bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral health behaviour, attitude towards, and knowledge of dental caries among mothers of 0‐ to 3‐year‐old children living in Kaunas, Lithuania
Authors: Petrauskienė Sandra , Narbutaitė Julija , Petrauskienė Aušra , Virtanen Jorma I.
Published: December 2019

Objectives

This study aimed to investigate the oral health behaviours of mothers with young children and their attitudes towards dental caries.

Methods

The survey targeted all mothers with children under 3 years attending a primary healthcare centre (Department of Family Medicine at the Lithuanian University of Health Sciences [LSMU] Hospital) in Kaunas, Lithuania. The Bioethics Centre of the LSMU approved the study (No. BEC‐OF‐14). Of 176 mothers, 123 (69.9%) took part in the 2016–2017 study. The self‐administered questionnaire enquired about mothers' attitudes towards oral health and behaviours related to the potential transmission of oral bacteria to their children, dietary habits, tooth brushing, smoking, and background factors. The chi‐squared test and univariate/multivariate logistic regression analyses served for the statistical analysis. (pvalues ≤ .05 indicated statistically significant differences).

Results

Most (76; 68.5%) of the mothers brushed their teeth twice daily, and 97 (87.4%) reported themselves as nonsmokers. We found a statistically significant association between mothers who brushed their own teeth twice daily and those who cleaned their children's teeth likewise (OR = 5.42, 95% CI [1.28–6.63];p= .005). We observed significant associations among mothers who gave their children sugar‐sweetened beverages (SSBs) daily and the mothers' college or lower education (OR = 6.51, 95% CI [1.59–27.19];p= .01) and maternal tooth brushing less than twice daily (OR = 3.88, 95% CI [0.99–15.18];p= .05).

Conclusions

A majority of mothers who took part in this survey did not brush their children's teeth as recommended. Mothers with a lower education and who brushed their teeth less than twice daily offered their children SSBs more frequently.
Treatment of lower limb ischaemia in patients with diabetes
Authors: Choke Edward , Tang Tjun Y. , Cheng Shin C. , Tay Jia S.
Published: December 2019

Diabetic chronic limb‐threatening ischaemia is a challenging clinical problem with patients at high risk of diabetic foot ulceration (DFU) and limb loss. Patients often remain asymptomatic even in the presence of severe pedal ischaemia until first presenting with tissue loss such as DFU or frank gangrene. Limb salvage units should have the facilities and expertise to provide multidisciplinary team‐based holistic care through best medical therapy, rapid diagnosis, prompt revascularisation with endovascular or open surgical techniques and expert wound management. Endovascular revascularisation has become the first line strategy in contemporary clinical practice because of similar outcomes in wound healing and amputation rates in most patients when compared with open surgery. The primary goal is restoration of pulsatile in‐line blood flow to the ankle or foot, with an angiosome‐directed approach possibly achieving superior outcomes especially in diabetics with poor collaterals. A comprehensive overview of conventional endovascular techniques (such as antegrade true lumen and subintimal approaches), advanced techniques for complex disease (such as retrograde subintimal and pedal‐plantar loop approaches or even deep venous arterialisation) and the various treatment options are described. Diabetic limb salvage rates can be excellent with suitable multidisciplinary expertise and care.
Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes
Authors: Dhage Shaishav , Ho Jan Hoong , Ferdousi Maryam , Kalteniece Alise , Azmi Shazli , Adam Safwaan , Marshall Andrew , Jeziorska Maria , Donn Rachelle , Soran Handrean , Malik Rayaz A.
Published: December 2019

Aims

The aim of this study was to evaluate the contribution of small and large fibre neuropathy to erectile dysfunction (ED) in men with type 2 diabetes (T2D).

Methods

Measures of small and large fibre neuropathy were evaluated in 49 participants with T2D and 20 age‐matched controls.

Results

ED was present in 59% of participants with T2D. There was no difference in age, duration of diabetes, blood pressure, lipid profile, vibration perception threshold (V) (14.3 ± 7.8 vs 11.2 ± 6.6, P = .429), peroneal (41.4 ± 8.2 vs 44.8 ± 4.4, P = .10) and sural (45.4 ± 5.6 vs 47.1 ± 5.8) nerve conduction velocities (m/s), cold (25.1 ± 3.8 vs 26.2 ± 2.9, P = .815) and warm (43.2 ± 4.0 vs 41.0 ± 3.8) perception thresholds (°C), and deep breathing heart rate variability (18 ± 8 vs 18 ± 8) between participants with and without ED. However, intraepidermal nerve fibre density (no./mm2) (4.6 ± 2.8 vs 13.7 ± 2.7, P < .001), corneal nerve fibre density (no./mm2) (23.5 ± 6.8 vs 31.3 ± 8.2, P < .001), corneal nerve fibre branch density (no./mm2) (55.4 ± 35.3 vs 97.7 ± 46.4, P = .004), corneal nerve fibre length (mm/mm2) (17.6 ± 6.8 vs 27.3 ± 6.8, P < .001), and sural (7.7 ± 6.1 vs 14.6 ± 6.7, P = .003) and peroneal (2.5 ± 2.0 vs 4.7 ± 2.0, P = .003) nerve amplitudes were significantly lower in participants with ED compared with those without ED.

