bluuebunny/crossref_metadata_2025 huggingface dataset:
Extending dew-point temperature scale up to +50 °C
Authors: El-Gelil Doaa Mohamed Abd , Ahmed Mohamed Gamal
Published: December 2018

Extension of dew-point temperature scale has been performed using a two-temperature (2-T), constant pressure humidity generator that is developed for the first time by the National Institute of Standard (NIS) in order to extend the calibration capabilities to the high dew-point temperature range at NIS. It relies on the saturation of a stream of gas flowing over a water surface maintained at constant, well-known, temperature. In this paper, primary realization of dew-point temperature scale in a dew-point temperature range up to +50 °C was performed to extend calibration capabilities and to improve the uncertainties of the dew-point temperature scale realization. Several experiments were carried out in order to characterize the generator. Characterization comprises studies of the saturator efficiency, temperature stability and a comparison with a calibrated chilled-mirror hygrometer. The results of the efficiency tests showed good performance of the generator. For uncertainty of measurements, a thorough analysis was also described representing estimations of contributions for all the sources that possibly affect measurements.
Harmonization of the assessment method for classifying the ecological quality status of very large Greek rivers
Authors: Lazaridou Maria , Ntislidou Chrysoula , Karaouzas Ioannis , Skoulikidis Nikolaos , Birk Sebastian
Published: December 2018

The intercalibration exercise is required by the European Water Framework Directive (WFD) to harmonize the national ecological class boundaries across Member States. It is applied to individual types of water bodies, comparing WFD-compliant biological assessment methods using specific quality elements. This study addresses the harmonization of the STAR_ICMi index for the ecological status assessment of very large Greek rivers in compliance with the completed intercalibration exercise for European very large rivers. River sites were sampled biannually for benthic invertebrates (as biological quality element) and environmental data during different surveys. The water quality of the samples ranged from high to bad. STAR_ICMi was significantly correlated to the Combined Abiotic Pressure index (CAPi) and its component pressures channelization, riparian vegetation alteration, and to a lesser extent to organic pollution. During the intercalibration approach benchmark standardization was applied to the component metrics of the intercalibration index prior to boundary comparison to minimize typological differences. The Greek class boundaries of high/good and good/moderate ecological status were compared and harmonized with the “Global Mean View” defined in the completed European intercalibration exercise. Similarity percentage analysis of biological community variation was performed for sites in high, good, and less than good ecological status according to the intercalibrated Greek classification.
Minimally invasive percutaneous plate osteosynthesis versus intramedullary nail fixation for closed distal tibial fractures: a meta-analysis of the clinical outcomes
Authors: Goh En Lin , Chidambaram Swathikan , Eigenmann Denise , Ma Shaocheng , Jones Gareth G.
Published: December 2018

Introduction: Minimally invasive percutaneous plate osteosynthesis (MIPPO) has emerged as a viable alternative for the treatment of distal tibial fractures. However, the clinical outcomes of this procedure compared to intramedullary (IM) nail fixation have yet to be established. The present meta-analysis aims to compare the clinical outcomes following MIPPO and IM nail fixation for closed distal tibial fractures.

Methods: MEDLINE and EMBASE databases were searched from date of inception to 10th April 2017. Randomized controlled trials (RCTs) comparing MIPPO with IM nail fixation for closed and Gustilo Grade I distal tibial fractures were included. Outcomes assessed included time to union, complications and functional outcomes. Quality and risk of bias of the RCTs were assessed using the Cochrane Collaboration Tool.

Results: Five RCTs comprising 497 patients were included. MIPPO was associated with a longer time to union (MD: 1.08, 95% CI: 0.26, 1.90, p = 0.010, I
2 = 84%) and increased risk of wound complications (RR: 1.58, 95% CI: 1.01, 2.46, p = 0.04, I
2 = 0%). Both MIPPO and IM nail fixation had comparable risks of malunion, delayed union, non-union and deep infections, with similar functional outcomes.

Discussion: Compared to IM nail fixation, a MIPPO fixation technique for distal tibial fractures is associated with a longer time to fracture union and an increased risk of wound complications. Neither technique demonstrates a clear advantage with regard to risk of malunion/non-union, or functional outcome. Assuming equivalent surgical expertise with both techniques, the results suggest that IM nail fixation is the treatment modality of choice for these challenging fractures.
Depression and Diabetic Peripheral Neuropathy: Birds of a Feather, But When do They Flock Together?
Authors: Vas Prashanth R.J. , Papanas Nikolaos
Published: December 2018

The association between diabetes and depression is well recognised. Similarly, diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes. Given the high prevalence of these conditions individually, it is hardly surprising they frequently interact, conferring additional morbidity and a higher mortality risk. Despite this, the specific clinical characteristics that underpin co-morbid depression and DPN remain unclear. Additionally, there is insufficient insight into causal pathways and temporal trends. High-quality epidemiological data is limited, but they suggest that these conditions may share certain common risk factors, although there are also distinct differences such as gender. Improved insights into the risk factors for the co-existence of DPN and depression may help towards improved screening for and treatment of these conditions.
Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells
Authors: Xing Shao-Fang , Liu Lin-Hua , Zu Ma-Li , Lin Man , Zhai Xin-Fang , Piao Xiang-Lan
Published: December 2018

Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.
Higher Serum Uric Acid is a Risk Factor of Vertebral Fractures in Postmenopausal Women with Type 2 Diabetes Mellitus
Authors: Tanaka Ken-ichiro , Kanazawa Ippei , Notsu Masakazu , Sugimoto Toshitsugu
Published: December 2018

Purpose Serum uric acid (UA) level may affect bone metabolism because it has an anti-oxidative effect. However, whether serum UA level is associated with a fracture risk in type 2 diabetes mellitus (T2DM) is unclear. We thus aimed to clarify the association between serum UA and bone parameters in T2DM.

Methods We conducted a cross-sectional study to investigate the association of serum UA with bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN), bone turnover markers such as osteocalcin and urine type I collagen cross-linked N-telopeptide (uNTX), and the prevalence of vertebral fractures (VF) in 356 postmenopausal women and 512 men with T2DM.

Results Multiple regression analyses adjusted for age, duration of diabetes, hemoglobin A1c, body mass index and log (serum creatinine) showed that serum UA level was significantly and negatively associated with uNTX in postmenopausal women with T2DM, whereas it was not associated with osteocalcin or BMD at each site. In men, serum UA was not associated with BMD or bone turnover markers. Because postmenopausal women with VF were significantly older and had longer duration of diabetes, higher serum creatinine level and lower BMD than those without it, logistic regression analyses adjusted for these confounding factors were performed. Higher serum UA level was significantly associated with the presence of VF.

Conclusions The present study showed that higher serum UA is a risk factor for VF independently of BMD in postmenopausal women with T2DM.
Impact of Time to Neonatal Transport on Outcomes of Transient Tachypnea of the Newborn
Authors: Hirata Katsuya , Nozaki Masatoshi , Mochizuki Narutaka , Hirano Shinya , Wada Kazuko
Published: December 2018

Objective To assess effects of neonatal transport on transient tachypnea of the newborn (TTN) in outborn term neonates.

Study Design This retrospective cohort study included 66 term neonates diagnosed with TTN and transported to the Osaka Women's and Children's Hospital neonatal intensive care unit between January 2003 and March 2018. A multivariate logistic regression analysis identified perinatal and neonatal transport factors associated with adverse short-term outcomes defined as mechanical ventilation >48 hours, continuous positive airway pressure >72 hours, pulmonary hemorrhage, and requirement for inhaled nitric oxide, thoracentesis, or surfactant replacement therapy.

Results A lower gestational age (GA) (37.7 [37.2, 38.3] vs. 39.6 [37.8, 40.3] weeks, p = 0.002), longer time to neonatal transport (10.0 [4.3, 25.5] vs. 5.5 [2.7, 9.7] hours, p = 0.01), and higher respiratory rates during transport (70 [60, 85] vs. 60 [55, 78.8] breaths/min, p = 0.04) were significantly associated with adverse short-term outcomes. After adjusting for GA, sex, cesarean section, and time to neonatal transport, GA (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.24–0.87) and time to neonatal transport (OR, 1.07; 95% CI, 1.01–1.13) were significantly associated with adverse outcomes.

Conclusion Short-term adverse prognosis of TTN is strongly associated with a lower GA and longer time between birth and neonatal transport.
Biotin-Thiamine Responsive Encephalopathy: Report of an Egyptian Family with a Novel SLC19A3 Mutation and Review of the Literature
Authors: Savasta Salvatore , Bassanese Francesco , Buschini Chiara , Foiadelli Thomas , Trabatti Chiara , Efthymiou Stephanie , Salpietro Vincenzo , Houlden Henry , Simoncelli Annamaria , Marseglia Gian
Published: December 2018

Biotin-thiamine responsive basal ganglia disease (BTRBGD) is an autosomal recessive neurometabolic disorder with poor genotype-phenotype correlation, caused by mutations in the SLC19A3 gene on chromosome 2q36.6. The disease is characterized by three stages: stage 1 is a sub-acute encephalopathy often triggered by febrile illness; stage 2 is an acute encephalopathy with seizures, loss of motor function, developmental regression, dystonia, external ophthalmoplegia, dysphagia, and dysarthria; stage 3 is represented by chronic or slowly progressive encephalopathy. Clinical and biochemical findings, as well as the magnetic resonance imaging (MRI) pattern, resemble those of Leigh's syndrome, so that BTRBGD can be misdiagnosed as a mitochondrial encephalopathy.Here we report the clinical and radiological phenotypes of two siblings diagnosed with BTRBGD in which a novel SLC19A3 mutation (NM_025243.3: c.548C > T; p.Ala183Val) was found by whole exome sequencing (WES) of the family members.
Ice friction: Glacier sliding on hard randomly rough bed surface
Authors: Persson B. N. J.
Published: December 2018

