bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurostimulation of the gastrointestinal tract in children: is it time to shock the gut?
Authors: Lu Peter L. , Di Lorenzo Carlo 
Published: June 2016

Purpose of reviewThe use of neurostimulation for treatment of gastrointestinal disorders has been growing over the past two to three decades. Our objective is to review current applications of neurostimulation in the treatment of gastrointestinal disorders with an emphasis on the use of these treatment modalities in children.Recent findingsGastric electrical stimulation can lead to symptomatic improvement in children with chronic nausea and vomiting refractory to conventional treatment, and a recent report of long-term outcomes is encouraging. Sacral nerve stimulation can be effective in the treatment of children with constipation and fecal incontinence refractory to conventional treatment, and patient satisfaction with treatment remains high despite the risk of complications requiring further surgery. Abdominal transcutaneous electrical stimulation and posterior tibial nerve stimulation are noninvasive neurostimulation techniques that may be effective in the treatment of children with constipation and fecal incontinence.SummaryAlthough neurostimulation-based treatments appear promising and offer advantages compared to more invasive surgical treatment options, evidence for their benefit in children remains limited. High-quality studies demonstrating safety and efficacy and a better understanding of the mechanism of each modality are needed before there is more widespread acceptance of neurostimulation in the treatment of children with gastrointestinal disorders.
Primary Care Physicians' Adherence to Expert Recommendations for Cervical Cancer Screening and Prevention in the Context of Human Papillomavirus Vaccination
Authors: Malo Teri L. , Perkins Rebecca B. , Lee Ji-Hyun , Vadaparampil Susan T. 
Published: June 2016

Background
Expert recommendations do not recommend using Papanicolaou (Pap) or human papillomavirus (HPV) test results to determine whether unvaccinated women should receive HPV vaccine, nor do they recommend using vaccine receipt to inform cervical cancer screening practices. This study characterizes physicians' HPV vaccine recommendations and practices in the context of HPV and Pap testing.

Methods
We surveyed family physicians and obstetrician-gynecologists randomly selected from the American Medical Association Masterfile in 2011 (n = 574). Physicians used a 5-point scale (never to always) to report the frequency of (1) using HPV testing results to decide whether to recommend HPV vaccine, and (2) recommending HPV vaccination to women (≤26 years) who had an abnormal Pap test. Physicians also reported (3) intention to change Pap screening frequency for vaccinated women.

Results
Across both specialties, 80% correctly reported rarely or never using HPV testing results to guide vaccine recommendations; 66% often or always recommended vaccination to patients with an abnormal Pap result; and 77% did not plan to change Pap screening frequency for vaccinated women. About 41% reported recommendation-consistent practices with all 3 measures. In multivariable analysis, obstetrician-gynecologist specialty and private practice type were associated with higher average overall adherence to recommendations.

Conclusions
Contrary to expert recommendations, a considerable minority of physicians reported recommending HPV vaccination based on HPV and Pap test results. If these clinical practices persist, many young adult women will not realize the benefits of HPV vaccination. Additional efforts are needed to ensure all young women are screened and vaccinated appropriately.
Anorectal Lymphogranuloma Venereum in Madrid: A Persistent Emerging Problem in Men Who Have Sex With Men
Authors: Cabello Úbeda Alfonso , Fernández Roblas Ricardo , García Delgado Rosa , Martínez García Laura , Sterlin Fabiola , Fernández Guerrero Manuel L. , Górgolas Miguel 
Published: June 2016

Background
Since 2003, outbreaks of lymphogranuloma venereum (LGV) with anorectal syndrome have been increasingly recognized in many Western countries. All of them have been classified as LGV serovar L2b, mainly occurring in human immunodeficiency virus (HIV)-infected men who have had sex with men (MSM). We describe a series of 26 diagnosed cases of LGV proctitis in downtown Madrid, Spain, in 2014, after implementing routine diagnostic procedures for this disease in symptomatic MSM.

Methods
We conducted an observational study of patients with symptomatic proctitis attending an outpatient infectious diseases clinic in Madrid, Spain during calendar year 2014. Clinical, epidemiological, laboratory, and therapeutic data were gathered and analyzed.

Results
Twenty-six patients were included in the analysis. All were MSM, and 24 of them were HIV-positive. All patients reported having acute proctitis symptoms including tenesmus (85%), pain (88%), constipation (62%), or anal discharge (96%). Proctoscopy showed mucopurulent exudate (25 patients [96%]), and rectal bleeding, with mucosal erythema and/or oedema in all cases. Rectal swabs were obtained from all patients, and LGV serovar L2 was confirmed in all of them. The cure rate was 100% after standard treatments with doxycycline 100 mg twice per day for 3 weeks. Simultaneous rectal infections with other sexually transmitted pathogens (gonorrhoea, herpes simplex virus, Mycoplasma genitalium) and systemic sexually transmitted diseases (STDs) (syphilis, acute HIV, and hepatitis C infections) were also documented in 12 patients (46%), but these co-infections did not appear to influence the clinical manifestations of LGV.

