bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on Neuroendocrine Carcinomas of the Larynx
Authors: Strosberg Carolina , Ferlito Alfio , Triantafyllou Asterios , Gnepp Douglas R , Bishop Justin A , Hellquist Henrik , Strojan Primoz , Willems Stefan M , Stenman Göran , Rinaldo Alessandra , Hernandez-Prera Juan C
Published: June 2019

Objectives

Laryngeal neuroendocrine carcinomas are heterogeneous neoplasms characterized by neuroendocrine differentiation. Their prognoses are dependent on tumor type, therefore different classifications have been developed. Moreover, other tumors have overlapping pathologic features posing a range of diagnostic possibilities.

Methods

A review of the literature was performed to comprehensively understand the classification and diagnosis of these tumors.

Results

We review the past and present classification systems, with emphasis to the latest 2017 World Health Organization Classification of Head and Neck Tumors. We highlight salient clinicopathologic features and discuss the presumptive etiologic role of human papilloma virus. We share a practical algorithmic approach to the diagnosis of suspected neuroendocrine neoplasms of the larynx including a novel marker for neuroendocrine differentiation, insulinoma-associated protein 1.

Conclusions

Accurate diagnosis and grading of laryngeal neuroendocrine carcinomas is critical for prognostication and therapeutic decision making. The use of an algorithm is instrumental in assuring the exclusion of mimickers.
Association Between Intra-arterial Invasive Central and Peripheral Blood Pressure and Endothelial Function (Assessed by Flow-Mediated Dilatation) in Stable Coronary Artery Disease
Authors: Park Kyoung-Ha , Park Woo Jung , Han Sang Jin , Kim Hyun-Sook , Jo Sang Ho , Kim Sung-Ai , Suh Sang Won
Published: June 2019

Background

Endothelial function is an independent predictor of coronary artery disease (CAD) and is regulated by a number of factors, including blood pressure.

Objectives

The current study was designed to test the hypothesis that intra-arterial invasive central blood pressure is strongly associated with endothelial function in patients with CAD.

Methods

In patient with CAD (diameter stenosis ≥30%), invasive central (aortic) and left peripheral (brachial) blood pressures were determined during transradial coronary angiography. The endothelial function was evaluated by way of flow-mediated dilatation (FMD) of the brachial artery.

Results

We enrolled 413 consecutive patients. There were 260 patients with significant CAD (sCAD, diameter stenosis ≥50%) and 153 patients with nonsignificant CAD (nsCAD, diameter stenosis <50% and ≤30%). FMD was significantly and inversely correlated with central and peripheral parameters in terms of systolic blood pressure, mean arterial pressure, and pulse pressure (PP) (r = −0.332, r = −0.184, and r = −0.407, respectively, all P < 0.001) and (r = −0.303, r = −0.190, and r = −0.319, respectively, all P < 0.001). Compared with sCAD, there was closer correlation between central PP with FMD in nsCAD (r = −0.548 vs. r = −0.345, both P < 0.001). After adjusting potential confounders such as age, body mass index and high-sensitivity C-reactive protein, multivariate analysis showed that FMD remained independently associated with central PP, degree of coronary artery stenosis, and brachial-ankle pulse wave velocity in all patients. In patients with nsCAD, the multivariate analysis showed that only central PP was independently correlated with FMD.

Conclusions

In patients with stable CAD, a decline in endothelial function is most closely associated with invasive central pulse pressure.
Whole-Body Vibration Associated with Dozer Operation at an Australian Surface Coal Mine
Authors: Lynas Danellie , Burgess-Limerick Robin
Published: June 2019

Bulldozers are used extensively on surface mine sites and have been previously identified as being associated with high amplitude whole-body vibration exposures. Previous investigations of this equipment have involved either a very small number of measurements, or measurements of very short duration (or both); or the data obtained were incompletely reported. This research reports 69 measurements (median duration 440 min) obtained from 15 different dozers during operation at a surface coal mine. More than one-third of vertical vibration measurements exceeded the ISO2631.1 Health Guidance Caution Zone when expressed as VDV(8). Considerable variability in measurement amplitudes was found. This was also true within measurements obtained from the same dozers on different shifts suggesting, by a process of elimination, that the remaining variability in whole-body vibration amplitude is a function of some combination of task characteristics, geology, and operator behaviour; rather than equipment-related variability, such as maintenance, suspension, seating, or track design. Short-comings in the evaluation methods provided by ISO2631.1 are highlighted.
Dispersal and local persistence shape the genetic structure of a widespread Neotropical plant species with a patchy distribution
Authors: Leal Bárbara Simões Santos , Graciano Vanessa Araujo , Chaves Cleber Juliano Neves , Huacre Luis Alberto Pillaca , Heuertz Myriam , Palma-Silva Clarisse
Published: June 2019

Background and Aims

Isolated populations constitute an ideal laboratory to study the consequences of intraspecific divergence, because intrinsic incompatibilities are more likely to accumulate under reduced gene flow. Here, we use a widespread bromeliad with a patchy distribution, Pitcairnia lanuginosa, as a model to infer processes driving Neotropical diversification and, thus, to improve our understanding of the origin and evolutionary dynamics of biodiversity in this highly speciose region.