I present a theory for ice friction for ice sliding on a hard randomly rough surface which includes ice melting-freezing (regelation), viscoelastic energy dissipation, and cavitation. The theory is an extension of earlier work by Weertman, Lliboutry, Nye, and Kamb. I present numerical results for surfaces with realistic surface roughness power spectra. I consider both airfilled and (pressurized) waterfilled cavities. The calculated frictional shear stresses are consistent with experimental observations for temperate glaciers.
Factors that affect the timing of the dispatch of initial attack resources to forest fires in northeastern Ontario, Canada
Authors: Paudel Ambika , Martell David L. , Woolford Douglas G.
Published: December 2018

The success of forest fire initial attack systems is believed to be affected by many factors including the initial attack response time. Despite the fact that fire managers typically strive to dispatch initial attack resources to most fires soon after they are reported in order to minimise their response time, they may not always be able to do so as the timing of the initial attack dispatch can be influenced by many factors. We examine the effects of the following factors on the initial attack dispatch process: the daily fire load (the number of fires reported each day), the time of day the fire was reported, fire weather conditions, fire cause and the month of the fire season, on the probability that initial attack resources are dispatched on the day that a fire is reported. Logistic regression methods are used to analyse a dataset composed of 4532 forest fires that were reported in our study area in a portion of northeastern region of Ontario, Canada, during 1963–2012 fire seasons. Our results indicate that the time of day a fire is reported, the total number of fires reported on that day and the Initial Spread Index are key factors that influence the timing of the initial attack response in our study area.
Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR
Authors: Sevilla J. P. , Bloom David E. , Cadarette Daniel , Jit Mark , Lipsitch Marc
Published: December 2018

We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.
Microbiome as a tool and a target in the effort to address antimicrobial resistance
Authors: Relman David A. , Lipsitch Marc
Published: December 2018

Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.
In crystallo
thermodynamic analysis of conformational change of the topaquinone cofactor in bacterial copper amine oxidase
Authors: Murakawa Takeshi , Baba Seiki , Kawano Yoshiaki , Hayashi Hideyuki , Yano Takato , Kumasaka Takashi , Yamamoto Masaki , Tanizawa Katsuyuki , Okajima Toshihide
Published: December 2018

In the catalytic reaction of copper amine oxidase, the protein-derived redox cofactor topaquinone (TPQ) is reduced by an amine substrate to an aminoresorcinol form (TPQ
amr
), which is in equilibrium with a semiquinone radical (TPQ
sq
). The transition from TPQ
amr
to TPQ
sq
is an endothermic process, accompanied by a significant conformational change of the cofactor. We employed the humid air and glue-coating (HAG) method to capture the equilibrium mixture of TPQ
amr
and TPQ
sq
in noncryocooled crystals of the enzyme from
Arthrobacter globiformis
and found that the equilibrium shifts more toward TPQ
sq
in crystals than in solution. Thermodynamic analyses of the temperature-dependent equilibrium also revealed that the transition to TPQ
sq
is entropy-driven both in crystals and in solution, giving the thermodynamic parameters that led to experimental determination of the crystal packing effect. Furthermore, we demonstrate that the binding of product aldehyde to the hydrophobic pocket in the active site produces various equilibrium states among two forms of the product Schiff-base, TPQ
amr
, and TPQ
sq
, in a pH-dependent manner. The temperature-controlled HAG method provides a technique for thermodynamic analysis of conformational changes occurring in protein crystals that are hardly scrutinized by conventional cryogenic X-ray crystallography.
F-box protein RAE1 regulates the stability of the aluminum-resistance transcription factor STOP1 in
Arabidopsis
Authors: Zhang Yang , Zhang Jie , Guo Jinliang , Zhou Fanglin , Singh Somesh , Xu Xuan , Xie Qi , Yang Zhongbao , Huang Chao-Feng
Published: December 2018

Aluminum (Al) toxicity is a major factor limiting crop production on acid soils, which represent over 30% of the world’s arable land. Some plants have evolved mechanisms to detoxify Al.
Arabidopsis
, for example, secretes malate via the AtALMT1 transporter to chelate and detoxify Al. The C2H2-type transcription factor STOP1 plays a crucial role in Al resistance by inducing the expression of a set of genes, including
AtALMT1
. Here, we identify and characterize an F-box protein-encoding gene
regulation of Atalmt1 expression 1
(
RAE1
) that regulates the level of STOP1. Mutation and overexpression of
RAE1
increases or decreases the expression of
AtALMT1
and other STOP1-regulated genes, respectively. RAE1 interacts with and promotes the degradation of STOP1 via the ubiquitin-26S proteasome pathway, while Al stress promotes the accumulation of STOP1. We find that STOP1 up-regulates
RAE1
expression by directly binding to the
RAE1
promoter, thus forming a negative feedback loop between STOP1 and RAE1. Our results demonstrate that RAE1 influences Al resistance through the ubiquitination and degradation of STOP1.
Implicit model of other people’s visual attention as an invisible, force-carrying beam projecting from the eyes
Authors: Guterstam Arvid , Kean Hope H. , Webb Taylor W. , Kean Faith S. , Graziano Michael S. A.
Published: December 2018

