bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic reduction of the extracellular matrix protein versican attenuates inflammatory cell infiltration and improves contractile function in dystrophic mdx diaphragm muscles
Authors: McRae Natasha L. , Addinsall Alex B. , Howlett Kirsten F. , McNeill Bryony , McCulloch Daniel R. , Stupka Nicole 
Published: July 2020

AbstractThere is a persistent, aberrant accumulation of V0/V1 versican in skeletal muscles from patients with Duchenne muscular dystrophy and in diaphragm muscles from mdx mice. Versican is a provisional matrix protein implicated in fibrosis and inflammation in various disease states, yet its role in the pathogenesis of muscular dystrophy is not known. Here, female mdx and male hdf mice (haploinsufficient for the versican allele) were bred. In the resulting F1 mdx-hdf male pups, V0/V1 versican expression in diaphragm muscles was decreased by 50% compared to mdx littermates at 20–26 weeks of age. In mdx-hdf mice, spontaneous physical activity increased by 17% and there was a concomitant decrease in total energy expenditure and whole-body glucose oxidation. Versican reduction improved the ex vivo strength and endurance of diaphragm muscle strips. These changes in diaphragm contractile properties in mdx-hdf mice were associated with decreased monocyte and macrophage infiltration and a reduction in the proportion of fibres expressing the slow type I myosin heavy chain isoform. Given the high metabolic cost of inflammation in dystrophy, an attenuated inflammatory response may contribute to the effects of versican reduction on whole-body metabolism. Altogether, versican reduction ameliorates the dystrophic pathology of mdx-hdf mice as evidenced by improved diaphragm contractile function and increased physical activity.
Histological assessment of optogenetic tools to study fronto-visual and fronto-parietal cortical networks in the rhesus macaque
Authors: Fortuna Michal G. , Hüer Janina , Guo Hao , Gruber Jens , Gruber-Dujardin Eva , Staiger Jochen F. , Scherberger Hansjörg , Treue Stefan , Gail Alexander 
Published: July 2020

AbstractOptogenetics offers unprecedented possibilities to investigate cortical networks. Yet, the number of successful optogenetic applications in non-human primates is still low, and the consequences of opsin expression in the primate brain are not well documented. We assessed histologically if we can target cerebrocortical networks with three common optogenetic constructs (AAV2/5-CaMKIIα-eNpHR3.0-mCherry, -ChR2-eYFP, -C1V1-mCherry). The frontal eye field or the dorsal premotor area of rhesus macaques were virally injected, and the resulting transduction spread, expression specificity, and opsin trafficking into axons projecting to parietal and visual areas were examined. After variable periods (2–24 months), expression was robust for all constructs at the injection sites. The CaMKIIα promoter driven-expression was predominant, but not exclusive, in excitatory neurons. In the case of eNpHR3.0-mCherry and ChR2-eYFP, opsins were present in axonal projections to target areas, in which sparse, retrogradely transduced neurons could also be found. Finally, the intracellular distribution of opsins differed: ChR2-eYFP had almost exclusive membrane localization, while eNpHR3.0-mCherry and C1V1-mCherry showed additional intracellular accumulations, which might affect neuronal survival in the long-term. Results indicate that all three constructs can be used for local neuronal modulation, but axonal stimulation and long-term use require additional considerations of construct selection and verification.
Association of maternal sleep before and during pregnancy with preterm birth and early infant sleep and temperament
Authors: Nakahara Kazushige , Michikawa Takehiro , Morokuma Seiichi , Ogawa Masanobu , Kato Kiyoko , Sanefuji Masafumi , Shibata Eiji , Tsuji Mayumi , Shimono Masayuki , Kawamoto Toshihiro , Ohga Shouichi , Kusuhara Koichi ,   The Japan Environment and Children’s Study Group, Kamijima Michihiro , Yamazaki Shin , Ohya Yukihiro , Kishi Reiko , Yaegashi Nobuo , Hashimoto Koichi , Mori Chisato , Ito Shuichi , Yamagata Zentaro , Inadera Hidekuni , Nakayama Takeo , Iso Hiroyasu , Shima Masayuki , Kurozawa Youichi , Suganuma Narufumi , Katoh Takahiko 
Published: July 2020

