bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prominent role of informal medicine vendors despite health insurance: a weekly diaries study in rural Nigeria
Authors: Nelissen Heleen E , Brals Daniëlla , Ameen Hafsat A , van der List Marijn , Kramer Berber , Akande Tanimola M , Janssens Wendy , van’t Hoog Anja H 
Published: December 2019

Abstract
In sub-Saharan Africa, accessibility to affordable quality care is often poor and health expenditures are mostly paid out of pocket. Health insurance, protecting individuals from out-of-pocket health expenses, has been put forward as a means of enhancing universal health coverage. We explored the utilization of different types of healthcare providers and the factors associated with provider choice by insurance status in rural Nigeria. We analysed year-long weekly health diaries on illnesses and injuries (health episodes) for a sample of 920 individuals with access to a private subsidized health insurance programme. The weekly diaries capture not only catastrophic events but also less severe events that are likely underreported in surveys with longer recall periods. Individuals had insurance coverage during 34% of the 1761 reported health episodes, and they consulted a healthcare provider in 90% of the episodes. Multivariable multinomial logistic regression analyses showed that insurance coverage was associated with significantly higher utilization of formal health care: individuals consulted upgraded insurance programme facilities in 20% of insured episodes compared with 3% of uninsured episodes. Nonetheless, regardless of insurance status, most consultations involved an informal provider visit, with informal providers encompassing 73 and 78% of all consultations among insured and uninsured episodes, respectively, and individuals spending 54% of total annual out-of-pocket health expenditures at such providers. Given the high frequency at which individuals consult informal providers, their position within both the primary healthcare system and health insurance schemes should be reconsidered to reach universal health coverage.
The intellectual disability PAK3 R67C mutation impacts cognitive functions and adult hippocampal neurogenesis
Authors: Castillon Charlotte , Gonzalez Laurine , Domenichini Florence , Guyon Sandrine , Da Silva Kevin , Durand Christelle , Lestaevel Philippe , Vaillend Cyrille , Laroche Serge , Barnier Jean-Vianney , Poirier Roseline 
Published: December 2019

Abstract
The link between mutations associated with intellectual disability (ID) and the mechanisms underlying cognitive dysfunctions remains largely unknown. Here, we focused on PAK3, a serine/threonine kinase whose gene mutations cause X-linked ID. We generated a new mutant mouse model bearing the missense R67C mutation of the Pak3 gene (Pak3-R67C), known to cause moderate to severe ID in humans without other clinical signs and investigated hippocampal-dependent memory and adult hippocampal neurogenesis. Adult male Pak3-R67C mice exhibited selective impairments in long-term spatial memory and pattern separation function, suggestive of altered hippocampal neurogenesis. A delayed non-matching to place paradigm testing memory flexibility and proactive interference, reported here as being adult neurogenesis-dependent, revealed a hypersensitivity to high interference in Pak3-R67C mice. Analyzing adult hippocampal neurogenesis in Pak3-R67C mice reveals no alteration in the first steps of adult neurogenesis, but an accelerated death of a population of adult-born neurons during the critical period of 18–28 days after their birth. We then investigated the recruitment of hippocampal adult-born neurons after spatial memory recall. Post-recall activation of mature dentate granule cells in Pak3-R67C mice was unaffected, but a complete failure of activation of young DCX + newborn neurons was found, suggesting they were not recruited during the memory task. Decreased expression of the KCC2b chloride cotransporter and altered dendritic development indicate that young adult-born neurons are not fully functional in Pak3-R67C mice. We suggest that these defects in the dynamics and learning-associated recruitment of newborn hippocampal neurons may contribute to the selective cognitive deficits observed in this mouse model of ID.
Enhanced amyloid-β generation by γ-secretase complex in DRM microdomains with reduced cholesterol levels
Authors: Hata Saori , Hu Anqi , Piao Yi , Nakaya Tadashi , Taru Hidenori , Morishima-Kawashima Maho , Murayama Shigeo , Nishimura Masaki , Suzuki Toshiharu 
Published: December 2019