Methods

We assessed the timing of lineage divergence, genetic structural patterns and historical demography of P. lanuginosa, based on microsatellites, and plastid and nuclear sequence data sets using coalescent analyses and an Approximate Bayesian Computation framework. Additionally, we used species distribution models (SDMs) to independently estimate potential changes in habitat suitability.

Key Results

Despite morphological uniformity, plastid and nuclear DNA data revealed two distinct P. lanuginosa lineages that probably diverged through dispersal from the Cerrado to the Central Andean Yungas, following the final uplift of the Andes, and passed through long-term isolation with no evidence of migration. Microsatellite data indicate low genetic diversity and high levels of inbreeding within populations, and restricted gene flow among populations, which are likely to be a consequence of bottlenecks (or founder events), and high selfing rates promoting population persistence in isolation. SDMs showed a slight expansion of the suitable range for P. lanuginosa lineages during the Last Glacial Maximum, although molecular data revealed a signature of older divergence. Pleistocene climatic oscillations thus seem to have played only a minor role in the diversification of P. lanuginosa, which probably persisted through adverse conditions in riparian forests.

Conclusions

Our results imply drift as a major force shaping the evolution of P. lanuginosa, and suggest that dispersal events have a prominent role in connecting Neotropical open and forest biomes.
A fully computational and reasonable representation for karyotypes
Authors: Warrender Jennifer D , Moorman Anthony V , Lord Phillip
Published: June 2019

The human karyotype has been used as a mechanism for describing and detecting gross abnormalities in the genome for many decades. It is used both for routine diagnostic purposes and for research to further our understanding of the causes of disease. Despite these important applications there has been no rigorous computational representation of the karyotype; rather an informal, string-based representation is used, making it hard to check, organize and search data of this form. In this article, we describe our use of OWL, the Ontology Web Language, to generate a fully computational representation of the karyotype; the development of this ontology represents a significant advance from the traditional bioinformatics use for tagging and navigation and has necessitated the development of a new ontology development environment called Tawny-OWL.

Availability and implementation

The Karyotype Ontology and associated Tawny-OWL source code is available on GitHub at https://github.com/jaydchan/tawny-karyotype, under a LGPL License, Version 3.0.
KinomeX: a web application for predicting kinome-wide polypharmacology effect of small molecules
Authors: Li Zhaojun , Li Xutong , Liu Xiaohong , Fu Zunyun , Xiong Zhaoping , Wu Xiaolong , Tan Xiaoqin , Zhao Jihui , Zhong Feisheng , Wan Xiaozhe , Luo Xiaomin , Chen Kaixian , Jiang Hualiang , Zheng Mingyue
Published: June 2019

Motivation

The large-scale kinome-wide virtual profiling for small molecules is a daunting task by experimental and traditional in silico drug design approaches. Recent advances in deep learning algorithms have brought about new opportunities in promoting this process.

Results

KinomeX is an online platform to predict kinome-wide polypharmacology effect of small molecules based solely on their chemical structures. The prediction is made by a multi-task deep neural network model trained with over 140 000 bioactivity data points for 391 kinases. Extensive computational and experimental validations have been performed. Overall, KinomeX enables users to create a comprehensive kinome interaction network for designing novel chemical modulators, and is of practical value on exploring the previously less studied or untargeted kinases.

Availability and implementation

KinomeX is available at: https://kinome.dddc.ac.cn.

Supplementary information

Supplementary data are available at Bioinformatics online.
Personalized Ertapenem Prophylaxis for Carriers of Extended-spectrum β-Lactamase–producing Enterobacteriaceae Undergoing Colorectal Surgery
Authors: Nutman Amir , Temkin Elizabeth , Harbarth Stephan , Carevic Biljana , Ris Frederic , Fankhauser-Rodriguez Carolina , Radovanovic Ivana , Dubinsky-Pertzov Biana , Cohen-Percia Shimrit , Kariv Yehuda , Buchs Nicolas , Schiffer Eduardo , Fallach Noga , Klausner Joseph , Carmeli Yehuda
Published: June 2019

Background

Carriers of extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) who receive cephalosporin-based prophylaxis have twice the risk of surgical site infection (SSI) following colorectal surgery as noncarriers. We tested whether ESBL-PE screening and personalized prophylaxis with ertapenem reduces SSI risk among carriers.

Methods

We conducted a prospective nonrandomized, nonblinded, interventional study in 3 hospitals in Israel, Switzerland, and Serbia. Patients were screened for ESBL-PE carriage before elective colorectal surgery. During the baseline phase, departmental guidelines advised prophylaxis with a cephalosporin plus metronidazole. In the intervention phase, guidelines were changed for ESBL-PE carriers to receive ertapenem. The primary outcome was any type of SSI within 30 days. We calculated adjusted risk differences (ARDs) following logistic regression.

Results

The intention-to-treat analysis compared 209 ESBL-PE carriers in the baseline phase to 269 in the intervention phase. SSI rates were 21.5% and 17.5%, respectively (ARD, –4.7% [95% confidence interval {CI}, –11.8% to 2.4%]). Unplanned crossover was high (15%), so to assess efficacy we performed an as-treated analysis comparing 247 patients who received cephalosporin-based prophylaxis with 221 who received ertapenem. SSI rates were 22.7% and 15.8%, respectively (ARD, –7.7% [95% CI, –14.6% to –.8%]), and rates of SSI caused by ESBL-PE were 6.5% and 0.9%, respectively (ARD, –5.6% [95% CI, –8.9% to –2.3%]). There was no significant difference in the rate of deep SSI. The number needed to treat to prevent 1 SSI in ESBL-PE carriers was 13.

