bluuebunny/crossref_metadata_2025 huggingface dataset:
The Power of None
Authors: Hulkower Neal D. , Neatrour John
Published: March 2019

Borda with None (BwN) adds the binding option of “None of these candidates,” N, to the Borda Count (BC), differing from a method of Dodgson in the scoring of ties. The method incorporates the benefits of approval voting, which allows a simple yes/no vote on each candidate and avoids the disadvantages of adding N as a binding outcome to plurality voting. We prove that BwN uniquely satisfies five rational properties which can be viewed as potential axioms that provide a theoretical basis for the method. It allows individual voters to express a personal veto over all or part of the slate which could, with sufficient numbers, become a veto by the electorate. The power of none, then, is offering a voice to otherwise disaffected voters. We introduce a metric similar to one used in the Bak–Sneppen Evolutionary model, candidate fitness, a number between 0 and 1, which measures a candidate’s ranking relative to N. We illustrate its evolution with a hypothetical example. We examine courses of action if N is ranked in the first place. Using BwN to accommodate partial voting is proposed. We explore the general applicability of BwN. Finally, we address the practical considerations for introducing BwN.
Trends in the Management of Isolated SLAP Tears in the United States
Authors: Cvetanovich Gregory L. , Gowd Anirudh K. , Agarwalla Avinesh , Forsythe Brian , Romeo Anthony A. , Verma Nikhil N.
Published: March 2019

Background:

The management of superior labrum anterior and posterior (SLAP) tears remains controversial, with surgical treatment options including SLAP repair, debridement, and open or arthroscopic biceps tenodesis (BT), based on patient factors and the type of tear.

Hypothesis:

We hypothesized that SLAP repair has become less frequently performed over time, while BT is more frequently performed, particularly in patients ≥ 40 years.

Study Design:

Descriptive epidemiology study.

Methods:

A retrospective query was performed using the Humana insurance database from years 2007 to 2016. For the management of a SLAP tear diagnosis (International Classification of Diseases–Ninth Edition [ICD-9] code: 840.7), independent and exclusive cohorts were formed using Current Procedural Terminology (CPT) codes for debridement (29822, 29823), SLAP repair (29807), open or arthroscopic BT (29828, 23430), and SLAP repair combined with BT (29828 OR 23430 AND 29807).

Results:

Of 46,650 diagnoses of a SLAP tear, there were 3347 patients who underwent operative management for an isolated SLAP tear from 2007 to 2016. There was a linear increase of SLAP tear diagnoses per year ( r2 = 0.800, P < .001) during this period. Overall, SLAP repair was performed in 1629 patients (48.7%), debridement was performed in 1076 patients (32.1%), BT was performed in 552 patients (16.5%), and combined SLAP repair and BT was performed in 90 patients (2.7%). There was a 69.3% decrease in isolated SLAP repair from 2007 to 2016 ( r2 = 0.882, P < .001). BT for the diagnosis of an isolated SLAP tear increased by 370.0% over the same period ( r2 = 0.800, P < .001). SLAP repair had an equivalent percentage of being performed in patients both older and younger than 40 years ( P = .218). There was a 1500.0% increase in BT performed in patients older than 40 years during the study period. There were no statistical differences in the postoperative incidence of stiffness, surgical site infections, and reoperations between all surgical treatment groups ( P > .05).

Conclusion:

An analysis of a large private-payer database revealed that surgical treatment of isolated SLAP tears in the United States has shifted from 2007 to 2016, with an increase in the frequency of BT and a decline in the frequency of SLAP repair, particularly in patients older than 40 years.
Too Many Hats? Conflicts of Interest in Learning Community Faculty Roles
Authors: Gliatto Peter , Colbert-Getz Jorie M , Bhutiani Monica , Cutrer William B , Edwards Sharon , Fleming Amy , Keeley Meg , Osterberg Lars , Pilla Michael A , Moynahan Kevin
Published: March 2019

Purpose:

Many US medical schools have adopted learning communities to provide a framework for advising and teaching functions. Faculty who participate in learning communities often have additional educator roles. Defining potential conflicts of interest (COIs) among these roles is an important consideration for schools with existing learning communities and those looking to develop them, both for transparency with students and also to comply with regulatory requirements.

Methods:

A survey was sent to the institutional contact for each of the 42 Learning Communities Institute (LCI) member medical schools to assess faculty opinions about what roles potentially conflict. The survey asked the role of learning community faculty in summative and formative assessment of students and whether schools had existing policies around COIs in medical education.

Results:

In all, 35 (85%) LCI representatives responded; 30 (86%) respondents agreed or strongly agreed that learning community faculty should be permitted to evaluate their students for formative purposes, while 19 (54%) strongly agreed or agreed that learning community faculty should be permitted to evaluate their students in a way that contributes to a grade; 31 (89%) reported awareness of the accreditation standard ensuring “that medical students can obtain academic counseling from individuals who have no role in making assessment or promotion decisions about them,” but only 10 (29%) had a school policy about COIs in education. There was a wide range of responses about what roles potentially conflict with being a learning community faculty.