Significance

Much of how people process other social agents is hidden under the surface of awareness. Here we report that people automatically and unconsciously treat other people’s eyes as if beams of force-carrying energy emanate from them, gently pushing on objects in the world. The findings show how the human brain constructs surprising, rich, and at the same time schematized models of other people’s internal processes such as visual attention.
Cryo-EM structures of the archaeal PAN-proteasome reveal an around-the-ring ATPase cycle
Authors: Majumder Parijat , Rudack Till , Beck Florian , Danev Radostin , Pfeifer Günter , Nagy István , Baumeister Wolfgang
Published: December 2018

Proteasomes occur in all three domains of life, and are the principal molecular machines for the regulated degradation of intracellular proteins. They play key roles in the maintenance of protein homeostasis, and control vital cellular processes. While the eukaryotic 26S proteasome is extensively characterized, its putative evolutionary precursor, the archaeal proteasome, remains poorly understood. The primordial archaeal proteasome consists of a 20S proteolytic core particle (CP), and an AAA-ATPase module. This minimal complex degrades protein unassisted by non-ATPase subunits that are present in a 26S proteasome regulatory particle (RP). Using cryo-EM single-particle analysis, we determined structures of the archaeal CP in complex with the AAA-ATPase PAN (proteasome-activating nucleotidase). Five conformational states were identified, elucidating the functional cycle of PAN, and its interaction with the CP. Coexisting nucleotide states, and correlated intersubunit signaling features, coordinate rotation of the PAN-ATPase staircase, and allosterically regulate N-domain motions and CP gate opening. These findings reveal the structural basis for a sequential around-the-ring ATPase cycle, which is likely conserved in AAA-ATPases.
The Relationship Between Ward Social Climate, Ward Sense of Community, and Incidents of Disruptive Behavior: A Study of a High Secure Psychiatric Sample
Authors: Puzzo Ignazio , Aldridge-Waddon Luke , Bush Emma , Farr Catherine
Published: December 2018

Assaults and seclusions within the UK obstruct patient recovery, and carry a combined UK cost of £106 million a year. Research has identified low ward social climate and lack of sense of community as potential factors that contributes to disruptive behavior. The current study investigates the relationship between self-reported sense of community and social climate scores with incidents of disruptive behavior (i.e., assaults and seclusions) within a UK high security psychiatric hospital. Findings reveal that both social climate and sense of community predict incidents of disruptive behaviour. This study suggests that both factors should be monitored in high security hospitals.
Precipitation‐based extracellular vesicle isolation from rat plasma co‐precipitate vesicle‐free microRNAs
Authors: Karttunen Jenni , Heiskanen Mette , Navarro‐Ferrandis Vicente , Das Gupta Shalini , Lipponen Anssi , Puhakka Noora , Rilla Kirsi , Koistinen Arto , Pitkänen Asla
Published: December 2018

The microRNA (miRNA) cargo contained in plasma extracellular vesicles (EVs) offers a relatively little explored source of biomarkers for brain diseases that can be obtained noninvasively. Methods to isolate EVs from plasma, however, are still being developed. For EV isolation, it is important to ensure the removal of vesicle‐free miRNAs, which account for approximately two‐thirds of plasma miRNAs. Membrane particle precipitation‐based EV isolation is an appealing method because of the simple protocol and high yield. Here, we evaluated the performance of a precipitation‐based method to obtain enriched EV‐specific miRNAs from a small volume of rat plasma. We performed size‐exclusion chromatography (SEC) on precipitation‐isolated EV pellets and whole plasma. The SEC fractions were analysed using Nanoparticle Tracking Analysis (NTA), protein and miRNA concentration assays, and droplet digital polymerase chain reaction for four miRNAs (miR‐142‐3p, miR‐124‐3p, miR‐23a, miR‐122). Precipitation‐isolated EVs and selected SEC fractions from the plasma were also analysed with transmission electron microscopy (TEM). Precipitation‐based EV isolation co‐precipitated 9% to 15% of plasma proteins and 21% to 99% of vesicle‐free miRNAs, depending on the individual miRNAs. In addition, the amount of miR‐142‐3p, found mainly in EV fractions, was decreased in the EV fractions, indicating that part of it was lost during precipitation‐based isolation. Western blot and TEM revealed both protein and lipoprotein contamination in the precipitation‐isolated EV‐pellets. Our findings indicate that a precipitation‐based method is not sufficient for purifying plasma EV‐contained miRNA cargo. The particle number measured by NTA is high, but this is mostly due to the contaminating lipoproteins. Although a part of the vesicle‐free miRNA is removed, vesicle‐free miRNA still dominates in plasma EV pellets isolated by the precipitation‐based method.
Unconditional Transfers and Tropical Forest Conservation: Evidence from a Randomized Control Trial in Sierra Leone
Authors: Wilebore Beccy , Voors Maarten , Bulte Erwin H. , Coomes David , Kontoleon Andreas
Published: December 2018

