bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital-based Surveillance Provides Insights Into the Etiology of Pediatric Bacterial Meningitis in Yaoundé, Cameroon, in the Post-Vaccine Era
Authors: Boula Angeline , Senghore Madikay , Ngoh Rose , Tassadjo Flaubert , Fonkoua Marie-Christine , Nzouankeu Ariane , Njiki Mina Kenkela , Musi Jeanne , Bebey Sandrine , Ngo Baleba Madeline , Nkembe Angeline , Médjina Sidonie , Ndow Peter S , Worwui Archibald , Kobela Marie , Nimpa Marceline , Mwenda Jason M , N’diaye Aboubacar , Kwambana-Adams Brenda A , Antonio Martin
Published: August 2019

Background

Meningitis is endemic to regions of Cameroon outside the meningitis belt including the capital city, Yaoundé. Through surveillance, we studied the etiology and molecular epidemiology of pediatric bacterial meningitis in Yaoundé from 2010 to 2016.

Methods

Lumbar puncture was performed on 5958 suspected meningitis cases; 765 specimens were further tested by culture, latex agglutination, and/or polymerase chain reaction (PCR). Serotyping/grouping, antimicrobial susceptibility testing, and/or whole genome sequencing were performed where applicable.

Results

The leading pathogens detected among the 126 confirmed cases were Streptococcus pneumoniae (93 [73.8%]), Haemophilus influenzae (18 [14.3%]), and Neisseria meningitidis (15 [11.9%]). We identified more vaccine serotypes (19 [61%]) than nonvaccine serotypes (12 [39%]); however, in the latter years non–pneumococcal conjugate vaccine serotypes were more common. Whole genome data on 29 S. pneumoniae isolates identified related strains (<30 single-nucleotide polymorphism difference). All but 1 of the genomes harbored a resistance genotype to at least 1 antibiotic, and vaccine serotypes harbored more resistance genes than nonvaccine serotypes (P < .05). Of 9 cases of H. influenzae, 8 were type b (Hib) and 1 was type f. However, the cases of Hib were either in unvaccinated individuals or children who had not yet received all 3 doses. We were unable to serogroup the N. meningitidis cases by PCR.

Conclusions

Streptococcus pneumoniae remains a leading cause of pediatric bacterial meningitis, and nonvaccine serotypes may play a bigger role in disease etiology in the postvaccine era. There is evidence of Hib disease among children in Cameroon, which warrants further investigation.
Predicted Effectiveness of Daily and Nondaily Preexposure Prophylaxis for Men Who Have Sex With Men Based on Sex and Pill-taking Patterns From the Human Immuno Virus Prevention Trials Network 067/ADAPT Study
Authors: Dimitrov Dobromir , Moore James R , Wood Daniel , Mitchell Kate M , Li Maoji , Hughes James P , Donnell Deborah J , Mannheimer Sharon , Holtz Timothy H , Grant Robert M , Boily Marie-Claude
Published: August 2019

Background

The HIV Prevention Trials Network (HPTN) 067/Alternative Dosing to Augment PrEP Pill Taking (ADAPT) Study evaluated the feasibility of daily and nondaily human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens.

Methods

An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the preexposure prophylaxis initiative (iPrEx) trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use.

Results

We estimated that PrEP was highly protective (85%–96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%–88% efficacy) than in Harlem (62%–81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85%, and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8–9 percentage points in Harlem and by 5–9 percentage points in Bangkok across regimens.

Conclusions

Our analysis suggests that PrEP was more effective among MSM in Thailand than in the United States as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, nondaily PrEP was less effective than daily PrEP, especially in the United States where the sex act coverage associated with daily use was substantially higher.
Lessons From Influenza Pandemics of the Last 100 Years
Authors: Monto Arnold S , Fukuda Keiji
Published: August 2019

Seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. Recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. Review of features of the 1918 influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. Key among such issues are likely risk groups and which interventions to employ. Past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. While a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. Improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza.
Information Propagation and Public Opinion Evolution Model Based on Artificial Neural Network in Online Social Network
Authors: Liu Xiaoyang , He Daobing
Published: August 2019

This paper proposes a new information dissemination and opinion evolution IPNN (Information Propagation Neural Network) model based on artificial neural network. The feedforward network, feedback network and dynamic evolution algorithms are designed and implemented. Firstly, according to the ‘six degrees separation’ theory of information dissemination, a seven-layer neural network underlying framework with input layer, propagation layer and termination layer is constructed; secondly, the information sharing and information interaction evolution process between nodes are described by using the event information forward propagation algorithm, opinion difference reverse propagation algorithm; finally, the external factors of online social network information dissemination is considered, the impact of external behavior patterns is measured by media public opinion guidance and network structure dynamic update operations. Simulation results show that the proposed new mathematical model reveals the relationship between the state of micro-network nodes and the evolution of macro-network public opinion. It accurately depicts the internal information interaction mechanism and diffusion mechanism in online social network. Furthermore, it reveals the process of network public opinion formation and the nature of public opinion explosion in online social network. It provides a new scientific method and research approach for the study of social network public opinion evolution.
The Transformation of Communicative Power Into Political Power
Authors: Reunanen Esa , Kunelius Risto
Published: August 2019

