bluuebunny/crossref_metadata_2025 huggingface dataset:
Rice‐derived peptide AAGALPS inhibits TNF‐α‐induced inflammation and oxidative stress in vascular endothelial cells
Authors: Tong Li‐Tao , Ju Zhiyuan , Liu Liya , Wang Lili , Zhou Xianrong , Xiao Tianzhen , Zhou Sumei
Published: December 2019

Injury of vascular endothelial cell is one of the main factors triggering atherosclerosis. Peptide AAGALPS was derived from digestion and absorption product of rice α‐globulin, which was proved to prevent atherosclerosis in previous study. This study aims to investigate the potential effects of AAGALPS on improving tumor necrosis factor‐α (TNF‐α)‐stimulated human umbilical vein endothelial cells’ (HUVECs) injury. As a result, the viability of HUVECs stimulated by tumor necrosis factor‐α was significantly increased by AAGALPS in a dose‐dependent manner until 25 μg/ml. The peptide obviously reduced the levels of intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, nitric oxide, inducible nitric oxide synthase, reactive oxygen species, and malondialdehyde and increased the concentrations of glutathione peroxidase. Furthermore, AAGALPS inhibited the nuclear factor κB (NF‐κB) activation and nuclear translocation through regulating inhibitor of nuclear factor κB kinase α and inhibitor of NF‐κB. These results indicated that AAGALPS protected vascular endothelial cells through mediating inflammation and oxidative stress.
Spermidine and other functional phytochemicals in soybean seeds: Spatial distribution as visualized by mass spectrometry imaging
Authors: Sagara Tatsuya , Bhandari Dhaka Ram , Spengler Bernhard , Vollmann Johann
Published: December 2019

Soybean seeds contain phytochemicals such as polyamines and isoflavones, which have been identified as functional components mediating health benefits in association with the consumption of soy foods. While a clear picture of the spatial distribution of these components within the seed is lacking, such information would be important to enhance or reduce their concentration in respective foods through processing. Thus, the objective of the present study was to visualize the most relevant components with respect to their distribution in soybean seeds. Mature soybean seeds were subject to atmospheric‐pressure scanning‐microprobe matrix‐assisted laser desorption/ionization (AP‐SMALDI) combined with a Fourier‐transform orbital trapping mass spectrometer to generate high‐resolution chemical images of phytochemical distribution. Based on seed cross sections, differential distributions of functional components were found between soybean cotyledon and germ (shoot, hypocotyl, root) regions. Spermidine and spermine were present in higher concentrations in the germ rather than in cotyledons with highest concentrations in root and shoot meristem tissues. Differential concentrations of spermidine and other components between the germ and cotyledon regions were confirmed by seed fractioning. In contrast to polyamines spermidine and spermine, the different types of daidzein, glycitein, and genistein isoflavones were all visualized in root parenchyma tissue exclusively. Overall, mass spectrometry imaging of soybean seeds revealed clear insights into the differential distribution of functional phytochemicals. Based on their distribution and depending on specific needs, spermidine and isoflavones can either be enriched or reduced during food processing by separating cotyledon and germ fractions.
Genesis of gold deposits in the Wulong orefield, Liaodong Peninsula, North China Craton: Constraints from ore deposit geology, REE, and C–H–O–S–Pb isotopes
Authors: Chen Cong , Li Dong‐Tao , Wu Tao‐Tao , Zhao Yan , Zhao Chun‐Qiang , Yang Jia‐Lin , Gu Yu‐Chao
Published: December 2019

The Wulong gold orefield is located in the eastern part of the Liaodong Peninsula, and contains the large Sidaogou and Wulong gold deposits, as well as several small gold deposits with a total of >100 tonnes of gold reserves. These deposits are hosted within Paleoproterozoic metamorphic rocks of the Liaohe Group and Mesozoic granitoids, and are structurally controlled by NNE–SSW‐ and NNW–SSE‐trending faults and interlayer fractures. The Sidaogou deposit is characterized by altered‐rock‐type mineralization occurring within interlayer fracture zones, whereas the mineralization in the Wulong deposit occurs as auriferous quartz veins along subsidiary faults. These two types of gold mineralization are representative of the mineralization in the Wulong orefield. The REE contents of quartz and calcite, together with previous studies of fluid inclusions, indicate that the ore‐forming fluids of the Sidaogou deposit were reduced NaCl–H2O–CO2 fluids. Quartz yielded δ18OH2O‐SMOW, δDSMOW, and δ13CCO2 values of +4.7‰ to +6.6‰, −82.2‰ to −79.0‰, and − 13.1‰ to −6.6‰, respectively, and calcite yielded δ13CCO2 and δ18OV‐SMOW values of −2.3‰ to −2.0‰ and + 7.4‰ to +7.9‰, respectively. These results indicate that the ore‐forming fluids of the Sidaogou deposit were derived primarily from magmatic water, and the C was sourced mainly from deep‐seated magma with a minor contribution from sedimentary organic matter. Pyrite crystals have δ34SCDT values of +4.9‰ to +12.9‰, indicating the S source was a combination of the magmatic system and ore‐bearing metamorphic rocks. Pyrite has 208Pb/204Pb ratios of 38.226–38.336, 207Pb/204Pb ratios of 15.606–15.683, and 206Pb/204Pb ratios of 18.345–18.492, suggesting that the Pb in the Sidaogou deposit was derived primarily from the upper crust, with minor input from the mantle. Taking into account previous studies of the Wulong deposit, we propose a metallogenic model for the Wulong gold orefield. Deep‐seated ore‐forming fluids were released from different intrusions hidden below the Wulong orefield for each of the deposits. The ore‐forming fluids moved through the metamorphic rocks of the Gaixian Formation along interlayer fracture zones, where intensive water–wallrock reactions, and episodic temperature and pressure drops resulted in the formation of altered‐rock‐type Sidaogou deposit. The fluids ascended to the Wulong and Sanguliu intrusions along NNE–SSW‐ and NNW–SSE‐trending faults, where temperature and pressure dropping, water–wallrock reactions, and fluid immiscibility generated the vein‐type Wulong deposit. The gold deposits in the Wulong orefield share many similarities with the Linglong‐ and Jiaojia‐type gold deposits in the Jiaodong Peninsula, including geological setting, mineralization style and age, and sources of ore‐forming fluids and metal.
Role of the right temporoparietal junction in intergroup bias in trust decisions
Authors: Fujino Junya , Tei Shisei , Itahashi Takashi , Aoki Yuta Y. , Ohta Haruhisa , Kubota Manabu , Hashimoto Ryu‐ichiro , Takahashi Hidehiko , Kato Nobumasa , Nakamura Motoaki
Published: December 2019