Conclusion:

The potential for COIs between learning community faculty and other educator roles concerns faculty at schools with learning communities, but most schools have not formally addressed these concerns.
A Case of a Combined Hamartoma of the Retina and RPE Concurrently Found in the Same Eye as Peripheral Astrocytic Hamartomas
Authors: Sherman Stefanie D. , Schechet Sidney A. , Shapiro Michael J. , Blair Michael P.
Published: March 2019

We report a case of a 7-year-old boy with neurofibromatosis 2 who was referred to our pediatric retina clinic for deteriorating vision of his left eye. Fundoscopy revealed a gray epiretinal and vitreous opacity extending to the fovea in the left eye. Optical coherence tomography (OCT) demonstrated an epiretinal membrane (ERM) with a distinct tissue plane and overlying vitreoretinal strands, consistent with combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). Intraoperative OCT-guided pars plana vitrectomy and membrane peel were performed and the tissue was sent for histopathologic evaluation. Intraoperative scleral-depressed examination also revealed multiple elevated, white-gray, semitranslucent masses near the ora serrata, consistent with astrocytic hamartomas. Histopathologic analysis of the epiretinal tissue revealed glial origin. Recognition of any of these lesions in a young patient should prompt neurologic and genetic evaluation.
Yìcún Wénzì (extant characters) in Japanese lexicon: Exploring characters of historically Chinese origin with evidence from Six dynasties, Sui and Tang dynasties, China
Authors: Sasahara Hiroyuki
Published: March 2019

A careful analysis of historical literary sources reveals that some supposedly Japanese native characters are in fact of historically Chinese origin, namely “extant characters” (yìcún wénzì). In this article, I examine the backgrounds of potential “extant characters” that appeared in the Heian period Wamyō Ruijushō 和名類聚抄 and similar materials. In so doing, I corroborate the findings of Edo-period scholar Kariya Ekisai 狩谷棭斎 and identify several new issues with evidence from digital archives that further research needs to focus on.
Sex and Depression
Authors: Manohar J. Shivananda , Koolwal Arpit , Rao T. S. Sathyanarayana
Published: March 2019

Sexual dysfunction is one of the more common features of depressive disorders, presenting with dysfunction across sexual response cycle. Variety of factors play a role in causing sexual dysfunction in these patients, such as psychological, biological, social and interpersonal factors. Another cause of sexual dysfunction in these patients can be the side effect of antidepressants making it difficult to conclude if the dysfunction is the result of the depression or the treatment of depression. Clinicians need to be aware about the sexual dysfunction as it can have big impact on the overall quality of life of an individual.
Psychosocial Aspects of Pornography
Authors: George Manju , Maheshwari Shreemit , Chandran Suhas , Rao T. S. Sathyanarayana
Published: March 2019

Introduction: Pornography is the term given for non-relational sex without any requirements for relational intimacy. It has appeared in all cultures and civilizations over centuries. Research into the area of addictive sexual behaviors on the Internet incorporates the various constructs surrounding compulsive sexual behavior.

Pornography and society: Excess viewing of pornography has been said to be associated with psychiatric comorbidities such as anxiety and depression, and even sexual dysfunction. Individuals with pornography addiction have lower degrees of social integration, increase in conduct problems, higher levels of delinquent behavior, higher incidence of depressive symptoms, and decreased emotional bonding with caregivers. Pornography is an expression of fantasies and is said to have the potential to rewire pleasure centers of the brain and alter structures and function.

Conclusion: Pornography can bring about significant changes in the brain similar to what can be seen in drug addictions. Owing to the boom of technology and easy access to such material, it is imperative to provide specifically designed pornography addiction education programs to educate students about the adverse effects of pornography.
A Chronicle of Sexuality in the Indian Subcontinent
Authors: Das Keya , Rao T. S. Sathyanarayana
Published: March 2019

Human sexuality has been researched, documented, and scrutinized through the centuries but persists in retaining its unfathomable depths in its layers. Sexuality in India has undergone paradigm shifts from the Bronze Age civilization to present-day India. Ever changing facets dependent on the cultural, social, religious, political, regional, and timely aura have resulted in sexuality in India having many hues. The manner of experience and expression has also undergone significant changes over time in individual desires, attitudes to sex, beliefs, values, behaviors, gender roles, and relationships. We chronicle the conceptualization of sexuality in its inception in ancient India and its journey through the ages.
l-arginine and Erectile Dysfunction
Authors: Koolwal Arpit , Manohar J. Shivananda , Rao T. S. Sathyanarayana , Koolwal Ghanshyam D.
Published: March 2019

l-arginine, being a natural precursor of nitric oxide, is one of the more commonly used adjuvants to regular medicines in the treatment of erectile dysfunction.

Objectives: Here, in this review article, we aim to highlight various studies and the research studies done on l-arginine in the treatment of erectile dysfunction.

Method: Reviewing the databases such as Medline (PubMed), Cochrane Library, Excerpta Medica dataBASE, Trip, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, and the British Nursing Index.

Results:l-arginine has been studied alone as well as in combination with various other molecules for the treatment of erectile dysfunction, but the studies are very limited in number and have very small sample sizes.

Conclusion: Positive evidence is available for the efficacy of l-arginine and its various combinations. Further research with larger sample sizes and standardized tools are required to recommend the routine use of these products in erectile dysfunction.
Divine Love: The Bridal Mysticism of Andal
Authors: Somasundaram O.
Published: March 2019

Introduction: Mankind’s history has witnessed many forms of expression of devotion (bhakti) including its expression as love.