Unconditional conservation payments are increasingly used by non‐governmental conservation organizations to further their environmental objectives. One key objective in many conservation projects that use such unconditional payments schemes is the protection of tropical forest ecosystems in buffer zone areas around protected parks where the scope of instating mandatory restrictions is more limited. We use a randomized controlled trial to evaluate the impact of unconditional livelihood payments to local communities on land use outside a protected area—the Gola Rainforest National Park—which is a biodiversity hotspot on the border of Sierra Leone and Liberia. High resolution RapidEye satellite imagery from before and after the intervention was used to determine land use changes in treated and control villages. We find support for the hypothesis that unconditional payments, in this setting, increase land clearance in the short run. The study constitutes one of the first attempts to use evidence from a randomized control trial to evaluate the efficacy of conservation payments and provides insights for further research.
Very low-depth whole-genome sequencing in complex trait association studies
Authors: Gilly Arthur , Southam Lorraine , Suveges Daniel , Kuchenbaecker Karoline , Moore Rachel , Melloni Giorgio E M , Hatzikotoulas Konstantinos , Farmaki Aliki-Eleni , Ritchie Graham , Schwartzentruber Jeremy , Danecek Petr , Kilian Britt , Pollard Martin O , Ge Xiangyu , Tsafantakis Emmanouil , Dedoussis George , Zeggini Eleftheria
Published: December 2018

Motivation

Very low-depth sequencing has been proposed as a cost-effective approach to capture low-frequency and rare variation in complex trait association studies. However, a full characterization of the genotype quality and association power for very low-depth sequencing designs is still lacking.

Results

We perform cohort-wide whole-genome sequencing (WGS) at low depth in 1239 individuals (990 at 1× depth and 249 at 4× depth) from an isolated population, and establish a robust pipeline for calling and imputing very low-depth WGS genotypes from standard bioinformatics tools. Using genotyping chip, whole-exome sequencing (75× depth) and high-depth (22×) WGS data in the same samples, we examine in detail the sensitivity of this approach, and show that imputed 1× WGS recapitulates 95.2% of variants found by imputed GWAS with an average minor allele concordance of 97% for common and low-frequency variants. In our study, 1× further allowed the discovery of 140 844 true low-frequency variants with 73% genotype concordance when compared to high-depth WGS data. Finally, using association results for 57 quantitative traits, we show that very low-depth WGS is an efficient alternative to imputed GWAS chip designs, allowing the discovery of up to twice as many true association signals than the classical imputed GWAS design.

Availability and implementation

The HELIC genotype and WGS datasets have been deposited to the European Genome-phenome Archive (https://www.ebi.ac.uk/ega/home): EGAD00010000518; EGAD00010000522; EGAD00010000610; EGAD00001001636, EGAD00001001637. The peakplotter software is available at https://github.com/wtsi-team144/peakplotter, the transformPhenotype app can be downloaded at https://github.com/wtsi-team144/transformPhenotype.

Supplementary information

Supplementary data are available at Bioinformatics online.
Disruption of ubiquitin specific protease 26 gene causes male subfertility associated with spermatogenesis defects in mice†
Authors: Tian Hong , Huo Yongwei , Zhang Jie , Ding Shangshu , Wang Zhiyong , Li Hecheng , Wang Lirong , Lu Ming , Liu Sen , Qiu Shudong , Zhang Qiuyang
Published: December 2018

Ubiquitin-specific protease 26 (USP26) is an X-linked gene exclusively expressed in the testis and codes for the USP26, a peptidase enzyme that belongs to the deubiquitinating enzyme family. Recent studies have indicated that mutations in USP26 affect spermatogenesis and are associated with male infertility in humans and mice. However, the exact role of USP26 in spermatogenesis and how it affects male reproduction remains unknown. In this study, we generated a conventional Usp26 knockout mouse model and found that deletion of Usp26 in male mice (Usp26−/Y) leads to significantly reduced pup numbers per litter and significantly increased intervals between two consecutive offspring. We also found that the serum follicle stimulating hormone and testosterone levels of adult Usp26−/Y mice were significantly decreased compared to those of Usp26+/Y mice. Histological examination results showed that Usp26−/Y mice had significantly increased percentage of abnormal seminiferous tubules at different ages. Flow cytometry results exhibited that Usp26−/Y mice had significantly reduced percentage of mature haploid cells in the testes compared to Usp26+/Y mice. Sperm counts in epididymis were also significantly declined in Usp26−/Y mice compared to those in Usp26+/Y mice. Immunohistochemistry and immunofluorescence staining and immunoprecipitation analysis results showed that USP26 and androgen receptor were co-localized in mouse testicular cells at different ages and they both had physiological interactions. All these results demonstrated that the loss of Usp26 affects spermatogenesis and hormone secretion and causes male subfertility. Our study also provides the evidence on the interactions between USP26 and androgen receptor in mouse testis, whereby pointing to a potential mechanism.
Theorizing Development of Parasocial Engagement
Authors: Tukachinsky Riva , Stever Gayle
Published: December 2018