Conclusions
Anorectal LGV is a common cause of acute proctitis and proctocolitis among HIV-infected MSM who practice unprotected anal sex, and it is frequently associated with other rectal STDs. The implementation of routine screening and prompt diagnosis of these rectal infections should be mandatory in all clinical settings attended by HIV and STD patients.
HIV Serodisclosure and Sexual Behavior During International Travel
Authors: Truong Hong-Ha M. , Chen Yea-Hung , Grasso Michael , Robertson Tyler , Tao Luke , Fatch Robin , Curotto Alberto , McFarland Willi , Grant Robert M. , Reznick Olga , Raymond H. Fisher , Steward Wayne T. 
Published: June 2016

Abstract
When traveling internationally, HIV serodisclosure and knowledge of partners' serostatus were hampered by the lack of a common language. Condomless anal intercourse was less likely to occur in partnerships where HIV serostatus was not disclosed or known. Taken together, these observations suggest that language barriers may affect sexual decision making.
Treponema pallidum pallidum Genotypes and Macrolide Resistance Status in Syphilitic Lesions among Patients at 2 Sexually Transmitted Infection Clinics in Lima, Peru
Authors: Flores Juan Antonio , Vargas Silver Keith , Leon Segundo Ramos , Perez Danny Giancarlo , Ramos Lourdes Beatriz , Chow Jeremy , Konda Kelika Anne , Calvo Gino Mauricio , Salvatierra Hector J. , Klaussner Jeffrey D. , Caceres Carlos Fernando 
Published: June 2016

Abstract
We report the circulating genotypes and the frequency of macrolide-resistance patterns among Treponema pallidum pallidum DNA isolated from syphilitic lesions from patients who attended 2 sexual health clinics in Lima, Peru. We implemented and used a molecular typing scheme to describe local T. pallidum pallidum strains. Among 14 specimens, subtype 14d/f was the most prevalent strain in 7 fully typed T. pallidum DNA specimens obtained from men who have sex with men and transgender women presenting with chancre-like lesions. No macrolide-resistance mutations were found in T. pallidum DNA from 10 lesions.
Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro
Authors: Tschan-Plessl Astrid , Stern Martin , Schmied Laurent , Retière Christelle , Hirsch Hans H. , Garzoni Christian , van Delden Christian , Boggian Katia , Mueller Nicolas J. , Berger Christoph , Villard Jean , Manuel Oriol , Meylan Pascal , Terszowski Grzegorz 
Published: June 2016

Background
Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive.

Methods
We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls.

Results
We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P < 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P < 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern.
Most importantly, we observed a significantly higher NK cell degranulation and IFNγ production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P < 0.001; IFNγ: mean increase, 6.6%; 95% CI, 1.6-11.1; P < 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNγ: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002).

Conclusions
We report evidence for an increased function of NK cells induced by CMV infection. This increased in vitro functionality was seen in NKG2C-positive and NKG2C-negative subsets, arguing for an NKG2C independent mechanism of action.
Prioritizing 2nd and 3rd order interactions via support vector ranking using sensitivity indices on static Wnt measurements†
Authors: sinha shriprakash 
Published: June 2016

AbstractIt is widely known that the sensitivity analysis plays a major role in computing the strength of the influence of involved factors in any phenomena under investigation. When applied to expression profiles of various intra/extracellular factors that form an integral part of a signaling pathway, the variance and density based analysis yields a range of sensitivity indices for individual as well as various combinations of factors. These combinations denote the higher order interactions among the involved factors that might be of interest in the working mechanism of the pathway. For example,DACT3 is known to be a epigenetic regulator of the Wnt pathway in colorectal cancer and subject to histone modifications. But many of thenth≥ 2 order interactions ofDACT3 that might be influential have not been explored/tested. In this work, after estimating the individual effects of factors for a higher order combination, the individual indices are considered as discriminative features. A combination, then is a multivariate feature set in higher order (≥ 2). With an excessively large number of factors involved in the pathway, it is difficult to search for important combinations in a wide search space over different orders. Exploiting the analogy of prioritizing webpages using ranking algorithms, for a particular order, a full set of combinations of interactions can then be prioritized based on these features using a powerful ranking algorithm via support vectors. The computational ranking sheds light on unexplored combinations that can further be investigated using hypothesis testing based on wet lab experiments. Here, the basic framework and results obtained on 2ndand 3rdorder interactions for members of family ofDACT,SFRP,DKK(to name a few) in both normal and tumor cases is presented using a static data set.SignificanceThe search and wet lab testing of unknown biological hypotheses in the form of combinations of various intra/extracellular factors that are involved in a signaling pathway, costs a lot in terms of time, investment and energy. To reduce this cost of search in a vast combinatorial space, a pipeline has been developed that prioritises these list of combinations so that a biologist can narrow down their investigation. The pipeline uses kernel based sensitivity indices to capture the influence of the factors in a pathway and employs powerful support vector ranking algorithm. The generic workflow and future improvements are bound to cut down the cost for many wet lab experiments and reveal unknown/untested biological hypothesis.
Modulation of global transcriptional regulatory networks as a strategy for increasing kanamycin resistance of EF-G mutants
Authors: Mogre Aalap , Seshasayee Aswin Sai Narain 
Published: June 2016