AbstractThis study aimed to investigate the association of maternal sleep before and during pregnancy with preterm birth, infant sleep and temperament at 1 month of age. We used the data of the Japan Environment and Children’s Study, a cohort study in Japan, which registered 103,099 pregnancies between 2011 and 2014. Participants were asked about their sleep before and during pregnancy, and the sleep and temperament of their newborns at 1 month of age. Preterm birth data were collected from medical records. Maternal sleep was not associated with preterm birth, but subjective sleep quality during pregnancy was associated with late preterm birth (birth at 34–36 weeks of gestation). For example, participants with extremely light subjective depth of sleep were more likely to experience preterm birth (RR = 1.19; 95% confidence interval [CI] = 1.04–1.35). Maternal sleep both before and during pregnancy seemed to be associated with infant sleep and temperament at 1 month of age. Infants, whose mothers slept for less than 6 hours before pregnancy, tended to cry intensely (RR = 1.15; 95% CI = 1.09–1.20). Maternal sleep problems before and during pregnancy were associated with preterm birth and child sleep problems and temperament.
The cellular heat shock response monitored by chemical exchange saturation transfer MRI
Authors: Kleimaier Dennis , Goerke Steffen , Nies Cordula , Zaiss Moritz , Kunz Patrick , Bachert Peter , Ladd Mark E. , Gottwald Eric , Schad Lothar R. 
Published: July 2020

AbstractCEST-MRI of the rNOE signal has been demonstrated in vitro to be closely linked to the protein conformational state. As the detectability of denaturation and aggregation processes on a physiologically relevant scale in living organisms has yet to be verified, the aim of this study was to perform heat-shock experiments with living cells to monitor the cellular heat-shock response of the rNOE CEST signal. Cancer cells (HepG2) were dynamically investigated after a mild, non-lethal heat-shock of 42 °C for 20 min using an MR-compatible bioreactor system at 9.4 T. Reliable and fast high-resolution CEST imaging was realized by a relaxation-compensated 2-point contrast metric. After the heat-shock, a substantial decrease of the rNOE CEST signal by 8.0 ± 0.4% followed by a steady signal recovery within a time of 99.1 ± 1.3 min was observed in two independent trials. This continuous signal recovery is in coherence with chaperone-induced refolding of heat-shock induced protein aggregates. We demonstrated that protein denaturation processes influence the CEST-MRI signal on a physiologically relevant scale. Thus, the protein folding state is, along with concentration changes, a relevant physiological parameter for the interpretation of CEST signal changes in diseases that are associated with pathological changes in protein expression, like cancer and neurodegenerative diseases.
Risk factors for endothelial cell loss after Descemet membrane endothelial keratoplasty (DMEK)
Authors: Hayashi Takahiko , Schrittenlocher Silvia , Siebelmann Sebastian , Le Viet Nhat Hung , Matthaei Mario , Franklin Jeremy , Bachmann Björn , Cursiefen Claus 
Published: July 2020

AbstractThis study aimed to identify the risk factors for endothelial cell density (ECD) loss after Descemet membrane endothelial keratoplasty (DMEK) and analyse whether donor tissues from cold versus organ culture differ in terms of ECD loss after DMEK. Consecutive DMEK cases from a prospective database for Fuchs’ endothelial corneal dystrophy were retrospectively analysed between 2011 and 2016 at the University of Cologne, and the possible risk factors for ECD loss, including patient-related factors, type of tamponade (air or 20% sulphur hexafluoride gas), type of surgery (triple DMEK or DMEK alone), re-bubbling, immune rejection, and donor-related factors were determined. Eight hundred and forty-one eyes were selected. There was no significant difference in the best-corrected visual acuity (logarithm of the minimal angle of resolution) and corneal thickness (P = 0.540 and P = 0.667) between groups. Immune reactions were more common in cold cultures (P = 0.019), but ECD loss (1 year after DMEK) was greater in organ cultures (38.3 ± 0.8%) than in cold cultures (34.7 ± 1.4%) (P = 0.022). Only re-bubbling was significantly associated with ECD loss (P < 0.001). Re-bubbling was found to be a key factor for ECD loss at 1 year after DMEK.
Water corrosivity of polluted reservoir and hydropower sustainability
Authors: Sunardi Sunardi , Ariyani Miranti , Agustian Mochammad , Withaningsih Susanti , Parikesit Parikesit , Juahir Hafizan , Ismail Azimah , Abdoellah Oekan S. 
Published: July 2020