The article proposes a theoretical model of the development of parasocial relationships (PSRs) building on Knapp’s model of relationship development. Through synthesis of research across disciplines, the model conceptualizes the relational goals and parasocial interactions (PSIs) specific to the PSR. The model identifies variables that predict engagement at that level, describes the stage’s outcomes/effects, and considers the utility of existing measures to assess these stages. The conceptualization of PSRs as a dynamic process rather than intensity of a monolithic experience offers new directions worthy of empirical examination.
Molecular Characterization of Two Mitogen-Activated Protein Kinases: p38 MAP Kinase and Ribosomal S6 Kinase From Bombyx mori (Lepidoptera: Bombycidae), and Insight Into Their Roles in Response to BmNPV Infection
Authors: Muhammad Azharuddin , Toufeeq Shahzad , Yu Hai-Zhong , Wang Jie , Zhang Shang-Zhi , Li Bing , Li Zhen , Yang Li-Ang , Hu Pei , Ma Yan , Xu Jia-Ping
Published: December 2018

Proteins p38 map kinase and ribosomal S6 kinase (S6K) as members of mitogen-activated protein kinases (MAPKs) play important roles against pathogens. In this study, Bmp38 and BmS6K were identified as differentially expressed proteins from iTRAQ database. Bmp38 and BmS6K were expressed, and recombinant proteins were purified. The bioinformatics analysis showed that both proteins have serine/threonine-protein kinases, catalytic domain (S_TKc) with 360 and 753 amino acids, respectively. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that Bmp38 and BmS6K had high expression in the midgut and hemolymph. The comparative expression level of Bmp38 and BmS6K in BC9 was upregulated than in P50 in the midgut after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Western bolt results showed a positive correlation between RT-qPCR and iTRAQ data for Bmp38, but BmS6K data showed partial correlation with iTRAQ. Injection of anti-Bmp38 and anti-BmS6K serum suggested that Bmp38 may be involved against BmNPV infection, whereas BmS6K may require phosphorylation modification to inhibit BmNPV infection. Taken together, our results suggest that Bmp38 and BmS6k might play an important role in innate immunity of silkworm against BmNPV.
Optimal dose of PG600 when given to progestogen-synchronized ewes during anestrus as affected by day of the year and temperature1
Authors: Cross Lucy J , Cross Robin M , Stormshak Fredrick
Published: December 2018

The objective of this long-term study was to improve the out-of-season breeding rates for ewes by examining effectiveness of dose levels of PG600, a combination of 80-IU/mL pregnant mare serum gonadotropin and 40-IU/mL human chorionic gonadotropin. Each week, during the anestrous season from 1998 through 2016, mature ewes were inserted with 1 of 2 progestogen devices. After 9 to 13 d, at removal of the device, ewes were injected intramuscularly with a specific dose of PG600. A total of 1,402 ewes were treated in this study, with weekly treatment groups ranging from 3 to 12 ewes. Ewes were assigned randomly in equal numbers to 1 of 2 ram pens with one fertile ram in each pen. Rams were fitted with a marking harness. Between 36 and 48 h after removal of the device, rams were switched. Ewes were checked for crayon marks (indicative of estrus) at 36, 48, and 96 h after removal of synchronizing devices. Rams were removed after 1 wk. Pregnancy status was diagnosed at 90 d of gestation using radiography and verified at 120 d or at lambing. To explore the impact of dose level, daylight, and temperature on pregnancy rate, we formulated an ordered multinomial probit model. The model controls statistically for dose level, synchronization device type, device reuse, and natural variation in minimum daily temperature and day of the year (DOY). Predicted pregnancy rate and type of birth at 90 d of gestation were significantly affected by DOY and temperature as well as dose level. Both observed and predicted pregnancy rates were higher for PG600 dose levels between 2.00 and 3.50 mL than for those below 2.00 mL or above 3.99 mL. By giving optimal amounts of PG600 to anestrous ewes, producers will have a greater number of pregnant ewes at lambing during the out-of-season lambing time.
Genomic Study of Severe Fetal Anomalies and Discovery of GREB1L Mutations in Renal Agenesis
Authors: Boissel Sarah , Fallet-Bianco Catherine , Chitayat David , Kremer Valérie , Nassif Christina , Rypens Françoise , Delrue Marie-Ange , Soglio Dorothée Dal , Oligny Luc L. , Patey Natalie , Flori Elisabeth , Cloutier Mireille , Dyment David , Campeau Philippe , Karalis Aspasia , Nizard Sonia , Fraser William D. , Audibert François , Lemyre Emmanuelle , Rouleau Guy A. , Hamdan Fadi F. , Kibar Zoha , Michaud Jacques L.
Published: December 2018

