bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome analysis reveals liver metabolism programming in kids from nutritional restricted goats during mid-gestation
Authors: Yang Chao , Zhou Xiaoling , Yang Hong , Gebeyew Kefyalew , Yan Qiongxian , Zhou Chuanshe , He Zhixiong , Tan Zhiliang
Published: January 2021

Background

Maternal nutrient restriction during pregnancy causes a metabolic disorder that threatens the offspring’s health in humans and animals. However, the molecular mechanism of how undernutrition affecting hepatic metabolism of fetal or postnatal offspring is still unclear. We aimed to investigate transcriptomic changes of fetal livers in response to maternal malnutrition in goats during mid-gestation and to explore whether these changes would disappear when the nutrition was recovered to normal level during mid-gestation using goats (Capra hircus) as the experimental animals.

Methods

Fifty-three pregnant goats were subjected to a control (100% of the maintenance requirements, CON) or a restricted (60% of the maintenance requirements on day 45 to day 100 of gestation and then realimentation, RES) diet. A total of 16 liver samples were collected from fetal goats on day 100 of gestation and goat kids of postnatal day 90 to obtain hepatic transcriptional profiles using RNA-Seq.

Results

Principal component analysis of the hepatic transcriptomes presented a clear separation by growth phase (fetus and kid) rather than treatment. Maternal undernutrition up-regulated 86 genes and down-regulated 76 genes in the fetal liver of the FR group as compared to the FC group. KEGG pathway analysis showed the DEGs mainly enriched in protein digestion and absorption, steroid biosynthesis, carbohydrate digestion and absorption and bile secretion. A total of 118 significant DEGs (fold change > 1.2 and FDR < 0.1) within KR vs. KC comparison was identified with 79 up-regulated genes and down-regulated 39 genes, and these DEGs mainly enriched in the biosynthesis of amino acids, citrate cycle, valine, leucine and isoleucine biosynthesis and carbon metabolism.

Conclusion

Hepatic transcriptome analysis showed that maternal undernutrition promoted protein digestion and absorption in the fetal livers, while which restrained carbohydrate metabolism and citric acid cycle in the livers of kid goats after realimentation. The results indicate that maternal undernutrition during mid-gestation causes hepatic metabolism programming in kid goats on a molecular level.
ATR-FTIR, EDS and SEM evaluations of enamel structure after treatment with hydrogen peroxide bleaching agents loaded with nano-hydroxyapatite particles
Authors: Orilisi Giulia , Tosco Vincenzo , Monterubbianesi Riccardo , Notarstefano Valentina , Özcan Mutlu , Putignano Angelo , Orsini Giovanna
Published: January 2021

Background

Tooth whitening is one of the most requested dental treatments, but it still presents some side effects. Indeed, the bleaching agent can generate patients’ discomfort and dental hard tissue damages, not achieving an efficient and long-lasting treatment with optimum whitening effect. To overcome these limitations, the bleaching agents containing nano-hydroxyapatite can represent a reliable solution to avoid these detrimental effects.

Methods

In this study, human third molars were treated with commercial bleaching agents, containing nano-hydroxyapatite (nHA) and 6% (at-home treatment), 12% and 18% (in-office treatments) of hydrogen peroxide (HP), named respectively G1, G2 and G3. The results were evaluated descriptively and analytically using Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray spectroscopy (EDS), comparing the treated groups with a commercial gel containing 10% carbamide peroxide (CONV) and with a non-treated control group (CTRL).

Results

ATR-FTIR analysis revealed a similar composition in carbonates and phosphates for CTRL, G1 and G2 groups, which showed no significant differences in their spectral profiles; an increased amount of organic matter was found in G3, while CONV displayed an intermediate behavior. SEM analysis did not highlight significant changes in the enamel microstructure of G1 and CONV when compared to CTRL; the pattern observed in G2 presented a slight increase of enamel irregularities, while G3 displayed a partial removal of the aprismatic layer and microporosities. No evident effects due to nHA were observed in the structure of the hydroxyapatite component of G1, G2 and CONV, if compared to CTRL, while G3 showed a slight loss of crystallinity. In all groups, EDS identified slight changes in the concentration of chemical elements O and Ca, while the Ca/P ratio was similar when compared to CTRL.

Conclusion

The obtained results suggest that the application of the tested commercial bleaching agents, with a concentration of HP up to 12%, does not alter the morphological and chemical composition of the enamel surface and maintains its crystallinity.
Multiple drivers behind mislabeling of fish from artisanal fisheries in La Paz, Mexico
Authors: Munguia-Vega Adrian , Weaver Amy Hudson , Domínguez-Contreras José F. , Peckham Hoyt
Published: January 2021