Intergroup bias, which is the tendency to behave more positively toward an in‐group member than toward an out‐group member, is pervasive in real life. In particular, intergroup bias in trust decisions substantially influences multiple areas of life and thus better understanding of this tendency can provide significant insights into human social behavior. Although previous functional magnetic resonance imaging studies showed the involvement of the right temporoparietal junction (TPJ) in intergroup trust bias, a causal relationship between the two has rarely been explored. By combining repetitive transcranial magnetic stimulation and a newly developed trust game task, we investigated the causal role of the right TPJ in intergroup bias in trust decisions. In the trust game task, the counterpart's group membership (in‐group or out‐group) and reciprocity were manipulated. We applied either neuronavigated inhibitory continuous theta burst stimulation (cTBS) or sham stimulation over the right TPJ before performing the trust game task in healthy volunteers. After the sham stimulation, the participants' degrees of investments with in‐group members were significantly higher than those with out‐group members. However, after cTBS to the right TPJ, this difference was not observed. The current results extend previous findings by showing that the causal roles of the right TPJ can be observed in intergroup bias in trust decisions. Our findings add to our understanding of the mechanisms of human social behavior.
Understanding the effect of catchment characteristics on suspended sediment dynamics during flood events
Authors: Haddadchi Arman , Hicks Murray
Published: December 2019

Hysteresis in the relationship between suspended sediment concentration and flow during run‐off events is commonly used to inform on sediment sources and hydrological pathways. Less attention, however, has been paid to comparing the water and sediment hydrographs, which provide a more direct appreciation of in‐event sediment dynamics and their relationship with the upstream catchment characteristics. The aim of this study is to better understand the catchment and hydrological controls on the phasing of water and sediment discharges during events and, in particular, to explore what controls sediment concentrations late on event recessions. Continuous records of flow and turbidity data (calibrated to suspended sediment concentration) were collected from 17 catchments across New Zealand for this purpose. Relationships between event sediment yield and peak flow showed, as anticipated, higher event sediment loads were generated in pasture compared with forested catchments and were also higher from catchments in more erodible terrain. One novel result was that these differences were greater during smaller, more frequent events, whereas the loads from larger flood events tended to converge between pasture and forest catchments. Another novel result was that event sediment load tends to be evenly split between rising and falling stages of the hydrograph in pasture catchments, but forested catchments yield more of their event loads on flood recessions, probably because of delayed erosion or more sediment sources remote from the channel network. Land cover, distance of the sediment sources from the monitoring site, and size of the catchments control sediment concentrations late on event recession. Pasture‐dominated and more erodible catchments show longer sediment recessions and therefore stay dirtier for longer time periods. In addition, the size of previous flood events appeared to control the extent of sediment exhaustion after the flood peaks in some catchments.
Recharge seasonality based on stable isotopes: Nongrowing season bias altered by irrigation in Nebraska
Authors: Cherry Mikaela , Gilmore Troy , Mittelstet Aaron , Gastmans Didier , Santos Vinicius , Gates John B.
Published: December 2019

