which right-handed neutrinos have zero charge. In these [Formula: see text] extensions of the minimal supersymmetric standard model (MSSM) a single discrete [Formula: see text] symmetry may be used to suppress the most dangerous operators, that give rise to proton decay as well as nondiagonal flavour transitions at low energies. The SUSY models under consideration involves [Formula: see text] and extra exotic matter beyond the MSSM. We discuss leptogenesis within this SUSY model and argue that the extra exotic states may lead to the nonstandard Higgs decays.
Field coupling-induced wave propagation and pattern stability in a two-layer neuronal network under noise
Authors: Qin Huixin , Ma Jun , Ren Guodong , Zhou Ping
Published: October 2018

Synapse coupling is critical for information encoding of neurons. The effect of electromagnetic induction in cell becomes distinct when the exchange of charged ions across membrane is frequently triggered by external electric field or synapse current from adjacent neurons. In this paper, Gaussian white noise is imposed on a two-layer network composed of neurons with electromagnetic induction. The gap junction coupling is applied to connect the adjacent neurons and external stimulus with diversity is applied to keep different excitabilities of neurons in each layer. Neurons on the second layer are activated and modulated by using field coupling rather than channel coupling. It is found that the pattern formation on the network is much dependent on the initial setting due to the memory effect based on induction current via memristive synapse. Furthermore, field coupling intensity (D0) and noise intensity (D1) are changed to detect the development of spiral waves, target waves on the network in presence of noise. It confirms that noise can be helpful for pattern selection and synchronization approach on the two-layer network under field coupling, while field coupling can suppress the self-organization for pattern formation.
Syntectonic quartz vein evolution during progressive deformation
Authors: Lloyd Geoffrey E.
Published: October 2018

Two models to explain the progressive deformation of syntectonic quartz veins are derived from conventional theories for simple and pure shears. The simple-shear model is based on reorientation and changes in length of linear vein elements, and predicts initial orientations of veins for imposed shear strains, elongations and strain ratios. The pure-shear model considers changes in length of lines variably orientated relative to the maximum compression direction, and yields estimates of elongation strains and strain ratios. Expectations of both models are different, as illustrated by analysis of quartz veins from the Rhoscolyn Anticline, Anglesey, NW Wales. The simple-shear model recognizes three distinct initial orientations, which predict different strains across the fold; the pure-shear model suggests veins were initially sub-parallel to the principal compression direction and predicts effectively constant strains across the fold. In addition, both models predict different patterns of fold vergence: for simple shear, vergence depends on magnitude and direction of shearing and may exhibit complex patterns; for pure shear, vergence patterns are predicted to be essentially constant. In general, the predictions of either model are critically dependent on the origin of the veins, particularly relative to the formation of the Rhoscolyn Anticline.
Perceptual Adjustment of Eyeball Rotation and Pupil Size Jitter for Virtual Characters
Authors: Jörg Sophie , Duchowski Andrew , Krejtz Krzysztof , Niedzielska Anna
Published: October 2018

Eye motions constitute an important part of our daily face-to-face interactions. Even subtle details in the eyes’ motions give us clues about a person’s thoughts and emotions. Believable and natural animation of the eyes is therefore crucial when creating appealing virtual characters. In this article, we investigate the perceived naturalness of detailed eye motions, more specifically of jitter of the eyeball rotation and pupil diameter on three virtual characters with differing levels of realism. Participants watched stimuli with six scaling factors from 0 to 1 in increments of 0.2, varying eye rotation and pupil size jitter individually, and they had to indicate if they would like to increase or decrease the level of jitter to make the animation look more natural. Based on participants’ responses, we determine the scaling factors for noise attenuation perceived as most natural for each character when using motion-captured eye motions. We compute the corresponding average jitter amplitudes for the eyeball rotation and pupil size to serve as guidelines for other characters. We find that the amplitudes perceived as most natural depend on the character, with our character with a medium level of realism requiring the largest scaling factors.
Koli Calling 2018 preview
Authors: Joy Mike , Ihantola Petri
Published: October 2018

