bluuebunny/crossref_metadata_2025 huggingface dataset:
A catastrophic flowslide that overrides a liquefied substrate: the 1983 Saleshan landslide in China
Authors: Zhang Fanyu , Peng Jianbing , Wu Xiugang , Pan Fazhen , Jiang Yao , Kang Chao , Wu Weijiang , Ma Wenguo
Published: May 2021

Flowslides that override a liquefied substrate can vastly enhance a disaster after failure initiation. These effects may result from the rapid velocity and long runout distance from slides mobilized into flows. It is thus crucial to provide an improved understanding of the transformation mechanisms of catastrophic flowslides for hazard evaluation. This study examines the Saleshan landslide in Gansu, China, which occurred in 1983 and killed more than 200 people. The Saleshan landslide travelled for approximately 1 km due to pore water pressure generation resulting from overrunning and liquefication of the alluvial sands in the river valley below. We used geomorphologic and topographic maps to determine its dynamic features and mobilization behaviors on the landslide body, and placemarks and seismic signals to identify its approximate velocity at different sites. Electrical resistivity tomography (ERT) surveys also revealed the hydrogeological conditions post‐landslide, showing a clear groundwater table along with the liquefied alluvial sand and gravel layers. Particle size distributions and triaxial shear behaviors confirmed more ready liquefaction of superficial loess and underlying alluvial sand in comparison with the red soil above and below them. Novel loading impact triaxial testing was also performed on the alluvial sand to elucidate its liquefaction potential in undrained and drained conditions. The alluvial sand was found to be markedly prone to liquefaction in undrained conditions due to impact‐induced increased pore water pressure. The results further demonstrated that the Saleshan landslide underwent a transformation from a slowing slide on a steep slope, where it originated, to flow on a nearly flat terrace with abundant groundwater that it overrode. The transformation mechanism involved the liquefied alluvium sand substrate, which greatly enhanced the landslide mobility. Along with recent, similar findings from landslides globally, substrate liquefaction may result in a widespread, significant increase in landslide mobility and thus hazard, and the present study identifies the requisite conditions for this phenomenon to occur.
Fate of chlorpyrifos, omethoate, cypermethrin, and deltamethrin during wheat milling and Chinese steamed bread processing
Authors: Yu Lili , Zhang Huijie , Niu Xinning , Wu Li , Zhang Yan , Wang Bujun
Published: May 2021

To investigate the fractioning of chlorpyrifos, omethoate, cypermethrin, and deltamethrin during wheat milling and the fate of four pesticides during Chinese steamed bread (CSB) processing, wheat samples, which were sprayed twice with chlorpyrifos, omethoate, cypermethrin, and deltamethrin at three levels of concentrations during the grain‐filling stage, were milled, and wheat flour was processed to CSB. The residues of four pesticides in the milling products, kneaded dough, fermented dough, and CSB were determined with GC‐MS/MS. The concentrations of chlorpyrifos, omethoate, cypermethrin, and deltamethrin in bran were 1.46–1.57, 1.85–2.13, 1.27–1.86, and 1.63–2.33 times higher than those in wheat, respectively, while the residues of the four pesticides in shorts decreased approximately 27.97% to 57.02% for chlorpyrifos, 6.22% to 44.77% for cypermethrin, and 13.13% to 61.15% for deltamethrin compared with the residues in wheat (p < .05); however, omethoate levels approximately doubled in the ten‐fold treatment group in shorts compared with those in wheat (p < .05). The residues of the four pesticides in flour were significantly lower than those in wheat, ranging from 38.68% to 98.04%. Chlorpyrifos and omethoate levels showed a slight decrease during the kneading and fermentation process, and further decreases of 2.46%–29.51% for chlorpyrifos and 14.22%–71.11% for omethoate were found in CSB; however, most of the groups of cypermethrin and deltamethrin showed various degrees of increases in kneaded and fermented dough and steamed bread compared with flour. The mechanism of this increase is unknown and needs further research.
Nephroprotective activity of natural products against chemical toxicants: The role of Nrf2/ARE signaling pathway
Authors: Molaei Emad , Molaei Ali , Abedi Farshad , Hayes A. Wallace , Karimi Gholamreza
Published: May 2021

