bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and odour evaluation of novel sulfur‐containing cyclic acetals
Authors: Miyazawa Yamato , Masuda Yui , Ohmori Yuichiro , Katsuta Ryo , Nukada Tomoo , Ishigami Ken 
Published: October 2018

AbstractSome sulfur‐containing compounds are known as useful flavours, but they have the drawback of instability in flavour composition. Therefore, we decided to develop stable sulfur‐containing compounds. We focused on 3‐mercapto‐2‐butanone (1), which is known for a meat‐like flavour. The carbonyl group of 1 was acetalized to improve the stability and to develop new flavouring compounds. We expected the resulting steric hindrance to also improve the stability of mercapto group. We synthesized 11 novel acetals based on these hypotheses. As a result, we were successful in the development of stable sulfur‐containing cyclic acetals with attractive odours.
A roadmap to climate data rescue services
Authors: Brönnimann Stefan , Brugnara Yuri , Allan Rob J. , Brunet Manola , Compo Gilbert P. , Crouthamel Richard I. , Jones Philip D. , Jourdain Sylvie , Luterbacher Jürg , Siegmund Peter , Valente Maria Antónia , Wilkinson Clive W. 
Published: October 2018

AbstractQuantitative approaches to climate risk management such as mapping or impact modelling rely on past meteorological data with daily or sub‐daily resolution, a large fraction of which have not yet been digitized. Over the last decade or so, a number of projects have contributed to the rescue of some of these data. Here we provide a summary of a survey we have undertaken of several meteorological and climate data rescue projects, in order to identify the needs of climate data rescue services. To make these efforts more sustainable, additional integrated activities are needed. We argue that meteorological and climate data rescue must be seen as a continuous, coordinated long‐term effort. Technical developments (e.g. data assimilation), new scientific questions (e.g. process understanding of extreme events) and new social (e.g. risk assessment, health) or economic (e.g. new renewable energy sources, agriculture and forestry, tourism, infrastructure, etc.) services are highlighting the immense value of data previously neglected or never considered. This continuous effort is currently undertaken by projects of various sizes, structure, funding and staffing, as well as by dedicated programmes, ranging from those within many national weather services down to “grassroots” initiatives. These activities are often not sufficiently coordinated, staffed, or funded at an international level and will benefit considerably from climate data rescue services being established within the Copernicus Climate Change Service (C3S) (https://climate.copernicus.eu/).Open PracticesThis article has earned an Open Data badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.
Socioeconomic factors and the risk of cognitive decline among the elderly population in Japan
Authors: Okamoto Shohei 
Published: October 2018

AimIn Japan, with the largest percentage of population aged 65 years or over, a dementia strategy is needed not only from a medical perspective, but also from a social policy viewpoint. This study aimed to verify the association between socioeconomic factors and cognitive decline among Japanese elderly people.MethodsCognitive decline was assessed over a 15‐year follow‐up period using memory tests or through identifying missing/proxy responses to survey questions due to cognitive dysfunction. I analysed 1886 men and 2102 women in Japan, using competing risk models for cognitive decline, to consider survival effects. Survival effects have not been considered so far although those who live longer may be more likely to experience cognitive decline.ResultsMen with higher income had a lower risk of cognitive decline (sub‐hazard ratio [SHR]: 0.997, 95% confidence interval (CI): 0.995‐0.999). Women with higher education had a lower risk of cognitive decline: 8 to 9 years (SHR: 0.646, 95% CI: 0.457‐0.914) and ≥12 years (SHR: 0.360, 95% CI: 0.164‐0.794) than women with 0 to 7 years of education.ConclusionThis study suggests that cognitive decline among the elderly Japanese population is associated with socioeconomic factors, such as income and education, even after taking survival effects into account.
Concomitant use of benzodiazepines and opioids in community‐dwelling older people with or without Alzheimer's disease—A nationwide register‐based study in Finland
Authors: Karttunen Niina , Taipale Heidi , Hamina Aleksi , Tanskanen Antti , Tiihonen Jari , Tolppanen Anna‐Maija , Hartikainen Sirpa 
Published: October 2018