This article examines Jürgen Habermas’ concept of communicative power and describes how it transforms into political power in actual decision-making. For this purpose, the article develops the use of Habermas’ typology of validity claims in communicative action as a framework for analysis. This means analyzing how public performances invoking these validity claims affect actors’ authority, which is then capitalized in policymaking. The article thus integrates Habermas’ procedural view on deliberative politics with the more culturally oriented view on political performances. It also contributes to the discussion about the “mediatization of politics” by introducing a communicative perspective to complement the more common institutional and systems perspectives. This theoretical and analytical approach is illustrated by examples drawn from evidence in 16 semi-structured interviews conducted with participants in the policy networks involved in the 2015 Finnish labor market negotiations.
Fropofol prevents disease progression in mice with hypertrophic cardiomyopathy
Authors: Huang Yiyuan , Lu Haisong , Ren Xianfeng , Li Fazhao , Bu Weiming , Liu Wenjie , Dailey William P , Saeki Harumi , Gabrielson Kathleen , Abraham Roselle , Eckenhoff Roderic , Gao Wei Dong
Published: August 2019

Aims 

Increased myofilament contractility is recognized as a crucial factor in the pathogenesis of hypertrophic cardiomyopathy (HCM). Direct myofilament desensitization might be beneficial in preventing HCM disease progression. Here, we tested whether the small molecule fropofol prevents HCM phenotype expression and disease progression by directly depressing myofilament force development.

Methods and results 

Force, intracellular Ca2+, and steady-state activation were determined in isolated trabecular muscles from wild-type (WT) and transgenic HCM mice with heterozygous human α-myosin heavy chain R403Q mutation (αMHC 403/+). αMHC 403/+ HCM mice were treated continuously with fropofol by intraperitoneal infusion for 12 weeks. Heart tissue was analysed with histology and real-time PCR of prohypertrophic and profibrotic genes. Fropofol decreased force in a concentration-dependent manner without significantly altering [Ca2+]i in isolated muscles from both WT and αMHC 403/+ HCM mouse hearts. Fropofol also depressed maximal Ca2+-activated force and increased the [Ca2+]i required for 50% activation during steady-state activation. In whole-animal studies, chronic intra-abdominal administration of fropofol prevented hypertrophy development and diastolic dysfunction. Chronic fropofol treatment also led to attenuation of prohypertrophic and profibrotic gene expression, reductions in cell size, and decreases in tissue fibrosis.

Conclusions 

Direct inhibition of myofilament contraction by fropofol prevents HCM disease phenotypic expression and progression, suggesting that increased myofilament contractile force is the primary trigger for hypertrophy development and HCM disease progression.
Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: dental anomalies in 8-year olds
Authors: Rizell Sara , Bellardie Haydn , Karsten Agneta , Sæle Paul , Mooney Jeanette , Heliövaara Arja , Küseler Annelise , Brinck Eli , Skaare Pål , Mølsted Kirsten , Chalien Midia Najar , Marcusson Agneta , Eyres Phil , Shaw W , Semb Gunvor
Published: August 2019

Background

Children born with unilateral cleft lip and palate (UCLP) are reported to display several dental anomalies including agenesis, supernumeraries, as well as variations in dental size, shape, and path of eruption. The extensive sample of individuals with UCLP included in the Scandcleft randomized control trials offers the opportunity to study more rare conditions, which is seldom possible with limited samples.

Objectives

The aim was to study dental anomalies at 8 years of age in children born with UCLP included in the Scandcleft randomized control trials.

Methods

Panoramic and intraoral radiographs from 425 individuals (279 males and 146 females) with a mean age of 8.1 years were assessed by four orthodontists regarding dental anomalies.

Results

Agenesis was found in 52.5 per cent and supernumerary teeth in 16.9 per cent of the participants. The cleft lateral was missing in 43.8 per cent and was found peg shaped in 44.7 per cent. The distribution of ectopic eruption was 14.6 per cent, mainly affecting maxillary first molars, while transposition was found in 3.4 per cent of the individuals. In addition, infraocclusion of one or several primary molars was registered in 7.2 per cent of the participants.

Conclusion

We conclude that 8-year-old children born with UCLP display multiple dental anomalies. The Scandcleft sample allowed rarely studied conditions such as infraocclusion of primary molars and transposition to be studied in children born with UCLP.

Trial registration

ISRCTN29932826.
Night sleep duration and sleep initiation time with hypertension in Chinese rural population: the Henan Rural Cohort
Authors: Zhang Haiqing , Zhao Xinyu , Li Yuqian , Mao Zhenxing , Huo Wenqian , Jiang Jingjing , Wang Yan , Liu Xiaotian , Abdulai Tanko , Tian Zhongyan , Tu Runqi , Qian Xinling , Liu Xue , Li Ruiying , Zhang Xia , Bie Ronghai , Wang Chongjian
Published: August 2019

Background

The study was conducted to evaluate the independent dose-response of the night sleep duration and sleep initiation time on hypertension, and to explore their combined effect with hypertension.