The Koli Calling International Conference on Computing Education Research is a single-track conference dedicated to publishing high quality work on teaching and learning in the computing disciplines. The 18th Koli Calling will be held from 22-25 November 2018 in the Koli National Park in Finland, organized by the University of Warwick, the University of Helsinki, and the University of Eastern Finland, in-cooperation with ACM SIGCSE.
ICER 2018 review
Authors: McCartney Robert , Malmi Lauri , Korhonen Ari
Published: October 2018

The 14th International Computing Education Research conference was held from 12-16 August 2018 in Espoo, Finland. The conference venue was the Dipoli building at Aalto University. We had the highest attendance for an ICER outside of the US (127) and overall were second only to ICER 2017 in Tacoma. The attendees came from 18 countries, and included 71 first-time attendees and 44 students. We had a record number of paper submissions (125), of which 28 were accepted, for an acceptance rate of 22%.
SIGCSE 2019 department chairs roundtable
Authors: Maher Mary Lou
Published: October 2018

The SIGCSE Department Chairs Roundtable will feature small group discussions on challenges of being a Department Chair and finish with a panel of diverse and experienced Department Chairs. The group discussions will tackle topics such as the significant administrative and personnel issues that chairs must handle; leadership and management styles, time management, legal issues, establishing priorities, and communication.
Progress in Measurements of 0.1–10 GeV Neutrino–Nucleus Scattering and Anticipated Results from Future Experiments
Authors: Mahn Kendall , Marshall Chris , Wilkinson Callum
Published: October 2018

Neutrino interactions with nuclei have been the subject of intense interest during the last 15 years. Current and future measurements of neutrino oscillation and exotic physics use order 0.1–10 GeV neutrinos on a range of nuclear targets (12C,16O,40Ar). As the precision of these experiments has increased, information from their detectors and dedicated experiments has indicated deficiencies in the modeling of neutrino interactions on nuclear targets. Here, we present the current state of knowledge about neutrino–nucleus interactions, the challenge of extracting the cross section of these processes, and current experimental puzzles in the field. We also look forward to new and novel measurements and future efforts that seek to resolve these questions.
Deep Learning and Its Application to LHC Physics
Authors: Guest Dan , Cranmer Kyle , Whiteson Daniel
Published: October 2018

Machine learning has played an important role in the analysis of high-energy physics data for decades. The emergence of deep learning in 2012 allowed for machine learning tools which could adeptly handle higher-dimensional and more complex problems than previously feasible. This review is aimed at the reader who is familiar with high-energy physics but not machine learning. The connections between machine learning and high-energy physics data analysis are explored, followed by an introduction to the core concepts of neural networks, examples of the key results demonstrating the power of deep learning for analysis of LHC data, and discussion of future prospects and concerns.
Effect of high-fat diet feeding and associated transcriptome changes in the peak lactation mammary gland in C57BL/6 dams
Authors: Cheng A. A. , Li W. , Hernandez L. L.
Published: October 2018

Maternal consumption of a high-fat diet (HFD) during pregnancy has established adverse effects on the developing neonate. In this study, we aimed to investigate the effect of an HFD on the murine mammary gland during midlactation. Female C57BL/6J mice were placed on either a low-fat diet (LFD/10% fat) or HFD (60% fat) from 3 wk of age through peak lactation (lactation day 11/L11). After 4 wk of consuming either the LFD or HFD, female mice were bred. There were no significant differences in milk yield between treatment groups, which was measured from L1 to L9. On L10, mice were subjected to an overnight fast and then euthanized on the morning of L11. Total RNA was isolated from inguinal mammary glands for whole transcriptome sequencing. We found 628 genes that were differentially expressed between the treatment groups. Notably, HFD feeding resulted in expression alterations of genes involved in collagen and cytoplasmic components. Additionally, genes related to inflammatory and immune responses were also impacted. Differential expression in gene transcript isoforms between the treatment groups was detected in three genes related to mammary duct development. This study sheds light as to how an HFD may affect the mammary gland transcriptome during midlactation.
TGFβ-Activated USP27X Deubiquitinase Regulates Cell Migration and Chemoresistance via Stabilization of Snail1
Authors: Lambies Guillem , Miceli Martina , Martínez-Guillamon Catalina , Olivera-Salguero Rubén , Peña Raúl , Frías Carolina-Paola , Calderón Irene , Atanassov Boyko S. , Dent Sharon Y. R. , Arribas Joaquín , García de Herreros Antonio , Díaz Víctor M.
Published: October 2018

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box–specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFβ during EMT and was required for TGFβ-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFβ-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance.