Seafood mislabeling has the potential to mask changes in the supply of species due to overfishing, while also preventing consumers from making informed choices about the origin, quality and sustainability of their food. Thus, there is a need to understand mislabeling and analyze the potential causes behind it to propose solutions. We conducted a COI DNA barcoding study in La Paz, Baja California Sur, Mexico, with 74 samples from fish markets and 50 samples from restaurants. We identified 38 species sold under 19 commercial names, from which at least ∼80% came from local small-scale fisheries. Overall, 49 samples, representing 40% (95% CI [31.4–48.3]) were considered mislabeled in our samples. Based on analyses where species were assigned to three price categories, economic incentives were associated with approximately half of the mislabeling events observed, suggesting that other motivating factors might simultaneously be at play. Using a network approach to describe both mislabeling (when species are mislabeled as the focal species) and substitution (when the focal species is used as substitute for others), we calculated proxies for the net availability of each species in the market. We found that local fish landings were a significant predictor of the net availability of the 10 most important commercial species at retail, but this true availability was masked to the eyes of the final consumer by both mislabeling and substitution. We hypothesize that the level of supply of each species could help explain mislabeling and substitution rates, where species in low supply and high demand could show higher mislabeling rates and rarely be used as substitutes, while species in high supply and low demand could be used as substitutes for the preferred species. Other factors affecting mislabeling include national regulations that restrict the fishing or commercialization of certain species and local and global campaigns that discourage specific patterns of consumption. We discuss how these factors might influence mislabeling and propose some solutions related to communication and education efforts to this local and global challenge.
Occupation and life satisfaction among individuals with mental illness: the mediation role of self-reported psychophysiological health
Authors: Granjard Alexandre , Mihailovic Marko , Amato Clara , Kazemitabar Maryam , Lucchese Franco , Jacobsson Christian , Kijima Nobuhiko , Garcia Danilo
Published: January 2021

Background

Unemployment can diminish physical, psychological and social health. In this context, research shows that people with mental illness have even more difficulties finding occupation. Thus, some countries, such as Sweden, strive after creating job opportunities for this specific group. We investigated the effect of having an occupation on life satisfaction among individuals with mental illness and whether self-reported physical and psychological health mediated the relationship between being (un)employed and life satisfaction.

Method

Two-hundred eighty-seven individuals (148 males, 134 females, and 5 missing information) with mental illness, who received support and services from Swedish Municipalities in Blekinge, self-reported occupation, life satisfaction, and physical and psychological health.

Results

Participants who reported having an occupation reported also significantly higher levels of life satisfaction, physical health, and psychological health compared to those without occupation. Nevertheless, these differences were rather small (Eta2< 0.06). Moreover, the indirect effect of having an occupation on life satisfaction through physical and psychological health was significant. Finally, the total indirect effect of physical and psychological health (i.e., psychophysiological health) accounted for 53% of the total effect of having an occupation on life satisfaction.

Conclusion

For individuals with mental illness there seems to be an almost equal importance of indirect and direct effects of having an occupation on their levels of life satisfaction. More specifically, while there are differences in life satisfaction within this population in relation to having an occupation, having an occupation leads to the sense of good psychophysiological health, which in turn helps individuals with mental illness to feel satisfied with their lives.
Some bryophytes newly reported for the Australian continent
Authors: Van Zanten Ben , During Heinjo , Sollman Philippus
Published: January 2021

Anoectangium euchloron (Schwägr.) Mitt., Campyliadelphus chrysophyllus (Brid.) R.S. Chopra and Tortula

caucasica Broth. are reported as new for the Australian continent.
Validation of two informally named species of Melichrus (Ericaceae subfam. Epacridoideae) from north-eastern New South Wales
Authors: Kennedy Helen Therese
Published: January 2021

Two narrowly endemic, endangered species of Melichrus (Ericaceae subfam. Epacridoideae) from north-eastern New South Wales currently bearing phrase names are formally named and described. Melichrus hirsutus J.B.Williams ex H.T.Kenn. & I.Telford is validly published more than 50 years after the first herbarium specimens were collected. Melichrus gibberagee J.B.Williams ex H.T.Kenn. & J.J.Bruhl is also described as new. Notes are provided on the distribution, habitat and conservation status of both species. An updated key to Melichrus species in New South Wales is provided.
Grevillea pieroniae Olde (Proteaceae: Grevilleoideae: Hakeinae), a rare new species in the Triloba Group from the Stirling Range, Western Australia, and a short history of the group
Authors: Olde Peter Maurice
Published: January 2021

Twenty-one Grevillea species currently comprise the Triloba Group sensu Flora of Australia, or Group 1 sensu The Grevillea Book. All species except the transcontinental species G. anethifolia R.Br. are distributed in south-west Western Australia. Grevillea pieroniae Olde, herein described, is currently treated as Grevillea sp. Stirling Range (D.J. McGillivray 3488 & A.S. George) by the Western Australian Herbarium. It has some affinity with Grevillea anethifolia through shared possession of similar truncate-conical to cylindrical pollen-presenters. Grevillea pieroniae is a rare species that is potentially threatened by Phytophthora cinnamomi, fire frequency, a drying climate, as well as feral and native herbivore-grazing, so requires careful assessment and ongoing monitoring. A short history of the Triloba Group is provided to give context to Grevillea pieroniae and as precursor to other related species soon to be recognised.
The moss family Octoblepharaceae A.Eddy ex Menzel in Australia
Authors: Cairns Andi , Meagher David , Seppelt Rodney , Franks Andrew
Published: January 2021

This is the first treatment of the family Octoblepharaceae for Australia. The sole Australian species, Octoblepharum albidum Hedw., is described and illustrated, and a map of its known and potential distribution in Australia is included.
The behavior of Brazilian companies shares return under social responsibility
Authors: Cavenaghi Fernanda Bojikian , Pimenta Junior Tabajara , Antônio Rafael Moreira , Lima Fabiano Guasti , Corrêa Ana Carolina Costa
Published: January 2021