The sustainability of groundwater resources for agricultural and domestic use is dependent on both the groundwater recharge rate and the groundwater quality. The main purpose of this study was to improve the understanding of the timing, or seasonality, of groundwater recharge through the use of stable isotopes. Based on 768 groundwater samples collected from aquifers underlying natural resources districts in Nebraska, the isotopic composition of groundwater (δ2H and δ18O) was compared with that of precipitation by (a) mapping the isotopic composition of groundwater samples and (b) mapping a seasonality index for groundwater. Results suggest that for the majority of the state, groundwater recharge has a nongrowing season signature (October–April). However, the isotopic composition of groundwater suggests that in some intensively irrigated areas, human intervention in the water cycle has shifted the recharge signature towards the growing season. In other areas, a different human intervention (diversion of Platte River water for irrigation) has likely produced an apparent but possibly misleading nongrowing season recharge signal because the Platte River water differs isotopically from local precipitation. These results highlight the need for local information even when interpreting isotopic data over larger regions. Understanding the seasonality of recharge can provide insight into the optimal times to apply fertilizer, specifically in highly conductive soils with high leaching potential. In areas with high groundwater nitrate concentrations, this information is valuable for protecting the groundwater from further degradation. Although previous studies have framed nongrowing season recharge within the context of future climate change, this study also illustrates the importance of understanding how historical human intervention in the water cycle has affected groundwater recharge seasonality and subsequent implications for groundwater recharge and quality.
The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut‐off level on yield of screening
Authors: Kooyker Arthur I. , Toes‐Zoutendijk Esther , Opstal‐van Winden Annemieke W.J. , Spaander Manon C.W. , Buskermolen Maaike , van Vuuren Hanneke J. , Kuipers Ernst J. , van Kemenade Folkert J. , Ramakers Chris , Thomeer Maarten G.J. , Dekker Evelien , Nagtegaal Iris D. , de Koning Harry J. , van Leerdam Monique E. , Lansdorp‐Vogelaar Iris
Published: December 2019

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information‐system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut‐off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut‐off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non‐participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut‐off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut‐off were detected in the subsequent round.
Antiviral therapy against chronic hepatitis C is associated with a reduced risk of oral cancer
Authors: Su Tung‐Hung , Tseng Tai‐Chung , Liu Chun‐Jen , Chou Shih‐Wan , Liu Chen‐Hua , Yang Hung‐Chih , Chen Pei‐Jer , Chen Ding‐Shinn , Chen Chi‐Ling , Kao Jia‐Horng
Published: December 2019

To identify the risk factors of oral cancer, we investigated the association between chronic hepatitis C (CHC) and oral cancer, and the development of oral cancer after anti‐hepatitis C virus (HCV) therapy. We conducted a nationwide, population‐based cohort study from 2004 to 2012 from the Taiwan National Health Insurance Research Database. CHC patients without anti‐HCV therapy were matched with those non‐HCV patients by age, sex and comorbidities. Moreover, CHC patients who underwent pegylated interferon and ribavirin (PegIFN/RBV) anti‐HCV therapy were matched with CHC patients without anti‐HCV therapy. A total of 100,058 patients were included in the HCV cohort and non‐HCV cohorts, respectively. Their mean age was 59 years and 50% of these were male. CHC infection significantly increased the cumulative incidence of lichen planus and oral cancer. After adjustment for confounders and competing mortality, CHC infection significantly increased the risk of oral cancer (hazard ratio [HR]: 1.677, 95% confidence interval [CI]: 1.392–2.020, p < 0.001). Another 23,735 CHC patients without anti‐HCV therapy were matched with 23,735 CHC patients in the treatment cohort. After adjustment for confounders and competing for mortality, the risk of oral cancer was significantly reduced in CHC patients receiving anti‐HCV therapy (HR: 0.652, 95% CI: 0.479–0.887, p = 0.007). To minimize the inclusion of pre‐existing unidentified oral cancer, we excluded oral cancer developed within the first year of CHC or anti‐HCV therapy and found these associations remained statistically significant. In conclusion, CHC significantly increases the risk of oral cancer. Moreover, PegIFN/RBV antiviral therapy significantly reduces the risk of HCV‐related oral cancer.
Solitude in context: On the role of culture, immigration, and acculturation in the experience of time to oneself
Authors: Lay Jennifer C. , Fung Helene H. , Jiang Da , Lau Chun Hoi , Mahmood Atiya , Graf Peter , Hoppmann Christiane A.
Published: December 2019

Older adults spend much time in solitude (without social interaction), putting them at risk of loneliness, especially if aging outside their country of origin (e.g., Chinese immigrants to Canada). Yet, cultural contextual factors that may reduce loneliness in moments of solitude are poorly understood. This study sought to disentangle the roles of culture, immigration, and acculturation in solitude‐loneliness associations across two countries. Community‐dwelling adults aged 51–85 in Vancouver (N = 58 East Asian, N = 37 European/North American) and in Hong Kong (N = 56 East/Southeast Asian) completed approximately 30 ecological momentary assessments over 10 days on their current affect and social situations. Participants in Vancouver spent more time in solitude, desired solitude more, and felt less lonely overall than those in Hong Kong. Multilevel models revealed that moments of solitude felt lonelier than moments spent in social interaction, but only for individuals less acculturated to their host culture or not concurrently desiring solitude. Associations held regardless of host culture, cultural heritage, or immigration status. Findings suggest that solitude need not feel lonely if it happens by choice and if individuals feel connected with their host culture, for both immigrant older adults and those aging in their birth country.
Recent progress in biomedical applications of RGD‐based ligand: From precise cancer theranostics to biomaterial engineering: A systematic review
Authors: Alipour Mohsen , Baneshi Marzieh , Hosseinkhani Saman , Mahmoudi Reza , Jabari Arabzadeh Ali , Akrami Mohammad , Mehrzad Jalil , Bardania Hassan
Published: December 2019