Significance:

These findings show that inhibition of USP27X destabilizes Snail1 to impair EMT and renders tumor cells sensitive to chemotherapy, thus opening new strategies for the inhibition of Snail1 expression and its protumoral actions.
Host Characteristics and Risk of Incident Melanoma by Breslow Thickness
Authors: Li Wen-Qing , Cho Eunyoung , Wu Shaowei , Li Suyun , Matthews Natalie H. , Qureshi Abrar A.
Published: October 2018

Background:

Several host characteristics, including pigmentary traits (hair color, sunburn susceptibility and tanning ability), number of common nevi (moles), and family history of melanoma, have been associated with risk of melanoma.

Methods:

We prospectively examined the associations between host characteristics and risk of incident melanoma by Breslow thickness (≤1 mm, thin melanoma; or >1 mm, “thicker melanoma”) based on the Nurses' Health Study (NHS, n = 86,380 women), NHS II (n = 104,100 women), and Health Professionals Follow-up Study (HPFS, n = 46,934 men).

Results:

During 22–30 years' follow-up, a total of 1,813 incident melanoma cases were identified with information on Breslow thickness, 1,392 (76.8%) of which had thin melanoma. No significant differences were observed for thin and thicker melanoma in associations with hair color, sunburn susceptibility, and tanning ability. However, we found significant differences for the association with family history of melanoma, with a higher risk estimate for thicker melanoma [HR = 2.55; 95% confidence interval (CI): 1.91–3.42] than thin melanoma (HR = 1.59; 95% CI: 1.21–2.08; Pheterogeneity = 0.02). Interestingly, women and men displayed differential associations between nevi count and risk of melanoma by Breslow thickness, with the association appearing stronger for thicker melanoma than thin melanoma in men (Pheterogeneity = 0.01), but not in women.

Conclusions:

Individuals with family history of melanoma may be more likely to develop thicker melanoma. Men with high number of common nevi may tend to develop thicker melanoma, which was not found for women.

Impact:

The findings further stress the risk of thicker melanoma for individuals with a family history of melanoma and men with a high nevi count.
LGALS3 Promotes Treatment Resistance in Glioblastoma and Is Associated with Tumor Risk and Prognosis
Authors: Wang Hongxiang , Song Xiao , Huang Qilin , Xu Tao , Yun Dapeng , Wang Yuqi , Hu Lingna , Yan Yong , Chen Hongyan , Lu Daru , Chen Juxiang
Published: October 2018

Background:

LGALS3 promotes tumor progression in diverse cancers. However, the involvement of LGALS3 in glioblastoma has not yet been broadly illuminated.

Methods:

Microarray was performed to detect the gene expression profiles of radioresistance in T98G cells and identified a universally upregulated gene, LGALS3. The impact of LGALS3 on the survival of glioblastoma cells facing ionizing irradiation or temozolomide was investigated by the Cell Counting Kit-8 (CCK-8). A total of 120 glioblastoma cases were collected to analyze the relationship between LGALS3 expression and patient prognosis. Another 961 patients with glioma and 1,351 healthy controls were recruited to study the association of SNPs across the LGALS3 gene with glioblastoma susceptibility. The functional SNP sites were also studied in cellular experiments.

Results:

An effective protection of LGALS3 from ionizing irradiation or temozolomide-induced cell death in T98G and U251 cells was found. In addition, high expression of LGALS3 could work as an independent risk factor for survival of patients with glioblastoma. Two SNP sites (rs4644 and rs4652) across the LGALS3 gene were associated with increased risk for glioblastoma, and the C allele of rs4652 and the A allele of rs4644 could enhance glioblastoma resistance to radio-chemotherapy, but not cell proliferation.