AbstractReservoirs play a strategic role in the context of sustainable energy supply. Unfortunately, the majority of the reservoirs are facing water-quality degradation due to complex pollutants originating from activities both in the catchment and inside the reservoir. This research was aimed at assessing the extent of the water degradation, in terms of corrosivity level, and at examining its impacts on hydropower capacity and operation. Water quality data (total dissolved solids, pH, calcium, bicarbonate, and temperature) were obtained from 20 sampling stations in the Cirata Reservoir from 2007 to 2016. The results show that the river water is already corrosive (Langelier Saturation Index, LSI = − 0.21 to − 1.08), and, the corrosiveness becoming greater when entering the reservoir (LSI = − 0.52 to − 1.49). The water corrosivity has caused damage to the hydro-mechanical equipment and lowering production capacity. The external environment of the catchment hosts complex human activities, such as agriculture, land conversion, urban and industrial discharge, which have all played a major role in the water corrosiveness. Meanwhile, the internal environment, such as floating net cage aquaculture, has intensified the problem. As the water corrosiveness has increased, the maintenance of the hydro-mechanical facilities has also increased. Strategies must be applied as current conditions are certainly a threat to the sustainability of the hydropower operation and, hence, the energy supply.
Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis
Authors: Kim Yeesuk , Tian Yuxi , Yang Jianxiao , Huser Vojtech , Jin Peng , Lambert Christophe G. , Park Hojun , You Seng Chan , Park Rae Woong , Rijnbeek Peter R. , Van Zandt Mui , Reich Christian , Vashisht Rohit , Wu Yonghui , Duke Jon , Hripcsak George , Madigan David , Shah Nigam H. , Ryan Patrick B. , Schuemie Martijn J. , Suchard Marc A. 
Published: July 2020

AbstractAlendronate and raloxifene are among the most popular anti-osteoporosis medications. However, there is a lack of head-to-head comparative effectiveness studies comparing the two treatments. We conducted a retrospective large-scale multicenter study encompassing over 300 million patients across nine databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporotic hip fracture, while secondary outcomes were vertebral fracture, atypical femoral fracture (AFF), osteonecrosis of the jaw (ONJ), and esophageal cancer. We used propensity score trimming and stratification based on an expansive propensity score model with all pre-treatment patient characteritistcs. We accounted for unmeasured confounding using negative control outcomes to estimate and adjust for residual systematic bias in each data source. We identified 283,586 alendronate patients and 40,463 raloxifene patients. There were 7.48 hip fracture, 8.18 vertebral fracture, 1.14 AFF, 0.21 esophageal cancer and 0.09 ONJ events per 1,000 person-years in the alendronate cohort and 6.62, 7.36, 0.69, 0.22 and 0.06 events per 1,000 person-years, respectively, in the raloxifene cohort. Alendronate and raloxifene have a similar hip fracture risk (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.94–1.13), but alendronate users are more likely to have vertebral fractures (HR 1.07, 95% CI 1.01–1.14). Alendronate has higher risk for AFF (HR 1.51, 95% CI 1.23–1.84) but similar risk for esophageal cancer (HR 0.95, 95% CI 0.53–1.70), and ONJ (HR 1.62, 95% CI 0.78–3.34). We demonstrated substantial control of measured confounding by propensity score adjustment, and minimal residual systematic bias through negative control experiments, lending credibility to our effect estimates. Raloxifene is as effective as alendronate and may remain an option in the prevention of osteoporotic fracture.
Plasmodium spp. mixed infection leading to severe malaria: a systematic review and meta-analysis
Authors: Kotepui Manas , Kotepui Kwuntida Uthaisar , De Jesus Milanez Giovanni , Masangkay Frederick Ramirez 
Published: July 2020