(Abstracted from Genet Med 2018;20(7):745–753)

Birth defects are a leading cause of mortality and mortality in infants and children. The etiology of birth defects is complex, and copy number variants (CNVs) detectable with chromosomal microarray currently represent the most commonly recognized cause of birth defects in fetuses and children.
Virtual Postoperative Visits for New Ostomates
Authors: White Tracie , Watts Penni , Morris Melanie , Moss Jacqueline
Published: December 2018

Postoperative education, discharge instructions, and follow-up appointments provide a foundation for new ostomates after discharge, but a gap in care remains. New ostomates utilize resources twice as much as other colorectal patients. Virtual visits allow visual inspection of the patient while providing verbal support. The purposes of this project were to determine the feasibility of Virtual Postoperative Visits, to define specific issues patients want addressed, and to assess patient satisfaction with a virtual format. In this pilot project, 10 patients attended two outpatient virtual visits following hospital discharge. The virtual visits were conducted using video conferencing software. Descriptive statistics were used to analyze data from a survey assessing patient satisfaction; content analysis described video interactions. All patients successfully completed two virtual visits from their homes. Ninety percent felt these visits helped with ostomy management and agreed they should be part of a discharge plan. All patients felt comfortable with a virtual format. Common themes discussed included pouching and skin irritation. We found that virtual visits are feasible, and patients are satisfied with this format to address goals of care. Future work will focus on large-scale implementation of virtual visits for new ostomates.
The experiences and needs of Asian women experiencing menopausal symptoms: a meta-synthesis
Authors: Shorey Shefaly , Ng Esperanza D.
Published: December 2018

Objective:

The aim of the study was to explore the experiences and needs of Asian women who were experiencing or had experienced menopause and to determine possible differences in experiences due to acculturation by comparing Asian women living in Asia and those living in Western countries.

Methods:

Six electronic databases were systematically searched: PubMed, CINAHL, Embase, Scopus, PsycINFO, and ProQuest. The search resulted in 17 qualitative studies that met the inclusion and exclusion criteria. Quality appraisal was conducted using the Critical Appraisal Skills Programme Checklist. All 17 studies were analyzed using meta-summaries and, then, using meta-synthesis.

Results:

Five themes were identified from the 17 included studies (United States, n = 5; Asia, n = 12): (1) perceptions and attitudes toward menopause (n = 14), (2) physical and emotional experiences during menopause (n = 16), (3) changes in life and relationships (n = 11), (4) needs and coping strategies (n = 13), and (5) unique Asian experiences in Western societies (n = 5). Asian women generally had neutral or positive attitudes toward menopause, but their negative physical, emotional, and psychosocial experiences highlighted their unmet needs and unpreparedness for this phase of life. Diverse self-management strategies were adopted, but there was a high demand for more trustworthy informational resources. Asian women in Western societies were not highly acculturated and retained traditional practices.

Conclusions:

Although cultural influences serve as a protective factor against menopausal symptoms, the traditional and conservative nature of the Asian society poses as a help-seeking barrier. Therefore, to ensure the healthy well-being of postmenopausal women, the implementation of culturally appropriate mitigation and management strategies is necessary.
The effects of swimming training on arterial function, muscular strength, and cardiorespiratory capacity in postmenopausal women with stage 2 hypertension
Authors: Wong Alexei , Kwak Yi-Sub , Scott Steven D. , Pekas Elizabeth J. , Son Won-Mok , Kim Ji-Seok , Park Song-Young
Published: December 2018

Objective:

Aging is associated with progressive decreases in arterial health as well as muscular strength and cardiorespiratory capacity. It is crucial to prevent or reduce the negative effects of aging on vasculature, muscular, and cardiorespiratory function by implementing appropriate lifestyle interventions, such as exercise training. We examined the effects of a swimming (SWM) regimen on arterial stiffness (pulse wave velocity [PWV]), blood pressure (BP), wave reflection (augmentation index [AIx]), muscle strength, and aerobic capacity in sedentary, postmenopausal women with stage 2 hypertension.

Methods:

One hundred participants (∼74 years of age) were recruited from multiple general practice centers. Using a parallel experimental design, participants were randomly assigned to either SWM (n = 52) or nonexercising control group (n = 48) for 20 weeks. Participants in the SWM group trained 3 to 4 days/week. Participants’ carotid to radial PWV, BP, AIx, muscular strength, and cardiorespiratory capacity were measured at baseline and after 20 weeks of their assigned intervention.

Results:

There was a significant group × time interaction (P < 0.05) for carotid to radial PWV (Δ−1.2 m/s), AIx (Δ−4%), and systolic (Δ−9 mm Hg) and diastolic BP (Δ − 9 mm Hg), which significantly decreased (P < 0.05); and strength (Δ3 kg) and cardiorespiratory capacity (Δ4 mL/kg/min), which significantly increased (P < 0.05) following SWM compared to no changes in control.