Conclusions:

Our results suggest that LGALS3 is an important biomarker influencing glioblastoma risk and prognosis and a potential target for treating the malignancy, especially ones with resistance against the standard therapy.

Impact:

LGALS3 promotes glioblastoma cells' resistance to ionizing irradiation and temozolomide and predicts poor prognosis. Targeting LGALS3 may limit the therapeutic resistance in glioblastoma and increase patient survival.
Leveraging Breadth and Depth: Strategies to Characterize Population Diversity to Address Cancer Disparities in the DF/HCC Catchment Area
Authors: McCloud Rachel Faulkenberry , Bekalu Mesfin Awoke , Maddox Nicole , Minsky Sara J. , Viswanath K.
Published: October 2018

Background:

NCI-Designated Cancer Centers provide key cancer research, prevention, and treatment services to members of their catchment area. Characterization of these areas may be complex given the diverse needs of the populations within, particularly those from low socioeconomic position (SEP). The purpose of this paper is to describe the characterization of the Dana-Farber/Harvard Cancer Center (DF/HCC) catchment area through using a two-pronged approach.

Methods:

Participants (n = 1,511) were recruited through (i) an online, probability-based survey (n = 1,013) and (ii) a supplementary, in-person survey from priority groups (African Americans, Latinos, blue-collar workers, low SEP, homeless; n = 498) within Massachusetts. Study staff worked closely with community partners across the state to reach individuals who may not usually be included in online surveys.

Results:

There were several differences across samples, with the community-based sample having a higher percentage of low SEP, low education, African Americans, and Latinos compared with the online sample. Differences were also noted in the cancer-related behaviors of the samples, with the community-based sample having higher rates of smoking, particularly within those who were homeless or make less than $20,000 per year. Fewer community-based subgroups were current with cancer screenings, and more showed more indication of potential communication inequalities compared with statewide estimates.

Conclusions:

The sampling strategy used to characterization of the DF/HCC catchment area provided broad, statewide estimates and additional focus on vulnerable populations, highlighting several potential areas for intervention.

Impact:

This study provides data to highlight the value of using multiple sampling strategies when characterizing cancer center catchment areas.
Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs
Authors: Christmas Brian J. , Rafie Christine I. , Hopkins Alexander C. , Scott Blake A. , Ma Hayley S. , Cruz Kayla A. , Woolman Skylar , Armstrong Todd D. , Connolly Roisin M. , Azad Nilo A. , Jaffee Elizabeth M. , Roussos Torres Evanthia T.
Published: October 2018

Immune-checkpoint inhibition (ICI) has revolutionized treatment in cancers that are naturally immunogenic by enabling infiltration of T cells into the tumor microenvironment (TME) and promoting cytotoxic signaling pathways. Tumors possessing complex immunosuppressive TMEs such as breast and pancreatic cancers present unique therapeutic obstacles as response rates to ICI remain low. Such tumors often recruit myeloid-derived suppressor cells (MDSCs), whose functioning prohibits both T-cell activation and infiltration. We attempted to sensitize these tumors to ICI using epigenetic modulation to target MDSC trafficking and function to foster a less immunosuppressive TME. We showed that combining a histone deacetylase inhibitor, entinostat (ENT), with anti–PD-1, anti–CTLA-4, or both significantly improved tumor-free survival in both the HER2/neu transgenic breast cancer and the Panc02 metastatic pancreatic cancer mouse models. Using flow cytometry, gene-expression profiling, and ex vivo functional assays, we characterized populations of tumor-infiltrating lymphocytes (TILs) and MDSCs, as well as their functional capabilities. We showed that addition of ENT to checkpoint inhibition led to significantly decreased suppression by granulocytic MDSCs in the TME of both tumor types. We also demonstrated an increase in activated granzyme-B–producing CD8+ T effector cells in mice treated with combination therapy. Gene-expression profiling of both MDSCs and TILs identified significant changes in immune-related pathways. In summary, addition of ENT to ICI significantly altered infiltration and function of innate immune cells, allowing for a more robust adaptive immune response. These findings provide a rationale for combination therapy in patients with immune-resistant tumors, including breast and pancreatic cancers.
A Proposed Role of Surfactant in Platelet Function and Treatment of Pulmonary Hemorrhage in Preterm and Term Infants
Authors: Sadeh-Vered Tal  , Rosenberg Nurit  , Morag Iris  , Berg Asaf A. , Kenet Gili , Strauss Tzipora
Published: October 2018