Arginine‐glycine‐aspartic acid (RGD) peptide family is known as the most prominent ligand for extracellular domain of integrin receptors. Specific expression of these receptors in various tissue of human body and tight association of their expression profile with various pathophysiological conditions made these receptors a suitable targeting candidate for several disease diagnosis and treatment as well as regeneration of various organs. For these reasons, various forms of RGD‐based integrins ligands have been greatly used in biomedical studies. Here, we summarized the last decade application progress of RGD for cancer theranostics, control of inflammation, thrombosis inhibition and critically discussed the effect of RGD peptides structure and sequence on the efficacy of gene/drug delivery systems in preclinical studies. Furthermore, we will show recent advances in application of RGD functionalized biomaterials for various tissue regenerations including cornea repair, artificial neovascularization and bone tissue regeneration. Finally, we analyzed clinically translatability of RGD peptides, considering examples of integrin ligands in clinical trials. In conclusion, prospects on using RGD peptide for precise drug delivery and biomaterial engineering are well discussed.
Clinically Negligible Pharmacokinetic and Pharmacodynamic Interactions Between Lanabecestat and Dabigatran Etexilate, a Prototypical P‐gp Substrate
Authors: Monk Scott A. , Kugler Alan R. , Andersen Scott W. , Ayan‐Oshodi Mosun A. , James Douglas E. , Mullen Jamie , Zimmer Jennifer A. , Willis Brian A.
Published: December 2019

Lanabecestat, a novel β‐site amyloid precursor protein–cleaving enzyme 1 inhibitor evaluated for Alzheimer treatment, inhibits P‐glycoprotein (P‐gp) activity in vitro. After oral 50‐mg lanabecestat administration, gastric fluid lanabecestat concentrations exceed half‐maximal inhibitory concentration (IC50), suggesting P‐gp inhibition at the intestinal wall. Plasma drug concentrations following 50 mg lanabecestat administered once daily are <10% of IC50, suggesting minimal systemic P‐gp interaction. Dabigatran etexilate (DE) is the prodrug of dabigatran, a thrombin inhibitor and P‐gp substrate, making dabigatran exposure an intestinal P‐gp activity indicator. This study (NCT02568397) was conducted in 60 healthy subjects receiving a single dose of 150 mg DE alone or during a lanabecestat treatment regimen. On day 16, lanabecestat and DE were coadministered; on day 20, DE was dosed 4 hours after lanabecestat. Safety was assessed using clinical labs, electrocardiogram, vital signs, Columbia Suicide Severity Rating Scale scores, adverse events, and eye and skin examinations. Pharmacokinetic/pharmacodynamic samples were collected up to 36 hours postdose. Geometric mean plasma dabigatran area under the curve from time 0 to infinity (AUC0‐∞) and the maximum plasma drug concentration (Cmax) increased by 15% and 17%, respectively, when coadministered with lanabecestat. When DE was dosed 4 hours after lanabecestat, there was no effect on plasma dabigatran AUC0‐∞, Cmax, or thrombin time. DE had no effect on lanabecestat's AUC0‐∞ and Cmax at steady state (day 16) versus lanabecestat alone (day 15). No clinically relevant safety concerns were observed. Lanabecestat has no clinically meaningful effect on dabigatran exposure or on P‐gp activity at the intestinal wall.
An Appeal to Intimacy: Consumer Response to Platform‐Appeal Fit on Social Media
Authors: Reich Brandon J. , Pittman Matthew
Published: December 2019

This research investigates a novel type of fit unique to digital marketing: that between the intimacy of an advertizing appeal and of the social media platform through which it is advertized. In doing so, we challenge the common marketing practice of posting identical content across platforms by showing how the same ad is received differently by consumers across differing platforms. Consistent with theories of processing fluency, we propose that platform‐appeal fit (in terms of intimacy) enhances consumers' social media engagement with the brand because the associated fluency enhances consumers' favorable cognitive judgments, affective state, and attitudes. A Pilot Study first maps the contours of platform intimacy through multidimensional scaling of several popular platforms. The resulting perceptual maps are then used to compare consumer response to an intimate or nonintimate appeal posted by actual (Experiment 1) and fictitious (Experiment 2) brands on platforms of varying intimacy. Results provide evidence for fluency as a mechanism for increased engagement following platform‐appeal fit, suggesting that a one‐size‐fits‐all approach to digital marketing may be suboptimal in terms of consumer response.
Fenton and solar photo‐Fenton processes in the depuration of wastewater resulting from production of grape juice. A factorial design
Authors: Poblete Rodrigo , Cortes Ernesto , Maldonado Manuel I
Published: December 2019

BACKGROUND

Grapes used in the production of juice have high total phenolic content due to the undesirable fermentation process, consequence of the high content of sugar ant fatty acids in grapes, which produce a high amount of ethanol. Therefore, the amount of wastewater with a high concentration of organic matter is an environmental concern related to juice production. We evaluated the potential of the use of these Fenton and photo‐Fenton processes in the depuration of organic matter in the juice production wastewater and determined the factors that affect the treatment.

RESULTS

We obtained different levels of organic matter removal, with a higher level for the experimental conditions, that is, a high concentration of H2O2 and Fe+2 and the use of UV irradiation (photo‐Fenton). In this case, COD and polyphenol elimination was 70.2 % and 36.1%, respectively, with juice wastewater under no pretreatment and applying UV irradiation. The most important factor in the removal of COD in juice wastewater was the concentration of Fe+2, followed by H2O2 and the presence of solar UV. The most important factor in the removal of polyphenols is the pretreatment of the juice wastewater, with better results whenthere is no pretreatment. The highest removal of polyphenols was obtained using the water without being pretreated.