Conclusions:

SWM led to reductions in arterial stiffness, wave reflection, and BP while increasing strength and aerobic capacity in postmenopausal women with stage 2 hypertension. SWM may be an effective intervention in the prevention and treatment of age-related vascular complications and declines in muscle strength and cardiorespiratory capacity.
Age at menarche and risk of all-cause and cardiovascular mortality: a systematic review and dose–response meta-analysis
Authors: Chen Xu , Liu Yu , Sun Xizhuo , Yin Zhaoxia , Li Honghui , Liu Xuejiao , Zhang Dongdong , Cheng Cheng , Liu Leilei , Liu Feiyan , Zhou Qionggui , Wang Chongjian , Li Linlin , Wang Bingyuan , Zhao Yang , Liu Dechen , Zhang Ming , Hu Dongsheng
Published: December 2018

Objective:

The evidence between age at menarche and mortality risk is controversial. We aimed to quantify the dose–response association of age at menarche and risk of all-cause and cardiovascular disease (CVD) mortality based on cohort studies.

Methods:

PubMed, EMBASE, Web of Science, and Scopus databases were searched up to March 15, 2018 for relevant articles. Random-effects models and restricted cubic splines were used for this meta-analysis.

Results:

Twelve cohort studies, with 79,363 deaths and 2,341,769 participants, met the inclusion criteria. With each 1-year increase in menarche age, the relative risk (RR) was reduced for all-cause mortality (RR: 0.977, 95% confidence interval [CI]: 0.970-0.984), CVD mortality (RR: 0.993, 95% CI: 0.975-1.011), ischemic heart disease (IHD) mortality (RR: 0.969, 95% CI: 0.947-0.993), and stroke mortality (RR: 0.983, 95% CI: 0.954-1.012). We found a nonlinear dose–response association (P
nonlinearity = 0.001) between age at menarche and all-cause mortality, with the lowest risk observed at menarche age 15 years (RR: 0.849 95% CI: 0.800-0.901), but no evidence of a nonlinear association between menarche age and CVD mortality (P
nonlinearity = 0.543), IHD mortality (P
nonlinearity = 0.310), or stroke mortality (P
nonlinearity = 0.824).

Conclusions:

Age at menarche is inversely associated with all-cause and IHD mortality.
What Is the Color of Your Lymph Node?
Authors: Ben Naftali Yeela , Brodsky Asia , Bar-Meir Eran D.
Published: December 2018

We describe a case of tattoo ink in an axillary lymph node, which was observed during an axillary dissection and mastectomy surgery. It is important to be aware of this phenomenon and correctly identify it at the time of surgery, as a misdiagnosis can have serious consequences.
Redefining the Anatomic Boundaries for Safe Dissection of the Skin Paddle in a Gracilis Myofasciocutaneous Free Flap: An Indocyanine Green Cadaveric Injection Study
Authors: Chidester Jeremy R. , Leland Hyuma A. , Navo Paul , Minneti Michael , Ghiassi Alidad , Stevanovic Milan
Published: December 2018

The gracilis free flap remains a versatile option in the reconstructive ladder. The flap itself can be harvested with or without a skin paddle. The gracilis myocutaneous free flap, however, is known for partial skin flap necrosis, especially in the distal one-third of the skin island. The gracilis myofasciocutaneous flap has been previously described as a technique to improve perfusion to the skin by harvesting surrounding deep fascia in a pedicled flap. However, limitations to this study required injection of multiple pedicles to demonstrate its perfusion. We demonstrate a novel technique using a cadaveric model that shows perfusion through injection via a single dominant pedicle (medial circumflex) with a large cutaneous paddle (average 770 cm2) with included deep fascia, using indocyanine green and near-infrared imaging. For comparison, we are also able to confirm the lack of perfusion to the distal cutaneous paddle when the fascia is not harvested, correlating with previous findings and ink injection studies. This novel technique is versatile, relatively inexpensive, and can demonstrate perfusion patterns via perforasomes that were otherwise not possible from previous techniques. Additionally, real-time imaging is possible, helping to elucidate the sequence of flow into the flap and potentially predict areas of flap necrosis.
Novel Treatment of a Malignant Peripheral Nerve Sheath Tumor of the Median Nerve
Authors: Liodaki Eirini , Robiller Sandra , Wenzel Eike , Mailaender Peter , Stang Felix
Published: December 2018

Malignant peripheral nerve sheath tumors are rare, associated with a poor prognosis and uncertainty regarding the appropriate management. We report a novel oncologic and reconstructive treatment of a young patient with a malignant peripheral nerve sheath tumor of the median nerve of the left hand. The patient underwent a wide local excision, an opponensplasty, a nerve reconstruction by nerve allografts followed by brachytherapy treatment. Two years later, the patient remains disease free with preserved function of her hand.