Background: We evaluated the effect of surfactant on platelet function as a potential contributing mechanism to the pathogenesis of pulmonary hemorrhage (PHEM) in term and preterm infants. Methods: Cord blood samples were collected from neonates following delivery. Complete blood count and platelet function were measured using a cone and platelet analyzer (CPA). Increasing surfactant concentrations were added to platelets in vitro, and the adhesion molecule P-selectin and the monoclonal antibody PAC-1 were evaluated following platelet activation by flow cytometry. Results: Forty-one infants (11 preterm and 30 term) were studied. CPA revealed a significant decrease in the average size of the aggregates and in platelet adhesion when surfactant was added. In term infants, the addition of surfactant to native platelets yielded an increased binding capacity of PAC-1 but did not affect P-selectin expression. In preterm infants, platelet activation with adenosine diphosphate in the presence of a high surfactant concentration (0.5 mg/mL) resulted in increased PAC-1 binding and no change in P-selectin expression. Conclusions: The platelets of preterm infants are less active (hyporesponsive) than those of term infants, both in their native state as well as after stimulation with various agonists. Surfactant may play an important role in treating PHEM in preterm infants.
High Genetic Risk Scores of ASIC2, MACROD2, CHRM3, and C2orf83 Genetic Variants Associated with Polycystic Ovary Syndrome Impair Insulin Sensitivity and Interact with Energy Intake in Korean Women
Authors: Kim Sung-Hoon , Liu Meiling , Jin Hyun Seok , Park Sunmin
Published: October 2018

Background: We explored the genetic variants that were associated with polycystic ovary syndrome (PCOS) by genome-wide association study (GWAS) and evaluated the association of genetic risk scores (GRS) of the selected genetic variants with insulin resistance and the interaction of the GRS with nutrient intake to develop insulin resistance. Methods: The 6 genetic variants involved in brain and nervous system (acid sensing ion channel subunit 2 rs8071961, rs1988598, and rs16589, macro domain containing 2 rs7262810 CHRM3 rs1867265 and chromosome 2 open reading frame 83 rs11889798) were selected from a GWAS of the PCOS study. GRS of the 6 single nucleotide polymorphisms was calculated in 3,723 Korean women in the Ansan/Ansung cohort of KARE study. Results: Fasting serum insulin and C-reactive protein (CRP) levels, homeostasis model assessment of insulin resistance (HOMA-IR), and psychological stress levels were significantly higher in the high-GRS group than the low-GRS group. However, serum-free T4 levels were significantly lower in the high-GRS group. HOMA-IR and CRP were higher OR (1.129 and 1.382) in the high-GRS group than the low-GRS group after adjusted for covariates. There was a significant interaction between GRS and daily energy intake (p = 0.004). The OR (1.233) for HOMA-IR was higher in the high-GRS group than the low-GRS group only in the group with lower energy intakes based on estimated energy requirement. Conclusion: Women with high-GRS for PCOS had increased risk of insulin resistance and low energy intake did not protect against the elevation of insulin resistance in women with high GRS. Low energy intake might be protective against PCOS in carriers with low and medium GRS.
Orthostatic Hypotension and Albuminocytologic Dissociation as Primary Manifestations of the Paraneoplastic Syndrome
Authors: Li Jingjing , Li Yi , Xing Shihui , Zhang Jian , Qiu Baoshan , Zeng Jinsheng , Fan Yuhua
Published: October 2018