Conclusion

ED affects almost 2/3 of men with T2D and is associated with small nerve fibre damage but preserved nerve conduction and cardiac autonomic function. Corneal confocal microscopy may serve as a useful non‐invasive imaging method to identify small fibre damage in patients with T2D and ED.
Symbiotic lifestyle triggers drastic changes in the gene expression of the algal endosymbiont Breviolum minutum (Symbiodiniaceae)
Authors: Maor‐Landaw Keren , van Oppen Madeleine J. H. , McFadden Geoffrey I.
Published: December 2019

Coral–dinoflagellate symbiosis underpins the evolutionary success of corals reefs. Successful exchange of molecules between the cnidarian host and the Symbiodiniaceae algae enables the mutualistic partnership. The algae translocate photosynthate to their host in exchange for nutrients and shelter. The photosynthate must traverse multiple membranes, most likely facilitated by transporters. Here, we compared gene expression profiles of cultured, free‐living Breviolum minutum with those of the homologous symbionts freshly isolated from the sea anemone Exaiptasia diaphana, a widely used model for coral hosts. Additionally, we assessed expression levels of a list of candidate host transporters of interest in anemones with and without symbionts. Our transcriptome analyses highlight the distinctive nature of the two algal life stages, with many gene expression level changes correlating to the different morphologies, cell cycles, and metabolisms adopted in hospite versus free‐living. Morphogenesis‐related genes that likely underpin the metamorphosis process observed when symbionts enter a host cell were up‐regulated. Conversely, many down‐regulated genes appear to be indicative of the protective and confined nature of the symbiosome. Our results emphasize the significance of transmembrane transport to the symbiosis, and in particular of ammonium and sugar transport. Further, we pinpoint and characterize candidate transporters—predicted to be localized variously to the algal plasma membrane, the host plasma membrane, and the symbiosome membrane—that likely serve pivotal roles in the interchange of material during symbiosis. Our study provides new insights that expand our understanding of the molecular exchanges that underpin the cnidarian–algal symbiotic relationship.
Rare species, functional groups, and evolutionary lineages drive successional trajectories in disturbed forests
Authors: Thorn Simon , Chao Anne , Bernhardt‐Römermann Markus , Chen Yan‐Han , Georgiev Kostadin B. , Heibl Christoph , Müller Jörg , Schäfer Hanno , Bässler Claus
Published: December 2019

Following natural disturbances, additional anthropogenic disturbance may alter community recovery by affecting the occurrences of species, functional groups, and evolutionary lineages. However, our understanding of whether rare, common, or dominant species, functional groups, or evolutionary lineages are most strongly affected by an additional disturbance, particularly across multiple taxa, is limited. Here, we used a generalized diversity concept based on Hill numbers to quantify the community differences of vascular plants, bryophytes, lichens, wood‐inhabiting fungi, saproxylic beetles, and birds in a storm‐disturbed, experimentally salvage logged forest. Communities of all investigated species groups showed dissimilarities between logged and unlogged plots. Most species groups showed no significant changes in dissimilarities between logged and unlogged plots over the first seven years of succession, indicating a lack of community recovery. In general, the dissimilarities of communities were mainly driven by rare species. Convergence of dissimilarities occurred more often than divergence during the early stages of succession for rare species, indicating a major role in driving decreasing taxonomic dissimilarities between logged and unlogged plots over time. Trends in species dissimilarities only partially match the trends in dissimilarities of functional groups and evolutionary lineages, with little significant changes in successional trajectories. Nevertheless, common and dominant species contributed to a convergence of dissimilarities over time in the case of the functional dissimilarities of wood‐inhabiting fungi. Our study shows that salvage logging following disturbances can alter successional trajectories in early stages of forest succession following natural disturbances. However, community changes over time may differ remarkably in different taxonomic groups and are best detected based on taxonomic, rather than functional or phylogenetic dissimilarities.
IL‐15 and CD155 expression regulate LAT expression in murine DNAM1+ NK cells, enhancing their effectors functions
Authors: Luu Thuy T. , Wagner Arnika K. , Schmied Laurent , Meinke Stephan , Freund Jacquelyn E. , Kambayashi Taku , Ravens Inga , Achour Adnane , Bernhardt Gunter , Chambers Benedict J. , Höglund Petter , Kadri Nadir
Published: December 2019

NK cells are innate immune cells characterized by their ability to spontaneously lyse tumor and virally infected cells. We have recently demonstrated that IL‐15‐sufficient DC regulate NK cell effector functions in mice. Here, we established that among ITAM‐proximal signaling molecules, the expression levels of the scaffold molecule Linker for Activation of T cells (LAT) and its transcription factor ELF‐1 were reduced 4 days after in vivo depletion of DC. Addition of IL‐15, a cytokine presented by DC to NK cells, regulates LAT expression in NK cells with a significant effect on the DNAM1+ subset compared to DNAM1− cells. We also found that LAT expression is regulated via interaction of the DNAM1 receptor with its ligand CD155 in both immature and mature NK cells, independently of NK cell education. Finally, we found that LAT expression within DNAM1+ NK cells might be responsible for enhanced calcium mobilization following the triggering of activating receptors on NK cells. Altogether, we found that LAT expression is tightly regulated in DNAM1+ NK cells, via interaction(s) with DC, which express CD155 and IL‐15, resulting in rapid activation of the DNAM1+ subset during activating receptor triggering.
Paired 10Be sampling of polished bedrock and erratic boulders to improve dating of glacial landforms: an example from the Western Alps
Authors: Prud'homme Charlotte , Vassallo Riccardo , Crouzet Christian , Carcaillet Julien , Mugnier Jean‐Louis , Cortés‐Aranda Joaquin
Published: December 2019