Nephropathy can occur following exposure of the kidneys to oxidative stress. Oxidative stress is the result of reactive oxygen species (ROS) formation due to intracellular catabolism or exogenous toxicant exposure. Many natural products (NPs) with antioxidant properties have been used to demonstrate that oxidative damage‐induced nephrotoxicity can be ameliorated or at least reduced through stimulation of the nuclear factor erythroid 2‐related factor 2 (Nrf2) signaling pathway. Nrf2 is a basic leucine zipper (bZip) transcription factor that regulates gene expression of the antioxidant response elements (ARE). Nrf2 is involved in the cellular antioxidant‐detoxification machinery. Nrf2 activation is a major mechanism of nephroprotective activity for these NPs, which facilitates its entry into the nucleus, primarily by inhibiting Kelch like‐ECH‐associated protein 1 (Keap1). The purpose of this article was to review the peer‐reviewed literature of NPs that have shown mitigating effects on renal disorder by stimulating Nrf2 and thereby suggesting potential new therapeutic or prophylactic strategies against kidney‐damaging xenobiotics.
The stage‐specifically accelerated brain aging in never‐treated first‐episode patients with depression
Authors: Han Shaoqiang , Chen Yuan , Zheng Ruiping , Li Shuying , Jiang Yu , Wang Caihong , Fang Keke , Yang Zhengui , Liu Liang , Zhou Bingqian , Wei Yarui , Pang Jianyue , Li Hengfen , Zhang Yong , Cheng Jingliang
Published: May 2021

Depression associated with structural brain abnormalities is hypothesized to be related with accelerated brain aging. However, there is far from a unified conclusion because of clinical variations such as medication status, cumulative illness burden. To explore whether brain age is accelerated in never‐treated first‐episode patients with depression and its association with clinical characteristics, we constructed a prediction model where gray matter volumes measured by voxel‐based morphometry derived from T1‐weighted MRI scans were treated as features. The prediction model was first validated using healthy controls (HCs) in two Chinese Han datasets (Dataset 1, N = 130 for HCs and N = 195 for patients with depression; Dataset 2, N = 270 for HCs) separately or jointly, then the trained prediction model using HCs (N = 400) was applied to never‐treated first‐episode patients with depression (N = 195). The brain‐predicted age difference (brain‐PAD) scores defined as the difference between predicted brain age and chronological age, were calculated for all participants and compared between patients with age‐, gender‐, educational level‐matched HCs in Dataset 1. Overall, patients presented higher brain‐PAD scores suggesting patients with depression having an “older” brain than expected. More specially, this difference occurred at illness onset (illness duration <3 months) and following 2 years then disappeared as the illness further advanced (>2 years) in patients. This phenomenon was verified by another data‐driven method and significant correlation between brain‐PAD scores and illness duration in patients. Our results reveal that accelerated brain aging occurs at illness onset and suggest it is a stage‐dependent phenomenon in depression.
The impact of the Oakland SSB tax on prices and volume sold: A study of intended and unintended consequences
Authors: Léger Pierre Thomas , Powell Lisa M.
Published: May 2021

We examine the effects of a sugar‐sweetened beverage (SSB) tax that took effect in Oakland, California in 2017. Using rich customized universal product code ‐level data, we estimate the effect of the SSB tax on prices and volume in the short to medium term in a difference‐in‐differences framework. We pay particular attention to tax‐avoidance strategies that may minimize the policy's intended effect including: (i) transfers to SSBs to the nontaxed border area (i.e., cross‐border shopping), (ii) a move from high‐priced per ounce single serve to their cheaper multipacks or larger format counterparts (i.e., format switching), and (iii) a move from high‐priced beverages to less expensive ones within a category and format (i.e., brand switching). We find that the year‐over‐year tax pass‐through is 49%. We find that volume sold of taxed beverages fell by 14%, but 46% of this decrease is offset with an increase in the border area. We also find evidence of substitution to lower‐priced taxed beverages but no evidence of switching to cheaper formats. Finally, we find important dynamic effects with respect to tax pass‐through, volume sold and cross‐border shopping.
Consequences of serious parental health events on child mental health and educational outcomes
Authors: Kristiansen Ida Lykke
Published: May 2021