ObjectiveThe study aims to determine the prevalence of concomitant use of benzodiazepines and opioids among community‐dwelling older people with or without Alzheimer's disease (AD). An additional aim was to describe the factors associated with prolonged concomitant use, and the most commonly used combinations of these drugs.MethodsThis study utilized data from the register‐based Medication Use and Alzheimer's disease (MEDALZ) study, including all community‐dwelling residents of Finland who received a clinically verified AD diagnosis between 2005 and 2011 (n = 70 718) and their matched comparison persons without AD. After exclusion of individuals who were hospitalized throughout the follow‐up, 69 353 persons with and 69 353 without AD were included in this study.ResultsBenzodiazepines and related drugs (BZDRs) were used by 28 475 (41.1%) of those with and 24 506 (35.3%) of those without AD. Prolonged (greater than or equal to 90 days) concomitant use of BZDRs and opioids was more common among BZDR users without AD (N = 3936; 16.1%) than among those with AD (N = 2963; 10.4%). A shorter duration of concomitant use (1‐89 days) revealed similar results, N = 3821; 15.6% and N = 3008; 10.6%, respectively. Prolonged concomitant use of BZDRs and opioids was associated with female sex, low socioeconomic position, most of the common comorbidities and history of substance abuse or long‐term benzodiazepine use. The most commonly used combinations were Z‐drug (31.7%) or benzodiazepine (29.9%) with a weak opioid.ConclusionsDespite the recommendations and risks, the prevalence of concomitant BZDR and opioid use was common in older persons with or without AD. It is important to develop strategies to reduce unnecessary concomitant use of these drugs.
Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr‐/‐.Leiden Mice
Authors: Morrison Martine C. , Verschuren Lars , Salic Kanita , Verheij Joanne , Menke Aswin , Wielinga Peter Y. , Iruarrizaga‐Lejarreta Marta , Gole Laurent , Yu Wei‐Miao , Turner Scott , Caspers Martien P.M. , Martínez‐Arranz Ibon , Pieterman Elsbet , Stoop Reinout , van Koppen Arianne , van den Hoek Anita M. , Mato José M. , Hanemaaijer Roeland , Alonso Cristina , Kleemann Robert 
Published: October 2018

Concerns have been raised about whether preclinical models sufficiently mimic molecular disease processes observed in nonalcoholic steatohepatitis (NASH) patients, bringing into question their translational value in studies of therapeutic interventions in the process of NASH/fibrosis. We investigated the representation of molecular disease patterns characteristic for human NASH in high‐fat diet (HFD)‐fed Ldlr‐/‐.Leiden mice and studied the effects of obeticholic acid (OCA) on these disease profiles. Multiplatform serum metabolomic profiles and genome‐wide liver transcriptome from HFD‐fed Ldlr‐/‐.Leiden mice were compared with those of NASH patients. Mice were profiled at the stage of mild (24 weeks HFD) and severe (34 weeks HFD) fibrosis, and after OCA intervention (24‐34 weeks; 10 mg/kg/day). Effects of OCA were analyzed histologically, biochemically, by immunohistochemistry, using deuterated water technology (de novo collagen formation), and by its effect on the human‐based transcriptomics and metabolomics signatures. The transcriptomics and metabolomics profile of Ldlr‐/‐.Leiden mice largely reflected the molecular signature of NASH patients. OCA modulated the expression of these molecular profiles and quenched specific proinflammatory‐profibrotic pathways. OCA attenuated specific facets of cellular inflammation in liver (F4/80‐positive cells) and reduced crown‐like structures in adipose tissue. OCA reduced de novo collagen formation and attenuated further progression of liver fibrosis, but did not reduce fibrosis below the level before intervention. Conclusion: HFD‐fed Ldlr‐/‐.Leiden mice recapitulate molecular transcriptomic and metabolomic profiles of NASH patients, and these signatures are modulated by OCA. Intervention with OCA in developing fibrosis reduces collagen deposition and de novo synthesis but does not resolve already manifest fibrosis in the period studied. These data show that human molecular signatures can be used to evaluate the translational character of preclinical models for NASH.
Sharp‐wave ripple features in macaques depend on behavioral state and cell‐type specific firing
Authors: Hussin Ahmed T. , Leonard Timothy K. , Hoffman Kari L. 
Published: October 2018