Conclusions

Screening for ESBL-PE carriage before colorectal surgery and personalizing prophylaxis for carriers is efficacious in reducing SSI.
The Pitt Bacteremia Score Predicts Mortality in Nonbacteremic Infections
Authors: Henderson Heather , Luterbach Courtney L , Cober Eric , Richter Sandra S , Salata Robert A , Kalayjian Robert C , Watkins Richard R , Doi Yohei , Kaye Keith S , Evans Scott , Fowler Vance G , Bonomo Robert A , Harris Anthony , Napravnik Sonia , Van Duin David
Published: June 2019

Background

Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSIs). We determined whether the PBS predicts 14-day inpatient mortality in nonbacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections.

Methods

Patients were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and Other Enterobacteriaceae, a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS.

Results

In a cohort of 475 patients with CRE infections, a PBS ≥4 was associated with mortality in patients with nonbacteremia infections (risk ratio [RR], 21.9; 95% confidence interval [CI], 7.0, 68.8) and with BSIs (RR, 6.0; 95% CI, 2.5, 14.4). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature <36.0°C vs ≥36°C was independently associated with mortality. A qPitt score ≥2 had similar discrimination as a PBS ≥4 in nonbacteremia infections.

Conclusions

Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in nonbacteremia CRE infections.
Levosimendan prevents doxorubicin-induced cardiotoxicity in time- and dose-dependent manner: implications for inotropy
Authors: Efentakis Panagiotis , Varela Aimilia , Chavdoula Evangelia , Sigala Fragiska , Sanoudou Despina , Tenta Roxane , Gioti Katerina , Kostomitsopoulos Nikolaos , Papapetropoulos Andreas , Tasouli Androniki , Farmakis Dimitrios , Davos Costantinos H , Klinakis Apostolos , Suter Thomas , Cokkinos Dennis V , Iliodromitis Efstathios K , Wenzel Philip , Andreadou Ioanna
Published: June 2019

Aims

Levosimendan (LEVO) a clinically-used inodilator, exerts multifaceted cardioprotective effects. Case-studies indicate protection against doxorubicin (DXR)-induced cardiotoxicity, but this effect remains obscure. We investigated the effect and mechanism of different regimens of levosimendan on sub-chronic and chronic doxorubicin cardiotoxicity.

Methods and results

Based on preliminary in vivo experiments, rats serving as a sub-chronic model of doxorubicin-cardiotoxicity and were divided into: Control (N/S-0.9%), DXR (18 mg/kg-cumulative), DXR+LEVO (LEVO, 24 μg/kg-cumulative), and DXR+LEVO (acute) (LEVO, 24 μg/kg-bolus) for 14 days. Protein kinase-B (Akt), endothelial nitric oxide synthase (eNOS), and protein kinase-A and G (PKA/PKG) pathways emerged as contributors to the cardioprotection, converging onto phospholamban (PLN). To verify the contribution of PLN, phospholamban knockout (PLN−/−) mice were assigned to PLN−/−/Control (N/S-0.9%), PLN−/−/DXR (18 mg/kg), and PLN−/−/DXR+LEVO (ac) for 14 days. Furthermore, female breast cancer-bearing (BC) mice were divided into: Control (normal saline 0.9%, N/S 0.9%), DXR (18 mg/kg), LEVO, and DXR+LEVO (LEVO, 24 μg/kg-bolus) for 28 days. Echocardiography was performed in all protocols. To elucidate levosimendan’s cardioprotective mechanism, primary cardiomyocytes were treated with doxorubicin or/and levosimendan and with N omega-nitro-L-arginine methyl ester (L-NAME), DT-2, and H-89 (eNOS, PKG, and PKA inhibitors, respectively); cardiomyocyte-toxicity was assessed. Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN−/− mice. Levosimendan’s cardioprotection was also evident in the BC model. Finally, in vitro PKA inhibition abrogated levosimendan-mediated cardioprotection, indicating that its cardioprotection is cAMP-PKA dependent, while levosimendan preponderated over milrinone and dobutamine, by ameliorating calcium overload.

Conclusion

Single dose levosimendan prevented doxorubicin cardiotoxicity through a cAMP-PKA-PLN pathway, highlighting the role of inotropy in doxorubicin cardiotoxicity.
Prevention of chronic diseases in middle-age women: a cross-sectional study on an Italian large sample
Authors: Colombo Alessandra , Voglino Gianluca , Sessa Aurelio , Bert Fabrizio , Maestroni Anna Maria , Lo Moro Giuseppina , Caielli Rosita , Siliquini Roberta , Della Rosa Maria Cristina
Published: June 2019

Background

The age around 50 years represents a crucial point for women: menopause leads to biological changes and it begins breast and colon-rectal cancer screening. This study aimed at assessing frequencies of cardiovascular risk factors and analyzing participation in screening and vaccination.