Cosmogenic nuclide dating of glacial landforms may lead to ambiguous results for ice retreat histories. The persistence of significant cosmogenic concentrations inherited from previous exposure may increase the apparent exposure ages for polished bedrocks affected by limited erosion under ice and for erratic boulders transported by glaciers and previously exposed in high‐altitude rock walls. In contrast, transient burying by moraines, sediments and snow decreases the apparent exposure age. We propose a new sampling strategy, applied to four sites distributed in the Arc and Arve valleys in the Western Alps, to better constrain the factors that can bias exposure ages associated with glacial processes. We used the terrestrial cosmogenic nuclide 10Be (TCN) to estimate the exposure time from paired sampling of depth profiles in polished bedrock and on overlying erratic boulders. For a given sampling site, the exposure ages for both the polished bedrock and boulder are expected to be the same. However, in six cases out of seven, boulders had significantly higher 10Be surface concentrations than those of the associated polished surfaces. In present and past glacial processes, the 10Be distribution with depth for boulders and bedrocks implies the presence of an inheritance concentration of 10Be. Our study suggests that 10Be concentrations in erratic boulders and in polished bedrocks provide maximum and minimum exposure ages of the glacial retreat, respectively. © 2019 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
The gender variation on the electroencephalographic activity in response to the exposure of black pepper essential oil from Kampong Cham, Cambodia
Authors: Kim Minju , Chhoeun Tith Bun , Kim Taehee , Sowndhararajan Kandhasamy , Kim Songmun
Published: December 2019

The present study was carried out to investigate the effect of exposure of Cambodian black pepper essential oil on the human electroencephalographic (EEG) activity. In the EEG study, 20 men and 20 women healthy volunteers participated. The EEG readings were recorded from 32 electrodes placed on the scalp according to the International 10‐20 system and 25 EEG indices were analyzed. The essential oil of black pepper mainly contains β‐caryophyllene (30.53%), 3‐carene (19.85%), limonene (14.26%), β‐pinene (9.45%), and α‐pinene (5.25%). The EEG data showed that the exposure of black pepper essential oil exhibited different brain wave activity according to the gender. In women, a significant increase of spectral edge frequency 50% of alpha at C4 region was observed due to the exposure of black pepper essential oil. In the case of men, relative gamma, the ratio of sensorimotor rhythm to theta, spectral edge frequency 50%, spectral edge frequency 90%, and spectral edge frequency 50% of alpha significantly increased during the exposure of black pepper essential oil. The result revealed that the gender variation plays a major role in the EEG activity of black pepper essential oil and the exposure of black pepper essential oil may improve the cognitive functions.
Optimizing synchronous extraction and antioxidant activity evaluation of polyphenols and polysaccharides from Ya'an Tibetan tea (Camellia sinensis)
Authors: Zheng Qiaoran , Li Wenfeng , Zhang Heng , Gao Xiaoxu , Tan Si
Published: December 2019

The optimal synchronous conditions to extract tea polysaccharides (TPS) and tea polyphenols (TPP) from Ya'an Tibetan tea were investigated, and the antioxidative capacity of TPS and TPP was measured, and the tea was analyzed to identify the polyphenol compounds it contained. On the basis of single‐factor experiments, a Box–Behnken design and response surface methodology were applied to optimize the hot water extraction conditions. The optimal extraction technology was determined as extraction temperature of 83°C, time of 104 min, and liquid‐to‐material ratio of 41 ml/g, yielding TPP and TPS at 42.70 ± 2.38 mg/g and 53.86 ± 3.79 mg/g, respectively. The TPS and TPP in Ya'an Tibetan tea have high eliminating activities on DPPH and strong reducing power, with TPP showing a higher antioxidant activity than TPS. UHPLC‐QqQ‐MS/MS analysis identified EGCG, GCG, and ECG as major polyphenol components in Ya'an Tibetan tea. These findings might promote the application of Ya'an Tibetan tea in the food industry.
Prediction kinetic, energy and exergy of quince under hot air dryer using ANNs and ANFIS
Authors: Abbaspour‐Gilandeh Yousef , Jahanbakhshi Ahmad , Kaveh Mohammad
Published: December 2019

This study aimed to predict the drying kinetics, energy utilization (Eu), energy utilization ratio (EUR), exergy loss, and exergy efficiency of quince slice in a hot air (HA) dryer using artificial neural networks and ANFIS. The experiments were performed at air temperatures of 50, 60, and 70°C and air velocities of 0.6, 1.2, and 1.8 m/s. The thermal parameters were determined using thermodynamic relations. Increasing air temperature and air velocity increased the effective moisture diffusivity (Deff), Eu, EUR, exergy efficiency, and exergy loss. The value of the Deff was varied from 4.19 × 10–10 to 1.18 × 10–9 m2/s. The highest value Eu, EUR, and exergy loss and exergy efficiency were calculated 0.0694 kJ/s, 0.882, 0.044 kJ/s, and 0.879, respectively. Midilli et al. model, ANNs, and ANFIS model, with a determination coefficient (R2) of .9992, .9993, and .9997, provided the best performance for predicting the moisture ratio of quince fruit. Also, the ANFIS model, in comparison with the artificial neural networks model, was better able to predict Eu, EUR, exergy efficiency, and exergy loss, with R2 of .9989, .9988, .9986, and .9978, respectively.
Deletion of astrocytic BMAL1 results in metabolic imbalance and shorter lifespan in mice
Authors: Barca‐Mayo Olga , Boender Arjen J. , Armirotti Andrea , De Pietri Tonelli Davide
Published: December 2019