AbstractA neuropathologic hallmark of Alzheimer’s disease (AD) is the presence of senile plaques that contain neurotoxic amyloid-β protein (Aβ) species, which are generated by the cleavage of amyloid β-protein precursor by secretases such as the γ-secretase complex, preferentially located in detergent-resistant membrane (DRM) regions and comprising endoproteolysed amino- and carboxy-terminal fragments of presenilin, nicastrin, anterior pharynx defective 1 and presenilin enhancer 2. Whereas some of familial AD patients harbor causative PSEN mutations that lead to more generation of neurotoxic Aβ42, the contribution of Aβ generation to sporadic/late-onset AD remains unclear. We found that the carboxy-terminal fragment of presenilin 1 was redistributed from DRM regions to detergent-soluble membrane (non-DRM) regions in brain tissue samples from individuals with sporadic AD. DRM fractions from AD brain sample had the ability to generate significantly more Aβ and had a lower cholesterol content than DRM fractions from non-demented control subjects. We further demonstrated that lowering the cholesterol content of DRM regions from cultured cells contributed to the redistribution of γ-secretase components and Aβ production. Taken together, the present analyses suggest that the lowered cholesterol content in DRM regions may be a cause of sporadic/late-onset AD by enhancing overall Aβ generation.
Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer
Authors: Salas Lucas A , Lundgren Sara N , Browne Eva P , Punska Elizabeth C , Anderton Douglas L , Karagas Margaret R , Arcaro Kathleen F , Christensen Brock C 
Published: December 2019

AbstractPrior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis, we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. DNA methylation was assessed using Illumina HumanMethylation450k in 87 breast milk samples. Through an epigenome-wide association study we explored CpG sites associated with a breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer using linear mixed effects models adjusted for history of breast biopsy, age, RefFreeCellMix cell estimates, time of delivery, array chip and subject as random effect. We identified 58 differentially methylated CpG sites associated with a subsequent breast cancer diagnosis (q-value &lt;0.05). Nearly all CpG sites associated with a breast cancer diagnosis were hypomethylated in cases compared with controls and were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has utility as a biospecimen for prospective assessment of disease risk, for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer.
Supporting early career researchers: insights from interdisciplinary marine scientists
Authors: Andrews Evan J , Harper Sarah , Cashion Tim , Palacios-Abrantes Juliano , Blythe Jessica , Daly Jack , Eger Sondra , Hoover Carie , Talloni-Alvarez Nicolás , Teh Louise , Bennett Nathan , Epstein Graham , Knott Christine , Newell Sarah L , Whitney Charlotte K 
Published: December 2019

AbstractThe immense challenges associated with realizing ocean and coastal sustainability require highly skilled interdisciplinary marine scientists. However, the barriers experienced by early career researchers (ECRs) seeking to address these challenges, and the support required to overcome those barriers, are not well understood. This study examines the perspectives of ECRs on opportunities to build interdisciplinary research capacity in marine science. We engaged 23 current and former graduate students and postdoctoral fellows in a policy Delphi method with three rounds of surveying that included semi-structured questionnaires and q-methodology. We identified the following five barriers that limit ECRs’ capacity for interdisciplinary research: (i) demanding workloads; (ii) stress linked to funding, publishing, and employment uncertainty; (iii) limited support for balancing personal and professional commitments; (iv) ineffective supervisory support; and (v) the steep learning curve associated with interdisciplinary research. Our analysis highlights three main types of responses to these barriers adopted by ECRs, including “taking on too much”, “coping effectively”, and “maintaining material wellbeing at any cost”. To overcome these barriers, we propose the following three institutional actions to build early career interdisciplinary researcher capacity: formalize mentorship, create interdisciplinary research groups, and mainstream mental health support.
Serological Evidence for Henipa-like and Filo-like Viruses in Trinidad Bats
Authors: Schulz Jonathan E , Seifert Stephanie N , Thompson John T , Avanzato Victoria , Sterling Spencer L , Yan Lianying , Letko Michael C , Matson M Jeremiah , Fischer Robert J , Tremeau-Bravard Alexandre , Seetahal Janine F R , Ramkissoon Vernie , Foster Jerome , Goldstein Tracey , Anthony Simon J , Epstein Jonathan H , Laing Eric D , Broder Christopher C , Carrington Christine V F , Schountz Tony , Munster Vincent J 
Published: December 2019