Methodology: In this article, we explore the love of Andal, belonging to the Vaishnavite tradition of South India, towards her chosen God.

Results: As we journey along her story and her works, we can see faith, fiction, and history merging into a seamless whole.
Mouse venous thrombosis upon silencing of anticoagulants depends on tissue factor and platelets, not FXII or neutrophils
Authors: Heestermans Marco , Salloum-Asfar Salam , Streef Tom , Laghmani El Houari , Salvatori Daniela , Luken Brenda M. , Zeerleder Sacha S. , Spronk Henri M. H. , Korporaal Suzanne J. , Kirchhofer Daniel , Wagenaar Gerry T. M. , Versteeg Henri H. , Reitsma Pieter H. , Renné Thomas , van Vlijmen Bart J. M.
Published: March 2019

Tissue factor, coagulation factor XII, platelets, and neutrophils are implicated as important players in the pathophysiology of (experimental) venous thrombosis (VT). Their role became evident in mouse models in which surgical handlings were required to provoke VT. Combined inhibition of the natural anticoagulants antithrombin (Serpinc1) and protein C (Proc) using small interfering RNA without additional triggers also results in a venous thrombotic phenotype in mice, most notably with vessel occlusion in large veins of the head. VT is fatal but is fully rescued by thrombin inhibition. In the present study, we used this VT mouse model to investigate the involvement of tissue factor, coagulation factor XII, platelets, and neutrophils. Antibody-mediated inhibition of tissue factor reduced the clinical features of VT, the coagulopathy in the head, and fibrin deposition in the liver. In contrast, genetic deficiency in, and small interfering RNA–mediated depletion of, coagulation factor XII did not alter VT onset, severity, or thrombus morphology. Antibody-mediated depletion of platelets fully abrogated coagulopathy in the head and liver fibrin deposition. Although neutrophils were abundant in thrombotic lesions, depletion of circulating Ly6G-positive neutrophils did not affect onset, severity, thrombus morphology, or liver fibrin deposition. In conclusion, VT after inhibition of antithrombin and protein C is dependent on the presence of tissue factor and platelets but not on coagulation factor XII and circulating neutrophils. This study shows that distinct procoagulant pathways operate in mouse VT, dependent on the triggering stimulus.
Calreticulin mutants as oncogenic rogue chaperones for TpoR and traffic-defective pathogenic TpoR mutants
Authors: Pecquet Christian , Chachoua Ilyas , Roy Anita , Balligand Thomas , Vertenoeil Gaëlle , Leroy Emilie , Albu Roxana-Irina , Defour Jean-Philippe , Nivarthi Harini , Hug Eva , Xu Erica , Ould-Amer Yasmine , Mouton Céline , Colau Didier , Vertommen Didier , Shwe Myat Marlar , Marty Caroline , Plo Isabelle , Vainchenker William , Kralovics Robert , Constantinescu Stefan N.
Published: March 2019

Calreticulin (CALR) +1 frameshift mutations in exon 9 are prevalent in myeloproliferative neoplasms. Mutant CALRs possess a new C-terminal sequence rich in positively charged amino acids, leading to activation of the thrombopoietin receptor (TpoR/MPL). We show that the new sequence endows the mutant CALR with rogue chaperone activity, stabilizing a dimeric state and transporting TpoR and mutants thereof to the cell surface in states that would not pass quality control; this function is absolutely required for oncogenic transformation. Mutant CALRs determine traffic via the secretory pathway of partially immature TpoR, as they protect N117-linked glycans from further processing in the Golgi apparatus. A number of engineered or disease-associated TpoRs such as TpoR/MPL R102P, which causes congenital thrombocytopenia, are rescued for traffic and function by mutant CALRs, which can also overcome endoplasmic reticulum retention signals on TpoR. In addition to requiring N-glycosylation of TpoR, mutant CALRs require a hydrophobic patch located in the extracellular domain of TpoR to induce TpoR thermal stability and initial intracellular activation, whereas full activation requires cell surface localization of TpoR. Thus, mutant CALRs are rogue chaperones for TpoR and traffic-defective TpoR mutants, a function required for the oncogenic effects.
Neutrophils and NETs in modulating acute and chronic inflammation
Authors: Castanheira Fernanda V. S. , Kubes Paul
Published: March 2019

Neutrophils are an absolutely essential part of the innate immune system, playing an essential role in the control of infectious diseases but more recently are also being viewed as important players in tissue repair. Neutrophils are able to counteract an infection through phagocytosis and/or the release of neutrophil extracellular traps (NETs). By contrast, neutrophils help repair damaged tissues, limiting NET production but still phagocytosing debris. However, when inflammation is recurrent, or the inciting agent persists, neutrophils through a frustrated inability to resolve the problem can release NETs to exacerbate tissue damage during inappropriate inflammation. In this review, we discuss the mechanisms of NET formation, as well as the apparent paradoxical role of neutrophils and NETs in host defense, chronic inflammation, and tissue disrepair.
Neutrophil transendothelial migration: updates and new perspectives
Authors: Filippi Marie-Dominique
Published: March 2019