Methods

In 2017, a cross-sectional study was performed in Northern Italy. Totally, 12 249 women, aged between 50 and 54 years, were enrolled by General Practitioners (GPs). It was used a 21-item form, with information about: socio-demographic, anamnestic and clinical data, execution of a booster shot of tetanus-diphtheria-acellular pertussis (Tdap) vaccine in the last decade and of PAP-test, mammography and faecal occult blood test in the last 2 years. Descriptive and crosstab χ2 analyses were performed with STATA MP13. The significance level was P ≤ 0.05.

Results

Our findings showed the presence of cardiovascular risk factors, such as obesity (10.95%), hypertension (13.76%), hyperlipidaemia (11.57%), glycaemia ≥ 100 mg dl−1 (16.97%), poor physical activity (73.49%), smoking (18.28%), cardiovascular family history (FH) (51.70%). There were a lower participation in colo-rectal cancer screening (45.09%) compared with breast (85.06%) and cervical (77.16%) cancer screening and an insufficient Tdap booster dose compliance (17.56%). Chi-square analyses showed correlations between cardiovascular FH and body mass index, hypertension, hyperlipidaemia, glycaemia and smoking, and between cancer FH and participation in breast and colo-rectal cancer screening (P < 0.05).

Conclusions

Women with cardiovascular disease FH represent a priority target of educational interventions considering the prevalence of concomitant risk factors. Programmes aimed at increasing screening and vaccination participation should be implemented.
Laurel (Litsea glaucescens Kunth) Regeneration in the Presence of Disturbance Events: A Case Study
Authors: Razo-Zárate Ramón , Retama-Cázares Laura Berenice , Rodríguez-Laguna Rodrigo , Palacios-Romero Abraham , Meza-Rangel Joel , Capulín-Grande Juan , Fragoso-López Pablo Irving , Jesús Cortés-Blobaum Hermann
Published: June 2019

A study was carried out in an Abies religiosa Kunth Schltdl. et Cham forest of the community of San Antonio Tecocomulco Tres Cabezas, Municipality of Singuilucan, Hidalgo, to evaluate the resprouting ability of laurel (Litsea glaucescens Kunth) in response to controlled burning treatments and removal of entire stems. The number of laurel bushes, shoots, and mean plant height were evaluated, and three treatments were applied: controlled surface burn; all sprouts cut from the base; and control treatment. Nine weeks after the treatments were applied, the plants in the stem removal treatment remained alive (100 percent), and the appearance of shoots with a mean height of 4.8 cm increased by 18 percent, whereas in the controlled burning treatment, the number of live plants and shoots decreased by 38.2 and 71.5 percent, respectively, with a mean height of 1.1 cm. In the control, the number of bushes remained at 100 percent, and shoots increased by 9.9 percent with a mean bush height of 7.6 cm. This indicates that although surface forest fires tend to affect laurel, surviving plants tend to emit more vigorous shoots, whereas stem removal in laurel bushes generates more shoots
A mutation inactivating the distal SF1 binding site on the human anti-Müllerian hormone promoter causes persistent Müllerian duct syndrome
Authors: Schteingart Helena F , Picard Jean-Yves , Valeri Clara , Marshall Ian , Treton Dominique , di Clemente Nathalie , Rey Rodolfo A , Josso Nathalie
Published: June 2019

The persistent Müllerian duct syndrome (PMDS) is a 46,XY disorder of sexual development characterized by the persistence of Müllerian duct derivatives, uterus and tubes, in otherwise normally masculinized males. The condition, transmitted as a recessive autosomal trait, is usually due to mutations in either the anti-Müllerian hormone (AMH) gene or its main receptor. Many variants of these genes have been described, all targeting the coding sequences. We report the first case of PMDS due to a regulatory mutation. The AMH promoter contains two binding sites for steroidogenic factor 1 (SF1), one at −102 and the other at −228. Our patient carries a single base deletion at −225, significantly decreasing its capacity for binding SF1, as measured by the electrophoresis mobility shift assay. Furthermore, by linking the AMH promoter to the luciferase gene, we show that the transactivation capacity of the promoter is significantly decreased by the mutation, in contrast to the disruption of the −102 binding site. To explain the difference in impact we hypothesize that SF1 could partially overcome the lack of binding to the −102 binding site by interacting with a GATA4 molecule linked to a nearby response element. We show that disruption of both the −102 SF1 and the −84 GATA response elements significantly decreases the transactivation capacity of the promoter. In conclusion, we suggest that the distance between mutated SF1 sites and potentially rescuing GATA binding motifs might play a role in the development of PMDS.
Intestinal Inflammation Modulates the Epithelial Response to Butyrate in Patients With Inflammatory Bowel Disease
Authors: Ferrer-Picón Elena , Dotti Isabella , Corraliza Ana M , Mayorgas Aida , Esteller Miriam , Perales José Carlos , Ricart Elena , Masamunt Maria C , Carrasco Anna , Tristán Eva , Esteve Maria , Salas Azucena
Published: June 2019

Ferrer-Picón et al. show that in active IBD patients, tumor necrosis factor alpha affects the response of the intestinal epithelium to bacteria-derived butyrate. This observation raises questions about the beneficial effects of butyrate supplementation during active inflammation.
Back to the Future: Democratic Responsiveness and the Estimation of Future Public Opinion
Authors: Merkley Eric , Owen Andrew
Published: June 2019