Several scientific studies seek to establish a relationship between the adoption of corporate social responsibility practices and financial and/or economic performance of companies. There are no definitive answers to this question. Compared performance of ISE – Índice de Sustentabilidade Empresarial (Index of Corporate Sustainability) and Ibovespa index, both from Brazilian stock market, is often used to characterize the influence of good business practices in this area. This work investigated this question in an innovative prism. Instead of using directly that index returns series, we constructed a portfolio composed only of companies that remained in ISE portfolio over the five years from 2012 to 2016, and compared their performance with a portfolio of an equal number of companies, taken among the most liquid ones that continuously participated in the Ibovespa portfolio in same period. For this purpose, we used Mann-Whitney averages comparison test, return series stationarity tests – Augumented Dickey-Fuller and Phillips-Perron - and Engle-Granger cointegration test. The results showed higher average returns for portfolio of socially responsible companies, indicating a growth of their returns compared to portfolio of conventional companies, and showed, however, a tendency to balance in long term run.
The Contribution of Innovation to Startups for Market Creation
Authors: Martins Eros Augusto Asturiano
Published: January 2021

This article examined how the innovation in startups contributes to the creation of markets. The constructs “Strategies for the creation of markets” and “Innovation” were covered in the theoretical framework. The scope of the research was startups and the specific objectives sought to analyze how innovation occurs and verifying the creation of the market through their innovation. The method of research was the qualitative exploratory, and data collection was performed by means of a structured script. Ten startup founders were interviewed and it was used the content analysis technique for data analysis. This article has shown that startups, even using an existing business model, innovate in the segment or the way they deliver their products, thus generating a value innovation and this is often caused by the ability to feel the pain of consumer. Some limitations were found in the research, such as the limited data on Brazilian startups, which already indicates a path for future research, as well as seeking to understand the functioning of the organizational structure of these companies, which still need to be better studied.
Neuroscience researcher's new book decries the demonization of drugs
Authors: Enos Gary
Published: January 2021

“Science should be driving our drug policies, even if it makes us uncomfortable.”
Wire and Arc Additive Manufacturing of High‐Strength Low‐Alloy Steel: Microstructure and Mechanical Properties
Authors: Duarte Valdemar R. , Rodrigues Tiago A. , Schell Norbert , Santos Telmo G. , Oliveira João P. , Miranda Rosa M.
Published: January 2021

Wire and arc additive manufacturing of high‐strength low‐alloy steel is performed. The microstructures and mechanical properties of the samples are investigated and correlated with the process heat input. Continuous and pulsed wave welding modes are studied and added material efficiencies are determined. The microstructural characterization and microhardness test reveal that the heat input effect is more impactful when parts are produced with pulsed wave mode. Microstrain evolution and phase fraction are evaluated via synchrotron X‐ray diffraction. A higher percentage of austenite in the samples built with higher heat input is determined. Uniaxial tensile testing results show that it is possible to improve ductility and mechanical strength by varying the process parameters.
Ti‐Based Surface Integrated Layer and Bulk Doping for Stable Voltage and Long Life of Li‐Rich Layered Cathodes
Authors: Luo Dong , Cui Jiaxiang , Zhang Bingkai , Fan Jianming , Liu Peizhi , Ding Xiaokai , Xie Huixian , Zhang Zuhao , Guo Junjie , Pan Feng , Lin Zhan
Published: January 2021

High‐energy‐density lithium‐rich layered oxides (LLOs) hold the greatest promise to address the range anxiety of electric vehicles. Their application, however, has been prevented by fast voltage decay and capacity fading for years, which mainly originate from irreversible transition‐metal migration and undesirable cathode‐electrolyte interfacial reactions. Herein, a Ti‐based surface integrated layer and bulk doping, which greatly improve the voltage and capacity stability of LLOs is synchronously constructed. More importantly, STEM and Raman results demonstrate that continuous and uniform surface Ti‐based integrated layer is a spinel‐like rocksalt structure with Fd‐3m space group, which is built through by several the replacement of Li ions in surface several atomic layers by Ti ions. After 500 cycles, Ti‐150 sample delivers a capacity retention of 85%, and its voltage decay rate from the 30th to the 500th cycle is only ≈0.72 mV/cycle. Spectral results and DFT calculations suggest that bulk Ti‐doping mitigates the migration of Mn and Ni ions in the bulk, while Ti‐based integrated layer significantly suppresses surface structure evolution and interfacial reactions by impeding the generation of surface Li vacancies during Li extraction as well as preventing direct contact between electrolyte and active materials.
Networking State of Ytterbium Ions Probing the Origin of Luminescence Quenching and Activation in Nanocrystals
Authors: Mei Sheng , Zhou Jiajia , Sun Hong‐Tao , Cai Yangjian , Sun Ling‐Dong , Jin Dayong , Yan Chun‐Hua
Published: January 2021