Neutrophils represent the first line of cellular defense against invading microorganism by rapidly moving across the blood–endothelial cell (EC) barrier and exerting effector cell functions. The neutrophil recruitment cascade to inflamed tissues involves elements of neutrophil rolling, firm adhesion, and crawling onto the EC surface before extravasating by breaching the EC barrier. The interaction between neutrophils and ECs occurs via various adhesive modules and is a critical event determining the mode of neutrophil transmigration, either at the EC junction (paracellular) or directly through the EC body (transcellular). Once thought to be a homogenous entity, new evidence clearly points to the plasticity of neutrophil functions. This review will focus on recent advances in our understanding of the mechanism of the neutrophil transmigration process. It will discuss how neutrophil–EC interactions and the subsequent mode of diapedesis, junctional or nonjunctional, can be context dependent and how this plasticity may be exploited clinically.
The resource group method in severe mental illness: study protocol for a randomized controlled trial and a qualitative multiple case study
Authors: Tjaden Cathelijn D. , Mulder Cornelis L. , van Weeghel Jaap , Delespaul Philippe , Keet Rene , Castelein Stynke , Boumans Jenny , Leeman Eva , Malm Ulf , Kroon Hans
Published: March 2019

Background

The resource group method provides a structure to facilitate patients’ empowerment and recovery processes, and to systematically engage significant others in treatment and care. A patient chooses members of a resource group (RG) that will work together on fulfilling patients’ recovery plan. By adopting shared decision-making processes and stimulating collaboration of different support systems, a broad and continuous support of patients’ chosen goals and wishes is preserved and problem solving and communication skills of the RG members are addressed.

Objective

The objectives of this study are (1) to establish the effectiveness of the RG method in increasing empowerment in patients with severe mental illnesses (SMI) in the Netherlands; (2) to investigate the cost-effectiveness and cost utility of the RG method; and (3) to qualitatively explore its dynamics and processes.

Methods/design

This multisite randomized controlled trial will compare the effects of the RG-method integrated in Flexible Assertive Community Treatment (FACT) (90 patients) with those of standard FACT (90 patients). Baseline assessments and 9-month and 18-month follow-up assessments will be conducted in face-to-face home visits. The primary outcome measure, empowerment, will be assessed using the Netherlands Empowerment List (NEL). The secondary outcomes will be quality of life (MANSA); personal, community and clinical recovery (I.ROC); general, social and community functioning (WHODAS 2.0); general psychopathological signs and symptoms (BSI-18); and societal costs (TiC-P). An economic evaluation of the cost-effectiveness and cost utility of the RG method will also be conducted. A qualitative multiple case-study will be added to collect patients’, RG members’ and professionals’ perspectives by in-depth interviews, observations and focus groups.

Discussion

This trial will be the first to study the effects of the RG method on empowerment in patients with SMI. By combining clinical-effectiveness data with an economic evaluation and in-depth qualitative information from primary stakeholders, it will provide a detailed overview of the RG method as a mean of improving care for patients with SMI.

Trial registrationThe study has been registered in the Dutch Trial Register, identifier: NTR6737, September 2017.
RETRACTED ARTICLE: LncRNA SNHG7 promotes pancreatic cancer proliferation through ID4 by sponging miR-342-3p
Authors: Cheng Dongfeng , Fan Juanjuan , Ma Yang , Zhou Yiran , Qin Kai , Shi Minmin , Yang Jingrui
Published: March 2019

Background

Small nucleolar RNA host gene 7 (SNHG7) is a novel identified oncogenic gene in tumorigenesis. However, the role that SNHG7 plays in pancreatic cancer (PC) remains unclear. In this study, we aimed to investigate the functional effects of SNHG7 on PC and the possible mechanism.

Methods

The expression levels of SNHG7 in tissues and cell lines were measured by RT-qPCR. Cell viability, apoptosis, migration and invasion were examined to explore the function of SNHG7 on PC. Bioinformatics methods were used to predict the target genes. The mechanism was further investigated by transfection with specific si-RNA, miRNA mimics or miRNA inhibitor. Tumor xenograft was carried out to verify the effects of SNHG7 in vivo.

Results

We found that SNHG7 was overexpressed in both PC tissues and cell lines. High expression level of SNHG7 was correlated with the poor prognosis. SNHG7 knockdown inhibited the proliferation, migration and invasion of PC cells. Moreover, SNHG7 was found to regulate the expression of ID4 via sponging miR-342-3p. Additionally, this finding was supported by in vivo experiments.

Conclusions

LncRNA SNHG7 was overexpressed in PC tissues, and knockdown of SNHG7 suppressed PC cell proliferation, migration and invasion via miR-342-3p/ID4 axis. The results indicated that SNHG7 as a potential target for clinical treatment of PC.
Patient-reported outcome measures in community mental health teams: pragmatic evaluation of PHQ-9, GAD-7 and SWEMWBS
Authors: Blenkiron Paul , Goldsmith Lucy
Published: March 2019

Aims and method

We evaluated routine use, acceptability and response rates for the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Scale (GAD-7) and Short Warwick-Edinburgh Mental Well-Being Scale (SWEMWBS) within adult community mental health teams. Measures were repeated 3 months later. Professionals recorded the setting, refusal rates and cluster diagnosis.