Methods

Participants from the Henan Rural Cohort were enrolled in this study. Information on sleep was collected using the Pittsburgh Sleep Quality Index. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or self-reported hypertension and current use of anti-hypertensive medicines. Logistic regression and restricted cubic spline were conducted to evaluate the association of night sleep duration and sleep initiation time with hypertension.

Results

Of the 37 317 included participants, 12 333 suffered from hypertension. 14 474 (38.79%) were men and 22 843 (61.21%) were women, the mean age were 57.18 ± 12.10 and 55.24 ± 11.98 in men and women. Compared to reference (7–h), fully adjusted odd ratios (ORs) and 95% confidence interval (CI) of hypertension were 0.91 (0.66–1.25) in <5 h group and 1.74 (1.41–2.16) in ≥10 h among men, respectively. Fully adjusted ORs (95% CIs) for hypertension compared with reference (21:00–22:00) were 1.05 (95% CI 0.78–1.41) in the <20:00 group, 1.52 (1.25–1.85) in ≥24:00 in men. The combined effect of sleep duration and sleep initiation time on hypertension were statistically significant in the category of (≥8 h)/night and ≥24:00 (OR 1.87, 95% CI 1.07–3.25) compared to reference in fully adjusted model among men.

Conclusions

Long night sleep duration and late sleep initiation time were associated with the higher odds of hypertension, and the sleep duration and sleep initiation time might cumulatively increase the prevalence of hypertension in men.

Clinical trial registration

The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). http://www.chictr.org.cn/showproj.aspx? proj=11375.
Turkey and Cyprus: A Poliheuristic Analysis of Decisions during the Crises of 1964, 1967, and 1974
Authors: Özdamar Özgür , Ercİyas Okhan
Published: August 2019

The Cyprus problem is one of the most protracted and complex conflicts in the world. This article uses poliheuristic (PH) theory to analyze Turkey's decision-making during the Cyprus crises of 1964, 1967, and 1974. We utilize the PH model (Mintz 1993, 2004) and its method to systematically examine the decision-making process and outcomes during the three crises. We present primary evidence from governmental archives and secondary from media sources. The two hypotheses derived from the PH literature are supported by evidence. Results confirm Turkish decision-makers employed two-stage decision-making during each crisis. In the first stage, Turkish leaders followed the noncompensatory rule and eliminated options that could incur losses. In the second stage, their calculations were more in line with expected utility maximization. Implications of the case study in terms of PH model, foreign policy analysis, and international relations theory are discussed in the conclusion.
Volvulus of the ileal pouch–anal anastomosis: a meta-narrative systematic review of frequency, diagnosis, and treatment outcomes
Authors: Jawoosh Muhammad , Haffar Samir , Deepak Parakkal , Meyers Alyssa , Lightner Amy L , Larson David W , Raffals Laura H , Murad M Hassan , Buttar Navtej , Bazerbachi Fateh
Published: August 2019

Background

Proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical procedure of choice for medically refractory ulcerative colitis and familial adenomatous polyposis. While rare, a pouch volvulus can occur. We aimed to determine the frequency, presentation, and management approach of pouch volvulus in patients with IPAA.

Methods

A systematic search of published literature was performed by a medical reference librarian on 10 August 2018 and two independent reviewers identified relevant publications, extracted data, and assessed the methodological quality based on a validated tool. A retrospective review of the Mayo Clinic electronic medical records identified one case of pouch volvulus between January 2008 and August 2018.

Results

The frequency of pouch volvulus from one large published study reporting long-term outcomes of IPAA was 0.18% (3/1,700). A total of 22 patients (18 ulcerative colitis) were included (median age 32 years, 73% females). Median time to volvulus after IPAA was 36 months while median interval to volvulus diagnosis from symptom onset was 24 hours. Abdominal pain was the most commonly reported symptom (76%). The diagnosis was made primarily by abdominal computed tomography (13/17 patients, 76%). Endoscopic treatment was successful in 1 of 11 patients (9%). Surgery was performed in 20 patients and pouch-pexy and pouch excision were the most frequent surgical operations. A redo IPAA was performed in five patients (25%).

Conclusion

Pouch volvulus is a rare but serious complication of IPAA and should be suspected even in the absence of obstruction symptoms. Endoscopic treatment often fails and surgery is effective when performed early.
A new compositionally based thermal conductivity model for plutonic rocks
Authors: Jennings S , Hasterok D , Payne J
Published: August 2019

Thermal conductivity is a physical parameter crucial to accurately estimating temperature and modelling thermally related processes within the lithosphere. Direct measurements are often impractical due to the high cost of comprehensive sampling or inaccessibility and thereby require indirect estimates. In this study, we report 340 new thermal conductivity measurements on igneous rocks spanning a wide range of compositions using an optical thermal conductivity scanning device. These are supplemented by a further 122 measurements from the literature. Using major element geochemistry and modal mineralogy, we produce broadly applicable empirical relationships between composition and thermal conductivity. Predictive models for thermal conductivity are developed using (in order of decreasing accuracy) major oxide composition, CIPW normative mineralogy and estimated modal mineralogy.