At the organic–inorganic interface of nanocrystals, electron‐phonon coupling plays an important but intricate role in determining the diverse properties of nanomaterials. Here, it is reported that highly doping of Yb3+ ions within the nanocrystal host can form an energy‐migration network. The networking state Yb3+ shows both distinct Stark splitting peak ratios and lifetime dynamics, which allows quantitative investigations of quenching and thermal activation of luminescence, as the high‐dimensional spectroscopy signatures can be correlated to the attaching and de‐attaching status of surface molecules. By in‐situ surface characterizations, it is proved that the Yb‐O coordination associated with coordinated water molecules has significantly contributed to this reversible effect. Moreover, using this approach, the prime quencher OH can be switched to CH in the wet‐chemistry annealing process, resulting in the electron‐phonon coupling probability change. This study provides the molecular level insights and dynamics of the surface dark layer of luminescent nanocrystals.
Boosting Production of HCOOH from CO2 Electroreduction via Bi/CeOx
Authors: Duan Yan‐Xin , Zhou Yi‐Tong , Yu Zhen , Liu Dong‐Xue , Wen Zi , Yan Jun‐Min , Jiang Qing
Published: January 2021

Formic acid (HCOOH) is one of the most promising chemical fuels that can be produced through CO2 electroreduction. However, most of the catalysts for CO2 electroreduction to HCOOH in aqueous solution often suffer from low current density and limited production rate. Herein, we provide a bismuth/cerium oxide (Bi/CeOx) catalyst, which exhibits not only high current density (149 mA cm−2), but also unprecedented production rate (2600 μmol h−1 cm−2) with high Faradaic efficiency (FE, 92 %) for HCOOH generation in aqueous media. Furthermore, Bi/CeOx also shows favorable stability over 34 h. We hope this work could offer an attractive and promising strategy to develop efficient catalysts for CO2 electroreduction with superior activity and desirable stability.
Structure‐Guided Discovery of a Potent and Selective Cell‐Active Inhibitor of SETDB1 Tudor Domain
Authors: Guo Yinping , Mao Xin , Xiong Liang , Xia Anjie , You Jing , Lin Guifeng , Wu Chengyong , Huang Luyi , Wang Yiwei , Yang Shengyong
Published: January 2021

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumour suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1), we discovered the first potent and selective small molecule SETDB1‐TTD inhibitor (R,R)‐59 through stepwise structure‐guided optimization. (R,R)‐59 showed a KD value of 0.088±0.045 μM in the ITC assay. The high potency of (R,R)‐59 was well explained by the cocrystal structure of the (R,R)‐59‐TTD complex. (R,R)‐59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)‐59 did not show activity in all the assays, highlighting the potential of (R,R)‐59 as a tool compound in exploring the biological functions of SETDB1‐TTD.
Preface: 9th international workshop on astronomy and relativistic astrophysics: From quarks to cosmos
Authors: Zen Vasconcellos César A. , Hess Peter O. , Piccinelli Gabriella , Magaña Mariana Vargas , Ureña‐Lopez Luis Arturo , Felipe Ricardo Gonzalez , Boller Thomas , Gullberg Steven
Published: January 2021

We outline our experience in organizing the 9th edition of the International Workshop on Astronomy and Relativistic Astrophysics: from Quarks to Cosmos, in virtual format, denominated IWARA2020 Video Conference, held from 6 to 12 September, 2020. The IWARA 2020 Video Conference aimed to bring together leading academic scientists, professors, students, and research scholars for exchanging experiences and research results and discuss the most recent innovations, trends, concerns, practical challenges, and solutions adopted in the research fields within the scope of the conference. The IWARA 2020 Video Conference offered to the participants a platform for scientific and academic projects, partnerships, and presentation of high‐quality research contributions describing original and unpublished results on several topics related as new phenomena and new states of matter in the Universe, general relativity, gravitation, cosmology, dwarf stars, neutron and exotic stars, pulsars, black holes, GRBs, astroparticles and nuclear physics, QCD and heavy‐ion reactions, quantum gravity and quantum cosmology, gravitational‐wave astronomy, dark energy, dark matter, strange matter, high‐energy cosmic rays, galaxies, blazars and quasars, strong magnetic fields in the Universe as well as laboratories, observatories, telescopes, and other experimental and observational facilities that will define the future directions of astrophysics, astronomy, cosmology, nuclear and astroparticle physics and the future of physics at the energy frontiers, and topics related to these.
A timed Phalen’s test predicts abnormal electrophysiology in carpal tunnel syndrome
Authors: Alanazy Mohammed H. , Albulaihe Hana , Alhumayyd Ziad , Albarrak Anas M. , Abuzinadah Ahmad R.
Published: January 2021

Objective

Previous studies reported variable sensitivity and specificity of the Phalen test. We investigated whether a timed Phalen’s test (TPT) could predict abnormal nerve conduction studies (NCS) results in carpal tunnel syndrome (CTS).

Methods

Patients with CTS were consecutively recruited. A neurologist confirmed the clinical diagnosis of CTS and recorded the TPT before NCS were performed. Another neurologist, blinded to the TPT, graded the severity of NCS. The TPT sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

Results

In total, 403 patients with 706 hands were recruited and diagnosed with CTS; 465 hands had positive TPT, and 611 hands showed abnormal NCS results. A positive TPT at ≤ 10 s had a specificity of 96.8% and a PPV of 96.6% in predicting abnormal NCS. The sensitivity and NPV of TPT were insignificant.