Research on the responsiveness of policy to public opinion has infrequently confronted the possibility that re-election seeking politicians’ policy choices may reflect their expectations about future public opinion. This article reports observational and experimental findings from a survey of senior Canadian policy-makers. Results from vignette-based experiments that manipulate the characteristics of current and estimates of future opinion show that policy-makers are responsive to the estimated direction of future opinion, but this relationship is conditional on high estimated future salience. Survey results shed additional light on the role that estimates of future opinion play in policy-making. Combined, these experimental and observational results suggest existing empirical work on policy responsiveness is incomplete.
Pediatric clinician perspectives on communicating diagnostic uncertainty
Authors: Meyer Ashley N D , Giardina Traber D , Khanna Arushi , Bhise Viraj , Singhal Geeta R , Street Richard L , Singh Hardeep
Published: June 2019

Objective

Diagnosis often evolves over time, involves uncertainty, and is vulnerable to errors. We examined pediatric clinicians’ perspectives on communicating diagnostic uncertainty to patients’ parents and how this occurs.

Design

We conducted semi-structured interviews, which were audiotaped, transcribed, and analyzed using content analysis. Two researchers independently coded transcripts and then discussed discrepancies to reach consensus.

Setting

A purposive sample of pediatric clinicians at two large academic medical institutions in Texas.

Participants

Twenty pediatric clinicians participated: 18 physicians, 2 nurse practitioners; 7 males, 13 females; 7 inpatient, 11 outpatient, and 2 practicing in mixed settings; with 0–16 years’ experience post-residency.

Intervention(s)

None.

Main outcome measure(s)

Pediatric clinician perspectives on communication of diagnostic uncertainty.

Results

Pediatric clinicians commonly experienced diagnostic uncertainty and most were comfortable seeking help and discussing with colleagues. However, when communicating uncertainty to parents, clinicians used multiple considerations to adjust the degree to which they communicated. Considerations included parent characteristics (education, socioeconomic status, emotional response, and culture) and strength of parent–clinician relationships. Communication content included setting expectations, explaining the diagnostic process, discussing most relevant differentials, and providing reassurance. Responses to certain parent characteristics, however, were variable. For example, some clinicians were more open to discussing diagnostic uncertainty with more educated parents- others were less.

Conclusions

While pediatric clinicians are comfortable discussing diagnostic uncertainty with colleagues, how they communicate uncertainty to parents appears variable. Parent characteristics and parent–clinician relationships affect extent of communication and content discussed. Development and implementation of optimal strategies for managing and communicating diagnostic uncertainty can improve the diagnostic process.
Overlapping Regionalism and Security Cooperation: Power-Based Explanations of Nigeria's Forum-Shopping in the Fight against Boko Haram
Authors: Henneberg Ingo , Plank Friedrich
Published: June 2019

Regional conflicts increasingly require multilevel efforts by regional, subregional, and international actors. When states are confronted with a cooperation problem, often there are several institutions available to address this issue. Drawing on the literature of overlapping regionalism and forum-shopping, we argue that existing explanatory models benefit from adding power-based explanations. By conceptualizing an issue-specific dimension and factors specific to the national environment as additional power-based criteria for forum-shopping, we expand the existing literature. Applying our framework to the response to the Boko Haram uprising, our study examines why Nigeria preferred specific regional entities to others. We find that Nigerian resistance toward external intervention and hegemonic interests inherent in national elites as power-based aspects of forum-shopping explain the counterintuitive creation of the Multinational Joint Task Force (MNJTF) under the umbrella of the rather unknown Lake Chad Bassin Commission (LCBC) instead of reliance on the Economic Community of West African States (ECOWAS) or the African Union (AU) as important security providers in Africa.
Pseudomonas aeruginosa populations in the cystic fibrosis lung lose susceptibility to newly applied β-lactams within 3 days
Authors: Tueffers Leif , Barbosa Camilo , Bobis Ingrid , Schubert Sabine , Höppner Marc , Rühlemann Malte , Franke Andre , Rosenstiel Philip , Friedrichs Anette , Krenz-Weinreich Annegret , Fickenscher Helmut , Bewig Burkhard , Schreiber Stefan , Schulenburg Hinrich
Published: June 2019

Background

Chronic pulmonary infections by Pseudomonas aeruginosa require frequent intravenous antibiotic treatment in cystic fibrosis (CF) patients. Emergence of antimicrobial resistance is common in these patients, which to date has been investigated at long-term intervals only.

Objectives

To investigate under close to real-time conditions the dynamics of the response by P. aeruginosa to a single course of antibiotic therapy and the potentially associated rapid spread of antimicrobial resistance, as well as the impact on the airway microbiome.

Methods

We investigated a cohort of adult CF patients that were treated with a single course of antimicrobial combination therapy. Using daily sampling during treatment, we quantified the expression of resistance by P. aeruginosa (median of six isolates per daily sample, 347 isolates in total), measured bacterial load by P. aeruginosa-specific quantitative PCR and characterized the airway microbiome with a 16S rRNA-based approach. WGS was performed to reconstruct intrapatient strain phylogenies.

Results

In two patients, we found rapid and large increases in resistance to meropenem and ceftazidime. Phylogenetic reconstruction of strain relationships revealed that resistance shifts are probably due to de novo evolution and/or the selection of resistant subpopulations. We observed high interindividual variation in the reduction of bacterial load, microbiome composition and antibiotic resistance.