Results

A total of 245 patients completed 674 measures, demonstrating good initial return rates (81%), excellent scale completion (98–99%) and infrequent refusal/unsuitability (11%). Only 32 (13%) returned follow-up measures. Significant improvements occurred in functioning (P= 0.01), PHQ-9 (P= 0.02) and GAD-7 (P= 0.003) scores (Cohen'sd= 0.52–0.77) but not in SWEMWBS (P= 0.91) scores. Supercluster A had higher initial PHQ-9 and GAD-7 scores (P< 0.001) and lower SWEMWBS scores (P= 0.003) than supercluster B. Supercluster C showed the greatest functional impairment (P= 0.003).

Clinical implications

PHQ-9 and GAD-7 appear acceptable as patient-reported outcome measures in community mental health team. SWEMWBS seems insensitive to change. National outcome programmes should ensure good follow-up rates.
Self-management interventions for people with severe mental illness: systematic review and meta-analysis
Authors: Lean Melanie , Fornells-Ambrojo Miriam , Milton Alyssa , Lloyd-Evans Brynmor , Harrison-Stewart Bronwyn , Yesufu-Udechuku Amina , Kendall Tim , Johnson Sonia
Published: March 2019

Background

Self-management is intended to empower individuals in their recovery by providing the skills and confidence they need to take active steps in recognising and managing their own health problems. Evidence supports such interventions in a range of long-term physical health conditions, but a recent systematic synthesis is not available for people with severe mental health problems.

Aims

To evaluate the effectiveness of self-management interventions for adults with severe mental illness (SMI).

Method

A systematic review of randomised controlled trials was conducted. A meta-analysis of symptomatic, relapse, recovery, functioning and quality of life outcomes was conducted, using RevMan.

Results

A total of 37 trials were included with 5790 participants. From the meta-analysis, self-management interventions conferred benefits in terms of reducing symptoms and length of admission, and improving functioning and quality of life both at the end of treatment and at follow-up. Overall the effect size was small to medium. The evidence for self-management interventions on readmissions was mixed. However, self-management did have a significant effect compared with control on subjective measures of recovery such as hope and empowerment at follow-up, and self-rated recovery and self-efficacy at both time points.

Conclusion

There is evidence that the provision of self-management interventions alongside standard care improves outcomes for people with SMI. Self-management interventions should form part of the standard package of care provided to people with SMI and should be prioritised in guidelines: research on best methods of implementing such interventions in routine practice is needed.

Declaration of interests

None.
Seismic Safety Assessment of Base-Isolated Buildings Using Lead-Rubber Bearings
Authors: Yang T. Y. , Zhang Hongzhou
Published: March 2019

Lead-rubber bearing (LRB) is a well developed and implemented isolation technology. One of the design challenges is to prevent LRBs from buckling during strong earthquake shaking. Although detailed component behavior of LRB under combined axial and shear loads has been well investigated, the seismic performance of base-isolated buildings with LRBs has not been systematically examined. In this study, the robust finite element model of the LRB, which accounts for the axial and shear coupling, has been used to examine the seismic performances of two prototype buildings, each with different LRB geometric properties, structural periods, and axial loads. The results of nonlinear dynamic analyses show that the axial and shear coupling response of the LRB play an important role in the safety of base-isolated buildings. A simple amplification factor of 2.5 is proposed to increase the axial capacity of the LRB when the shear deformation reaches the maximum total displacement. The results show that such a simple amplification factor can produce low probability of failure of LRB buildings during strong earthquake shaking.
Does the One-Dimensional Assumption Hold for Site Response Analysis? A Study of Seismic Site Responses and Implication for Ground Motion Assessment Using KiK-Net Strong-Motion Data
Authors: Pilz Marco , Cotton Fabrice
Published: March 2019

The one-dimensional (1-D) approach is still the dominant method to incorporate site effects in engineering applications. To bridge the 1-D to multidimensional site response analysis, we develop quantitative criteria and a reproducible method to identify KiK-net sites with significant deviations from 1-D behavior. We found that 158 out of 354 show two-dimensional (2-D) and three-dimensional (3-D) effects, extending the resonance toward shorter periods at which 2-D or 3-D site effects exceed those of the classic 1-D configurations and imposing an additional amplification to that caused by the impedance contrast alone. Such 2-D and 3-D effects go along with a large within-station ground motion variability. Remarkably, these effects are found to be more pronounced for small impedance contrasts. While it is hardly possible to identify common features in ground motion behavior for stations with similar topography typologies, it is not over-conservative to apply a safety factor to account for 2-D and 3-D site effects in ground motion modeling.
Stochastic Evolution of Pancreatic Cancer Metastases During Logistic Clonal Expansion
Authors: Yamamoto Kimiyo N. , Liu Lin L. , Nakamura Akira , Haeno Hiroshi , Michor Franziska
Published: March 2019