Abstract
Bat-borne zoonotic pathogens belonging to the family Paramxyoviridae, including Nipah and Hendra viruses, and the family Filoviridae, including Ebola and Marburg viruses, can cause severe disease and high mortality rates on spillover into human populations. Surveillance efforts for henipaviruses and filoviruses have been largely restricted to the Old World; however, recent studies suggest a potentially broader distribution for henipaviruses and filoviruses than previously recognized. In the current study, we screened for henipaviruses and filoviruses in New World bats collected across 4 locations in Trinidad near the coast of Venezuela. Bat tissue samples were screened using previously established reverse-transcription polymerase chain reaction assays. Serum were screened using a multiplex immunoassay to detect antibodies reactive with the envelope glycoprotein of viruses in the genus Henipavirus and the family Filoviridae. Serum samples were also screened by means of enzyme-linked immunosorbent assay for antibodies reactive with Nipah G and F glycoproteins. Of 84 serum samples, 28 were reactive with ≥1 henipavirus glycoprotein by ≥1 serological method, and 6 serum samples were reactive against ≥1 filovirus glycoproteins. These data provide evidence of potential circulation of viruses related to the henipaviruses and filoviruses in New World bats.
Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study
Authors: Cornely Oliver A , Cisneros José M , Torre-Cisneros Julian , Rodríguez-Hernández María Jesús , Tallón-Aguilar Luis , Calbo Esther , Horcajada Juan P , Queckenberg Christian , Zettelmeyer Ulrike , Arenz Dorothee , Rosso-Fernández Clara M , Jiménez-Jorge Silvia , Turner Guy , Raber Susan , O’Brien Seamus , Luckey Alison ,   COMBACTE-CARE consortium/REJUVENATE Study Group, Aguado Ana Cristina Padial , Baranda Miguel Montejo , Bernedo Carlos García , Bludau Marc , Boix-Palop Lucía , Cheng Karen , de Jonge Boudewijn , de Molina Francisco Javier González , Gentil Pilar Retamar , Guzmán-Puche Julia , Jiménez Virginia Palomo , López-Ruiz José A , Mateos Enrique Montero , Oporto Cristina Roca , Piessen Guillaume , Postil Deborah , Rodríguez Rosa M Jiménez , Ruiz Javier Padillo , Rupp Jan , Soriano Rafael Morales , Wible Michele , Yuste Ángela Cano , Gómez-Zorrilla Silvia 
Published: December 2019

Abstract

Objectives
To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/β-lactamase inhibitor combination aztreonam/avibactam in patients with complicated intra-abdominal infection (cIAI).

Methods
This Phase 2a open-label, multicentre study (NCT02655419; EudraCT 2015-002726-39) enrolled adults with cIAI into sequential cohorts for 5–14 days treatment. Cohort 1 patients received an aztreonam/avibactam loading dose of 500/137 mg (30 min infusion), followed by maintenance doses of 1500/410 mg (3 h infusions) q6h; Cohort 2 received 500/167 mg (30 min infusion), followed by 1500/500 mg (3 h infusions) q6h. Cohort 3 was an extension of exposure at the higher dose regimen. Doses were adjusted for creatinine clearance of 31–50 mL/min (Cohorts 2 + 3). All patients received IV metronidazole 500 mg q8h. PK, safety and efficacy were assessed.

Results
Thirty-four patients (Cohort 1, n = 16; Cohorts 2 + 3, n = 18) comprised the modified ITT (MITT) population. Mean exposures of aztreonam and avibactam in Cohorts 2 + 3 were consistent with those predicted to achieve joint PK/pharmacodynamic target attainment in &gt;90% patients. Adverse events (AEs) were similar between cohorts. The most common AEs were hepatic enzyme increases [n = 9 (26.5%)] and diarrhoea [n = 5 (14.7%)]. Clinical cure rates at the test-of-cure visit overall were 20/34 (58.8%) (MITT) and 14/23 (60.9%) (microbiological-MITT population).

