bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer
Authors: Kuroki Lindsay M. , Frolova Antonina I. , Wu Ningying , Liu Jingxia , Powell Matthew , Thaker Premal H. , Massad L. Stewart 
Published: June 2017

Objectives
The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer.

Materials and Methods
We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer.

Results
Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50–7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76–9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29–5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26–10.83).

Conclusions
Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.
The ins and outs of endocytic trafficking in platelet functions
Authors: Banerjee Meenakshi , Whiteheart Sidney W. 
Published: June 2017

Purpose of review
Although platelet endocytosis has been recognized in granule cargo loading and the trafficking of several platelet surface receptors, its acute physiological relevance is poorly understood as is its mechanism. The present review discusses the current understanding of platelet endocytosis and its implications for platelet function.

Recent findings
Recent studies are beginning to identify and define the proteins that mediate platelet endocytosis. These studies have shown that platelets contain different endosomal compartments and may use multiple endocytic routes to take in circulating molecules and surface proteins. The studies have also shown that platelet endocytosis is involved in several aspects of platelet function such as signaling, spreading, and granule cargo loading.

Summary
Mechanistic studies of platelet endocytosis have shown it to be not only involved in granule cargo loading but also in various other platelet functions important for hemostasis and beyond.
How Accurately Do Both Parents and Health Professionals Assess Overweight in Children?
Authors: Hong Ickpyo , Dodds Cynthia Brown , Coker-Bolt Patty , Simpson Annie N. , Velozo Craig A. 
Published: June 2017

Background:
An accurate perception of weight status is important to prevent childhood obesity.

Objective:
We investigated whether parents and health professionals accurately identify children's weight status.

Methods:
On the 2012 National Health and Nutrition Examination Survey: National Youth Fitness Survey, parents and health professionals rated the same child's weight status as overweight or healthy. The sensitivity and specificity of their answers were computed by comparing parents' and health professionals' ratings to the age growth chart from the US Centers for Disease Control and Prevention.

Results:
Participants were 1571 children. Parents' sensitivity and specificity were 0.386 and 0.992, respectively. Health professionals' sensitivity and specificity were 0.343 and 0.981, respectively.

Conclusions:
Parents and health professionals demonstrate low sensitivity in identifying children's weight status. Health professionals should use the Centers for Disease Control and Prevention categories to more accurately identify children who are overweight.
A Range of Service Delivery Modes for Children With Developmental Coordination Disorder Are Effective: A Randomized Controlled Trial
Authors: Ward Emily J. , Hillier Susan , Raynor Annette , Petkov John 
Published: June 2017

Purpose:
To investigate whether the environment and personnel providing intervention to children with developmental coordination disorder make a difference in motor outcomes and perceived competency.

Methods:
Ninety-three children (66 males), aged 5 years 1 month to 8 years 11 months, with developmental coordination disorder were randomized to receive a 13-week group-based task-oriented intervention, either at school by a school assistant or physical therapist, or in a health clinic by a physical therapist. The Movement Assessment Battery for Children (MABC) assessed motor skills pre- and postintervention. Self-perception and cost-effectiveness were also assessed.

Results:
Participants demonstrated a significant improvement in motor skills following intervention for all modes of delivery up to 6 months postintervention, MABC mean difference 7.20 (95% confidence interval, 5.89-8.81), effect size = 0.98.

Conclusion:
Group intervention programs for developmental coordination disorder can be run by either a health professional or a school assistant (supported by physical therapist) in either the school or clinic environment and provide successful outcomes.
Percutaneous Vascular Interventions Versus Bypass Surgeries in Patients With Critical Limb Ischemia
Authors: Wang Jiarong , Shu Chi , Wu Zhoupeng , Zhao Jichun , Ma Yukui , Huang Bin , Yuan Ding , Yang Yi , Bian He , He Yazhou , Wang Ziqiang 
Published: June 2017

Objective:
The aim of our study was to compare percutaneous vascular interventions (PVI) versus bypass surgeries (BSX) in patients with critical limb ischemia (CLI).

Background:
Previous relevant reviews with limited numbers of included studies did not strictly confine the inclusion criteria to CLI, also involving patients with severe claudication, which may introduce bias in the decision-making of CLI revascularization. Current treatment strategies for CLI still remain controversial.

Methods:
We performed a meta-analysis of all available randomized controlled trials and observational clinical studies comparing PVI with BSX in CLI patients. Primary endpoints included overall survival, amputation-free survival, 30-day mortality, and major adverse cardiovascular and cerebrovascular events.