I show that serious, yet common, parental health events in childhood have immediate and lasting effects on mental health and educational outcomes for children. Following a parental health event, the children are more likely to receive therapy and consume anti‐depressant (AD) medication. More so, the children achieve lower test scores and have lower school enrollment rates. The effect immediately occurs following the event and persists at least into early adulthood. I find that the effect on test scores doesn't differ significantly across family income, but that children from low‐income families are more likely to be prescribed ADs following the event, while children from high‐income families are more likely to receive therapy. Exploiting differences in general practitioners' behavior in prescribing AD and referring children to therapy, I find suggestive evidence that children who are more exposed to medical treatment of mental health issues have lower educational attainments in early adulthood.
Treatment of Retinoblastoma 1–Intact Hepatocellular Carcinoma With Cyclin‐Dependent Kinase 4/6 Inhibitor Combination Therapy
Authors: Sheng Jindan , Kohno Susumu , Okada Nobuhiro , Okahashi Nobuyuki , Teranishi Kana , Matsuda Fumio , Shimizu Hiroshi , Linn Paing , Nagatani Naoko , Yamamura Minako , Harada Kenichi , Horike Shin‐ichi , Inoue Hiroshi , Yano Seiji , Kumar Sharad , Kitajima Shunsuke , Ajioka Itsuki , Takahashi Chiaki
Published: May 2021

Background and Aims

Synthetic cyclin‐dependent kinase (CDK) 4/6 inhibitors exert antitumor effects by forcing RB1 in unphosphorylated status, causing not only cell cycle arrest but also cellular senescence, apoptosis, and increased immunogenicity. These agents currently have an indication in advanced breast cancers and are in clinical trials for many other solid tumors. HCC is one of promising targets of CDK4/6 inhibitors. RB family dysfunction is often associated with the initiation of HCC; however, this is revivable, as RB family members are not frequently mutated or deleted in this malignancy.

Approach and Results

Loss of all Rb family members in transformation related protein 53 (Trp53)−/− mouse liver resulted in liver tumor reminiscent of human HCC, and re‐expression of RB1 sensitized these tumors to a CDK4/6 inhibitor, palbociclib. Introduction of an unphosphorylatable form of RB1 (RB7LP) into multiple liver tumor cell lines induced effects similar to palbociclib. By screening for compounds that enhance the efficacy of RB7LP, we identified an I kappa B kinase (IKK)β inhibitor Bay 11‐7082. Consistently, RB7LP expression and treatment with palbociclib enhanced IKKα/β phosphorylation and NF‐κB activation. Combination therapy using palbociclib with Bay 11‐7082 was significantly more effective in hepatoblastoma and HCC treatment than single administration. Moreover, blockade of IKK–NF‐κB or AKT pathway enhanced effects of palbociclib on RB1‐intact KRAS Kirsten rat sarcoma viral oncogene homolog mutated lung and colon cancers.

Conclusions

In conclusion, CDK4/6 inhibitors have a potential to treat a wide variety of RB1‐intact cancers including HCC when combined with an appropriate kinase inhibitor.
Metabotropic Glutamate Receptor 5 in Natural Killer Cells Attenuates Liver Fibrosis by Exerting Cytotoxicity to Activated Stellate Cells
Authors: Choi Won‐Mook , Ryu Tom , Lee Jun‐Hee , Shim Young‐Ri , Kim Myung‐Ho , Kim Hee‐Hoon , Kim Ye Eun , Yang Keungmo , Kim Kyurae , Choi Sung Eun , Kim Won , Kim Seok‐Hwan , Eun Hyuk Soo , Jeong Won‐Il
Published: May 2021

Background and Aims

The important roles of glutamate and metabotropic glutamate receptor 5 (mGluR5) in HSCs have recently been reported in various liver diseases; however, the mechanism linking the glutamine/glutamate metabolism and mGluR5 in liver fibrosis remains unclear. Here, we report that mGluR5 activation in natural killer (NK) cells attenuates liver fibrosis through increased cytotoxicity and interferon‐γ (IFN‐γ) production in both mice and humans.