Background: Orthostatic hypotension (OH) is the key manifestation of autonomic dysfunction with many causes. Systemic neurological causes such as paraneoplastic syndrome are usually ignored. Methods: We retrospectively analyzed clinical and examination data of 2 patients who were hospitalized, with onset symptom of OH and who were diagnosed as paraneoplastic syndrome. Results: The patients were characteristic of an initial symptom of OH, positive anti-Hu antibody and albuminocytologic dissociation in the cerebrospinal fluid. Patient 2 died and Patient 1 worsened during follow-up. Conclusions: The diagnosis of paraneoplastic syndrome is usually neglected when the onset symptoms are autonomic dysfunctions such as OH. Neurologists should improve their knowledge to diagnose accurately.
Probiotic Treatment in Individuals with Euthymic Bipolar Disorder: A Pilot-Study on Clinical Changes and Compliance
Authors: Reininghaus Eva Z. , Wetzlmair Lisa-Christin , Fellendorf Frederike T. , Platzer Martina , Queissner Robert , Birner Armin , Pilz Ren , Hamm Carlo , Maget Alexander , Rieger Alexandra , Prettenhofer Antonia , Wurm Walter , Mörkl Sabrina , Dalkner Nina
Published: October 2018

The importance of the microbiome for psychological well-being has gained rising interest in the last decade. A strategy to examine the role of the microbiome in different diseases is the intake of supplements that modulate the gut microbiome. Despite promising results in animal studies, research in humans is sparse to date and especially in individuals with psychiatric disorders almost missing. The current report of the ProbioBIP-one pilot study aims at describing general effects of the intake of the probiotic OMNi-BiOTiC Stress repair® on psychological parameters as well as gastrointestinal symptoms and general compliance in a cohort of euthymic individuals with bipolar disorder (BD), receiving daily probiotic treatment over a time period of 3 months. Twenty-seven individuals with BD took part in the present study (mean age = 50.7 years, SD = 12.2; females 40.7%). In sum, there was a high compliance rate with 81.5% of the study participants completing all 3 study visits and 85% of planned probiotic ingestions taken. Gastrointestinal problems were prevalent in more than half of the patients at the time of inclusion (t1). Expectedly, in the whole cohort, a high proportion of study participants experienced changes concerning digestion during probiotic treatment, around one third reported positive changes (reduced flatulence and easier and more frequent bowel movements) after 1 month (t2) and further after 3 months (t3). In contrast, a smaller part of study participants reported gastrointestinal discomfort after 1 and after 3 months (mainly flatulence and obstipation). We found a significantly reduced cognitive reactivity to sad mood between t2 and t3 indicating that participants under probiotic supplementation perceived themselves to be less distracted by ruminative thoughts. Further changes in psychiatric symptoms were small due to the euthymic state and already low scoring at the time of inclusion. Nevertheless, we found a significant symptom reduction in the rating scales measuring manic symptoms. From a clinical point of view, probiotic supplementation might provide a well-tolerated tool to positively influence gastrointestinal quality of life as well as mental and somatic health, cognition and immune response and potentially have effects on psychiatric symptoms.
Prevention of Stent Thrombosis in Rats by a Direct Oral Factor Xa Inhibitor Edoxaban
Authors: Morishima Yoshiyuki , Honda Yuko , Kamisato Chikako
Published: October 2018

Background/Aims: Stent thrombosis is a serious complication after percutaneous coronary intervention and femoropopliteal endovascular intervention. The aim of this study was to determine the antithrombotic effects of a direct factor Xa inhibitor edoxaban alone or in combination with antiplatelet agents in a rat model of stent thrombosis. Methods: Stainless steel stents (4 stents per rat) were placed in an extracorporeal arteriovenous shunt. The shunt was inserted into the carotid artery and the jugular vein in each rat to circulate blood. Stent thrombosis was induced by exposing the stents to arterial blood for 30 min. Protein content of the thrombus was measured. Edoxaban and antiplatelet agents (aspirin, clopidogrel, and ticagrelor) were orally administered before the thrombus induction. Results: Edoxaban (0.3–3 mg/kg), clopidogrel (1–10 mg/kg), aspirin (10–100 mg/kg), and ticagrelor (0.3–3 mg/kg) exerted significant and dose-dependent antithrombotic effects in a rat stent thrombosis model. The effect of edoxaban was comparable to that of antiplatelet agents. The combination of submaximal doses of edoxaban and clopidogrel or aspirin significantly potentiated the antithrombotic effects compared with antiplatelet agents alone. Conclusion: These results suggest that edoxaban alone and in combination with clopidogrel or aspirin are promising antithrombotic therapies for the prevention of stent thrombosis.
Gastrointestinal Disorders in Peritoneal Dialysis Patients
Authors: Kosmadakis George , Albaret Julie , da Costa Correia Enrique , Somda Frederic , Aguilera Didier
Published: October 2018