Four common mixing relationships (arithmetic, geometric, square-root and harmonic) are tested and, while results are similar, the geometric model consistently produces the best fit. For our preferred model, $k_{\text{eff}} = \exp ( 1.72 \, C_{\text{SiO}_2} + 1.018 \, C_{\text{MgO}} - 3.652 \, C_{\text{Na}_2\text{O}} - 1.791 \, C_{\text{K}_2\text{O}})$, we find that SiO2 is the primary control on thermal conductivity with an RMS of 0.28 W m−1 K−1or ∼10 per cent. Estimates from normative mineralogy work to a similar degree but require a greater number of parameters, while forward and inverse modelling using estimated modal mineralogy produces less than satisfactory results owing to a number of complications. Using our model, we relate thermal conductivity to both P-wave velocity and density, revealing systematic trends across the compositional range. We determine that thermal conductivity can be calculated from P-wave velocity in the range 6–8 km s−1 to within 0.31 W m−1 K−1 using $k({V_p}) = 0.5822 \, V_p^2 - 8.263 \, V_p + 31.62$. This empirical model can be used to estimate thermal conductivity within the crust where direct sampling is impractical or simply not possible (e.g. at great depths). Our model represents an improved method for estimating lithospheric conductivity than present formulas which exist only for a limited range of compositions or are limited by infrequently measured parameters.
Predicting fluid pressure in sedimentary basins from seismic tomography
Authors: O’Reilly Brian M , Prada Manel , Lavoué François , Lebedev Sergei
Published: August 2019

Gravitational compaction of thick (2–10 km) sediment accumulations in sedimentary basins is controlled by the interplay of mechanical and chemical processes that operate over many orders of magnitude in spatial scale. The compaction of sediments into rock typically involves a density increase of ≈500 to 1000 kg m−3, occurring over a depth-scale of several kilometres. The volume decrease in the compacting sediments releases vast volumes of water, which plays an important part in the global hydrological cycle and also in tectonic and geochemical processes; including the formation of hydrocarbon and mineral deposits. This study utilizes recently developed tomographic seismic images from the Porcupine Basin, which lies in the deep-water North Atlantic Ocean. A generic method for predicting fluid pressure variations that are driven by gravitational compaction is developed over the scale of the entire sedimentary basin. The methodology is grounded upon both observational evidence and empirically based theories, relying on geophysical measurements and relationships between sediment porosities and densities. The method is based upon physical concepts that are widely used in the petroleum industry and applied extensively in models of overpressure development in sedimentary basins. Geological and geophysical data from exploration wells are used to test the predictions of the method at two locations within the basin and are found to be in good agreement with the theory.
Strengthening prevention in communities through systems change: lessons from the evaluation of Healthy Families NZ
Authors: Matheson Anna , Walton Mat , Gray Rebecca , Wehipeihana Nan , Wistow Jonathon
Published: August 2019

This article presents the findings from the first 3 years of the evaluation of Healthy Families NZ, a systems-change intervention to prevent chronic diseases in 10 communities. The initiative, which builds on existing prevention activities, aims to strengthen the health prevention system through evidence-driven action to enable people to make good food choices, be physically active, smoke-free and free from alcohol-related harm. Key investment areas are a dedicated systems thinking and acting health promotion workforce, and activating leaders who can influence transformational change. The evaluation to date has found the initiative is being implemented with integrity. Evidence indicates a shift towards greater action on prevention, and the prevention system being strengthened. Māori ownership has been enabled, and prioritizing equity has led teams to utilize methods that amplify diverse local perspectives. There is progress on developing a flexible workforce through adaptive learning, flexible resources, professional development and a responsive National team. There is also progress in activating local leadership and empowering local teams. The initiative design has explicitly taken into account the context of complexity within which it is being implemented. It has evolved to focus on action that can accelerate sharing information and practices within communities, and between policy and decision-makers. Healthy Families NZ and its evaluation have been refunded to 2022. This provides an important opportunity to gather further insight into effective ways to strengthen the community agency and trust needed to promote and deliver evidence-based action on prevention.
Genetic variants in TRPM7 associated with unexplained stillbirth modify ion channel function
Authors: Cartwright James H , Aziz Qadeer , Harmer Stephen C , Thayyil Sudhin , Tinker Andrew , Munroe Patricia B
Published: August 2019

Stillbirth is the loss of a fetus after 22 weeks of gestation, of which almost half go completely unexplained despite post-mortem. We recently sequenced 35 arrhythmia-associated genes from 70 unexplained stillbirth cases. Our hypothesis was that deleterious mutations in channelopathy genes may have a functional effect in utero that may be pro-arrhythmic in the developing fetus. We observed four heterozygous, nonsynonymous variants in transient receptor potential melastatin 7 (TRPM7), a ubiquitously expressed ion channel known to regulate cardiac development and repolarization in mice.