Discussion

A positive TPT at ≤ 10 s can be useful in predicting NCS abnormalities in patients with CTS.
Interactive learning in the classroom: A mobile augmented reality assistance application for learning
Authors: Yoon Jong‐Chul , Kang HyeongYeop
Published: January 2021

The rapid evolution of augmented reality (AR) technology has presented new opportunities in the domain of education. Acting as a bridge between the virtual and real worlds, AR technology overcomes the physical limitations of our classrooms at a low cost and provides an interactive learning experience. In this study, we present a smartphone AR application, named the AR‐E‐Helper, which assists the learning of students in higher education lectures. Our goal is to provide an AR‐enhanced learning experience for students. To validate the effectiveness of the AR‐E‐Helper, we conducted an experiment that compares three classes: AR‐enhanced, smartphone‐enhanced, and nontechnology‐enhanced classes. Through the experiment, we observed that our application was helpful in maintaining student's focus in class, promoting their interest, and increasing their satisfaction. Furthermore, we also found how to improve our application based on the observations that the application brought some downsides to the learning activities. We expect that this study will be helpful to design AR learning tools in the future.
Air Stable Iridium Catalysts for Direct Reductive Amination of Ketones
Authors: Polishchuk Iuliia , Sklyaruk Jan , Lebedev Yury , Rueping Magnus
Published: January 2021

Half‐sandwich iridium complexes bearing bidentate urea‐phosphorus ligands were found to catalyze the direct reductive amination of aromatic and aliphatic ketones under mild conditions at 0.5 mol % loading with high selectivity towards primary amines. One of the complexes was found to be active in both the Leuckart–Wallach (NH4CO2H) type reaction as well as in the hydrogenative (H2/NH4AcO) reductive amination. The protocol with ammonium formate does not require an inert atmosphere, dry solvents, as well as additives and in contrast to previous reports takes place in hexafluoroisopropanol (HFIP) instead of methanol. Applying NH4CO2D or D2 resulted in a high degree of deuterium incorporation into the primary amine α‐position.
A Molecular Low‐Coordinate [Fe‐S‐Fe] Unit in Three Oxidation States
Authors: Schneider Christian , Demeshko Serhiy , Meyer Franc , Werncke C. Gunnar
Published: January 2021

A [Fe‐S‐Fe] subunit with a single sulfide bridging two low‐coordinate iron ions is the supposed active site of the iron‐molybdenum co‐factor (FeMoco) of nitrogenase. Here we report a dinuclear monosulfido bridged diiron(II) complex with a similar complex geometry that can be oxidized stepwise to diiron(II/III) and diiron(III/III) complexes while retaining the [Fe‐S‐Fe] core. The series of complexes has been characterized crystallographically, and electronic structures have been studied using, inter alia, 57Fe Mössbauer spectroscopy and SQUID magnetometry. Further, cleavage of the [Fe‐S‐Fe] unit by CS2 is presented.
Notwendigkeit und Vermarktung von Flexibilitätsoptionen im Energiesystem der Zukunft
Authors: Zipperling Erik , Dahlmann Benedikt , Zdrallek Markus , Derksen Christian , Eicker Stefan , Serafin Heiko
Published: January 2021

Ansprüche an Erzeugung, Verteilung und Verbrauch elektrischer Energie wandeln sich mit der Energiewende fundamental. Energiebezugskosten unflexibler Verbraucher steigen und Erlöse unflexibler Erzeuger sinken. Unternehmen können mit der Vermarktung von Flexibilitäten Kosten senken. Dieser Artikel legt die Notwendigkeit von Flexibilität im Energiesystem und die neuen Vermarktungsoptionen dar. Im vorgestellten Forschungsprojekt FlexChemistry werden Flexibilitätspotenziale der Intrastrukturanlagen eines Chemieparks systematisch untersucht, hinsichtlich ihrer Vermarktung bewertet und aktiviert.
A Phase 1 Study of KHK4083: A Single‐Blind, Randomized, Placebo‐Controlled Single‐Ascending‐Dose Study in Healthy Adults and an Open‐Label Multiple‐Dose Study in Patients With Ulcerative Colitis
Authors: Furihata Kenichi , Ishiguro Yoh , Yoshimura Naoki , Ito Hiroaki , Katsushima Shinji , Kaneko Etsuji , Shimabe Munetake , Mukai Mayumi , Watanabe Risa , Morishige Takuya
Published: January 2021

OX40 plays an essential role in maintaining late T‐cell proliferation and survival by suppressing apoptosis and by inducing T‐cell memory formation. Here, we report the results of the phase 1 study of KHK4083, a fully human antimonoclonal antibody specific for OX40. In this study, we aimed to assess the safety and tolerability of a single intravenous or subcutaneous administration of KHK4083 compared with placebo in healthy Japanese and Caucasian subjects and determined the pharmacokinetics (PK) and immunogenicity. Also, we assessed the preliminary efficacy and pharmacodynamics of multiple intravenous doses in Japanese patients with moderate to severe ulcerative colitis (UC). Drug‐related treatment emergent adverse events occurred in 21 healthy subjects (58.3%) and 5 patients with UC (62.5%) after administration of KHK4083. There were no serious adverse events. The PK profile of a single intravenous dose of 10 mg/kg KHK4083 was similar in healthy Japanese and Caucasian subjects. Of 8 UC patients, a clinical response was observed in 3 patients (37.5%) and clinical remission in 2 patients (25.0%) in week 6. Our study demonstrated the safety and tolerability of single and multiple administrations of KHK4083 in healthy Japanese and Caucasian subjects and Japanese patients with moderate to severe UC. It also indicated favorable pharmacological properties of the drug.
Gene x responsive parenting interactions in social development: Characterizing heterogeneity in autism spectrum disorder
Authors: Caplan Barbara , Blacher Jan , Eisenhower Abbey , Baker Bruce L. , Lee Steve S.
Published: January 2021