AbstractSharp‐wave ripples (SWRs) are spontaneous, synchronized neural population events in the hippocampus widely thought to play a role in memory consolidation and retrieval. They occur predominantly in sleep and quiet immobility, and in primates, they also appear during active visual exploration. Typical measures of SWRs in behaving rats include changes in the rate of occurrence, or in the incidence of specific neural ensemble activity contained within the categorical SWR event. Much less is known about the relevance of spatiotemporal SWR features, though they may index underlying activity of specific cell types including ensemble‐specific internally generated sequences. Furthermore, changes in SWR features during active exploratory states are unknown. In this study, we recorded hippocampal local‐field potentials and single‐units during periods of quiescence and as macaques performed a memory‐guided visual search task. We observed that (a) ripples during quiescence have greater amplitudes and larger postripple waves (PRW) compared to those in task epochs, and (b) during “remembered” trials, ripples have larger amplitudes than during “forgotten” trials, with no change in duration or PRWs. We further found that spiking activity influences SWR features as a function of cell type and ripple timing. As expected, larger ripple amplitudes were associated with putative pyramidal or putative basket interneuron (IN) activity, even when the spikes in question exceed the duration of the ripple. In contrast, the PRW was attenuated with activity from low firing rate cells and enhanced with activity from high firing rate cells, with putative IN spikes during ripples leading to the most prominent PRW peaks. The selective changes in SWR features as a function of time window, cell type, and cognitive/vigilance states suggest that this mesoscopic field event can offer additional information about the local network and animal's state than would be appreciated from SWR event rates alone.
Induction chemotherapy followed by allogeneic HCT versus upfront allogeneic HCT for advanced myelodysplastic syndrome: A propensity score matched analysis
Authors: Konuma Takaaki , Shimomura Yoshimitsu , Ozawa Yukiyasu , Ueda Yasunori , Uchida Naoyuki , Onizuka Makoto , Akiyama Megumi , Mori Takehiko , Nakamae Hirohisa , Ohno Yuju , Shiratori Souichi , Onishi Yasushi , Kanda Yoshinobu , Fukuda Takahiro , Atsuta Yoshiko , Ishiyama Ken ,   Adult Myelodysplastic Syndrome Working Group of the Japan Society for Hematopoietic Cell Transplantation
Published: October 2018

AbstractTo reduce post‐transplant relapse, acute myeloid leukemia (AML) type remission induction chemotherapy has been attempted to reduce disease burden before allogeneic hematopoietic cell transplantation (HCT) in patients with advanced myelodysplastic syndrome (MDS). However, the efficacy of induction chemotherapy before HCT is unclear. We retrospectively analyzed the Japanese registration data of 605 adult patients, who had received allogeneic HCT for advanced MDS between 2001 and 2016, to compare the post‐transplant relapse between patients who received induction chemotherapy followed by allogeneic HCT and those who received upfront HCT. Propensity score matching identified 230 patients from each cohort. There were no significant differences in overall survival and non‐relapse mortality between the two groups. The cumulative incidence of relapse was significantly higher in patients who received induction chemotherapy than those who received upfront HCT. In the subgroup analyses, upfront HCT had a significantly reduced relapse incidence among patients with poor cytogenetics, those with higher international prognostic scoring system at diagnosis, and those who received reduced‐intensity conditioning. Our results suggested that AML type remission induction chemotherapy before HCT did not improve post‐transplant relapse and survival for adult patients with advanced MDS. Upfront HCT is preferable for patients with a poor karyotype.
Conditional cash transfer policies in maternal health service utilization in Nepal: Analysis of safe delivery incentive program (Aama Surakshya Karyakram) using Kingdon's multiple streams framework
Authors: Khanal Geha Nath 
Published: October 2018