AbstractMixedPlasmodiummalaria infections can lead to severe malaria. This systematic review and meta-analysis aimed to explore the prevalence of severe mixedPlasmodiummalaria infection and to compare it with the prevalence of severeP. falciparummalaria mono-infection across the included studies. Original English-language research articles from PubMed, Scopus, and ISI Web of Science were identified and screened. Articles reporting the number of mixed infections and the number of severe mixed infections were used to determine the main outcome of this study, while the number ofP. falciparuminfections and the number of severeP. falciparuminfections were used to determine the secondary outcome of this study. For the main outcome, the pooled prevalence and 95% confidence interval (CI) of severe mixed infections was analysed using STATA software version 15.0 (Stata Corp, College Station, TX, USA). For the secondary outcome, the rate of severe mixed infections compared to severeP. falciparuminfections was analysed using the meta-analysis approach, and summary odds ratios (ORs) and 95% CIs were calculated. Random-effects models were used to produce the summary ORs. The Mantel–Haenszel method and calculated I2were also reported to test whether there was heterogeneity among the included studies. Publication bias was also assessed using funnel plots. The meta-analysis of secondary outcomes was conducted using Review Manager 5.3 software (Cochrane Community). A total of 894,561 malaria patients were reported in all 16 included studies. Overall, a pooled analysis showed that 9% (2,006/35,768, 95% CI 7.0–12.0%) of patients with mixedPlasmodiuminfection had severe mixed infection. A meta-analysis of 14 studies demonstrated that patients with mixedPlasmodiuminfection (1,999/35,755) and patients withP. falciparummalaria (9,249/294,397) had an equal risk of developing severe malaria (OR 0.93, 95% CI 0.59–1.44). Both mixed infection andP. falciparummono-infection showed a similar trend of complications in which severe anaemia, pulmonary failure, and renal impairment were the three most common complications found. However, patients with mixed infection had a higher proportion of severe anaemia and pulmonary complications than those withP. falciparuminfection. Moreover, patients with mixed infection had a higher proportion of multiple organ failure than those withP. falciparummono-infection. MixedPlasmodiumspp. infections were common but often unrecognized or underestimated, leading to severe complications among these malaria patients.Therefore, in routine clinical laboratories, using an accurate combination of diagnostic procedures to identify suspected patients with mixed infections is crucial for therapeutic decisions, prompt treatment, and effective patient management.
Rapid identification of tsunamigenic earthquakes using GNSS ionospheric sounding
Authors: Manta Fabio , Occhipinti Giovanni , Feng Lujia , Hill Emma M. 
Published: July 2020

AbstractThe largest tsunamis are generated by seafloor uplift resulting from rupture of offshore subduction-zone megathrusts. The rupture of the shallowest part of a megathrust often produces unexpected outsize tsunami relative to their seismic magnitude. These are so called ‘tsunami earthquakes’, which are difficult to identify rapidly using the current tsunami warning systems, even though, they produce some of the deadliest tsunami. We here introduce a new method to evaluate the tsunami risk by measuring ionospheric total electron content (TEC). We examine two Mw 7.8 earthquakes (one is a tsunami earthquake and the other is not) generated in 2010 by the Sunda megathrust, offshore Sumatra, to demonstrate for the first time that observations of ionospheric sounding from Global Navigation Satellite System (GNSS) can be used to evaluate the tsunamigenic potential of earthquakes as early as 8 min after the mainshock.
Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase
Authors: Shepelev Nikita M. , Mariasina Sofia S. , Mantsyzov Alexey B. , Malyavko Alexander N. , Efimov Sergey V. , Petrova Olga A. , Rodina Elena V. , Zvereva Maria I. , Dontsova Olga A. , Polshakov Vladimir I. 
Published: July 2020