Emerging research suggests that caregiving environments and genetic variants independently contribute to social functioning in children with typical development or autism spectrum disorder (ASD). However, biologically plausible interactive models and complimentary assessment of mechanisms are needed to: (a) explain considerable social heterogeneity, (b) resolve inconsistencies in the literature, and (c) develop and select optimal treatments based on individual differences. This study examined the role of child genotypes and responsive parenting in the social development of 104 children with ASD (ages 4–7 years). We utilized a longitudinal, multi‐informant design and structural equation models to evaluate: (a) the additive and interactive effects of biologically plausible candidate genes (5‐HTTLPR, OXTR, DRD4) and responsive parenting in predicting prospective social development in ASD across three time points spanning 1.5 years, and (b) whether child emotion regulation mediated observed gene x environment interactions (GxEs). Responsive parenting positively predicted prospective change in child social skills; these associations were moderated by 5‐HTTLPR and DRD4 in teacher‐report models, and DRD4 in parent‐report models. No GxE effects were found for OXTR. Emotion regulation did not significantly mediate the GxEs involving 5‐HTTLPR and DRD4. Acknowledging the complexities of GxE research, implications for future research, and targeted intervention efforts are discussed.
Causal inference for quantile treatment effects
Authors: Sun Shuo , Moodie Erica E. M. , Nešlehová Johanna G.
Published: January 2021

Analyses of environmental phenomena often are concerned with understanding unlikely events such as floods, heatwaves, droughts, or high concentrations of pollutants. Yet the majority of the causal inference literature has focused on modeling means, rather than (possibly high) quantiles. We define a general estimator of the population quantile treatment (or exposure) effects (QTE)—the weighted QTE (WQTE)—of which the population QTE is a special case, along with a general class of balancing weights incorporating the propensity score (PS). Asymptotic properties of the proposed WQTE estimators are derived. We further propose and compare PS regression and two weighted methods based on these balancing weights to understand the causal effect of an exposure on quantiles, allowing for the exposure to be binary, discrete, or continuous. Finite sample behavior of the three estimators is studied in simulation. The proposed methods are applied to data taken from the Bavarian Danube catchment area to estimate the 95% QTE of phosphorus on copper concentration in the river.
Ex vivo three‐dimensional elemental imaging of mouse brain tissue block by laser‐induced breakdown spectroscopy
Authors: Lin Qingyu , Wang Shuai , Duan Yixiang , Tuchin Valery V
Published: January 2021

Measurement and reconstruction of an elemental image of large brain tissue will be beneficial to the diagnosis of neurological brain diseases. Herein, laser‐induced breakdown spectroscopy (LIBS) is introduced for three dimensional (3D) elemental analysis of paraffin‐embedded mouse brain tissue blocks. It is used for the first time towards the mapping of mouse brain block samples. A micro‐LIBS prototype is developed for brain elemental imaging and a layer‐by‐layer approach is used to reconstruct the 3D distribution of Ca, Mg, Na, Cu, and P in the brain tissue. Images are captured with 50 μm lateral resolution and 300 μm depth resolution. The images show that the reclamation area of the cortex surface is enriched with Ca and Mg. In contrast, the Cu distribution is circular and is found primarily in the entirety of the cerebral cortex for the paraffin‐embedded brain samples. Elemental imaging results suggest that the highest P intensity is found in the cerebellum nearby the middle sagittal plane in the left‐brain paraffin block. These preliminary results indicate that LIBS is a potentially powerful tool for elemental bioimaging of the whole brain and may further improve the understanding of complex brain mechanisms.
Hemostatic strategies for uncontrolled bleeding: A comprehensive update
Authors: Malik Annum , Rehman Fiza Ur , Shah Kifayat Ullah , Naz Syeda Sohaila , Qaisar Sara
Published: January 2021

Uncontrolled bleeding remains the leading cause of morbidity and mortality across the entire macrocosm. It refers to excessive loss of blood that occurs inside of body, due to unsuccessful platelet plug formation at the injury site. It is not only limited to the battlefield, but remains the second leading cause of death amongst the civilians, as a result of traumatic injury. Startlingly, there are no effective treatments currently available, to cater the issue of internal bleeding, even though early intervention is of utmost significance in minimizing the mortality rates associated with it. The fatal issue of uncontrolled bleeding is ineffectively being dealt with the use of pressure dressings, tourniquet, and surgical procedures. This is not a practical approach in combat arenas or in emergency situations, where the traumatic injury inflicted is deep inside the body, and cannot be addressed externally, by the application of topical dressings. This review focuses on the traditional hemostatic agents that are used to augment the process of hemostasis, such as mineral zeolites, chitosan based products, biologically active agents, anti‐fibrinolytics, absorbable agents, and albumin and glutaraldehyde, as well as the micro‐ and nano‐based hemostatic agents such as synthocytes, thromboerythrocytes, thrombosomes, and the synthetic platelets.
γ‐Fe2O3@HAp@PBABMD@Cu magnetic nanoparticles: Efficient, green, and recyclable novel nanocatalyst for the synthesis of densely functionalized pyrrole‐pyrido[2,3‐d]pyrimidine hybrids
Authors: Saberikhah Elham , Mamaghani Manouchehr , Mahmoodi Nosrat Ollah
Published: January 2021