SummaryVarious factors limit access to and utilization of health services even when provided at subsidized cost. This results in poor utilization of services that contributes to further economic impoverishment and health care disparity. Many countries are experimenting with various approaches to tackle the poor utilization of health care services including demand‐side financing policy. This paper explains the policymaking process during the formulation of safe delivery incentive program, a conditional cash transfer program in Nepal using Kindgon's multiple streams framework. Analysis of earlier policies and programs around safe motherhood concludes that high transportation cost was a major cause for poor utilization of institutional obstetric care, despite being provided at free of cost. Health was recognized as fundamental constitutional right in 2007. This assured societal support and political commitments for protecting health constitutionally. Furthermore, there was commitment from external development partners (EDPs) for investment in maternal health. Together, these problem, policy, and politics opened Kingdon's “windows of opportunity” for formulation of conditional cash transfer policy. This paper presents evolution of Aama Surakshya Karyakram and uses Kingdon's multiple streams framework to explain how problem, policy, and politics streams converged together to allow this program to be introduced in Nepal.
Reforms in the Portuguese health care sector: Challenges and proposals
Authors: Nunes Alexandre Morais , Ferreira Diogo Cunha 
Published: October 2018

SummaryPortugal has one of the most complete public systems worldwide. Since 1979, the Portuguese National Health Service (NHS) was developed based on the integration and complementarity between different levels of care (primary, secondary, continued, and palliative care). However, in 2009, the absence of economic growth and the increased foreign debt led the country to a severe economic slowdown, reducing the public funding and weakening the decentralized model of health care administration. During the austerity period, political attention has focused primarily on reducing health care costs and consolidating the efficiency and sustainability with no structural reform. After the postcrisis period (since 2016), the recovery of the public health system begun. Since then, some proposals have required a reform of the health sector's governance structure based on the promotion of access, quality, and efficiency. This study presents several key issues involved in the current postcrisis reform of the Portuguese NHS response structure to citizens' needs. The article also discusses the implications of this Portuguese experience based on current reforms with impact on the future of citizens' health.
Prediction of river temperature surges is dependent on precipitation method
Authors: Croghan Danny , Van Loon Anne F. , Sadler Jon P. , Bradley Chris , Hannah David M. 
Published: October 2018

AbstractUrban river systems are particularly sensitive to precipitation‐driven water temperature surges and fluctuations. These result from rapid heat transfer from low‐specific heat capacity surfaces to precipitation, which can cause thermally polluted surface run‐off to enter urban streams. This can lead to additional ecological stress on these already precarious ecosystems. Although precipitation is a first‐order driver of hydrological response, water temperature studies rarely characterize rain event dynamics and typically rely on single gauge data that yield only partial estimates of catchment precipitation. This paper examines three precipitation measuring methods (a statutory automatic weather station, citizen science gauges, and radar estimates) and investigates relationships between estimated rainfall inputs and subhourly surges and diurnal fluctuations in urban river water temperature. Water temperatures were monitored at 12 sites in summer 2016 in the River Rea, in Birmingham, UK. Generalized additive models were used to model the relationship between subhourly water temperature surges and precipitation intensity and subsequently the relationship between daily precipitation totals and standardized mean water temperature. The different precipitation measurement sources give highly variable precipitation estimates that relate differently to water temperature fluctuations. The radar catchment‐averaged method produced the best model fit (generalized cross‐validation score [GCV] = 0.30) and was the only model to show a significant relationship between water temperature surges and precipitation intensity (P < 0.001, R2 = 0.69). With respect to daily metrics, catchment‐averaged precipitation estimates from citizen science data yielded the best model fit (GCV score = 0.20). All precipitation measurement and calculation methods successfully modelled the relationship between standardized mean water temperature and daily precipitation (P < 0.001). This research highlights the potential for the use of alternative precipitation datasets to enhance understanding of event‐based variability in water quality studies. We conclude by recommending the use of spatially distributed precipitation data operating at high spatial (<1 km2) and temporal (<15 min) resolutions to improve the analysis of event‐based water temperature and water quality studies.
Effect of Direct Electrical Current on Bones Infected with Staphylococcus epidermidis
Authors: Schmidt‐Malan Suzannah M , Brinkman Cassandra L , Karau Melissa J , Brown Robert A , Waletzki Brian E , Berglund Lawrence J , Schuetz Audrey N , Greenwood‐Quaintance Kerryl E , Mandrekar Jayawant N , Patel Robin 
Published: October 2018