CONCLUSIONS

The specific energy consumption and the electrical energy per order under the photo‐Fentonprocess was lower than under the Fenton process, indicating a more efficient energy use. This is because the natural UV irradiation enhances the chemical reaction of the oxidation process, producing a higher difference in the concentration of COD and polyphenols in comparison to the process carried out without UV solar irradiation. © 2019 Society of Chemical Industry
Number and time in acquisition, extinction and recovery
Authors: Gallistel C. R. , Papachristos E. B.
Published: December 2019

We measured rate of acquisition, trials to extinction, cumulative responses in extinction, and the spontaneous recovery of anticipatory hopper poking in a Pavlovian protocol with mouse subjects. We varied by factors of 4 number of sessions, trials per session, intersession interval, and span of training (number of days over which training extended). We find that different variables affect each measure: Rate of acquisition [1/(trials to acquisition)] is faster when there are fewer trials per session. Terminal rate of responding is faster when there are more total training trials. Trials to extinction and amount of responding during extinction are unaffected by these variables. The number of training trials has no effect on recovery in a 4‐trial probe session 21 days after extinction. However, recovery is greater when the span of training is greater, regardless of how many sessions there are within that span. Our results and those of others suggest that the numbers and durations and spacings of longer‐duration “episodes” in a conditioning protocol (sessions and the spans in days of training and extinction) are important variables and that different variables affect different aspects of subjects' behavior. We discuss the theoretical and clinical implications of these and related findings and conclusions—for theories of conditioning and for neuroscience.
An ethical framework for genetic counseling in the genomic era
Authors: Jamal Leila , Schupmann Will , Berkman Benjamin E.
Published: December 2019

The field of genetic counseling has grown and diversified since the profession emerged in the early 1970s. In the same period, genomic testing has become more complex, profitable, and widespread. With these developments, the scope of ethical considerations relevant to genetic counseling has expanded. In light of this, we find it helpful to revisit how ethical and relational variables are used to inform genetic counseling practice. Our specific focus is on whether, and to what extent, it is ethically acceptable for genetic counselors to make normative recommendations to patients. This article builds on prior literature that has critiqued nondirectiveness, a concept that has influenced and constrained the modern profession of genetic counseling since its origin. In it, we review scholarly efforts to move beyond nondirectiveness, which we believe privilege patient autonomy at the expense of other important values. We then argue that genetic counselors should favor a more explicit commitment to the principles of beneficence and non‐maleficence, as well as a broader understanding of autonomy and the relational variables that impact genetic counseling. Finally, to translate our arguments into practice, we present a framework of six considerations that genetic counselors should take into account when deciding whether it is ethically acceptable, or even desirable, to make recommendations to patients in certain areas of their work.
Epidemiological impact and cost‐effectiveness of providing long‐acting pre‐exposure prophylaxis to injectable contraceptive users for HIV prevention in South Africa: a modelling study
Authors: van Vliet Marjolein M , Hendrickson Cheryl , Nichols Brooke E , Boucher Charles AB , Peters Remco PH , van de Vijver David AMC
Published: December 2019

Introduction

Although pre‐exposure prophylaxis (PrEP.) is an efficacious HIV prevention strategy, its preventive benefit has not been shown among young women in sub‐Saharan Africa, likely due to non‐adherence. Adherence may be improved with the use of injectable long‐acting PrEP methods currently being developed. We hypothesize that providing long‐acting PrEP to women using injectable contraceptives, the most frequently used contraceptive method in South Africa, could improve adherence to PrEP, result in a reduction of new HIV infections, and be a relatively easy‐to‐reach target population. In this modelling study, we assessed the epidemiological impact and cost‐effectiveness of providing long‐acting PrEP to injectable contraceptive users in Limpopo, South Africa.

Methods

We developed a deterministic mathematical model calibrated to the HIV epidemic in Limpopo. Long‐acting PrEP was provided to 50% of HIV negative injectable contraceptive users in 2018 and scaled‐up over two years. We estimated the number of HIV infections that could be averted by 2030 and the drug price of long‐acting PrEP for which this intervention would be cost‐effective over a time horizon of 40 years, from a healthcare payer perspective. In the base‐case scenario we assumed long‐acting PrEP is 75% effective in preventing HIV infections and 85% of infected individuals are on antiretroviral drug therapy (ART) by 2030. In sensitivity analyses we adjusted PrEP effectiveness and ART coverage. Costs between $519 and $1119 per disability‐adjusted life‐year (DALY) averted were considered potentially cost‐effective, and <$519 as cost‐effective.

Results

Without long‐acting injectable PrEP, 224,000 (interquartile range 176,000 to 271,000) new infections will occur by 2030; use of long‐acting injectable PrEP could prevent 21,000 (17,000 to 26,000) or 9.8% (8.9% to 10.6%) new HIV infections by 2030 (including 6000 (4000 to 7000) in men). Long‐acting PrEP would prevent 34,000 (29,000 to 39,000) or 12,000 (8000 to 15,000) at 75% and 95% ART coverage by 2030 respectively. To be considered potentially cost‐effective the annual long‐acting PrEP drug price should be <$16, and/or ART coverage remains at <85% in 2030.