Despite recent progress in diagnostic and multimodal treatment approaches, most cancer deaths are still caused by metastatic spread and the subsequent growth of tumor cells in sites distant from the primary organ. So far, few quantitative studies are available that allow for the estimation of metastatic parameters and the evaluation of alternative treatment strategies. Most computational studies have focused on situations in which the tumor cell population expands exponentially over time; however, tumors may eventually be subject to resource and space limitations so that their growth patterns deviate from exponential growth to adhere to density-dependent growth models. In this study, we developed a stochastic evolutionary model of cancer progression that considers alterations in metastasis-related genes and intercellular growth competition leading to density effects described by logistic growth. Using this stochastic model, we derived analytical approximations for the time between the initiation of tumorigenesis and diagnosis, the expected number of metastatic sites, the total number of metastatic cells, the size of the primary tumor, and survival. Furthermore, we investigated the effects of drug administration and surgical resection on these quantities and predicted outcomes for different treatment regimens. Parameter values used in the analysis were estimated from data obtained from a pancreatic cancer rapid autopsy program. Our theoretical approach allows for flexible modeling of metastatic progression dynamics.
Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non–Germinal Center B-Cell Diffuse Large B-Cell Lymphoma
Authors: Younes Anas , Sehn Laurie H. , Johnson Peter , Zinzani Pier Luigi , Hong Xiaonan , Zhu Jun , Patti Caterina , Belada David , Samoilova Olga , Suh Cheolwon , Leppä Sirpa , Rai Shinya , Turgut Mehmet , Jurczak Wojciech , Cheung Matthew C. , Gurion Ronit , Yeh Su-Peng , Lopez-Hernandez Andres , Dührsen Ulrich , Thieblemont Catherine , Chiattone Carlos Sergio , Balasubramanian Sriram , Carey Jodi , Liu Grace , Shreeve S. Martin , Sun Steven , Zhuang Sen Hong , Vermeulen Jessica , Staudt Louis M. , Wilson Wyndham ,   on behalf of the PHOENIX investigators
Published: March 2019

PURPOSE

Ibrutinib has shown activity in non–germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non–germinal center B-cell DLBCL.

PATIENTS AND METHODS

Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.

RESULTS

A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%).

CONCLUSION

The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.
Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule
Authors: Yabut Julian M , Crane Justin D , Green Alexander E , Keating Damien J , Khan Waliul I , Steinberg Gregory R
Published: March 2019

Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).
Obesity, Bariatric Surgery, and Fractures
Authors: Lespessailles Eric , Paccou Julien , Javier Rose-Marie , Thomas Thierry , Cortet Bernard ,   GRIO Scientific Committee
Published: March 2019

Context

Obesity and its associated comorbidities are a recognized and growing public health problem. For a long time, obesity-associated effects on bone were considered to strengthen the bone, mainly because of the known relationship between body weight and bone mass and the long-term weight-bearing load effect on bone. However, recent epidemiologic studies have shown that obesity may not have a fully protective effect on the occurrence of fragility fractures. The goal of this article is to review updated information on the link between obesity, bariatric surgery, and fractures.

Methods

The primary source literature for this review was acquired by searching a published database for reviews and articles up to January 2018. Additional references were selected through the in-depth analysis of the relevant studies.

Results

We present data showing that overweight and obesity are often encountered in fracture cases. We also analyzed possible reasons and risk factors for fractures associated with overweight and patients with obesity. In addition, this review focuses on the complex effects of dramatic changes in body composition when interpreting dual-energy X-ray absorptiometry readings and findings. Finally, we review the data on the effects and consequences of bariatric surgery on bone metabolism and the risk of fractures in patients undergoing these procedures.

Conclusion

Because of various adiposity-induced effects, patients with obesity are at risk for fracture in certain sites. Bariatric surgery increases the risk of fractures in patients undergoing malabsorptive procedures.
Microparticle Responses to Aerobic Exercise and Meal Consumption in Healthy Men
Authors: HIGHTON PATRICK J. , GOLTZ FERNANDA R. , MARTIN NAOMI , STENSEL DAVID J. , THACKRAY ALICE E. , BISHOP NICOLETTE C.
Published: March 2019

Purpose

Microparticles (MP) are shed extracellular vesicles that express the prothrombotic tissue factor (TF). Aerobic exercise may reduce MP count and TF expression. This study investigated the impact of acute running or rest followed by standardized meal consumption on MP phenotypes and TF expression.

Methods

Fifteen males (age, 22.9 ± 3.3 yr; body mass, 81.9 ± 11.4 kg; V˙O2max, 54.9 ± 6.5 mL·kg−1·min−1; mean ± SD) completed 1 h of running (70% V˙O2max) or rest at 9:00 am and consumed a standardized meal (1170 kcal, 43% CHO, 17% PRO, 40% fat) at 10:45 am. Venous blood samples were taken at 9:00 am, 10:00 am, and 11:30 am. The MP concentration, diameter, phenotypes, and TF expression were assessed using nanoparticle tracking analysis and flow cytometry.

Results

Nanoparticle tracking analysis identified no changes in MP concentration or diameter in response to time or trial. Flow cytometry revealed total MP count increased from 9:00 am to 10:00 am (1.62 ± 2.28 to 1.74 ± 2.61 × 1010 L−1, P = 0.016, effect size (η
2) = 0.105), but was unaffected by trial. TF+ platelet-derived MP % reduced from 9:00 am to 10:00 am (44.0% ± 21.2% to 21.5% ± 9.3%, P = 0.001, η
2 = 0.582) after exercise only (control, 36.8% ± 18.2% to 34.9% ± 11.9%; P = 0.972). TF+ neutrophil-derived MP percentage reduced from 9:00 am to 11:30 am (42.3% ± 17.2% to 25.1% ± 14.9%; P = 0.048, η
2 = 0.801) in the exercise trial only (control, 28.5% ± 15.7% to 32.2% ± 9.6%; P = 0.508).