We used site-directed mutagenesis and single-cell patch-clamp to analyze the functional effect of the four stillbirth mutants on TRPM7 ion channel function in heterologous cells. We also used cardiomyocytes derived from human pluripotent stem cells to model the contribution of TRPM7 to action potential morphology.

Our results show that two TRPM7 variants, p.G179V and p.T860M, lead to a marked reduction in ion channel conductance. This observation was underpinned by a lack of measurable TRPM7 protein expression, which in the case of p.T860M was due to rapid proteasomal degradation. We also report that human hiPSC-derived cardiomyocytes possess measurable TRPM7 currents; however, siRNA knockdown did not directly affect action potential morphology.

TRPM7 variants found in the unexplained stillbirth population adversely affect ion channel function and this may precipitate fatal arrhythmia in utero.
RAB8, RAB10 and RILPL1 contribute to both LRRK2 kinase–mediated centrosomal cohesion and ciliogenesis deficits
Authors: Lara Ordónez Antonio Jesús , Fernández Belén , Fdez Elena , Romo-Lozano María , Madero-Pérez Jesús , Lobbestael Evy , Baekelandt Veerle , Aiastui Ana , López de Munaín Adolfo , Melrose Heather L , Civiero Laura , Hilfiker Sabine
Published: August 2019

Mutations in the LRRK2 kinase are the most common cause of familial Parkinson’s disease, and variants increase risk for the sporadic form of the disease. LRRK2 phosphorylates multiple RAB GTPases including RAB8A and RAB10. Phosphorylated RAB10 is recruited to centrosome-localized RILPL1, which may interfere with ciliogenesis in a disease-relevant context. Our previous studies indicate that the centrosomal accumulation of phosphorylated RAB8A causes centrosomal cohesion deficits in dividing cells, including in peripheral patient-derived cells. Here, we show that both RAB8 and RAB10 contribute to the centrosomal cohesion deficits. Pathogenic LRRK2 causes the centrosomal accumulation not only of phosho-RAB8 but also of phospho-RAB10, and the effects on centrosomal cohesion are dependent on RAB8, RAB10 and RILPL1. Conversely, the pathogenic LRRK2-mediated ciliogenesis defects correlate with the centrosomal accumulation of both phospho-RAB8 and phospho-RAB10. LRRK2-mediated centrosomal cohesion and ciliogenesis alterations are observed in patient-derived peripheral cells, as well as in primary astrocytes from mutant LRRK2 mice, and are reverted upon LRRK2 kinase inhibition. These data suggest that the LRRK2-mediated centrosomal cohesion and ciliogenesis defects are distinct cellular readouts of the same underlying phospho-RAB8/RAB10/RILPL1 nexus and highlight the possibility that either centrosomal cohesion and/or ciliogenesis alterations may serve as cellular biomarkers for LRRK2-related PD.
Differential north–south response of juvenile Chinook salmon (Oncorhynchus tshawytscha) marine growth to ecosystem change in the eastern Bering Sea, 1974–2010
Authors: Yasumiishi Ellen M , Farley Edward V , Maselko Jacek , Aydin Kerim Y , Kearney Kelly A , Hermann Albert J , Ruggerone Gregory T , Howard Katherine G , Strasburger Wesley W
Published: August 2019

Chinook salmon (Oncorhynchus tshawytscha, Salmonidae) returns to western Alaska were historically high and variable but recently reached record lows. Understanding the differential influence of climatic and oceanic conditions on the growth of juvenile Chinook salmon in the north and south eastern Bering Sea is key to understanding mechanisms and factors affecting the production dynamics of Chinook salmon from western Alaska and the Arctic. Summer growth was lower and more variable among years for Chinook salmon in the south than the north eastern Bering Sea. Summer growth decreased with a rise in sea temperatures in the north and south and increased with more sea ice coverage and a later time of ice retreat in the south but not in the north. Capelin (Mallotus villosus), an important prey for juvenile Chinook salmon in the north and during cold years may link increased growth to cooler sea temperatures. Reduced and more variable summer growth of juvenile Chinook salmon from the eastern Bering Sea with warming may have implications on overwintering survival.
Controllability criteria of fractional differential dynamical systems with non-instantaneous impulses
Authors: Vadivoo B Sundara , Raja R , Cao Jinde , Rajchakit G , Seadawy Aly R
Published: August 2019

This manuscript prospects the controllability criteria of non-instantaneous impulsive Volterra type fractional differential systems. By enroling an appropriate Gramian matrix that is often defined by the Mittag-Leffler function and with the assistance of Laplace transform, the necessary and sufficiency conditions for the controllability of non-instantaneous impulsive Volterra-type fractional differential equations are derived by using algebraic approach and Cayley–Hamilton theorem. An important feature present in our paper is that we have taken non-instantaneous impulses into the fractional order dynamical system and studied the controllability analysis, since this do not exist in the available source of literature. Inclusively, we have provided two illustrative examples with the existence of non-instantaneous impulse into the fractional dynamical system. So this demonstrates the validity and efficacy of our obtained criteria of the main section.
On Analytic Todd Classes of Singular Varieties
Authors: Bei Francesco , Piazza Paolo
Published: August 2019