AbstractEvolve and resequence experiments have provided us a tool to understand bacterial adaptation to antibiotics by the gain of genomic mutations. In our previous work, we used short term evolution to isolate mutants resistant to the ribosome targeting antibiotic kanamycin. We had reported gain of resistance to kanamycin via multiple different point mutations in the translation elongation factor G (EF-G). Furthermore, we had shown that the resistance of EF-G mutants could be increased by second site mutations in the genesrpoD/cpxA/topA/cyaA.Mutations in three of these genes had been discovered in earlier screens for aminoglycoside resistance. In this work we expand on our understanding of these second site mutations. Using genetic tools we asked how mutations in the cell envelope stress sensor kinase (CpxAF218Y) and adenylate cyclase (CyaAN600Y) could alter their activities to result in resistance. We found that the mutation incpxAmost likely results in an active Cpx stress response. Further evolution of an EF-G mutant in a higher concentration of kanamycin than what was used in our previous experiments identified thecpxAlocus as a primary target for a significant increase in resistance. The mutation incyaAresults in a loss of catalytic activity and probably results in resistance via altered CRP function. Despite a reduction in cAMP levels, the CyaAN600Ymutant has a transcriptome indicative of increased CRP activity, pointing to an unknown non-catalytic role for CyaA in gene expression. From the transcriptomes of double and single mutants we describe the epistasis between the mutation in EF-G and these second site mutations. We show that the large scale transcriptomic changes in the topoisomerase I (FusAA608E-TopAS180L) mutant likely result from increased negative supercoiling in the cell. Finally, genes with known roles in aminoglycoside resistance were present among the mis-regulated genes in the mutants.
Genomics implicates adaptive and innate immunity in Alzheimer’s and Parkinson’s
Authors: Gagliano Sarah A , Pouget Jennie G , Hardy John , Knight Jo , Barnes Michael R , Ryten Mina , Weale Michael E 
Published: June 2016

AbstractObjectivesWe assessed the current genetic evidence for the involvement of various cell types and tissue types in the aetiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases.MethodsWe obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control. We applied stratified LD score regression to determine if functional marks for cell type and tissue activity, and gene set lists were enriched for genetic heritability. We compared our results to those from two gene-set enrichment methods (Ingenuity Pathway Analysis and enrichr).ResultsThere were no significant heritability enrichments for annotations marking genes active within brain regions, but there were for annotations marking genes active within cell-types that form part of both the innate and adaptive immune systems. We found this for MS (as expected) and also for AD and PD. The strongest signals were from the adaptive immune system (e.g. T cells) for PD, and from both the adaptive (e.g. T cells) and innate (e.g. CD14: a marker for monocytes, and CD15: a marker for neutrophils) immune systems for AD. Annotations from the liver were also significant for AD. Pathway analysis provided complementary results.InterpretationFor Alzheimer’s and Parkinson’s disease, we found significant enrichment of heritability in annotations marking gene activity in immune cells.
Recent thymic emigrants produce antimicrobial IL-8, express complement receptors and are precursors of a tissue-homing Th8 lineage of memory cells
Authors: Pekalski Marcin L , García Arcadio Rubio , Ferreira Ricardo C , Rainbow Daniel B , Smyth Deborah J , Mashar Meghavi , Brady Jane , Savinykh Natalia , Dopico Xaquin Castro , Mahmood Sumiyya , Duley Simon , Stevens Helen E , Walker Neil M , Cutler Antony J , Waldron-Lynch Frank , Dunger David B , Shannon-Lowe Claire , Coles Alasdair J , Jones Joanne L , Wallace Chris , Todd John A , Wicker Linda S 
Published: June 2016