Conclusions

Running induced a significant reduction in %TF+ platelet and neutrophil MP, suggesting a transient reduction in cardiovascular risk via reduced TF-stimulated thrombosis. This requires further investigation over longer periods in cardiovascular disease populations.
Ethnographic accounts of linguistic issues in the Yugoslav successor states: An introduction
Authors: Kersten-Pejanić Roswitha
Published: March 2019

Doing ethnographic linguistics (or linguistic ethnography) in the area of what used to be Yugoslavia is both a challenging and a promising undertaking. Challenging, in that there are so many ideological traps to take into consideration. Promising, in that there are so many complex matters to take a closer look at. These matters, even when exclusively realized in linguistic means, may have great influence on people’s everyday political, cultural, and social meaning-making. Especially so, as indexical relations and the ideological premises and effects of choosing to use one linguistic realization over the other, has played an important role for all speech communities in the region.
ΑΠΟΜΟΝΩΣΙΣ ΚΑΙ ΤΑΥΤΟΠΟΙΗΣΙΣ ΙΟΥ ΠΑΡΑΙΝΦΛΟΥΕΝΤZΑ-3 ( P I - 3 ) ΕΚ ΒΟΟΕΙΔΩΝ ΕΝ ΕΛΛΑΔΙ
Authors: ΣΤΟΥΡΑΪΤΗΣ Π. , ΚΑΡΔΑΣΗΣ Ι.
Published: March 2019

NO ABSTRACT AVAILABLE
ΤΕΪΛΕΡΙΑΣΕΙΣ ΒΟΟΕΙΔΩΝ
Authors: ΓΕΩΡΓΟΥΛΑΚΗΣ Ι.
Published: March 2019

NO ABSTRACT AVAILABLE
ΕΡΕΥΝΑ ΕΠΙ ΤΗΣ ΔΟΚΙΜΗΣ ΕΥΑΙΣΘΗΣΙΑΣ ΣΤΕΛΕΧΩΝ ΠΑΘΟΓΟΝΩΝ ΣΤΑΦΥΛΟΚΟΚΚΩΝ ΠΡΟΣ ΤΑ ΑΝΤΙΒΙΟΤΙΚΑ, ΔΙΑ ΤΗΝ ΘΕΡΑΠΕΙΑΝ ΤΩΝ ΣΤΑΦΥΛΟΚΟΚΚΙΚΩΝ ΜΑΣΤΙΤΙΔΩΝ
Authors: ΡΩΣΣΗΣ Θ. , ΚΑΡΒΟΥΝΑΡΗΣ Π. , ΠΑΠΑΚΥΡΙΑΚΟΥ Ε.
Published: March 2019

NO ABSTRACT AVAILABLE
ΤΟ ΨΥΧΟΣ ΩΣ ΜΕΣΟΝ ΣΥΝΤΗΡΗΣΕΩΣ ΤΩΝ ΤΡΟΦΙΜΩΝ Α.' ΣΤΝΤΗΡΗΣΙΣ ΤΟΥ ΚΡΕΑΤΟΣ ΔΙΑ ΤΟΥ ΨΥΧΟΥΣ
Authors: ΑΝΔΡΙΟΠΟΥΛΟΣ Α.
Published: March 2019

NO ABSTRACT AVAILABLE
MSF: Modulated Sub-graph Finder
Authors: Farman Mariam R. , Hofacker Ivo L. , Amman Fabian
Published: March 2019

High throughput techniques such as RNA-seq or microarray analysis have proven tobe invaluable for the characterization of global transcriptional gene activity changesdue to external stimuli or diseases. Differential gene expression analysis (DGEA) is the first step in the course of data interpretation, typically producing lists of dozens to thousands of differentially expressed genes. To further guide the interpretation of these lists, different pathway analysis approaches have been developed. These tools typically rely on the classification of genes into sets of genes, such as pathways, based on the interactions between the genes and their function in a common biological process. Regardless of technical differences, these methods do not properly account for cross talk between different pathways and rely on binary separation into differentially expressed gene and unaffected genes based on an arbitrarily set p-value cut-off.

To overcome this limitation, we developed a novel approach to identify concertedly modulated sub-graphs in the global cell signaling network, based on the DGEA results of all genes tested. To this end, expression patterns of genes are integrated according to the topology of their interactions and allow potentially to read the flow of information and identify the effectors. The described software, named Modulated Sub-graph Finder (MSF) is freely available at https://github.com/Modulated-Subgraph-Finder/MSF.
Do you cov me? Effect of coverage reduction on species identification and genome reconstruction in complex biological matrices by metagenome shotgun high-throughput sequencing
Authors: Cattonaro Federica , Spadotto Alessandro , Radovic Slobodanka , Marroni Fabio
Published: March 2019