Conclusions

We show that CF-associated P. aeruginosa populations can quickly respond to antibiotic therapy and that responses are patient specific. Thus, resistance evolution can be a direct consequence of treatment, and drug efficacy can be lost much faster than usually assumed. The consideration of these patient-specific rapid resistance shifts can help to improve treatment of CF-associated infections, for example by deeper sampling of bacteria for diagnostics, repeated monitoring of pathogen susceptibility and switching between drugs.
RAPID COMMUNICATION: Differential skeletal muscle mitochondrial characteristics of weanling racing-bred horses1
Authors: Latham Christine M , Fenger Clara K , White Sarah H
Published: June 2019

Responses of equine skeletal muscle characteristics to growth and training have been shown to differ between breeds. These differential responses may arise in part because muscle fiber type and mitochondrial density differ between breeds, even in untrained racing-bred horses. However, it is not known when these breed-specific differences manifest. To test the hypothesis that weanling Standardbreds (SB) and Thoroughbreds (TB) would have higher mitochondrial measures than Quarter Horses (QH), gluteus medius samples were collected from SB (mean ± SD; 6.2 ± 1.0 mo; n = 10), TB (6.1 ± 0.5 mo; n = 12), and QH (7.4 ± 0.6 mo; n = 10). Citrate synthase (CS) and cytochrome c oxidase (CCO) activities were assessed as markers of mitochondrial density and function, respectively. Mitochondrial oxidative (P) and electron transport system (E) capacities were assessed by high-resolution respirometry (HRR). Data for CCO and HRR are expressed as integrated (per mg protein and per mg tissue wet weight, respectively) and intrinsic (per unit CS). Data were analyzed using PROC MIXED in SAS v 9.4 with breed as a fixed effect. Mitochondrial density (CS) was higher for SB and TB than QH (P ≤ 0.0007). Mitochondrial function (integrated and intrinsic CCO) was higher in TB and QH than SB (P ≤ 0.01). Integrated CCO was also higher in TB than QH (P < 0.0001). However, SB had higher integrated maximum P (PCI+II) and E (ECI+II) than QH (P ≤ 0.02) and greater integrated and intrinsic complex II-supported E (ECII) than both QH and TB (P ≤ 0.02), whereas TB exhibited higher integrated P with complex I substrates (PCI) than SB and QH (P ≤ 0.003) and higher integrated PCI+II and ECI+II than QH (P ≤ 0.02). In agreement, TB and QH had higher contribution of complex I (CI) to max E than SB (P ≤ 0.001), whereas SB had higher contribution of CII than QH and TB (P ≤ 0.002). Despite having higher mitochondrial density than QH and TB, SB showed lower CCO activity and differences in contribution of complexes to oxidative and electron transport system capacities. Breed differences in mitochondrial parameters are present early in life and should be considered when developing feeding, training, medication, and management practices.
Entomology in the 21st Century: Tackling Insect Invasions, Promoting Advancements in Technology, and Using Effective Science Communication—2018 Student Debates
Authors: Parker Casey , Bernaola Lina , Lee Benjamin W , Elmquist Dane , Cohen Abigail , Marshall Adrian , Hepler James , Pekarcik Adrian , Justus Emily , King Kendall , Lee Tae-Young , Esquivel Carlos , Hauri Kayleigh , McCullough Christopher , Hadden Whitney , Ragozzino Max , Roth Morgan , Villegas James , Kraus Emily , Becker Michael , Mulcahy Megan , Chen Rui , Mittapelly Priyanka , Clem C Scott , Skinner Rachel , Josek Tanya , Pearlstein Daniel , Tetlie Jonathan , Tran Anh , Auletta Anthony , Benkert Edwin , Tussey Dylan
Published: June 2019

The 2018 student debates of the Entomological Society of America were held at the Joint Annual Meeting for the Entomological Societies of America, Canada, and British Columbia in Vancouver, BC. Three unbiased introductory speakers and six debate teams discussed and debated topics under the theme ‘Entomology in the 21st Century: Tackling Insect Invasions, Promoting Advancements in Technology, and Using Effective Science Communication’. This year’s debate topics included: 1) What is the most harmful invasive insect species in the world? 2) How can scientists diffuse the stigma or scare factor surrounding issues that become controversial such as genetically modified organisms, agricultural biotechnological developments, or pesticide chemicals? 3) What new/emerging technologies have the potential to revolutionize entomology (other than Clustered Regularly Interspaced Short Palindromic Repeats)? Introductory speakers and debate teams spent approximately 9 mo preparing their statements and arguments and had the opportunity to share this at the Joint Annual Meeting with an engaged audience.
Hemophagocytic lymphohistiocytosis associated with Epstein–Barr virus infection: case report and literature review
Authors: Bahabri Saeed , Al Rikabi Ammar C , Alshammari Amjad O , Alturkestany Sara I
Published: June 2019

Hemophagocytic lymphohistiocytosis (HLH) is rare and life threatening syndrome. There are only a few reported cases of HLH with GI symptoms. We describe the case of an 18 months old boy who presented with a history of fever for 40 days, abdominal distention and hepatosplenomegaly. Abdominal x-ray showed a pneumoperitoneum. Urgent laparotomy was done which revealed an isolated cecal perforation. The histopathological findings in the subsequent resected bowel was HLH with evidence of positive EBV Barr infection.
Mapping migration studies: An empirical analysis of the coming of age of a research field
Authors: Pisarevskaya Asya , Levy Nathan , Scholten Peter , Jansen Joost
Published: June 2019