Conclusions

Providing long‐acting PrEP to injectable contraceptive users in Limpopo is only potentially cost‐effective when long‐acting PrEP drug prices are low. If low prices are not feasible, providing long‐acting PrEP only to women at high risk of HIV infection will become important.
Phenotypes and genotypes of mitochondrial aminoacyl‐tRNA synthetase deficiencies from a single neurometabolic clinic
Authors: Al Balushi Aaisha , Matviychuk Diana , Jobling Rebekah , Salomons Gajja S. , Blaser Susan , Mercimek‐Andrews Saadet
Published: December 2019

Mitochondrial aminoacyl‐tRNA synthetases play a major role in protein translation, synthesis, and oxidative phosphorylation. We reviewed all patients diagnosed with mitochondrial aminoacyl‐tRNA synthetase deficiencies diagnosed in a single neurometabolic clinic. We report five patients with mitochondrial aminoacyl‐tRNA synthetase deficiencies including DARS2, EARS2, PARS2, and RARS2 deficiencies. Siblings with DARS2 deficiency presented with global developmental delay within the first year of life. DARS2, EARS2, PARS2, and RARS2 deficiencies were identified by whole exome sequencing. We report coagulation factor abnormalities in PARS2 deficiency for the first time. We also report symmetric increased signal intensity in globus pallidi in FLAIR images in brain MRI in EARS2 deficiency for the first time. One patient with RARS2 deficiency had compound heterozygous variants in RARS2. One of those variants was an intronic variant. We confirmed the pathogenicity by mRNA studies. Mitochondrial aminoacyl‐tRNA synthetase deficiencies are diagnosed by molecular genetic investigations. Clinically available non‐invasive biochemical investigations are non‐specific for the diagnosis of mitochondrial aminoacyl‐tRNA synthetase deficiencies. A combination of brain MRI features and molecular genetic investigations should be undertaken to confirm the diagnosis of mitochondrial aminoacyl‐tRNA synthetase deficiencies.
Evaluation of CCR5‐Δ32 mutation among individuals with high risk behaviors, neonates born to HIV‐1 infected mothers, HIV‐1 infected individuals, and healthy people in an Iranian population
Authors: Donyavi Tahereh , Bokharaei‐Salim Farah , Nahand Javid Sadri , Garshasbi Saba , Esghaei Maryam , Sadeghi Mohsen , Jamshidi Sogol , Khanaliha Khadijeh
Published: December 2019

One of the important genetic factors related to resistance to HIV‐1 infection is the presence of the C–C chemokine receptor type 5 delta 32 (CCR5‐Δ32) homozygous genotype (Δ32/Δ32). The aim of this study was to evaluate the CCR5‐Δ32 mutation among individuals with high‐risk behaviors, neonates born to HIV‐1‐infected mothers in the prevention of mother‐to‐child transmission (PMTCT) project, HIV‐1‐infected individuals, and healthy people. The frequency of the CCR5‐Δ32 genotype was assessed in a cross‐sectional survey carried out from March 2014 to March 2019 among four different groups of the Iranian population. Genomic DNA was extracted from peripheral blood mononuclear cells of 140 Iranian healthy people, 84 neonates born to HIV‐1‐infected mothers in the PMTCT project, 71 people with high‐risk behaviors, and 76 HIV‐1‐infected individuals. The polymerase chain reaction method was used for the amplification of the CCR5 gene. The CCR5‐Δ32 heterozygous deletion was detected in five (6.6%) HIV‐1‐infected individuals, four (4.7%) neonates born to HIV‐1 positive mothers, two (1.4%) healthy people, and also three (4.2%) people with high‐risk behaviors whereas the CCR5‐Δ32 homozygous deletion was absent in all the groups (Fisher's exact test, P = .0242). The allele of CCR5‐Δ32 homozygous was not detected in the four study groups, and no significant difference was seen in the frequency of the CCR5Δ32 heterozygous allele between HIV seropositive and seronegative individuals. Therefore, it seems that this allele alone cannot explain the natural resistance to HIV‐1 infection and probably several mechanisms are responsible for these processes and it should be further investigated.
Developmental stages of biofilm and characterization of extracellular matrix of manglicolous fungus Aspergillus niger BSC‐1
Authors: Chatterjee Shreosi , Das Surajit
Published: December 2019

Fungal biofilm is ubiquitous in natural environment. The major constituent of fungal biofilm other than biomass is the extracellular matrix (ECM), in which fungal hyphae are embedded. Physical properties of biofilms such as attachment, mechanical strength, and antibiotic resistance can be attributed to ECM. The present work probes various stages of biofilm formation by filamentous manglicolous fungus Aspergillus niger BSC‐1. The spectroscopic analysis revealed that with an increase in incubation time the biofilm formation was significantly increased (p < .0001) up to 36 h. Scanning electron micrograph and confocal micrograph depicted the development of fungal biofilm comprising of six stages, that is, (a) adsorption, (b) active attachment, (c) germling and monolayer formation, (d) hyphal development and formation of ECM, (e) maturation of ECM, and (f) dispersal of spores. At maturation stage, thickness of biofilm was observed upto approximately 15 μm. Approximately, 8.1 mg of ECM materials were extracted from 20 ml of broth culture using ethanol precipitation method. Furthermore, attenuated total reflectance Fourier‐transformed infrared spectroscopic analysis exhibited peaks at 3,398, 2,930, 1,571, 1,391, 1,092, 977 cm−1 which confirmed the presence of protein, carbohydrate, and lipid in the biofilm‐associated matrix.
The interpretative value of transformed tephra sequences
Authors: Dugmore Andrew J. , Thompson Polly I. J. , Streeter Richard T. , Cutler Nick A. , Newton Anthony J. , Kirkbride Martin P.
Published: December 2019