AbstractTelomerase is a ribonucleoprotein enzyme, which maintains genome integrity in eukaryotes and ensures continuous cellular proliferation. Telomerase holoenzyme from the thermotolerant yeast Hansenula polymorpha, in addition to the catalytic subunit (TERT) and telomerase RNA (TER), contains accessory proteins Est1 and Est3, which are essential for in vivo telomerase function. Here we report the high-resolution structure of Est3 from Hansenula polymorpha (HpEst3) in solution, as well as the characterization of its functional relationships with other components of telomerase. The overall structure of HpEst3 is similar to that of Est3 from Saccharomyces cerevisiae and human TPP1. We have shown that telomerase activity in H. polymorpha relies on both Est3 and Est1 proteins in a functionally symmetrical manner. The absence of either Est3 or Est1 prevents formation of a stable ribonucleoprotein complex, weakens binding of a second protein to TER, and decreases the amount of cellular TERT, presumably due to the destabilization of telomerase RNP. NMR probing has shown no direct in vitro interactions of free Est3 either with the N-terminal domain of TERT or with DNA or RNA fragments mimicking the probable telomerase environment. Our findings corroborate the idea that telomerase possesses the evolutionarily variable functionality within the conservative structural context.
Public health benefits of water purification using recycled hemodialyzers in developing countries
Authors: Raimann Jochen G. , Boaheng Joseph Marfo , Narh Philipp , Matti Harrison , Johnson Seth , Donald Linda , Zhang Hongbin , Port Friedrich , Levin Nathan W. 
Published: July 2020

AbstractIn rural regions with limited resources, the provision of clean water remains challenging. The resulting high incidence of diarrhea can lead to acute kidney injury and death, particularly in the young and the old. Membrane filtration using recycled hemodialyzers allows water purification. This study quantifies the public health effects. Between 02/2018 and 12/2018, 4 villages in rural Ghana were provided with a high-volume membrane filtration device (NuFiltration). Household surveys were collected monthly with approval from Ghana Health Services. Incidence rates of diarrhea for 5-month periods before and after implementation of the device were collected and compared to corresponding rates in 4 neighboring villages not yet equipped. Data of 1,130 villagers over 10 months from the studied communities were studied. Incidence rates showed a decline following the implementation of the device from 0.18 to 0.05 cases per person-month (ppm) compared to the control villages (0.11 to 0.08 ppm). The rate ratio of 0.27 for the study villages is revised to 0.38 when considering the non-significant rate reduction in the control villages. Provision of a repurposed hemodialyzer membrane filtration device markedly improves health outcomes as measured by diarrhea incidence within rural communities.
VARENN: graphical representation of periodic data and application to climate studies
Authors: Ise Takeshi , Oba Yurika 
Published: July 2020

AbstractAnalyzing and utilizing spatiotemporal big data are essential for studies concerning climate change. However, such data are not fully integrated into climate models owing to limitations in statistical frameworks. Herein, we employ VARENN (visually augmented representation of environment for neural networks) to efficiently summarize monthly observations of climate data for 1901–2016 into two-dimensional graphical images. Using red, green, and blue channels of color images, three different variables are simultaneously represented in a single image. For global datasets, models were trained via convolutional neural networks. These models successfully classified the rises and falls in temperature and precipitation. Moreover, similarities between the input and target variables were observed to have a significant effect on model accuracy. The input variables had both seasonal and interannual variations, whose importance was quantified for model efficacy. We successfully illustrated the importance of short-term (monthly) fluctuations in the model accuracy, suggesting that our AI-based approach grasped some previously unknown patterns that are indicators of succeeding climate trends. VARENN is thus an effective method to summarize spatiotemporal data objectively and accurately.
β-amyloid and tau drive early Alzheimer’s disease decline while glucose hypometabolism drives late decline
Authors: Hammond Tyler C. , Xing Xin , Wang Chris , Ma David , Nho Kwangsik , Crane Paul K. , Elahi Fanny , Ziegler David A. , Liang Gongbo , Cheng Qiang , Yanckello Lucille M. , Jacobs Nathan , Lin Ai-Ling 
Published: July 2020

AbstractClinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer’s disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer’s Disease Neuroimaging Initiative dataset, we show that A/T/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of Aβ and tau better predicting early dementia status, and biomarkers of neurodegeneration, especially glucose hypometabolism, better predicting later dementia status. Our results suggest that AD treatments may also need to be disease stage-oriented with Aβ and tau as targets in early AD and glucose metabolism as a target in later AD.