A green heterogeneous nanocatalyst, Cu(II)‐PBABMD complex immobilized on core‐shell magnetic γ‐Fe2O3@HAp, was successfully designed, synthesized, and characterized by FTIR, XRD, FESEM, EDX, VSM, TGA, BET, ICP‐OES, and TEM techniques. The magnetic Cu(II) nanocatalyst was employed as a novel, ecofriendly, recyclable, and safe catalyst for the one‐pot, three‐component condensation of 6‐amino‐2‐thioxo‐2,3‐dihydropyrimidin‐4(1H)‐one, 3‐(1‐methyl‐1H‐pyrrol‐2‐yl)‐3‐oxopropanenitrile and aromatic aldehydes to produce new pyrido[2,3‐d]pyrimidine derivatives, in refluxing EtOH with excellent yield (90–97%) and short reaction time (8–13 min). The nanocatalyst was used and recycled in eight runs without significant leaching or loss of its catalytic activity.
Diagnostic value of macrophage inhibitory cytokine 1 as a novel prognostic biomarkers for early gastric cancer screening
Authors: Ge Xin , Zhang Xiaolei , Ma Yanling , Chen Shaohua , Chen Zhaowu , Li Ming
Published: January 2021

Background

Early diagnosis is very important to improve the survival rate of patients with gastric cancer (GC), especially in asymptomatic participants. However, low sensitivity of common biomarkers has caused difficulties in early screening of GC. In this study, we explored whether MIC‐1 can improve the detection rate of early GC.

Methods

We screened 8257 participants based on risk factors such as age, gender, and family history for physical examination including gastroscopy. Participant blood samples were taken for measure MIC‐1, CA‐199, CA72‐4, and PG1/PG2 levels. The diagnostic performance of MIC‐1 was assessed and compared with CA‐199, CA72‐4, and PG1/PG2, and its role in early GC diagnosis and the assessment of the risk of precancerous lesions have also been studied.

Results

Based on endoscopic and histopathological findings, 55 participants had GC, 566 participants had low‐grade neoplasia, and 2605 participants had chronic gastritis. MIC‐1 levels were significantly elevated in GC serum samples as compared to controls (P < .001). The sensitivity of serum MIC‐1 for GC diagnosis was much higher than that of CA‐199 (49.1% vs 20.0%) with similar specificities. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MIC‐1 had a better performance compared with CA‐199, CA72‐4, and PG1/PG2 in distinguishing early‐stage GC (AUC: 72.9% vs 69.5%, 67.5%, 44.0%, respectively).

Conclusions

Serum MIC‐1 is significantly elevated in most patients with early GC. MIC‐1 can serve as a novel diagnostic marker of early GC and value the risk of GC.
THE ILLUSIONS OF SUCCESS
Authors: Douglas Holladay J.
Published: January 2021

The author reflects on life lessons drawn from a varied career in business, government service, and education. Examples of meaning and purpose are drawn from interactions with individuals ranging from a Morgan Stanley banker to Mother Teresa. Topics such as loneliness and isolation are explored, and statistics are cited about recent suicide rates. The author notes that “after four decades of working closely with leaders, observing them and listening to their deepest thoughts and concerns, I have distilled the pursuit of meaning and purpose into eight practices.” In brief, those practices are (1) know and live your own story, (2) maintain deep connections in your core relationships, (3) regularly express gratitude, (4) learn to forgive and serve, (5) define success and failure for yourself, (6) make sure risk continues to play a role in your life, (7) integrate your life, rather than compartmentalizing it, and (8) work to leave a legacy for others. Solitude is also essential and provides the space to reflect upon our lives, relationships, challenges, and blessings. Solitude differs from loneliness. Solitude fills our hearts with gratitude and renewed energy for living. Loneliness kills our very souls and often spirals into sadness and despair.
LEADERS DEVELOPING LEADERS
Authors: Archambeau Shellye
Published: January 2021

The author contends that despite the importance of developing the next generation of organizational leaders, the results to date have been frustrating. Various failures are enumerated and outlined: program failures, personal failures, and institutional failures. Organizations must develop a “bench” of developing leaders who can move into increasingly senior positions. Chief executive officers (CEOs) must be involved and engaged, and not completely leave it up to their senior teams. The CEO should help people recognize talent in high‐potential people in the areas of competence, motivation, and interpersonal skills. The planning process is outlined in detail; leaders should share their knowledge about goals and timelines, and that there are two jobs for every level someone hits, and that each new level represents a new starting point. Flexibility belongs in a plan, and resilience is critical. It is important to take risks and to create an environment that supports risk taking. The latter inevitably involves some failure. The importance of mentoring and sponsorship is discussed, with the assertion that most people and companies tend to get these areas wrong. The ongoing challenge of developing the next generation of leaders is a critical—and current—strategic challenge facing senior executives.
New study highlights ACOs' need for parity, equity in BH
Authors: Canady Valerie A.
Published: January 2021

Efforts to understand how accountable care organizations (ACOs) are faring across the country at providing behavioral health services, and to address barriers faced by ACOs to integrate behavioral health into their care models, are at the heart of a new report authored by Advocates for Human Potential Inc. (AHP), a national research, technical assistance and consulting firm.
Phamacological treatment of persistant lower urinary tract symptoms after a transurethral resection of the prostate is predictive of a new surgical treatment: 10 years follow‐up study
Authors: De Nunzio Cosimo , Franco Antonio , Lombardo Riccardo , Baldassarri Valeria , Borghesi Alessandro , Li Marzi Vincenzo , Trucchi Alberto , Agrò Enrico Finazzi , Tubaro Andrea ,   The Publications Committee of Italian Society of Urodynamics (SIUD)
Published: January 2021

Aim

To evaluate possible risk factors of re intervention in patients with benign prostatic enlargement (BPE) undergoing transurethral resection of the prostate (TURP).