Disruption of the circadian cycle is strongly associated with metabolic imbalance and reduced longevity in humans. Also, rodent models of circadian arrhythmia, such as the constitutive knockout of the clock gene Bmal1, leads to metabolic disturbances and early death. Although astrocyte clock regulates molecular and behavioral circadian rhythms, its involvement in the regulation of energy balance and lifespan is unknown. Here, we show that astrocyte‐specific deletion of Bmal1 is sufficient to alter energy balance, glucose homeostasis, and reduce lifespan. Mutant animals displayed impaired hypothalamic molecular clock, age‐dependent astrogliosis, apoptosis of hypothalamic astrocytes, and increased glutamate and GABA levels. Importantly, modulation of GABAA‐receptor signaling completely restored glutamate levels, delayed the reactive gliosis as well as the metabolic phenotypes and expanded the lifespan of the mutants. Our results demonstrate that the astrocytic clock can influence many aspects of brain function and neurological disease and suggest astrocytes and GABAA receptor as pharmacological targets to prevent the metabolic dysfunctions and shortened lifespan associated with alterations of circadian rhythms.
Multivariate adaptive regression splines for estimating riverine constituent concentrations
Authors: Huang Hong , Ji Xiaoliang , Xia Fang , Huang Shuhui , Shang Xu , Chen Han , Zhang Minghua , Dahlgren Randy A. , Mei Kun
Published: December 2019

Regression‐based methods are commonly used for riverine constituent concentration/flux estimation, which is essential for guiding water quality protection practices and environmental decision making. This paper developed a multivariate adaptive regression splines model for estimating riverine constituent concentrations (MARS‐EC). The process, interpretability and flexibility of the MARS‐EC modelling approach, was demonstrated for total nitrogen in the Patuxent River, a major river input to Chesapeake Bay. Model accuracy and uncertainty of the MARS‐EC approach was further analysed using nitrate plus nitrite datasets from eight tributary rivers to Chesapeake Bay. Results showed that the MARS‐EC approach integrated the advantages of both parametric and nonparametric regression methods, and model accuracy was demonstrated to be superior to the traditionally used ESTIMATOR model. MARS‐EC is flexible and allows consideration of auxiliary variables; the variables and interactions can be selected automatically. MARS‐EC does not constrain concentration‐predictor curves to be constant but rather is able to identify shifts in these curves from mathematical expressions and visual graphics. The MARS‐EC approach provides an effective and complementary tool along with existing approaches for estimating riverine constituent concentrations.
Diel discharge variations in dormant and growing seasons in a headwater catchment suggest potential sources of an evapotranspiration signal
Authors: Gannon John P. , Kinner David , Styers Diane , Lord Mark
Published: December 2019

Diel fluctuations in discharge not associated with precipitation have been identified in streams around the world and attributed to evapotranspiration of both hillslope and near‐stream vegetation. Several mechanisms have been hypothesized to explain the generation of these signals, but a consensus has not been reached. In order to investigate the origin of these daily discharge fluctuations, we measured discharge and groundwater levels in a 43‐ha headwater catchment near Cullowhee, NC, USA. The catchment was logged at least twice in the past 120 years, allowing the evergreen invasive Chinese privet (Ligustrum sinense) to become established in near‐stream areas. Stream discharge was measured at the outlet, and stream stage and near‐stream groundwater level were measured at a second location higher in the catchment. Daily fluctuations in discharge were quantified and found to increase in magnitude with daily mean discharge. Interestingly, daily discharge fluctuations were observed in the dormant season, and our analysis suggests that their magnitude may increase more with discharge than during the growing season. Two previously hypothesized processes may explain our observations. A decrease in signal dampening due to faster transmission of an evapotranspiration signal at elevated flows may explain the increased diel fluctuation magnitude at higher flows. Additionally, because the primary active vegetation in our catchment in the dormant season is in near‐stream areas, we suggest that this indicates most of the evapotranspiration signal in stream discharge is derived from near‐stream vegetation, not hillslopes.
Evaluating next‐generation intensity–duration–frequency curves for design flood estimates in the snow‐dominated western United States
Authors: Yan Hongxiang , Sun Ning , Wigmosta Mark , Leung L. Ruby , Hou Zhangshuan , Coleman Andre , Skaggs Richard
Published: December 2019

Civil infrastructure such as culverts and bridges are commonly designed using precipitation‐based intensity–duration–frequency (PREC‐IDF) curves, which assume that the occurrence of precipitation is in the form of rainfall and immediately available for the rainfall‐runoff process. In snow‐dominated regions, where most winter precipitation occurs as snow that melts during spring to early summer, the use of standard PREC‐IDF curves may lead to substantial underestimation of design floods and high failure risk of infrastructure. In this context, we developed next‐generation IDF (NG‐IDF) curves that characterize the actual water reaching the land surface (i.e., rainfall plus snowmelt) to enhance standard infrastructure design in snow‐dominated regions. This study evaluates the performance of NG‐IDF curves coupled with U.S. Department of Agriculture Technical Release 55 hydrologic model in estimating design floods for 246 snowy locations in different hydroclimate regimes of the western United States. Design flood estimates from a well‐validated continuous simulation using a physics‐based hydrologic model, the Distributed Hydrology Soil Vegetation Model (DHSVM), were used as the performance benchmark. Compared with the benchmark estimates, the standard PREC‐IDF curves led to substantial errors in design flood estimates, while the NG‐IDF curves significantly reduced these errors. For example, the averaged error in the 50‐year design flood estimates over the 246 locations was reduced from 31% with the use of PREC‐IDF curves to 12% with the use of NG‐IDF curves. Despite the different model structures, the single‐event NG‐IDF approach versus the continuous simulation DHSVM did not exhibit statistically significant differences in 91% of the 246 locations for the 50‐year design flood estimates. This indicates a satisfactory performance of NG‐IDF curves to estimate design flow under the conditions tested in the snow‐dominated western United States. This article also presents technical suggestions and the limitations of infrastructure design using NG‐IDF curves for regulatory agencies and practicing engineers.
Controls on evapotranspiration from jack pine forests in the Boreal Plains Ecozone
Authors: Nazarbakhsh Mahtab , Ireson Andrew M. , Barr Alan G.
Published: December 2019