Let $(X,h)$ be a compact and irreducible Hermitian complex space. This paper is devoted to various questions concerning the analytic K-homology of $(X,h)$. In the 1st part, assuming either $\dim (\operatorname{sing}(X))=0$ or $\dim (X)=2$, we show that the rolled-up operator of the minimal $L^2$-$\overline{\partial }$ complex, denoted here $\overline{\eth }_{\textrm{rel}}$, induces a class in $K_0 (X)\equiv KK_0(C(X),\mathbb{C})$. A similar result, assuming $\dim (\operatorname{sing}(X))=0$, is proved also for $\overline{\eth }_{\textrm{abs}}$, the rolled-up operator of the maximal $L^2$-$\overline{\partial }$ complex. We then show that when $\dim (\operatorname{sing}(X))=0$ we have $[\overline{\eth }_{\textrm{rel}}]=\pi _*[\overline{\eth }_M]$ with $\pi :M\rightarrow X$ an arbitrary resolution and with $[\overline{\eth }_M]\in K_0 (M)$ the analytic K-homology class induced by $\overline{\partial }+\overline{\partial }^t$ on $M$. In the 2nd part of the paper we focus on complex projective varieties $(V,h)$ endowed with the Fubini–Study metric. First, assuming $\dim (V)\leq 2$, we compare the Baum–Fulton–MacPherson K-homology class of $V$ with the class defined analytically through the rolled-up operator of any $L^2$-$\overline{\partial }$ complex. We show that there is no $L^2$-$\overline{\partial }$ complex on $(\operatorname{reg}(V),h)$ whose rolled-up operator induces a K-homology class that equals the Baum–Fulton–MacPherson class. Finally in the last part of the paper we prove that under suitable assumptions on $V$ the push-forward of $[\overline{\eth }_{\textrm{rel}}]$ in the K-homology of the classifying space of the fundamental group of $V$ is a birational invariant.
Notch1 Signaling Pathway Promotes Proliferation and Mediates Differentiation Direction in Hippocampus of Streptococcus pneumonia Meningitis Rats
Authors: Zhang Zhijie , Xu Danfeng , Zhao Shengnan , Lian Di , Wu Jing , He Dake , Li Ling
Published: August 2019

Background

Streptococcus pneumonia meningitis (PM) is a major cause of childhood neurological deficits. Although the Notch1 signaling pathway regulates neurogenesis and neuroinflammation, we know little about its expression or influence on hippocampal neurogenesis and gliogenesis during PM.

Methods

We used immunofluorescence and Western blots to detect Notch1 signaling expression during experimental PM. Through double-labeling immunofluorescence, we investigated proliferation and differentiation in the dentate gyrus (DG) in PM before and after treatment with exogenous Notch1 activator (Jagged1) and inhibitor (IMR-1).

Results

Our results showed that Notch1 was activated after 24 hours in PM. Compared with the phosphate-buffered saline (PBS) control, Jagged1 increased the proliferation of neural stem cells and progenitor cells (NS/PCs) in DG. After 14 and 28 days of meningitis, astrocyte differentiation increased compared with control. Astrocyte differentiation was higher in the Jagged1 versus the PBS group. In contrast, IMR-1 increased neuronal differentiation but decreased astrocyte differentiation compared with dimethyl sulfoxide treatment.

Conclusions

Under PM, Notch1 signaling promotes NS/PC proliferation and astrocyte differentiation in DG, while decreasing neuronal differentiation. Transient activation of the Notch1 signaling pathway explains the reactive gliogenesis and limited neuronal differentiation observed in PM.
qRT-PCR versus IFA-based Quantification of Male and Female Gametocytes in Low-Density Plasmodium falciparum Infections and Their Relevance for Transmission
Authors: Gruenberg Maria , Hofmann Natalie E , Nate Elma , Karl Stephan , Robinson Leanne J , Lanke Kjerstin , Smith Thomas A , Bousema Teun , Felger Ingrid
Published: August 2019

Background

Accurate quantification of female and male gametocytes and sex ratios in asymptomatic low-density malaria infections are important for assessing their transmission potential. Gametocytes often escape detection even by molecular methods, therefore ultralow gametocyte densities were quantified in large blood volumes.

Methods

Female and male gametocytes were quantified in 161 PCR-positive Plasmodium falciparum infections from a cross-sectional survey in Papua New Guinea. Ten-fold concentrated RNA from 800 µL blood was analyzed using female-specific pfs25 and male-specific pfmget or mssp qRT-PCR. Gametocyte sex ratios from qRT-PCR were compared with those from immunofluorescence assays (IFA).

Results

Gametocytes were identified in 58% (93/161) P. falciparum-positive individuals. Mean gametocyte densities were frequently below 1 female and 1 male gametocyte/µL by qRT-PCR. The mean proportion of males was 0.39 (95% confidence interval, 0.33–0.44) by pfs25/pfmget qRT-PCR; this correlated well with IFA results (Pearsons r2 = 0.91; P < .001). A Poisson model fitted to our data predicted 16% P. falciparum-positive individuals that are likely to transmit, assuming at least 1 female and 1 male gametocyte per 2.5 µL mosquito bloodmeal.