Conclusions
Observed AEs were consistent with the known safety profile of aztreonam monotherapy, with no new safety concerns identified. These data support selection of the aztreonam/avibactam 500/167 mg (30 min infusion) loading dose and 1500/500 mg (3 h infusions) maintenance dose q6h regimen, in patients with creatinine clearance &gt;50 mL/min, for the Phase 3 development programme.
308 Changes in calf feeding behavior in response to sickness
Authors: Sutherland Mhairi , Lowe Gemma , Stewart Mairi , Cox Neil , Waas Joseph , Schutz Karin 
Published: December 2019

Abstract
Feeding behavior can be measured using automated calf milk feeding systems, that record total number of visits consisting of rewarded (milk consumed) or unrewarded (no milk consumed) visits. Unrewarded visits can be either when the calf is entitled to milk, but does not drink (“Entitled”), or is not entitled to milk, so cannot drink (“Non-entitled”). Feeding behavior can be used as an indicator of sickness in calves; fewer unrewarded visits to an automated feeder has been shown to be a sensitive measure of the onset of illness. However, a greater understanding of sickness behavior would aid in early detection of disease in calves. This study aimed to evaluate unrewarded visits prior to signs of clinical illness in calves. Calves were group-housed in pens with an automated feeder from approximately 1 wk of age and examined daily for signs of illness. Of the 74 calves, 16 were diagnosed with neonatal calf diarrhea. To examine the feeding behavior during the 5 days leading up to calves displaying clinical signs of illness, we calculated a robust estimate of the daily rate of change (the Kendall-Theil slope) over this time and used the one sample t-test to test whether the slopes were significantly different from zero. During the 5 days before clinical signs of illness, there was a decrease in unrewarded visits, in accordance with other studies. Interestingly, the proportion of “Non-entitled” unrewarded visits decreased (KT slope = -0.05, P = 0.037) whereas “Entitled” increased (KT slope = 0.04, P = 0.038). These results suggest that during the days leading up to clinical signs of neonatal calf diarrhea, calves may be less motivated to drink even though they are entitled to, possibly due to reduced appetite
12 Effects of excess iron and dietary fat on lipid metabolism
Authors: Ma Wan 
Published: December 2019

Abstract
Diets rich in fat and energy are associated with metabolic syndrome. Imbalanced systemic iron status has long been epidemiologically associated with obesity-related diseases. The aim of this study is to investigate the interaction between dietary fat and injected iron in the context of glucose and lipid metabolism. C57BL6/J mice were divided into four groups and fed normal chow (NC) and high-fat diet (HFD) with adequate or excess iron for 16 weeks. Excess iron was added by intraperitoneal injection with iron dextran (120 mg/g of body weight) every other week from 4th week (NC+Fe and HFD+Fe), six times in total. The results showed that high iron levels decreased the growth rates of mice without affecting their feed intake. High iron levels increased the adipocyte numbers by 1.6-fold in subcutaneous adipose tissue (SAT) and 3.5-fold in visceral adipose tissue (VAT), while excess iron inhibited their adipocyte hypertrophy. These changes were paralleled by alterations in the levels of enzymes related to hepatic lipid storage and β-oxidation. Especially two key enzymes, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) (P &lt; 0.01) and fat specific protein 27 (FSP27) (P &lt; 0.01) were markedly decreased in iron-treated groups compared with their counterparts. In addition, high iron levels decreased insulin sensitivity by increasing 15% of fasting blood glucose and 23% of insulin levels and the average under curve of intraperitoneal glucose tolerance test (IPGTT) was also decreased (P &lt; 0.05). These results were consistent with the decrease of mRNA expression of enzymes related to hepatic gluconeogenesis, phosphoenolpyruvate carboxykinase 1 (PCK1) (P &lt; 0.05) and fructose-1,6-bisphosphatase 1 (FBP1) (P &lt; 0.05) in iron-treated mice. Thus, high-fat diets and iron overload were associated with insulin resistance, modified lipid deposition and iron metabolism. High iron levels could protect mice from high-fat diet induced obesity by decreasing insulin sensitivity.
13 Lipocalin 2 exerts protective activity by alleviating inflammatory responses
Authors: Li Shuhui 
Published: December 2019