We explore developments in tephra science that consider more than chronology, using case studies of morphological transformations of tephra deposits. Volcanic processes and prevailing weather conditions determine the distribution of tephra deposits immediately after an eruption, but as these freshly fallen tephra become part of the stratigraphic record, the thickness, morphology and definition of the layers they form changes, reflecting the interplay of the tephra, climate, Earth surface processes, topography and vegetation structure, plus direct or indirect modification caused by people and animals. Once part of the stratigraphic record, there can be further diagnostic changes to the morphology of tephra layers, such as the creation of over folds by cryoturbation. Thus, tephra layers may contain proxy evidence of both past surface environments and subsurface processes. Transformations of tephra deposits can complicate the reconstruction of past volcanic processes and make the application of classical tephrochronology as pioneered by Thorarinsson (Sigurður Þórarinsson in Icelandic) challenging. However, as Thorarinsson also noted, novel sources of environmental data can exist within transformed tephra sequences that include the spread or removal of tephra, variations in layer thickness and internal structures, the nature of contact surfaces and the orientation of layers.
Dawson tephra, a widespread 29‐ka marker bed, in a marine core from Patton Seamount off the Alaska Peninsula and its potential marine–terrestrial correlation
Authors: Aoki Kaori
Published: December 2019

A tephra layer with normal grading in the sub‐bottom depth interval 119–122 cm in marine core SO202‐27‐6 was collected on Patton Seamount in the northeast North Pacific Ocean. Based on the geochemistry of volcanic glass shards determined by a wavelength dispersive electron probe micro‐analyser and an X‐ray fluorescence analyser, this layer is correlated to the Dawson tephra, a widespread late Pleistocene time marker tephra in Alaska and the Yukon. The age of the Dawson tephra in the core is 29.03 ± 0.178 ka (1 sigma) based on a published age model. The Dawson tephra is revealed to have been deposited in the transition from marine isotope stage 3 to 2, i.e. the last stage of Heinrich Stadial 3 derived from the ice‐rafted debris signal. According to the correlation between Greenland (NGRIP ice core) and this core, the Dawson tephra occupies the record immediately before inter stadial 4 in the δ18O stratigraphy of NGRIP. The Dawson tephra on Patton Seamount includes lithic fragments, which suggests that it was deposited not only by fall‐out but also in part via another mechanism, such as icebergs from the Cordilleran ice sheet or seasonal sea ice.
Combinatorial conditioning of adipose derived‐mesenchymal stem cells enhances their neurovascular potential: Implications for intervertebral disc degeneration
Authors: Binch Abbie. L. A. , Richardson Stephen M. , Hoyland Judith A. , Barry Frank P.
Published: December 2019

Background

Mesenchymal stem cells (MSCs) are becoming an increasingly attractive option for regenerative therapies due to their availability, self‐renewal capacity, multilineage potential, and anti‐inflammatory properties. Clinical trials are underway to test the efficacy of stem cell‐based therapies for the repair and regeneration of the degenerate intervertebral disc (IVD), a major cause of back pain. Recently, both bone marrow‐derived MSCs and adipose‐derived stem cells (ASCs) have been assessed for IVD therapy but there is a lack of knowledge surrounding the optimal cell source and the response of transplanted cells to the low oxygen, pro‐inflammatory niche of the degenerate disc. Here, we investigated several neurovascular factors from donor‐matched MSCs and ASCs that may potentiate the survival and persistence of sensory nerve fibers and blood vessels present within painful degenerate discs and their regulation by oxygen tensions and inflammatory cytokines.

Methods

Donor‐matched ASCs and MSCs were conditioned with either IL‐1β or TNFα under normoxic (21% O2) or hypoxic (5% O2) conditions. Expression and secretion of several potent neurovascular factors were assessed using qRT‐PCR and human magnetic Luminex assay.

Results

ASCs and MSCs expressed constitutive levels of key neurotrophic factors; and stimulation of ASCs with hypoxia triggered increased secretion of both angiogenic factors (Ang‐2 and VEGF‐A) and neurotrophic (NGF and NT‐3) compared to MSCs. We also report increased transcriptional regulation of pain‐associated neuropeptides in hypoxia stimulated ASCs compared to those in normoxic conditions. We demonstrate transcriptional and translational upregulation of NGF, NT‐3, Ang‐1, and FGF‐2 in response to cytokines in ASCs in 21% and 5% O2.

Conclusions

This work highlights fundamental differences between the neurovascular secretome of donor‐matched ASCs and MSCs, demonstrating the importance of cell‐selection for tissue specific regeneration to reduce ectopic sensory nerve and blood vessel survival and improve patient outcomes.
Prevention of Local Tumor Recurrence After Surgery by Thermosensitive Gel‐Based Chemophotothermal Therapy in Mice
Authors: Fan Yanyan , Yu Dujuan , Li Duan , Wang Xue
Published: December 2019

Background and Objectives

Local recurrence of cancer after surgery has long been a tough problem. In the present study, thermosensitive gel‐based chemophotothermal therapy was applied to prevent the recurrence of liver cancer after surgery.