The exchanges of water, energy and carbon between the land surface and the atmosphere are tightly coupled, so that errors in simulating evapotranspiration lead to errors in simulating both the water and carbon balances. Areas with seasonally frozen soils present a particular challenge due to the snowmelt‐dominated hydrology and the impact of soil freezing on the soil hydraulic properties and plant root water uptake. Land surface schemes that have been applied in high latitudes often have reported problems with simulating the snowpack and runoff. Models applied at the Boreal Ecosystem Research and Monitoring Sites in central Saskatchewan have consistently over‐predicted evapotranspiration as compared with flux tower estimates. We assessed the performance of two Canadian land surface schemes (CLASS and CLASS‐CTEM) for simulating point‐scale evapotranspiration at an instrumented jack pine sandy upland site in the southern edge of the boreal forest in Saskatchewan, Canada. Consistent with past reported results, these models over‐predicted evapotranspiration, as compared with flux tower observations, but only in the spring period. Looking systematically at soil properties and vegetation characteristics, we found that the dominant control on evapotranspiration within these models was the canopy conductance. However, the problem of excessive spring ET could not be solved satisfactorily by changing the soil or vegetation parameters. The model overestimation of spring ET coincided with the overestimation of spring soil liquid water content. Improved algorithms for the infiltration of snowmelt into frozen soils and plant‐water uptake during the snowmelt and soil thaw periods may be key to addressing the biases in spring ET.
Event‐based classification for global study of river flood generating processes
Authors: Stein Lina , Pianosi Francesca , Woods Ross
Published: December 2019

Better understanding of which processes generate floods in a catchment can improve flood frequency analysis and potentially climate change impacts assessment. However, current flood classification methods are either not transferable across locations or do not provide event‐based information. We therefore developed a location‐independent, event‐based flood classification methodology that is applicable in different climates and returns a classification of all flood events, including extreme ones. We use precipitation time series and very simply modelled soil moisture and snowmelt as inputs for a decision tree. A total of 113,635 events in 4155 catchments worldwide were classified into one of five hydro‐climatological flood generating processes: short rain, long rain, excess rainfall, snowmelt and a combination of rain and snow. The new classification was tested for its robustness and evaluated with available information; these two tests are often lacking in current flood classification approaches. According to the evaluation, the classification is mostly successful and indicates excess rainfall as the most common dominant process. However, the dominant process is not very informative in most catchments, as there is a high at‐site variability in flood generating processes. This is particularly relevant for the estimation of extreme floods which diverge from their usual flood generation pattern, especially in the United Kingdom, Northern France, Southeastern United States, and India.
Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes
Authors: Mubarak M. Qadri E. , de Visser Sam P.
Published: December 2019

Heme haloperoxidases are unique enzymes in biology that react H2O2 and halides on a heme center to generate hypohalide, which reacts with a substrate by halide transfer. We studied model complexes of the active site of heme haloperoxidase and investigated the reaction mechanism starting from an iron(III)‐hydrogen peroxide‐heme complex. We find two stepwise proton transfers by active site Glu and His residues to form Compound I and water, whereby the second proton transfer step is rate‐determining. In a subsequent reaction with chloride the oxygen atom transfer is studied to form hypohalide. Overall, the free energy of activation of the second proton transfer and oxygen atom transfer to halide are similar in energy with free energies of activation of around 20 kcal mol−1. The calculations show that during oxygen atom transfer from Compound I to halide, significant charge‐transfer happens prior to the transition state. This implies that the reaction may be enhanced in polar environments and through second‐coordination sphere effects. The studies show that the conversion of H2O2 and halide on a heme center is fast and few intermediates along the reaction mechanism will have a lifetime that is long enough to enable trapping and characterization with experimental methods. A range of active site models and density functional theory methods were tested, but little effect is seen on the mechanism and optimized geometries.
Empirical Double‐Hybrid Density Functional Theory: A ‘Third Way’ in Between WFT and DFT
Authors: Martin Jan M. L. , Santra Golokesh
Published: December 2019