Abstract
Lipocalin 2 (Lcn2) is an essential component of the innate immune system and exerts significant immunomodulatory effects in vitro. The aim of current study was to investigate the expression profile of Lcn2 during inflammatory process and explore the role of Lcn2 in the anti-inflammatory responses. Western blot, real-time quantitative PCR, immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA) were employed. Firstly, we evaluated the temporospatial expression of Lcn2 of mice after inflammatory stimuli by lipopolysaccharides (LPS). In vivo, LPS induced both mRNA and protein levels of Lcn2 significantly (P &lt; 0.01) in liver, jejunum and ileum. Lcn2 exhibited a continuous increase by 8 h and peaked by 24 h post challenges. Secondly, we challenged Lcn2-deficient (Lcn2-/-) mice and wild-type (WT) mice with peripheral LPS and determined effects on inflammation. In contrast to WT mice, Lcn2-/- mice showed distinct inflammatory injury in liver, jejunum, ileum and spleen with significantly elevated pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1b (IL-1b) and decreased anti-inflammatory cytokine interleukin-10 (IL-10). Thirdly, we isolated bone marrow-derived macrophages (BMDM) from Lcn2-/- mice and WT mice to evaluate their functions. After LPS challenge, Lcn2-/- BMDM showed aggravated inflammatory reaction as pro-inflammatory factors tumour necrosis factor-α (TNF-α), IL-6, IL-1b and inducible nitric oxide synthase (iNOS) increased (P &lt; 0.05) while anti-inflammatory cytokines IL-10, transforming growth factor β1 (TGF-β1) and arginase-1(Arg-1) decreased significantly (P &lt; 0.05) compared with WT BMDM. This phenomenon could be relieved when adding recombinant Lcn2 (P &lt; 0.05). The exogenous addition of Lcn2 on mice RAW264.7 macrophages stimulated by LPS also conformed this point. These findings demonstrated that Lcn2 served as a potent protective factor in response to systemic inflammation, and elevated Lcn2 expression during inflammatory conditions was presumed to play an effective role in alleviating inflammatory responses.
21 Profiling sow vaginal and fecal and piglet gastrointestinal microbiome and the passage of sow microbiome to their progeny from birth to weaning
Authors: Tran Huyen , de Rodas Brenda , Lahoti Manohar M , Johnson Timothy J 
Published: December 2019

Abstract
The objectives of this study were 1) to profile the sow vaginal and fecal microbiome and the corresponding piglet gastrointestinal microbiome from birth to weaning, and 2) to identify the core microbiome shared between sows and piglets. A total of 226 samples collected from sows (vaginal swabs pre-farrow; fecal samples at farrow, d 3, 7, 10, 17 post-farrow) and their progenies (stomach, ileum, and colon digesta at birth, d 2, and 14 after birth) were used for the analyses of microbial community structure using 16S rRNA V4 amplicon sequencing with Illumina MiSeq. Our data indicated that the piglet and sow microbiome were quite distinct. Piglets had lower bacterial alpha diversity (chao1, richness, Shannon, Simpson indices; P &lt; 0.01) than sows across all timepoints. Beta diversity of piglets by sample types was significantly different (P &lt; 0.001) than sows by sample types when averaged across all timepoints or separation by timepoints. Feature selection by the Linear discriminant analysis effect size (LEfSe) indicated that the genera associated with piglets included those classified as Lactobacillus, unclassified Micrococcaceae, and Rothia when averaged across sampling points and sample types. Genera associated with sows included those classified as Treponema, YRC22, Unclassified RF39, Unclassified Christensenellaceae, Turicibacter, Unclassified RFP12, Unclassified F16, Collinsella, Coprococcus, Unclassified Coriobacteriaceae, and Unclassified Mogibacteriaceae. The genera shared between sow vaginal samples and piglets included those classified as Bacteroides, Fusobacterium, Haemophilus, Prevotella, Veillonella, and unclassified Clostridiadiaceae. The genera shared between sow fecal and piglet samples included those classified as Bacteroides, Lactobacillus, unclassified Clostridiadiaceae, unclassified Ruminococceae, and Prevotella. Overall, there are evidences that bacterial genera were passed from sows to piglets and influenced the microbial communities of piglets later in life.