ABSTRACTThe adaptive immune system utilizes multiple mechanisms linked to innate immune cell functions to respond appropriately to pathogens and commensals. Here we discover further aspects of this connectivity by demonstrating that naïve T cells as they emerge from the thymus (recent thymic emigrants, RTEs) express complement receptors (CR1 and CR2), the bacterial pathogen recognition receptor TLR1 and an enzyme that deactivates bacterial lipopolysaccharide (AOAH) and following activation secrete the anti-microbial cytokine IL-8. CR2+naïve T cells also express a selection of genes associated with tissue migration, consistent with the hypothesis that following emigration from the thymus RTEs seed peripheral compartments where some pursue their anti-microbial potential by becoming IL-8-producing CR2+memory cells while others undergo homeostatic expansion. CR2+naïve and memory cells are abundant in children but decrease with age, coinciding with the involution of the thymus. The ability of CR2, which is also a receptor for Epstein-Barr Virus (EBV), to identify recent thymic emigrants will facilitate assessment of thymic function during aging and aid investigations of multiple clinical areas including the occurrence of T cell lymphomas caused by EBV.
Analyzing climate variations on multiple timescales can guide Zika virus response measures
Authors: Muñoz Á.G. , Thomson M. C. , Goddard L. , Aldighieri S. 
Published: June 2016

AbstractBackgroundThe emergence of Zika virus (ZIKV) as a public health emergency in Latin America and the Caribbean (LAC) occurred during a period of severe drought and unusually high temperatures. Speculation in the literature exists that these climate conditions were associated with the 2015/2016 El Niño event and/or climate change but to date no quantitative assessment has been made. Analysis of relatedflaviviruses–such as dengue and chikungunya, which are transmitted by the same vectors– suggests that ZIKV dynamics is sensitive to climate seasonality and longer-term variability and trends. A better understanding the climate conditions conducive to the 2014-2016 epidemic may permit the development of climate-informed short- and long-term strategies for ZIKV prevention and control.ResultsUsing a novel timescale-decomposition methodology, we demonstrate that extreme climate anomalies observed in most parts of South America during the current epidemic are not caused exclusively by El Niño or climate change –as speculated–, but are the result of a particular combination of climate signals acting at multiple timescales. In Brazil, the heart of the epidemic, we find that dry conditions present during 2013-2015 are explained primarily by year-to-year variability superimposed on decadal variability, but with little contribution of long-term trends. In contrast, the extreme warm temperatures of 2014-2015 resulted from the compound effect of climate change, decadal and year-to-year climate variability.ConclusionsZIKV response strategies adapted for a drought context in Brazil during El Niño 2015/2016 may need to be revised to accommodate the likely return of heavy rainfall associated with the probable 2016/2017 La Niña. Temperatures are likely to remain warm given the importance of long term and decadal scale climate signals.
BlastPhyMe: A toolkit for rapid generation and analysis of protein-coding sequence datasets
Authors: Schott Ryan K , Gow Daniel , Chang Belinda SW 
Published: June 2016

AbstractSummaryWe present BlastPhyMe (BLAST, Phylogenies, and Molecular Evolution) a new application to facilitate the fast and easy generation and analysis of protein-coding sequence datasets. The application uses a portable database framework to manage and organize sequences along with a graphical user interface (GUI) that makes the application extremely easy to use. BlastPhyMe utilizes several existing services and applications in a unique way that save researchers considerable time when building and analyzing protein-coding datasets. The application consists of two modules that can be used separately or together. The first module enables the assembly of coding sequence datasets. BLAST searches can be used to obtain all related sequences of interest from NCBI. Full GenBank records are saved within the database and coding sequences are automatically extracted. A feature of particular note is that sequences can be sorted based on NCBI taxonomic hierarchy before export for visualization using existing tools, such as fast. The application provides GUIs for automatic alignment of sequences with the popular tools MUSCLE and PRANK, as well as for reconstructing phylogenetic trees using PhyML. The second module incorporates selection analyses using codon-based likelihood methods. The alignments and phylogenetic trees generated with the dataset module, or those generated elsewhere, can be used to run the models implemented in the codeml PAML package. A GUI allows easy selection of models and parameters. Importantly, replicate analyses with different parameter starting values can be automatically performed in order to ensure selection of the best-fitting model. Multiple analyses can be run simultaneously based on the number of processor cores available, while additional analyses will be run iteratively until completed. Results are saved within the database and can be exported to publication-ready Excel tables, which further automatically compute the appropriate likelihood ratio test between models in order to determine statistical significance. Future updates will add additional options for phylogenetic reconstruction (eg, MrBayes) and selection analyses (eg, HYPHY). BlastPhyMe saves researches of all bioinformatics experience levels considerable time by automating the numerous tasks required for the generation and analysis of protein-coding sequence datasets using a straightforward graphical interface.AvailabilityInstallation package and source code available from:https://github.com/ryankschott/BlastPhyMeContactschottr@si.edu