Study Design/Materials and Methods

Mesoporous silica nanoparticles (MSNs) were used as first‐level carrier to co‐load doxorubicin (DOX) and ICG. Then, the drug‐loaded MSNs (D‐I@MSN) were incorporated into poloxamer gel. A mimic model of liver cancer recurrence after surgery was prepared by subcutaneously injecting H22 cells into the armpit of mice. Then the two‐level composite gel (D‐I@MSN/gel) was also subcutaneously injected at the same site before the formation of tumor, followed by 808 nm laser irradiation.

Results

The loading efficiency and entrapment efficiency of DOX were as high as 8.85% and 96.9%, and that of ICG were 9.24% and 99.3%, respectively. The results of in vitro cytotoxicity showed that cell viability in D‐I@MSN+Laser group was only 5.8% after being irradiated by 808 nm laser for 5 minutes (0.5 W/cm2). In animal studies, tumor formation (tumor recurrence) was greatly inhibited in D‐I@MSN+Laser group.

Conclusions

The thermosensitive gel‐based chemophotothermal therapy showed excellent safety and efficacy when applied in the prevention of mimic local tumor replase after surgery in mice, presenting its great potential clinically. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Temperature Responsive Shape‐Memory Scaffolds with Circumferentially Aligned Nanofibers for Guiding Smooth Muscle Cell Behavior
Authors: Chen Minmin , Li Linlin , Xia Li , Zhang Feng , Jiang Suwei , Hu Hailiang , Li Xingjiang , Wang Hualin
Published: December 2019

Structural simulation of the smooth muscle layer plays an important role in tissue engineering of blood vessels for the replacement of damaged arteries. However, it is difficult to construct small‐diameter tubular scaffolds to homogenously locate and align smooth muscle cells (SMCs). In this work, novel temperature responsive shape‐memory scaffolds are designed for SMC culturing. The scaffolds are composed of an outer layer of poly(lactide–glycolide–trimethylene carbonate) (PLGATMC) for programming the deformation from planar to small‐diameter tubular shape and an inner layer of aligned nanofibrous membrane of poly(lactide–glycolide)/chitosan (PLGA/CS) to regulate cell adhesion, proliferation, and morphology. The SMC behaviors and functions are dependent on the PLGA/CS ratios of membranes, and the scaffold with PLGA/CS 7:3 membrane exhibits the most suitable ability to regulate SMC behavior. The PLGA/CS@PLGATMC scaffold can be deformed into a temporary planar at 20 °C for convenient seeding and attachment of SMCs and then immediately self‐rolled into 3D tube at 37 °C. The proposed strategy offers a practical approach for the development of small‐diameter vascular scaffolds from 2D planar into 3D tubular shape by self‐rolling.
Synthesis and Properties of Novel Polyethylene‐Based Antioxidants with Hindered Phenols as Side Groups
Authors: Zhang Yin , Li Huayi , Li Mengru , Liu Weiwei , Li Qian , Hu Youliang
Published: December 2019

Novel polyethylene‐based (PE‐based) antioxidants derived from commercially available ethylene‐vinyl acetate copolymer (EVA) with PE as the backbone and hindered phenols as side groups are prepared, and their potential for application as non‐migrating polyolefin stabilizers is investigated. The synthesis route contains the typical hydrolysis of EVA and transesterification reaction between the hydrolysis product and methyl 3‐(3,5‐di‐tert‐butyl‐4‐hydroxyphenyl) propionate. Thermal stabilities of these PE‐based antioxidants (AO‐PE) are studied through thermal analysis under an air atmosphere and shown to be higher than those of antioxidant 1076 and antioxidant 1010 (AO‐1010) due to their macromolecular structures. Antioxidant activities of the AO‐PE are evaluated in polypropylene (PP) by measuring the melt flow index of multiple‐extruded stabilized PP, and the results demonstrate that the antioxidant effectiveness of these antioxidants is strongly related to the molecular weight.
Electrospraying the Triblock Copolymer SEBS: The Effect of Solvent System and the Embedding of Quantum Dots
Authors: Koekoekx Robin , Zawacka Natalia C. , Van den Mooter Guy , Hens Zeger , Clasen Christian
Published: December 2019

This work reports on ABA triblock copolymer microparticles encoded with CdSe/CdS core–shell quantum dots (QDs) realized by electrospraying. This method allows for simple but efficient embedding of QDs in polymer beads while retaining the fluorescent properties of the original QDs. The creation of poly(styrene‐ethylene‐butylene‐styrene) (SEBS) monodisperse spherical microparticles with a tunable morphology for applications of the final QD‐loaded product is attainable via solvent variation. By varying the selectivity of the solvent for one of the distinct blocks in the polymer, the final particle morphology can be selectively altered while maintaining the same overall process conditions, allowing to tailor the particles from homogeneously flat in a nonselective solvent to dense spherical particles in an endblock selective solvent system. The mechanism responsible for this transition in morphology can be related to differences in mass transfer in the droplets and thus solvent evaporation rates arising from particular microphase structures. Finally, fluorescence characteristics of the final QD‐embedded polymer particles and photodegradation stability are investigated by spectrophotometry and are compared to the temporal evolution of the original QDs, indicating significant stability improvement and well‐dispersed QDs in an optimized polymer matrix morphology.