Conclusions

Based on model estimates of female and male gametocytes per 2.5 µL blood, P. falciparum-positive individuals detected exclusively by ultrasensitive diagnostics are negligible for human-to-mosquito transmission.

Estimating the transmission potential of ultralow-density malaria infections informs interventions. Almost all infections with ≥1 female and male gametocyte per 2.5 µL mosquito bloodmeal, and thus with highest likelihood of contributing to human-to-mosquito transmission, were detectable by standard molecular diagnostics.
Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus
Authors: Isnard Stéphane , Ramendra Rayoun , Dupuy Franck P , Lin John , Fombuena Brandon , Kokinov Nikola , Kema Ido , Jenabian Mohammad-Ali , Lebouché Bertrand , Costiniuk Cecilia T , Ancuta Petronela , Bernard Nicole F , Silverman Michael S , Lakatos Peter L , Durand Madeleine , Tremblay Cécile , Routy Jean-Pierre ,   Montreal Primary HIV Infection Study, the Canadian Cohort of HIV+ Slow Progressors, and the Canadian HIV and Aging Cohort Groups, Milne C , Lavoie S , Friedman J , Duchastel M , Villielm F , Asselin F , Boissonnault M , Maziade P J , Lavoie S , Milne M , Miaki N Z , Thériault M E , Lessard B , Charron M A , Dufresne S , Turgeon M E , Vézina S , Huchet E , Kerba J P , Poliquin M , Poulin S , Rochette P , Junod P , Longpré D , Pilarski R , Sasseville E , Charest L , Hamel A , Cloutier-Blais A , Massoud S , Chano F , Trottier B , Labrecque L , Fortin C , Hal-Gagne V , Munoz M , Deligne B , Martel-Laferrière V , Trottier B , Goyer M E , Teltscher M , de Pokomandy A , Cox J , Beauchamp E , Klein M , Haraoui L P
Published: August 2019

Background

Regenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH.

Methods

Plasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)–uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers.

Results

Cross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH.

Conclusions

Plasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.
In vitro synergy of β-lactam combinations against KPC-producing Klebsiella pneumoniae strains
Authors: Lawandi Alexander , Leite Gleice , Cheng Matthew P , Lefebvre Brigitte , Longtin Jean , Lee Todd C
Published: August 2019

Background

Double carbapenem therapy has been promoted as an alternative treatment for infections due to carbapenemase-producing Enterobacteriaceae where carbapenemase inhibitors are unavailable or when other agents have demonstrated toxicity with equally limited evidence. The capacity of other β-lactams and β-lactamase inhibitors to provide synergistic activity with carbapenems is unclear.

Objectives

This study sought to investigate the in vitro synergistic potential of other β-lactam/β-lactamase combinations with meropenem against KPC producers.

Methods

Time–kill assays were performed on 24 unique strains of KPC-producing Klebsiella pneumoniae. Combinations evaluated included meropenem or imipenem with one of the following: ertapenem, piperacillin/tazobactam or ceftolozane/tazobactam. Concentrations used for each drug were those considered physiologically attainable in patients with a time above the concentration exceeding 40%–50% of the dose interval. Combinations were considered to be synergistic when they reduced bacterial cfu/mL by ≥2 log10 at 24 h as compared with the single most active agent.

Results

The combination of piperacillin/tazobactam with meropenem was found to be synergistic against 70.8% of the isolates, followed by ertapenem with meropenem (58.3%) and ceftolozane/tazobactam with meropenem (41.7%). The piperacillin/tazobactam combination was found to be more bactericidal than the other combinations, with 58.3% of isolates demonstrating a ≥4 log10 cfu/mL reduction at 24 h, as compared with 37.5% for ertapenem and 20.8% for ceftolozane/tazobactam combinations.

Conclusions

The combination of piperacillin/tazobactam with meropenem may be a potential therapy against KPC-producing K. pneumoniae when other therapies are unavailable or prohibitively toxic.
Extracting entities with attributes in clinical text via joint deep learning
Authors: Shi Xue , Yi Yingping , Xiong Ying , Tang Buzhou , Chen Qingcai , Wang Xiaolong , Ji Zongcheng , Zhang Yaoyun , Xu Hua
Published: August 2019

Objective

Extracting clinical entities and their attributes is a fundamental task of natural language processing (NLP) in the medical domain. This task is typically recognized as 2 sequential subtasks in a pipeline, clinical entity or attribute recognition followed by entity-attribute relation extraction. One problem of pipeline methods is that errors from entity recognition are unavoidably passed to relation extraction. We propose a novel joint deep learning method to recognize clinical entities or attributes and extract entity-attribute relations simultaneously.