Materials and Methods

A consecutive series of patients with LUTS and BPE underwent TURP in our center in 2004 and 2005 and they were then followed up to September 2016. Patients were assessed at baseline, 3‐, 6‐month postoperatively and yearly thereafter with medical history, international prostate symptom score, prostate specific antigen, maximal urinary flow rate, post void residual urine. Reoperation was defined as the requirement of a new TURP to relieve bothersome LUTS. Cox regression was used to determine covariates associated with reoperation rate and the Kaplan–Meier curve assessed the time to reoperation.

Results

Overall, 92 patients were enrolled. Median follow up was 142 months. 13 patients underwent a second TURP during the follow‐up period (reoperation rate was 14%); out of them 9/13 (69%) received medical treatment for persistent LUTS (p = .001). The need of LUTS/BPE pharmacological treatment after TURP is an independent risk factor for a second surgical procedure (odds ratio 9,3; p = .001). Out of the 13 patients treated with a re‐TURP, 12 (92%) underwent surgery within 5 years of follow‐up.

Conclusion

In our single center study, the need of LUTS/BPE pharmacological treatment was a predictive factor of a re‐TURP. Considering that more than 90% of re‐TURP were performed during the first 5 years of follow‐up, it is assumable that a follow‐up longer than 5 years is not needed in these patients.
Deep Targeted Sequencing and Its Potential Implication for Cancer Therapy in Chinese Patients with Gastric Adenocarcinoma
Authors: Yu Pengfei , Wang Yusheng , Yu Yanfei , Wang Aodi , Huang Ling , Zhang Yuan , Liu Wenjing , Wu Haiyan , Yao Ming , Du Yi-An , Cheng Xiangdong
Published: January 2021

Introduction

Gastric cancer (GC) has a high incidence and mortality rate, especially in East Asians, and about 90% of GCs are adenocarcinomas. Histological and etiological heterogeneity and ethnic diversity make molecular subtyping of GC complicated, thus making it difficult to determine molecular division systems and standard treatment modalities. Limited cohorts from South Korea, Singapore, Australia, and Japan have been studied; however, the mutational landscape of gastric adenocarcinomas in Chinese patients is still unknown.

Methods

We performed a targeted sequencing panel focusing on cancer-related genes and tumor-associated microorganisms of 529 gastric adenocarcinoma samples with matched blood controls. We identified 449 clinically relevant gene mutations.

Results

Approximately 47.1% of Chinese patients with GC harbored at least one actionable mutation. The top somatic mutations were TP53, ARID1A, LRP1B, PIK3CA, ERBB2, CDH1, KRAS, FAT4, CCNE1, and KMT2D. Truncation mutations of ARID1A, KMT2D, RNF43, TGFBR2, and CIC occurred in patients with high tumor mutational burden. Gene amplifications of ERBB2, CCNE1, CDK12, and CCND1 were detected in patients with low tumor mutational burden. Pathway analysis revealed common gene alterations in the Wnt and PI3K/Akt signaling pathways. The ratio of patients with high microsatellite instability was significantly lower than other cohorts, and high microsatellite instability and Epstein-Barr virus (EBV)–positive features seemed mutually inclusive in Chinese patients with GC. In 44 (8.3%) patients, 45 germline mutations were identified, among which SPINK1 mutations, all SPINK1 c.194 + 2T > C, were present in 15.9% (7/44) of patients. Microorganisms found in Chinese patients with GC included Helicobacter pylori, EBV, hepatitis B virus, and human papillomavirus types 16 and 18.

Conclusion

Identification of varied molecular features by targeted next-generation sequencing provides more insight into patient stratification and offers more possibilities for both targeted therapies and immunotherapies of Chinese patients with GC.

Implications for Practice

This study investigated the genomic alteration profile of 529 Chinese patients with gastric adenocarcinoma by deep targeting sequencing, which might be the largest Chinese cohort on the genomic research of gastric adenocarcinoma up to now.
The effect of family support on student engagement: Towards the prevention of dropouts
Authors: Gil Alfonso J. , Antelm‐Lanzat Ana M. , Cacheiro‐González María L. , Pérez‐Navío Eufrasio
Published: January 2021

The literature on school dropout indicates a set of predictors of dropout. These factors are fundamentally grouped into three dimensions: behavioral, academic, and social. This study aims to analyze the relationships between of dropout. It is proposed that students' socialization abilities in the classroom affect their behavioral engagement, and that family support mediates the relationship between the student's skills and behavioral engagement. The participants in the study are 754 adolescents from Spain (age M = 15.75 years). This study uses the partial least squares method. The results show, first, a direct relationship between the student's socialization skills and, second, engagement and the mediating role of family support in the relationship between students' skills and behavioral engagement. The work proposes implications and interventions to examine the problem of school dropout.