Approach and Results

Following 2‐week injection of carbon tetrachloride (CCl4) or 5‐week methionine‐deficient and choline‐deficient diet, liver fibrosis was more aggravated in mGluR5 knockout mice with significantly decreased frequency of NK cells compared with wild‐type mice. Consistently, NK cell–specific mGluR5 knockout mice had aggravated CCl4‐induced liver fibrosis with decreased production of IFN‐γ. Conversely, in vitro activation of mGluR5 in NK cells significantly increased the expression of anti‐fibrosis‐related genes including Ifng, Prf1 (perforin), and Klrk1 (killer cell lectin like receptor K1) and the production of IFN‐γ through the mitogen‐activated extracellular signal‐regulated kinase/extracellular signal‐related kinase pathway, contributing to the increased cytotoxicity against activated HSCs. However, we found that the uptake of glutamate was increased in activated HSCs, resulting in shortage of extracellular glutamate and reduced stimulation of mGluR5 in NK cells. Consequently, this could enable HSCs to evade NK cell cytotoxicity in advanced liver fibrosis. In vivo, pharmacologic activation of mGluR5 accelerated CCl4‐induced liver fibrosis regression by restoring NK cell cytotoxicity. In humans, mGluR5 activation enhanced the cytotoxicity of NK cells isolated from healthy donors, but not from patients with cirrhosis with significantly reduced mGluR5 expression in NK cells.

Conclusions

mGluR5 plays important roles in attenuating liver fibrosis by augmenting NK cell cytotoxicity, which could be used as a potential therapeutic target for liver fibrosis.
The impact of reclassifying cancers of unspecified histology on international differences in survival for small cell and non‐small cell lung cancer (ICBP SurvMark‐2 project)
Authors: Morgan Eileen , Arnold Melina , Rutherford Mark J. , Bardot Aude , Ferlay Jacques , De Prithwish , Engholm Gerda , Jackson Christopher , Little Alana , Saint‐Jacques Nathalie , Walsh Paul , Woods Ryan R. , O'Connell Dianne L. , Bray Freddie , Parkin D. Max , Soerjomataram Isabelle
Published: May 2021

Survival from lung cancer remains low, yet is the most common cancer diagnosed worldwide. With survival contrasting between the main histological groupings, small‐cell lung cancer (SCLC) and non‐small cell lung cancer (NSCLC), it is important to assess the extent that geographical differences could be from varying proportions of cancers with unspecified histology across countries. Lung cancer cases diagnosed 2010‐2014, followed until 31 December 2015 were provided by cancer registries from seven countries for the ICBP SURVMARK‐2 project. Multiple imputation was used to reassign cases with unspecified histology into SCLC, NSCLC and other. One‐year and three‐year age‐standardised net survival were estimated by histology, sex, age group and country. In all, 404 617 lung cancer cases were included, of which 47 533 (11.7%) and 262 040 (64.8%) were SCLC and NSCLC. The proportion of unspecified cases varied, from 11.2% (Denmark) to 29.0% (The United Kingdom). After imputation with unspecified histology, survival variations remained: 1‐year SCLC survival ranged from 28.0% (New Zealand) to 35.6% (Australia) NSCLC survival from 39.4% (The United Kingdom) to 49.5% (Australia). The largest survival change after imputation was for 1‐year NSCLC (4.9 percentage point decrease). Similar variations were observed for 3‐year survival. The oldest age group had lowest survival and largest decline after imputation. International variations in SCLC and NSCLC survival are only partially attributable to differences in the distribution of unspecified histology. While it is important that registries and clinicians aim to improve completeness in classifying cancers, it is likely that other factors play a larger role, including underlying risk factors, stage, comorbidity and care management which warrants investigation.
A retrospective review of clinical and non‐clinical factors associated with unscheduled cesarean deliveries at one urban medical center
Authors: Hamilton A. Rebecca L. , Drzymalski Dan M.
Published: May 2021

Objective

To investigate factors associated with unscheduled cesarean delivery at one urban tertiary medical center.