Materials and Methods

The proposed method integrates 2 state-of-the-art methods for named entity recognition and relation extraction, namely bidirectional long short-term memory with conditional random field and bidirectional long short-term memory, into a unified framework. In this method, relation constraints between clinical entities and attributes and weights of the 2 subtasks are also considered simultaneously. We compare the method with other related methods (ie, pipeline methods and other joint deep learning methods) on an existing English corpus from SemEval-2015 and a newly developed Chinese corpus.

Results

Our proposed method achieves the best F1 of 74.46% on entity recognition and the best F1 of 50.21% on relation extraction on the English corpus, and 89.32% and 88.13% on the Chinese corpora, respectively, which outperform the other methods on both tasks.

Conclusions

The joint deep learning–based method could improve both entity recognition and relation extraction from clinical text in both English and Chinese, indicating that the approach is promising.
Ensuring electronic medical record simulation through better training, modeling, and evaluation
Authors: Zhang Ziqi , Yan Chao , Mesa Diego A , Sun Jimeng , Malin Bradley A
Published: August 2019

Objective

Electronic medical records (EMRs) can support medical research and discovery, but privacy risks limit the sharing of such data on a wide scale. Various approaches have been developed to mitigate risk, including record simulation via generative adversarial networks (GANs). While showing promise in certain application domains, GANs lack a principled approach for EMR data that induces subpar simulation. In this article, we improve EMR simulation through a novel pipeline that (1) enhances the learning model, (2) incorporates evaluation criteria for data utility that informs learning, and (3) refines the training process.

Materials and Methods

We propose a new electronic health record generator using a GAN with a Wasserstein divergence and layer normalization techniques. We designed 2 utility measures to characterize similarity in the structural properties of real and simulated EMRs in the original and latent space, respectively. We applied a filtering strategy to enhance GAN training for low-prevalence clinical concepts. We evaluated the new and existing GANs with utility and privacy measures (membership and disclosure attacks) using billing codes from over 1 million EMRs at Vanderbilt University Medical Center.

Results

The proposed model outperformed the state-of-the-art approaches with significant improvement in retaining the nature of real records, including prediction performance and structural properties, without sacrificing privacy. Additionally, the filtering strategy achieved higher utility when the EMR training dataset was small.

Conclusions

These findings illustrate that EMR simulation through GANs can be substantially improved through more appropriate training, modeling, and evaluation criteria.
Excess dietary leucine in diets for growing pigs reduces growth performance, biological value of protein, protein retention, and serotonin synthesis1
Authors: Kwon Woong B , Touchette Kevin J , Simongiovanni Aude , Syriopoulos Kostas , Wessels Anna , Stein Hans H
Published: August 2019

An experiment was conducted to test the hypothesis that excess dietary Leu affects metabolism of branched-chain amino acids (BCAA) in growing pigs. Forty barrows (initial body weight [BW]: 30.0 ± 2.7 kg) were housed individually in metabolism crates and allotted to 5 dietary treatments (8 replicates per treatment) in a randomized complete block design. The 5 diets were based on identical quantities of corn, soybean meal, wheat, and barley and designed to contain 100%, 150%, 200%, 250%, or 300% of the requirement for standardized ileal digestible Leu. Initial and final (day 15) BW of pigs were recorded. Daily feed consumption was also recorded. Urine and fecal samples were collected for 5 d following 7 d of adaptation to the diets. At the end of the experiment, blood and tissue samples were collected to analyze plasma urea N (PUN), plasma and hypothalamic serotonin, tissue BCAA, serum and tissue branched-chain α-keto acids, and messenger ribonucleic acid abundance of genes involved in BCAA metabolism. Results indicated that acid detergent fiber, average daily feed intake, and gain-to-feed ratio decreased (linear, P < 0.05) as dietary Leu increased. A trend (linear, P = 0.082) for decreased N retention and decreased (linear, P < 0.05) biological value of dietary protein was also observed, and PUN increased (linear, P < 0.05) as dietary Leu increased. A quadratic reduction (P < 0.05) in plasma serotonin and a linear reduction (P < 0.05) in hypothalamic serotonin were observed with increasing dietary Leu. Concentrations of BCAA in liver increased (linear, P < 0.001), whereas concentrations of BCAA in skeletal muscle decreased (linear, P < 0.05) as dietary Leu increased. Concentration of α-ketoisovalerate was reduced (linear and quadratic, P < 0.001) in liver, skeletal muscle, and serum, and α-keto-β-methylvalerate was reduced (linear, P < 0.001; quadratic, P < 0.001) in skeletal muscle and serum. In contrast, α-keto isocaproate increased (linear, P < 0.05) in liver and skeletal muscle and also in serum (linear and quadratic, P < 0.001) with increasing dietary Leu. Expression of mitochondrial BCAA transaminase and of the E1α subunit of branched-chain α-keto acid dehydrogenase increased (linear, P < 0.05) in skeletal muscle as dietary Leu increased. In conclusion, excess dietary Leu impaired growth performance and nitrogen retention, which is likely a result of increased catabolism of Ile and Val, which in turn reduces availability of these amino acids resulting in reduced protein retention, and excess dietary Leu also reduced hypothalamic serotonin synthesis.