Shotgun metagenomics sequencing is a powerful tool for the characterization of complex biological matrices, enabling analysis of prokaryotic and eukaryotic organisms and viruses in a single experiment, with the possibility of reconstructing de novo the whole metagenome or a set of genes of interest. One of the main factors limiting the use of shotgun metagenomics on wide scale projects is the high cost associated with the approach. However, we demonstrate that—for some applications—it is possible to use shallow shotgun metagenomics to characterize complex biological matrices while reducing costs. We measured the variation of several summary statistics simulating a decrease in sequencing depth by randomly subsampling a number of reads. The main statistics that were compared are alpha diversity estimates, species abundance, detection threshold, and ability of reconstructing the metagenome in terms of length and completeness. Our results show that a classification of prokaryotic, eukaryotic and viral communities can be accurately performed even using very low number of reads, both in mock communities and in real complex matrices. With samples of 100,000 reads, the alpha diversity estimates were in most cases comparable to those obtained with the full sample, and the estimation of the abundance of all the present species was in excellent agreement with those obtained with the full sample. On the contrary, any task involving the reconstruction of the metagenome performed poorly, even with the largest simulated subsample (1M reads). The length of the reconstructed assembly was smaller than the length obtained with the full dataset, and the proportion of conserved genes that were identified in the meta-genome was drastically reduced compared to the full sample. Shallow shotgun metagenomics can be a useful tool to describe the structure of complex matrices, but it is not adequate to reconstruct—even partially—the metagenome.
Impact of pathogenic mutations of the GLUT1 glucose transporter on channel dynamics using ConsDYN enhanced sampling
Authors: Mouhib Halima , Higuchi Akiko , Abeln Sanne , Yura Kei , Feenstra K. Anton
Published: March 2019

Background: The solute carrier (SLC) family of membrane proteins is a large class of transporters for many small molecules that are vital for the cell. Several pathogenic mutations are reported in the glucose transporter subfamily SLC2, causing Glut1-deficiency syndrome (GLUT1DS1, GLUT1DS2), epilepsy (EIG2) and cryohydrocytosis with neurological defects (Dystonia-9). Understanding the link between these mutations and transporter dynamics is crucial to elucidate their role in the dysfunction of the underlying transport mechanism.

Methods: Predictions from SIFT and PolyPhen provided an impression of the impact upon mutation in the highly conserved RXGRR motifs, but no clear differentiation could be made by these methods between pathogenic and non-pathogenic mutations. Therefore, to identify the molecular effects on the transporter function, insight from molecular dynamic simulations is required. We studied a variety of pathogenic and non-pathogenic mutations, using a newly developed coarse-grained simulation approach ‘ConsDYN’, which allows the sampling of both inward-open and outward-occluded states. To guarantee the sampling of large conformational changes, we only include conserved restraints of the elastic network introduced upon coarse-graining, which showed similar reference distances between the two conformational states (≤1 Å difference).

Results: We capture the ‘conserved dynamics’ between both states using ConsDYN. Simultaneously, it allowed us to considerably lower the computational costs of our study. This approach is sufficiently sensitive to capture the effect of different mutations, and our results clearly indicate that the pathogenic mutation in GLUT1, G91D, situated at the highly conserved RXGRR motif between helices 2 and 3, has a strong impact on channel function, as it blocks the protein from sampling both conformational states. 

Conclusions: Using our approach, we can explain the pathogenicity of the mutation G91D when we observe the configurations of the transmembrane helices, suggesting that their relative position is crucial for the correct functioning of the GLUT1 protein.
Young people in HIV care in Ukraine: a national survey on characteristics and service provision
Authors: Kyselyova Galyna , Martsynovska Violeta , Volokha Alla , Nizova Nataliya , Malyuta Ruslan , Judd Ali , Thorne Claire , Bailey Heather
Published: March 2019

Background: Ukraine’s perinatally HIV-infected (PHIV) young people are ageing into adolescence/young adulthood and, alongside those with behaviourally-acquired infections (BHIV), require transitional and other support services. We aimed to map this population and policies/service provision at specialist HIV centres, to inform future service development.

Methods: A national survey was conducted of 28 HIV/AIDS centres on number, characteristics (age group, HIV acquisition mode) and care setting (paediatric/adult) of 10-24 year olds in HIV care in each of 24 regions in January 2016. Information was collected on policies/service provision at each centre.

Results: Of 13,286 young people aged 10-24 years registered for HIV care nationally in Ukraine in January 2016, 1,675 were aged 10-18 years. Three-quarters of ≤19 year olds were PHIV, while 72% of 20-24-year-olds had sexually-acquired infection. Five regions accounted for two-thirds of 10-18 year olds in paediatric and 85% of 19-24 year olds in adult services.

In 2015, 97 young people transitioned from paediatric to adult services nationally, typically at 18 years although with flexibility in timing at 17/28 centres. At 27/28 centres, BHIV young people aged <18 years began their HIV care in paediatric services sometimes (5) or always (22). Transition support most commonly consisted of a joint appointment with paediatrician and adult doctor, and support from a psychologist/social worker (both at 24/28 centres).

Only 5/28 centres offered routine HIV care during the evening or weekend, and availability of integrated sexual/reproductive health and harm reduction services was uneven. Of 16/28 centres selectively following-up patients who did not attend for care, 15 targeted patients in paediatric services.

Conclusions: Heterogeneity in the population and in service availability at the main regional/municipal HIV/AIDS centres has implications for potential structural barriers to HIV care, and development of services for this group.