Results:
We identified 45 cohorts and 1 RCT in over 20,903 patients. In overall population, PVI reduced the risks of 30-day mortality [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.51–0.95), major adverse cardiovascular and cerebrovascular events (OR 0.42, 95% CI 0.29–0.61), and surgical site infection (OR 0.31, 95% CI 0.19–0.51), but increased the risks of long-term all-cause mortality [hazard ratio (HR) 1.16, 95% CI 1.05–1.27) and primary patency failure (HR 1.31, 95% CI 1.08–1.58). When compared with autogenous BSX, PVI was also associated with additional increased risks of long-term death or amputation (HR 1.41, 95% CI 1.02–1.94) and secondary patency failure (HR 1.51, 95% CI 1.17–1.95). In patients with infrapopliteal lesions, we found PVI had inferior primary patency (HR 1.39, 95% CI 1.10–1.75) compared with BSX.

Conclusion:
For patients in good physical condition with long life-expectancy, BSX may represent a better choice compared with PVI, particularly when autogenous bypass is available. While enhanced perioperative care for cardiovascular events and surgical site should be considered in patients underwent BSX to achieve comparable short-term outcomes provided by PVI.
The Effect of Resident Involvement in Pelvic Prolapse Surgery: A Retrospective Study From a Nationwide Inpatient Sample
Authors: Caveney Maxx , Matthews Catherine , Mirzazadeh Majid 
Published: June 2017

Objective
The primary aim of this study was to assess the effect of resident involvement on perioperative complication rates in pelvic organ prolapse surgery using the National Surgical Quality Improvement database.

Methods
All pelvic organ prolapse operations from 2006 to 2012 were identified and dichotomized by resident participation. Preoperative characteristics and 30-day perioperative outcomes were compared using χ2 and Student t test. To control for nonrandomization of cases, propensity scores representing the probability of resident involvement as a function of a case's comorbidities were calculated. They were then divided into quartiles, and because of equal probabilities for the first and second quartiles, 3 groups were created (Q1/2, Q3, and Q4), followed by substratification and analysis. As a control, complications of transurethral resection of prostate and nephrectomy were dichotomized by resident involvement.

Results
We identified 2637 cases. Resident involvement was associated with increased postoperative urinary tract infections, perioperative complications, and procedure length. After stratification by propensity scoring, the following unique findings occurred in each group: in the first group, resident involvement was associated with increased rates of readmission, pulmonary embolism, and sepsis; in the second and third groups, resident involvement was associated with increased rates of superficial surgical site infection. Resident involvement in nephrectomy observed increased perioperative complications and procedural length. In prostate resection, increased procedure lengths and decreased postoperative length of stay were observed.

Conclusions
Resident involvement in pelvic organ prolapse surgery was associated with an increased risk of adverse outcomes. A similar effect was seen with nephrectomy but not with a more simple endoscopic urologic procedure.
Suppression of drug resistance reveals a genetic mechanism of metabolic plasticity in malaria parasites
Authors: Guggisberg Ann M. , Frasse Philip M. , Jezewski Andrew J. , Kafai Natasha M. , Gandhi Aakash Y. , Erlinger Samuel J. , Odom John Audrey R. 
Published: June 2017

ABSTRACTIn the malaria parasitePlasmodium falciparum, synthesis of isoprenoids from glycolytic intermediates is essential for survival. The antimalarial fosmidomycin (FSM) inhibits isoprenoid synthesis. InP. falciparum, we identify a loss-of-function mutation inHAD2(PF3D7_1226300) as necessary for FSM resistance. Enzymatic characterization reveals that HAD2, a member of the haloacid dehalogenase-like hydrolase (HAD) superfamily, is a phosphatase. Harnessing a growth defect in resistant parasites, we select for suppression of HAD2-mediated FSM resistance and uncover hypomorphic suppressor mutations in the locus encoding the glycolytic enzyme phosphofructokinase (PFK9). Metabolic profiling demonstrates that FSM resistance is achieved via increased steady-state levels of MEP pathway and glycolytic intermediates and confirms reduced PFK9 function in the suppressed strains. We identify HAD2 as a novel regulator of malaria parasite metabolism and drug sensitivity and uncover PFK9 as a novel site of genetic metabolic plasticity in the parasite. Our study informs the biological functions of an evolutionarily conserved family of metabolic regulators and reveals a previously undescribed strategy by which malaria parasites adapt to cellular metabolic dysregulation.IMPORTANCEUnique and essential aspects of parasite metabolism are excellent targets for development of new antimalarials. An improved understanding of parasite metabolism and drug resistance mechanisms are urgently needed. The antibiotic fosmidomycin targets the synthesis of essential isoprenoid compounds from glucose and is a candidate for antimalarial development. Our study identifies a novel mechanism of drug resistance and further describes a family of metabolic regulators in the parasite. Using a novel forward genetic approach, we also uncover mutations that suppress drug resistance in the glycolytic enzyme PFK9. Thus, we identify an unexpected genetic mechanism of adaptation to metabolic insult that influences parasite fitness and tolerance to antimalarials.
Combining Semantic Similarity and GO Enrichment for Computation of Functional Similarity
Authors: Liu Wenting , Liu Jianjun , Rajapakse Jagath C. 
Published: June 2017