Methods

A retrospective chart review was performed on 11 162 deliveries between 2009 and 2019. The dependent variable was unscheduled cesarean delivery. Covariates examined included time of delivery, as well as several maternal and pregnancy‐related factors.

Results

There were a total of 7037 (63.1%) vaginal, 1133 (10.1%) elective cesarean, and 2992 (26.8%) unscheduled cesarean deliveries. Independent factors associated with increased odds for unscheduled cesarean delivery included daytime delivery (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.18–1.42, P < 0.001); advanced maternal age (OR 1.40, 95% CI 1.26–1.56, P < 0.001); obesity (OR 1.04, 95% CI 1.03–1.05, P < 0.001); history of previous cesarean delivery (OR 2.77, 95% CI 1.91–4.01, P < 0.001); hypertension (OR 1.72, 95% CI 1.27–2.32, P < 0.001); multiparity (OR 3.99, 95% CI 2.82–5.64, P < 0.001); pre‐eclampsia (OR 1.96, 95% CI 1.33–2.89, P = 0.001); and HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome (OR 5.45, 95% CI 1.13–26.28, P = 0.035).

Conclusion

Factors associated with unscheduled cesarean delivery in this study cohort included daytime delivery, advanced maternal age, obesity, hypertension, previous cesarean delivery, multiparity, preterm labor, pre‐eclampsia, and HELLP syndrome.
Fibronectin grafting to enhance skin sealing around transcutaneous titanium implant
Authors: Ghadhab Souhaila , Bilem Ibrahim , Guay‐Bégin Andrée‐Anne , Chevallier Pascale , Auger François A. , Ruel Jean , Pauthe Emmanuel , Laroche Gaétan
Published: May 2021

Intraosseous transcutaneous amputation prosthesis is a new approach in orthopedic implants that overcomes socket prosthesis problems. Its long‐term performance requires a tight skin‐implant seal to prevent infections. In this study, fibronectin (Fn), a widely used adhesion protein, was adsorbed or grafted onto titanium alloy. Fn grafting was performed using two different linking arms, dopamine/glutaric anhydride or phosphonate. The characterization of Fn‐modified surfaces showed that Fn grating via phosphonate has led to the highest amount of Fn cell‐binding site (RGD, arginine, glycine, and aspartate) available on the surface. Interestingly, cell culture studies revealed a strong correlation between the amount of available RGD ligands and cellular behavior, since enhanced proliferation and spreading of fibroblasts were noticed on Fn‐grafted surfaces via phosphonate. In addition, an original in vitro mechanical test, inspired from the real situation, to better predict clinical outcomes after implant insertion, has been developed. Tensile test data showed that the adhesion strength of a bio‐engineered dermal tissue was significantly higher around Fn‐grafted surfaces via phosphonate, as compared to untreated surfaces. This study sheds light on the importance of an appropriate selection of the linking arm to tightly control the spatial conformation of biomolecules on the material surface, and consequently cell interactions at the interface tissue/implant.
The best density functional theory functional for the prediction of 1H and 13C chemical shifts of protonated alkylpyrroles
Authors: Zahn Sarah L. V. , Hammerich Ole , Hansen Poul Erik , Sauer Stephan P. A.
Published: May 2021

The prediction of 13C chemical shifts can be challenging with density functional theory (DFT). In this study 39 different functionals and three different basis sets were tested on three neutral alkylpyrroles and their corresponding protonated species. The calculated shielding constants were compared to experimental data and results from previous calculations at the MP2. We find that the meta‐hybrid functional TPSSh with either the Pople style basis set 6‐311++G(2d,p) or the polarization consistent basis set pcSseg‐1 gives the best results for the 13C chemical shifts, whereas for the 1H chemical shifts it is the TPSSh functional with either the 6‐311++G(2d,p) or pcSseg‐2 basis set. Including an explicit solvent molecule hydrogen bonded to NH in the alkylpyrroles improves the results slightly for the 13C chemical shifts. On the other hand, for 1H chemical shifts the opposite is true. Compared to calculations at the MP2 level none of the DFT functionals can compete with MP2 for the 13C chemical shifts but for the 1H chemical shifts the investigated DFT functionals are shown to give better agreement with experiment than MP2 calculations.
MoSDeF Cassandra: A complete Python interface for the Cassandra Monte Carlo software
Authors: DeFever Ryan S. , Matsumoto Ray A. , Dowling Alexander W. , Cummings Peter T. , Maginn Edward J.
Published: May 2021