Background: Gastrointestinal (GI) disorders in peritoneal dialysis (PD) patients are relatively understudied in the literature, even though they have a serious impact in the morbidity parameters and the quality of life for this group of patients. Various diagnostic tools have been used, including instrumental methods and questionnaires, invariably validated in comparative studies. Summary: The prevalence of GI disorders is very high in PD patients. Compared to the haemodialysis patients they present a higher prevalence of reflux, eating dysfunction, gastroesophageal reflux, intestinal obstruction or adhesions and abdominal hernia. They may be divided into Gastric disorders (Gastroesophageal reflux disease, pathological Gastric emptying, Dyspepsia, Helicobacter pylori infection, peptic ulcers) and Intestinal disorders (Peritonitis, Diverticulosis, Constipation). Key Messages: The current paper is a review of the literature involving GI disorders in PD patients. This special group of patients with a special role of the peritoneal cavity and the GI motility in the physiology of their dialysis merit a larger number of studies dealing with the interrelation of the GI tract and the PD physiological, functional and pathophysiological parameters.
The Role of Sex Hormones in Multiple Sclerosis
Authors: Avila Mirla , Bansal Arpana , Culberson John , Peiris Alan N.
Published: October 2018

Multiple sclerosis (MS) is a chronic inflammatory demyelination disorder with an immune-mediated pathophysiology that affects the central nervous system (CNS). Like other autoimmune conditions, it has a predilection for female gender. This suggests a gender bias and a possible hormonal association. Inflammation and demyelination are hallmarks of MS. Oligodendrocytes are the myelinating cells of the CNS and these continue to be generated by oligodendrocyte precursor cells (OPCs). The process of remyelination represents a major form of plasticity in the developing adult CNS. Remyelination does occur in MS, but the process is largely inadequate and/or incomplete. Current treatment strategies primarily focus on reducing inflammation or immunosuppression, but there is a need for more extensive research on re-myelination as a possible mechanism of treatment. Previous studies have shown that pregnancy leads to an increase in OPC proliferation, oligodendrocyte generation and the number of myelinated axons in the maternal CNS. Studies have also suggested that this remyelination is possibly mediated by estriol. Sex hormones in particular have been shown to have an immuno-protective effect in TH1-driven autoimmunity diseases. The aim of our article is to review the available research on sex hormone-specific immune modulatory effects, assess its remyelination potential in MS, and suggest a future path for more extensive research on sex hormone as a target for therapeutics in MS.
Halal Dating and Norwegian Youth Culture
Authors: Bøe Marianne
Published: October 2018

Through conversations with Norwegian youth of Muslim background, this article explores how such young people negotiate religious identity, intimacy and sexuality within Norwegian youth culture. In light of recent statistics on marriage patterns in Norway, it further investigates norms and approaches significant to these youths’ choices. Marriage and intimate relationships are central to how this study’s participants connect the expectations of their minority background with the norms of Norwegian society. Some choose to engage in informal religious marriages—such as “halal dating”—while others are in love relationships and define for themselves the boundaries of what is and is not allowed.
A Frame for Turkey’s Foreign Policy via the Diyanet in the Balkans
Authors: Öztürk Ahmet Erdi , Gözaydın İştar
Published: October 2018

This article deals with Turkey’s increasing involvement and activism in the Balkans between 2002 and 2016, under the government of the Justice and Development Party. The central focus is Turkey’s pliable state apparatus; the Presidency of Religious Affairs and its activities in the region. The article therefore aims to answer the following questions: Why does Turkey use these various state apparatuses specifically as a foreign policy tool and how does their influence differ from country to country? What factors determine the scope of activity of Turkish transnational state apparatuses in the case of each country? And, how do local actors and public opinion respond to Turkey’s newly-emerging activities in the region?