Double hybrid density functional theory arguably sits on the seamline between wavefunction methods and DFT: it represents a special case of Rung 5 on the “Jacob's Ladder” of John P. Perdew. For large and chemically diverse benchmarks such as GMTKN55, empirical double hybrid functionals with dispersion corrections can achieve accuracies approaching wavefunction methods at a cost not greatly dissimilar to hybrid DFT approaches, provided RI‐MP2 and/or another MP2 acceleration techniques are available in the electronic structure code. Only a half‐dozen or fewer empirical parameters are required. For vibrational frequencies, accuracies intermediate between CCSD and CCSD(T) can be achieved, and performance for other properties is encouraging as well. Organometallic reactions can likewise be treated well, provided static correlation is not too strong. Further prospects are discussed, including range‐separated and RPA‐based approaches.
Pd‐Decorated Tungsten as Pt‐Free Bimetallic Catalysts for Hydrogen Oxidation Reaction in Alkaline Electrolyte
Authors: Arulrajan Antony Cyril , Subramanian Palaniappan , Singh Ramesh Kumar , Schechter Alex
Published: December 2019

Developing Pt‐free catalysts for hydrogen oxidation reaction (HOR) in alkaline solution is becoming a key challenge in the development of anion exchange membrane fuel cells and electrochemical reactors. Herein, we present the preparation, HOR activity, and stability of Pd‐decorated tungsten (Pd‐d‐W) catalysts. The Pd‐d‐W catalysts were prepared by the chemically activated surface of tungsten nanoparticles by Pd ions. The resultant bimetallic catalysts consisted of crystalline phases of both Pd and W nanoparticles. The CO stripping voltammograms and H‐desorption (Hdes) peak potential of hydrogen desorption in Pd suggests that the enhancement of HOR catalytic activity observed in Pd‐d‐W catalyst can be ascribed to the modification of electronic property of Pd and availability of OHad near‐surface Pd atoms.
Effect of a smartphone intervention on self‐managed medication abortion experiences among safe‐abortion hotline clients in Indonesia: A randomized controlled trial
Authors: Gerdts Caitlin , Jayaweera Ruvani T. , Kristianingrum Ika A. , Khan Zara , Hudaya Inna
Published: December 2019

Objective

To investigate the impact of a smartphone application (app) providing information and support for medication abortion (MA) on the primary outcomes of ‘feelings of support’ and ‘preparedness’ among clients of Samsara, a safe‐abortion hotline in Indonesia.

Methods

In a parallel‐arm, non‐clinical, randomized controlled trial, women (ages ≥15) who contacted Samsara between February 2017‐ July 2018 seeking information on MA for pregnancies ≤13 weeks gestation were randomized to receive either an app with abortion information, or standard of care (high‐quality comprehensive and empathic counseling on pregnancy options). Participants completed a questionnaire 24 days after enrollment; Fisher exact tests and risk differences were used to assess differences in self‐reported feelings of preparedness and support throughout the process of self‐managed MA.

Results

No differences in feelings of support or preparedness were detected between participants in the app arm versus the standard of care arm.

Conclusion

This study represents the first‐ever randomized control trial (and prospective study) among those who contacted a safe‐abortion hotline for information about and support for self‐managed abortion. Levels of preparedness, confidence, and feelings of support were all extremely high among both control and intervention arms–indicative of the high‐quality, evidence‐based information, comprehensive, and supportive abortion counseling that safe‐abortion hotline clients receive.
Association between passive smoking and cardiovascular disease: A systematic review and meta‐analysis
Authors: Khoramdad Malihe , Vahedian‐azimi Amir , Karimi Leila , Rahimi‐Bashar Farshid , Amini Hossein , Sahebkar Amirhossein
Published: December 2019

Background

The association between passive smoking (PS) and cardiovascular disease (CVD) has not yet been fully clarified.

Objective

This meta‐analysis was performed to evaluate the association between PS and the incidence of CVDs and mortality due to CVD.

Methods

PubMed/Medicine, Science Direct, Scopus, Web of Knowledge, and ProQuest were searched to identify observational studies that met the inclusion criteria without time, language, age, gender, ethnicity, and design restrictions until July 30, 2018. In case–control studies, relative risk (RR) with 95% confidence interval (CI) was calculated for the relationship between PS and CVD incidence. Also, in cohort studies, hazard ratio (HR) with 95% CI was calculated for the relationship between PS and CVD mortality.

Results

Eighteen studies (10 cohort and 8 case–control studies) were included with 10,672 participants (2,542 cases and 8,130 controls) in case–control studies and 2,313,935 participants in cohort studies. This meta‐analysis in case–control studies revealed that the PS could increase the risk of CVD incidence by 28% (adjusted RR = 1.28 [95% CI 1.09, 1.50]), where the highest risk was associated with those who were exposed to second‐hand smoke at home and at work (Adjusted RR = 1.41 [95% CI 0.73, 2.70]). Also, the meta‐analysis in cohort studies indicated that PS was associated with a 12% higher increase in the risk of CVD mortality (Adjusted HR = 1.12 [95% CI 1.06, 1.20]) with the highest risk of mortality being observed for those who were exposed to second‐hand smoking at home, work, and public places (Adjusted HR = 1.26 [95% CI 1.13, 1.40]).