AbstractFunctional similarity between genes is widely used in many bioinformatics applications including detecting molecular pathways, finding co-expressed genes, predicting protein-protein interactions, and prioritization of candidate genes. Methods evaluating functional similarity of genes are mostly based on semantic similarity of gene ontology (GO) terms. Though there are hundreds of functional similarity measures available in the literature, none of them considers the enrichment of the GO terms by the querying gene pair. We propose a novel method to incorporate GO enrichment into the existing functional similarity measures. Our experiments show that the inclusion of gene enrichment significantly improves the performance of 44 widely used functional similarity measures, especially in the prediction of sequence homologies, gene expression correlations, and protein-protein interactions.Software availabilityThe software (python code) and all the benchmark datasets evaluation (R script) are available athttps://gitlab.com/liuwt/EnrichFunSim.
Rap1, AF6 and Pak4 cooperate with Par3 to promoteZAassembly and remodeling in the fly photoreceptor
Authors: Walther Rhian F. , Burki Mubarik , Pinal Noelia , Rogerson Clare , Pichaud Franck 
Published: June 2017

AbstractThe epithelialZonula adherens (ZA)is a main adhesion compartment that enables organogenesis by allowing epithelial cells to assemble into sheets. HowZAassembly is regulated during epithelial cell morphogenesis is not fully understood. We show that duringZAmorphogenesis, the function of the small GTPase Rap1 and the F-actin binding protein AF6/Cno are both linked to that of the P21-activated kinase Pak4/Mbt. We find that Rap1 and Mbt regulate each other’s localization at theZAand cooperate in promoting ECadherin stabilization. During this process Cno regulates the recruitment of Baz at theZA,a process that is also regulated by Arm phosphorylation by Mbt. Altogether, we propose that Rap1, Cno and Mbt regulateZAmorphogenesis by coordinating ECadherin stabilization and Baz recruitment and retention. In addition, our work uncovers a new link between two main oncogenes, Rap1 and Pak4/Mbt, in a model developing epithelial cell.
A transgenic toolkit for visualizing and perturbing microtubules in mice reveals unexpected functions for non-centrosomal arrays in epidermal morphogenesis
Authors: Muroyama Andrew , Lechler Terry 
Published: June 2017

AbstractDifferentiation induces reorganization of microtubules (MTs) into non-centrosomal arrays in a variety of tissues. The physiological functions of these microtubule arrays are just beginning to be understood as few tools currently exist to genetically perturb microtubule organizationin vivo, particularly in mammals. We developed a genetic toolkit that can be broadly applied to the study of microtubule dynamics and function in many cell types. Using a TRE-EB1-GFP mouse we demonstrate that distinct differentiation transitions in the epidermis cause a decrease in microtubule growth rates and microtubule growth lifetimes, resulting in strong suppression of dynamics. To understand the physiological functions of these stable, non-centrosomal microtubules, we generated a TRE-spastin mouse, which can be used to perturb microtubule organization in a wide-variety of tissuesin vivo.Unexpectedly, microtubule perturbation exclusively in post-mitotic keratinocytes had profound consequences on epidermal morphogenesis. We uncoupled novel cell-autonomous roles for MTs in differentiation-driven cell flattening from non-cell autonomous functions in regulating proliferation, differentiation, and tissue architecture. Taken together, we have created tools that will be broadly useful for the study of microtubule dynamics and function in mammalian tissue physiology and have used them to uncover previously unknown functions for non-centrosomal microtubules during mammalian epidermal development.
Variation in the oxidative burst in response to wounding and bacterial infection among native and invading genotypes of yellow starthistle(Centaurea solstitialis)
Authors: Kaczowka Angela M. , Lu-Irving Patricia , Baltrus David A , Dlugosch Katrina M. 
Published: June 2017