Migration studies have developed rapidly as a research field over the past decades. This article provides an empirical analysis not only on the development in volume and the internationalization of the field, but also on the development in terms of topical focus within migration studies over the past three decades. To capture volume, internationalisation, and topic focus, our analysis involves a computer-based topic modelling of the landscape of migration studies. Rather than a linear growth path towards an increasingly diversified and fragmented field, as suggested in the literature, this reveals a more complex path of coming of age of migration studies. Although there seems to be even an accelerated growth for migration studies in terms of volume, its internationalisation proceeds only slowly. Furthermore, our analysis shows that rather than a growth of diversification of topics within migration topic, we see a shift between various topics within the field. Finally, our study shows that there is no consistent trend to more fragmentation in the field; in contrast, it reveals a recent recovery of connectedness between the topics in the field, suggesting an institutionalisation or even theoretical and conceptual coming of age of migration studies.
High-velocity H i jet-like feature towards the SNR candidate G351.7–1.2
Authors: Veena V S , Vig Sarita , Roy Nirupam , Roy Jayanta
Published: June 2019

We present the H i 21 cm spectral line and continuum observations of the Galactic supernova remnant (SNR) candidate G351.7–1.2 using the upgraded Giant Metrewave Radio Telescope. Strong absorption features are observed towards the H ii regions in the star-forming complex associated with G351.7–1.2. Along with H i emission towards the outer periphery of the SNR shell, we distinguish a high-velocity jet-like feature in the velocity range +40 to +52 km s−1 in H i. This unusual and highly collimated feature, with a projected length of ∼7 pc and an opening angle of 14.4°, is located towards the interior of the radio shell. This is the first report of a well collimated H i jet-like emission. The peculiar location and the detection of a γ-ray source towards the central peak of this H i jet suggests its plausible association with the SNR candidate.
An assessment ofRaphitomaand allied genera (Neogastropoda: Raphitomidae)
Authors: Fassio Giulia , Russini Valeria , Pusateri Francesco , Giannuzzi-Savelli Riccardo , Høisæter Tore , Puillandre Nicolas , Modica Maria Vittoria , Oliverio Marco
Published: June 2019

The systematics of several Eastern Atlantic conoidean species, traditionally ascribed to the genus RaphitomaBellardi, 1847, are revised on the basis of DNA sequence data from three gene regions (cytochrome c oxidase subunit I, 16S rRNA and 12S rRNA). We assign genus ranking to three major lineages (Raphitoma, CyrilliaKobelt, 1905 and LeufroyiaMonterosato, 1884) and suggest that two West African species belong in the subgenus Daphnella (Paradaphne) Laseron, 1954. A new classification, based on molecular systematics and critical study of morphology, is provided for all Eastern Atlantic and Mediterranean species that are currently ascribed to Raphitoma s.l. The genus ClathromangeliaMonterosato, 1884 is confirmed as belonging to Raphitomidae. Phylogenetic relationships and genetic distances suggest that Raphitoma maculosaHøisæter, 2016 and R. obesaHøisæter, 2016 may be divergent morphotypes of R. bicolor (Risso, 1826) and Cyrillia aequalis (Jeffreys, 1867), respectively.
On the systematics and ecology of two new species ofProvanna(Gastropoda: Provannidae) from deep-sea hydrothermal vents in the Caribbean Sea and Southern Ocean
Authors: Linse Katrin , Nye Verity , Copley Jonathan T , Chen Chong
Published: June 2019

The recent discovery and exploration of deep-sea hydrothermal vent fields in the Mid-Cayman Spreading Centre, Caribbean Sea (Beebe Vent Field, 4956–4972 m depth) and the East Scotia Ridge, Southern Ocean (E2 and E9 vent fields, 2394–2641 m depth) have yielded extensive collections of two new provannid species, Provanna beebei n. sp. and P. cooki n. sp. Morphological and molecular taxonomy (530 bp of the mitochondrial cytochrome c oxidase subunit I gene) confirm P. beebei n. sp. and P. cooki n. sp. as distinct species; these species are formally described, and details are provided of their distribution, habitat and species associations. Bayesian and maximum likelihood analyses support the placement of P. beebei n. sp. and P. cooki n. sp within the genus Provanna and show that these two new deep-sea species form a well-supported clade with the abyssal West Pacific P. cingulata. Provanna beebei n. sp. and P. cooki n. sp. represent the first records of Provanna from hydrothermal vents in the Caribbean Sea and Southern Ocean, respectively, and extend the known geographic range of the genus. For the first time, intraspecific phenotypic variation in size and sculpture has been reported for Provanna. At the East Scotia Ridge, shell-size frequency distributions and median shell size of P. cooki n. sp. varied significantly between the E2 and E9 vent fields, as well as between diffuse flow and high-temperature venting habitats within each field. The variation in shell sculpture in relation to habitat was also observed in P. cooki n. sp.
Nucleotide excision repair of abasic DNA lesions
Authors: Kitsera Nataliya , Rodriguez-Alvarez Marta , Emmert Steffen , Carell Thomas , Khobta Andriy
Published: June 2019