Conclusions

PS is significantly associated with an increased risk of incidence and mortality of CVD.
On Binary Methods
Authors: Bruce Kim , Cardelli Luca , Castagna Giuseppe ,   The Hopkins Objects Group, Leavens Gary T. , Pierce Benjamin
Published: December 2019

Giving types to binary methods causes significant problems for object‐oriented language designers and programmers. This paper offers a comprehensive description of the problems arising from typing binary methods and collects and contrasts diverse views and solutions. It summarizes the current debate on the problem of binary methods for a wide audience.
The shale revolution and shifting crude dynamics
Authors: Sy Malick , Wu Liuren
Published: December 2019

Oil price fluctuates in response to both demand and supply shocks. This paper proposes a new methodology that allows for timely identification of the shifting contribution from the two types of shock through a joint analysis of crude futures options and stock index options. Historical analysis shows that crude oil price movements are dominated by supply shocks from 2004 to 2008, but demand shocks have become much more dominant since then. The large demand shock following the 2008 financial crisis contributes to the start of this dynamics shift, whereas the subsequent shale revolution has fundamentally altered the crude supply behavior.
Effect of type of contact, counterface surface roughness, and contact area on the wear and friction of extensively cross‐linked, vitamin E stabilized UHMWPE
Authors: Saikko Vesa
Published: December 2019

Novel extensively cross‐linked, vitamin E stabilized polyethylene (VEXLPE) materials are expected to provide improved wear and oxidation resistance in orthopedic implants. Noncyclic, multidirectional pin‐on‐disk (POD) wear tests were performed for VEXLPE with flat‐on‐flat (FoF) and ball‐on‐flat (BoF) specimen configurations against CoCr counterfaces of varying surface roughness (Sa = 0.02–0.74 μm). In addition, wear tests (FoF) were performed for VEXLPE pins of varying nominal contact area (7.07–113 mm2) with consistent load regimen against polished CoCr disks. All specimen couples were also friction tested with a multidirectional, circularly translating POD device. In all tests, calf serum was used as the lubricant. In comparison with earlier, similar tests for conventional, gamma‐sterilized ultra‐high molecular weight polyethylene (UHMWPE) and for extensively cross‐linked, heat treated UHMWPE (XLPE), the tribological findings for the present VEXLPE appeared promising with respect to its possible clinical use in prosthetic joints, particularly as an acetabular liner against large‐diameter femoral heads, and in nonconforming contacts. Contrary to the well‐known, paradoxical behavior of conventional UHMWPE, the VEXLPE wear factor decreased with increasing contact area.
Efficacy and safety of hepatic arterial infusion chemotherapy combined with transarterial embolization for unresectable hepatocellular carcinoma: A propensity score‐matching cohort study
Authors: Guo Wenbo , Gao Jian , Zhuang Wenquan , Wu Zhiqiang , Li Bin , Chen Song
Published: December 2019

Purpose

The aim of this study was to assess the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) using the FOLFOX regimen combined with transarterial embolization (TAE + HAIC) in patients with unresectable hepatocellular carcinoma (HCC).

Methods

Unresectable HCC patients treated with TAE + HAIC and conventional transcatheter arterial chemoembolization (TACE), respectively, between January 2015 and October 2016 in China were retrospectively assessed. The primary outcome was progression‐free survival (PFS), while secondary outcomes included the objective response rate (ORR), the disease control rate (DCR), and main complications. Propensity score matching (PSM) was estimated by multiple logistic regression using caliper matching (caliper 0.2). A Cox proportional hazards model was used to identify those factors shown to be associated with PFS.

Results

A total of 113 patients were analyzed, with 41 and 72 receiving TAE + HAIC and TACE, respectively. After PSM, 35 pairs of patients were assessed. The median PFS was 7.93 months (95% confidence interval [CI], 4.44–11.42) for the TAE + HAIC group, which was higher compared with 2.60 months (95% CI, 0.93–4.27, P = 0.003) for TACE. The subgroup with Barcelona clinic liver cancer (BCLC) stage C obtained more PFS benefit from TAE + HAIC (P = 0.002). ORRs in the TAE + HAIC and TACE groups were 37.14% (13/35) and 20.00% (7/35, P = 0.112), respectively; DCRs were 88.57% (31/35) and 60.00% (21/35, P = 0.006), respectively. Abundant blood supply (hazard ratio [HR] =0.327, 95% CI 0.173–0.615, P < 0.001) and TAE + HAIC (HR = 0.332, 95% CI 0.177–0.621, P < 0.001) were associated with longer PFS in multivariate analysis.

Conclusions

Compared with conventional TACE, TAE + HAIC provides more PFS benefits to patients with unresectable HCC, especially in those with BCLC stage C.
A facile synthesis and antioxidant evaluation of conjugated 8‐azacoumarins based on DFT parameters
Authors: Rizk Sameh A. , Shaban Safa , Sallam Hanan A.
Published: December 2019

A series of 8‐azacoumarin, naphthyridine, and dioxazphenalene derivatives bearing conjugated moieties were intended and prepared by a concise and smooth approach using grinding and ultrasonic irradiation. A sustainable one pot reactions have emerged and progressed smoothly as an efficient and eco‐safe methods in solvent less organic synthesis. The desired products were obtained in high yields, and the structures of all products were established on the basis of spectroscopic data and elemental analysis. Using the density functional theory (DFT) realized the electronic and structure characterization of synthesized azacoumarin. These heterocyclic compounds are chemically stable and are tested as antioxidants. Antioxidant potential was assessed using ABTS, and anti‐hemolytic activity was evaluated by induced peroxide hemolysis. They gave good antioxidant results that showed potency ranging from good azacoumarin analogues 8, 9, 13, 17, and 20, among compounds, showed much potency than that of commercial ascorbic acid.
Biological role of GITR/GITRL in attributes and immune responses of macrophage
Authors: Fu Zhuo , Wang Shuang , Li Jinhua , Zhang Yunfeng , Li Han , Li Guangquan , Wan Xue , Zhang Yu
Published: December 2019

Glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL), a member of the tumor necrosis factor superfamily, is expressed in APCs and acts as a costimulatory molecule in the immune system. Although the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR)/GITRL system has been modulated to promote or decrease T cell-related responses in multiple diseases, studies in macrophages are limited. To address this issue, we compared the expression of GITRL in various types of macrophages and analyzed whether GITRL can affect the fundamental properties and major functions of these cells. Our results demonstrated that M1 polarized macrophages had the highest GITRL levels. Furthermore, GITRL overexpression skewed macrophage polarization toward the M1 phenotype, accelerating proliferation and migration and regulating phagocytosis and killing function. Moreover, GITRL-silenced cells showed a loss of these functions, further confirming its vital role. We also developed an acute peritonitis mouse model, in which macrophages were driven to differentiate into a proinflammatory phenotype with GITRL up-regulation, triggering a positive feedback loop. Our results provide molecular insight into how the GITR/GITRL system modulates innate immune responses, suggesting that manipulation of the GITR/GITRL system to treat diseases depends not only on T cell regulation but also on macrophage participation.
Bispecific antibodies enhance tumor-infiltrating T cell cytotoxicity against autologous HER-2-expressing high-grade ovarian tumors
Authors: Oberg Hans-Heinrich , Janitschke Lisa , Sulaj Vjola , Weimer Jörg , Gonnermann Daniel , Hedemann Nina , Arnold Norbert , Kabelitz Dieter , Peipp Matthias , Bauerschlag Dirk , Wesch Daniela
Published: December 2019

Epithelial ovarian cancer displays the highest mortality of all gynecological tumors. A relapse of the disease even after successful surgical treatment is a significant problem. Resistance against the current platinum-based chemotherapeutic standard regime requires a detailed ex vivo immune profiling of tumor-infiltrating cells and the development of new therapeutic strategies.

In this study, we phenotypically and functionally characterize tumor cells and autologous tumor-derived αβ and γδ T lymphocyte subsets. Tumor-infiltrating (TIL) and tumor-ascites lymphocytes (TAL) were ex vivo isolated out of tumor tissue and ascites, respectively, from high-grade ovarian carcinoma patients (FIGO-stage IIIa-IV). We observed an increased γδ T cell percentage in ascites compared to tumor-tissue and blood of these patients, whereas CD8+ αβ T cells were increased within TAL and TIL. The number of Vδ1 and non-Vδ1/Vδ2-expressing γδ T cells was increased in the ascites and in the tumor tissue compared to the blood of the same donors. Commonly in PBL, the Vγ9 chain of the γδ T cell receptor is usually associated exclusively with the Vδ2 chain. Interestingly, we detected Vδ1 and non-Vδ1/Vδ2 T cells co-expressing Vγ9, which is so far not described for TAL and TIL.

Importantly, our data demonstrated an expression of human epidermal growth factor receptor (HER)-2 on high-grade ovarian tumors, which can serve as an efficient tumor antigen to target CD3 TIL or selectively Vγ9-expressing γδ T cells by bispecific antibodies (bsAbs) to ovarian cancer cells. Our bsAbs efficiently enhance cytotoxicity of TIL and TAL against autologous HER-2-expressing ovarian cells.
High‐dose hydroxocobalamin achieves biochemical correction and improvement of neuropsychiatric deficits in adults with late onset cobalamin C deficiency
Authors: Higashimoto Tomoyasu , Kim Alexander Y. , Ogawa Jessica T. , Sloan Jennifer L. , Almuqbil Mohammed A. , Carlson Julia M. , Manoli Irini , Venditti Charles P. , Gunay‐Aygun Meral , Wang Tao
Published: December 2019

Cobalamin C (cblC) deficiency is the most common inborn error of intracellular cobalamin metabolism caused by pathogenic variant(s) in MMACHC and manifests with methylmalonic acidemia, hyperhomocysteinemia, and hypomethioninemia with a variable age of presentation. Individuals with late‐onset cblC may be asymptomatic until manifesting neuropsychiatric symptoms, thromboembolic events, and renal disease. Although hydroxocobalamin provides a foundation for therapy, optimal dose regimen for adult patients has not been systematically evaluated. We report three adult siblings with late‐onset cblC disease, and their biochemical and clinical responses to high‐dose hydroxocobalamin. The 28‐year‐old proband presented with severe psychosis, progressive neurological deterioration, and deep venous thrombosis complicated by a pulmonary embolism. MRI studies identified lesions in the spinal cord, periventricular white matter, and basal ganglia. Serum homocysteine and methylmalonic acid levels were markedly elevated. Hydroxocobalamin at standard dose (1 mg/day) initially resulted in partial metabolic correction. A regimen of high‐dose hydroxocobalamin (25 mg/day) together with betaine and folic acid resulted in rapid and sustainable biochemical correction, resolution of psychosis, improvement of neurological functions, and amelioration of brain and spinal cord lesions. Two siblings who did not manifest neuropsychiatric symptoms or thromboembolism achieved a satisfactory metabolic control with the same high‐dose regimen. Hydroxocobalamin injection was then spaced out to 25 mg weekly with good and sustainable metabolic control. All three patients are compound heterozygotes for c.271dupA p.Arg91LysfsX14 and c.389A > G p.Tyr130Cys. This study highlights the importance of evaluating intracellular cobalamin metabolism in adults with neuropsychiatric manifestations and/or thromboembolic events, and demonstrates that high‐dose hydroxocobalamin achieves rapid and sustainable metabolic control and improvement in neuropsychiatric outcomes in adults with late‐onset cblC disease.