AbstractPremise of the study:Invasive plants may leave enemies behind when they colonize a new habitat, allowing selection to favor increased investment in growth and/or reproduction over defensive traits. Previous studies have identified reduced diversity of potential bacterial pathogens and evolutionary increases in growth and reproduction in invading populations of yellow starthistle (Centaurea solstitialis). This study leverages a recently developed high-throughput assay of immune function to test for evidence of a trade-off between increased growth and defense against bacterial pathogens in yellow starthistle’s invasion of California (USA).Methods:Seven bacterial strains were cultured from infected leaf tissue in the native range. Healthy leaf tissue from five native European collections and six invading collections were exposed to these native bacterial strains. A standardized assay of peroxidase activity was used measure the oxidative burst immune response to pathogen recognition by the leaf. Immune responses were compared to plant growth within and between ranges to assess evidence for a trade-off.Key Results:Plant genotypes from the native range demonstrated a higher immune response to bacterial strains than did invading genotypes, consistent with a trade-off with plant growth across regions. The same trade-off was also apparent across genotypes from the native range, but not across genotypes from the invaded range.Conclusions:Our results provide evidence that increased growth in a highly invasive plant species may come at a cost to immune function, consistent with the hypothesis that escape from enemies can provide opportunities for shifts in resource allocation that favor the proliferation of non-native species.
Intestine-to-neuronal signaling alters risk-taking behaviors in food-deprivedCaenorhabditis elegans
Authors: Matty Molly A. , Lau Hiu E. , Singh Anupama , Haley Jessica A. , Chakraborty Ahana , Kono Karina , Reddy Kirthi C. , Hansen Malene , Chalasani Sreekanth H. 
Published: June 2017

AbstractAnimals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. We use the nematodeC. elegansto decode how changes in internal nutritional status affects chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (Mondo A) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm upon food deprivation. Next, we identify insulin-like peptides INS-23 and INS-31 as candidate ligands relaying food-status signals from the intestine to other tissues. Furthermore, we show that ASI chemosensory neurons use the DAF-2 insulin receptor, PI-3 Kinase, and the mTOR complex to integrate these intestine-released peptides. Together, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors.Author SummaryWe have all experienced behavioral changes when we are hungry - the pang in our stomach can cause us to behave erratically. In particular, hungry animals, including humans, are known to pursue behaviors that involve higher risk compared to when they are well-fed. Here we explore the molecular details of this behavior in the invertebrate animal model C. elegans. This behavior, termed sensory integration, shows that C. elegans display reduced copper sensitivity when hungry. Copper is toxic and repellant to C. elegans; reduced avoidance indicates that these animals use riskier food search behaviors when they are hungry. Luckily, like us, this behavioral change is reversible upon re-feeding. This hunger-induced behavioral change is not due to increased attraction to food or depletion of fat stores, but rather insulin signaling between the intestine and specific neurons. We use genetic tools, microscopy, and behavioral tests to determine that this risky behavior involves sensation of “lack of food” in the intestine, release of signaling molecules, and engagement with sensory neurons. Our work highlights new and potentially evolutionarily conserved ways in which intestinal cells and neurons communicate leading to largescale behavioral change, providing further support for the importance of the gut-brain-axis.
Competition of Charge-Mediated and Specific Binding by Peptide-Tagged Cationic Liposome–DNA NanoparticlesIn VitroandIn Vivo
Authors: Wonder Emily , Simón-Gracia Lorena , Scodeller Pablo , Majzoub Ramsey N. , Kotamraju Venkata Ramana , Ewert Kai K. , Teesalu Tambet , Safinya Cyrus R. 
Published: June 2017

AbstractCationic liposome–nucleic acid (CL–NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly(ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells. Such guidelines are desirable to accelerate the optimization of formulations with novel peptides. Using PEG-lipids functionalized with a library of prototypical tumor-homing peptides, we varied the peptide density and other parameters (binding motif, peptide charge, CL/DNA charge ratio) to study their effect on the binding and uptake of the corresponding NPs. We used flow cytometry to quantitatively assess binding as well as internalization of NPs by cultured cancer cells. Surprisingly, full peptide coverage resulted in less binding and internalization than intermediate coverage, with the optimum coverage varying between cell lines. In, addition, our data revealed that great care must be taken to prevent nonspecific electrostatic interactions from interfering with the desired specific binding and internalization. Importantly, such considerations must take into account the charge of the peptide ligand as well as the membrane charge density and the CL/DNA charge ratio. To test our guidelines, we evaluated thein vivotumor selectivity of selected NP formulations in a mouse model of peritoneally disseminated human gastric cancer. Intraperitoneally administered peptide-tagged CL–DNA NPs showed tumor binding, minimal accumulation in healthy control tissues, and preferential penetration of smaller tumor nodules, a highly clinically relevant target known to drive recurrence of the peritoneal cancer.Graphical Abstract