Apurinic/apyrimidinic (AP) sites are a class of highly mutagenic and toxic DNA lesions arising in the genome from a number of exogenous and endogenous sources. Repair of AP lesions takes place predominantly by the base excision pathway (BER). However, among chemically heterogeneous AP lesions formed in DNA, some are resistant to the endonuclease APE1 and thus refractory to BER. Here, we employed two types of reporter constructs accommodating synthetic APE1-resistant AP lesions to investigate the auxiliary repair mechanisms in human cells. By combined analyses of recovery of the transcription rate and suppression of transcriptional mutagenesis at specifically positioned AP lesions, we demonstrate that nucleotide excision repair pathway (NER) efficiently removes BER-resistant AP lesions and significantly enhances the repair of APE1-sensitive ones. Our results further indicate that core NER components XPA and XPF are equally required and that both global genome (GG-NER) and transcription coupled (TC-NER) subpathways contribute to the repair.
Valvular heart disease and calcification in CKD: more common than appreciated
Authors: Ureña-Torres Pablo , D’Marco Luis , Raggi Paolo , García–Moll Xavier , Brandenburg Vincent , Mazzaferro Sandro , Lieber Ari , Guirado Lluis , Bover Jordi
Published: June 2019

Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10–20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.
Potential Moderating Effects of Sex/Gender on the Acute Relative Reinforcing and Subjective Effects of Reduced Nicotine Content Cigarettes in Vulnerable Populations
Authors: Streck Joanna M , Davis Danielle R , Pang Raina D , Sigmon Stacey C , Bunn Janice Y , Bergeria Cecilia L , Tidey Jennifer W , Heil Sarah H , Gaalema Diann E , Hughes John R , Stitzer Maxine L , Reed Ellaina , Higgins Stephen T
Published: June 2019

Introduction

Reports in relatively healthy smokers suggest men are more sensitive than women to the subjective effects of reduced nicotine content cigarettes (RNCCs). We know of no reports examining sex differences in the relative reinforcing effects of RNCCs, an important outcome in assessing smoking’s addiction potential. The aim of the present study is to address this gap by examining sex/gender differences on reinforcing effects while examining whether sex differences in subjective effects are discernible in vulnerable populations.

Methods

Secondary analysis of a within-subject, double-blinded experiment examining acute effects of cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among 169 adult smokers with psychiatric conditions or socioeconomic disadvantage. Effects of dose, sex, and their interaction were examined on reinforcing (concurrent-choice and Cigarette Purchase Task [CPT] testing), and subjective effects (Cigarette Evaluation Questionnaire [CEQ] and craving/withdrawal ratings).

Results

Reducing nicotine content decreased the relative reinforcing effects of smoking in concurrent-choice and CPT testing (p’s < .05) with no significant effects of sex nor dose × sex/gender interactions. Reducing nicotine content decreased CEQ ratings with only a single significant effect of sex (higher Psychological Reward scores among women than men, p = .02) and no significant dose × sex/gender interactions. Results on craving/withdrawal paralleled those on the CEQ.

Conclusions

Reducing nicotine content decreases the addiction potential of smoking independent of sex in populations highly vulnerable to smoking and addiction, with no indication that women are less sensitive to subjective effects of RNCCs or would benefit less from a policy reducing the nicotine content of cigarettes.

Implications

A policy reducing the nicotine content of cigarettes has the potential to reduce the addiction potential of smoking across men and women who are especially vulnerable to smoking, addiction, and tobacco-related adverse health impacts.
Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients
Authors: Liu Yanying , Xue Miao , Wang Zhenfan , Zeng Qiaozhu , Ren Limin , Zhang Yanyan , Zhang Shanshan , Wang Yi , Shen Danhua , Xia Changsheng , Yu Guangyan , Li Zhan-Guo
Published: June 2019

Objectives

IgG4-related disease (IgG4-RD) has recently been recognized as a fibro-inflammatory condition featuring tumefactive lesions in multiple organs, and the salivary gland is one of the most commonly involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with salivary gland lesions (IgG4-RD SG+) and salivary-gland-free IgG4-RD (IgG4-RD SG−) in a large cohort.

Methods

We carried out a retrospective review of the medical records of 428 cases of IgG4-RD diagnosed at Peking University People’s Hospital between March 2006 and May 2018.

Results

Among 428 patients, 249 had salivary glands that were affected. IgG4-RD SG+ patients showed younger age at disease onset and diagnosis, and a longer interval between symptom onset and diagnosis. The IgG4-RD SG+ group involved more female patients, and allergic diseases were more common in this group. In terms of organ involvement, the IgG4-RD SG+ group were more frequently presented with lacrimal gland involvement, while lymph node, retroperitoneal fibrosis, pancreas, biliary system, kidney and aorta were more prominent in the IgG4-RD SG− group. In addition, the serum IgG4 level, IgG4/IgG ratio and IgE level were significantly higher in IgG4-RD SG+ patients. Patients with eosinophilia were more common in the IgG4-RD SG+ group, while elevated ESR, CRP and positive ANA were more common in the IgG4-RD SG− group.

Conclusion

We have revealed demographic, clinical and laboratory differences between IgG4-RD SG+ and SG− patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.