ABSTRACTWe are developing electrical approaches to treat biofilm‐associated orthopedic foreign‐body infection. Although we have previously shown that such approaches have antibiofilm activity, the effects on bone have not been assessed. Herein, low‐amperage 200 μA fixed direct current (DC) was compared with no current, in a rat femoral foreign‐body infection model. In the infected group, a platinum implant seeded with S. epidermidis biofilm (105 CFU/cm2), plus 50 μL of a 109 CFU suspension of bacteria, were placed in the femoral medullary cavity of 71 rats. One week later, rats were assigned to one of four groups: infected with no current or DC, or uninfected with no current or DC. After 2 weeks, bones were removed and subjected to histopathology, micro‐computed tomography (μCT), and strength testing. Histopathology showed no inflammation or bony changes/remodeling in the uninfected no current group, and some osteoid formation in the DC group; bones from the infected no current group had evidence of inflammation without bony changes/remodeling; along with inflammation, there was moderate osteoid present in the DC group. μCT showed more cortical bone volume and density, trabecular thickness, and cancellous bone volume in the DC group compared with the no current group, for both uninfected and infected bones (p < 0.05). There was no difference in torsional strength or stiffness between the no current versus DC groups, for both infected and uninfected bones (p > 0.05). © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
Mechanistic insight into the attenuation of gouty inflammation by Taiwanese green propolis via inhibition of the NLRP3 inflammasome
Authors: Hsieh Chih‐Yu , Li Lan‐Hui , Rao Yerra Koteswara , Ju Tz‐Chuen , Nai Yu‐Shin , Chen Yue‐Wen , Hua Kuo‐Feng 
Published: October 2018

AbstractDysregulation of NACHT, LRR, and PYD domains‐containing protein 3 (NLRP3) inflammasome is involved in many chronic inflammatory diseases, including gouty arthritis. Activation of the NLRP3 inflammasome requires priming and activation signals: the priming signal controls the expression of NLRP3 and interleukin (IL)‐1β precursor (proIL‐1β), while the activation signal leads to the assembly of the NLRP3 inflammasome and to caspase‐1 activation. Here, we reported the effects of the alcoholic extract of Taiwanese green propolis (TGP) on the NLRP3 inflammasome in vitro and in vivo. TGP inhibited proIL‐1β expression by reducing nuclear factor kappa B activation and reactive oxygen species (ROS) production in lipopolysaccharide‐activated macrophages. Additionally, TGP also suppressed the activation signal by reducing mitochondrial damage, ROS production, lysosomal rupture, c‐Jun N‐terminal kinases 1/2 phosphorylation and apoptosis‐associated speck‐like protein oligomerization. Furthermore, we found that TGP inhibited the NLRP3 inflammasome partially via autophagy induction. In the in vivo mouse model of uric acid crystal‐induced peritonitis, TGP attenuated the peritoneal recruitment of neutrophils, and the levels of IL‐1β, active caspase‐1, IL‐6 and monocyte chemoattractant protein‐1 in lavage ﬂuids. As a proof of principle, in this study, we purified a known compound, propolin G, from TGP and identified this compound as a potential inhibitor of the NLRP3 inflammasome. Our results indicated that TGP might be useful for ameliorating gouty inflammation via inhibition of the NLRP3 inflammasome.