We introduce a new Python interface for the Cassandra Monte Carlo software, molecular simulation design framework (MoSDeF) Cassandra. MoSDeF Cassandra provides a simplified user interface, offers broader interoperability with other molecular simulation codes, enables the construction of programmatic and reproducible molecular simulation workflows, and builds the infrastructure necessary for high‐throughput Monte Carlo studies. Many of the capabilities of MoSDeF Cassandra are enabled via tight integration with MoSDeF. We discuss the motivation and design of MoSDeF Cassandra and proceed to demonstrate both simple use‐cases and more complex workflows, including adsorption in porous media and a combined molecular dynamics – Monte Carlo workflow for computing lateral diffusivity in graphene slit pores. The examples presented herein demonstrate how even relatively complex simulation workflows can be reduced to, at most, a few files of Python code that can be version‐controlled and shared with other researchers. We believe this paradigm will enable more rapid research advances and represents the future of molecular simulations.
A computational investigation of the selectivity and mechanism of the Lewis acid catalyzed oxa‐Diels–Alder cycloaddition of substituted diene with benzaldehyde
Authors: Khorief Nacereddine Abdelmalek , Merzoud Lynda , Morell Christophe , Chermette Henry
Published: May 2021

The selectivity and the mechanism of the uncatalyzed and AlCl3 catalyzed hetero‐Diels–Alder reaction (HDR) between ([E]‐4‐methylpenta‐2,4‐dienyloxy)(tert‐butyl)dimethylsilane 1 and benzaldehyde 2 have been studied using density functional theory at the MPWB1K/6‐31G(d) level of theory. The uncatalyzed HDR between diene 1 and alkene 2 is characterized by a polar character and proceeds via an asynchronous one‐step mechanism for the meta paths and synchronous for the ortho ones. In the presence of AlCl3 catalyst, the mechanism changes to be stepwise, while the first step is the rate‐determining step. The activation energies widely decrease, and the polar character increases dramatically. A large analysis of the mechanism is performed using the activation strain model/energy decomposition analysis (ASM/EDA) model, the natural bond orbital (NBO) and state specific dual descriptors (SSDDs). The obtained results indicate that the combined interaction energy associated with the distortion of the reactants in these HDR are at the origin of the observed kinetics. NBO analyses were applied to estimate the Lewis‐acid catalyst donor‐acceptor interaction with the molecular system. The SSDD analysis shed light into the orientation effects on the reaction kinetics by providing important information about charge transfer interactions during the chemical reaction. It indicates that the more favorable HDR pathway have the lowest excitation energies, facilitating the interaction between diene 1 and benzaldehyde 2 moieties. Non‐covalent interaction (NCI) and QTAIM analyses of the meta‐endo structure indicate that the presence of several weak NCIs formed at this approach is at the origin of the meta‐endo selectivity.
Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk
Authors: Gouda Nawal S. , Fawzy Manal S. , Toraih Eman A.
Published: May 2021

Background

Cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population.

Methods

The CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated.

Results

A higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61–5.35, p < 0.001), dominant (OR = 1.87, 95% CI = 1.14–3.06, p = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73–6.42, p = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34–1.75) than A/A (median = 1.43, IQR = 0.39–4.25, p = 0.018) and A/G carriers (median = 1.68, IQR = 0.49–3.92, p = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed.

Conclusion

The CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large‐scale studies in different populations are warranted.
The Role of Cultural Congruence in the Art Infusion Effect
Authors: Seo Yuri , Septianto Felix , Ko Eunju
Published: May 2021

The art infusion effect posits that exposure to visual artworks heightens the perceived luxuriousness of related brands. Across six studies conducted in different cultural settings, we establish that the art infusion effect is dependent on cultural congruence. That is, when the artwork’s country‐of‐origin (CO) is culturally congruent (vs. incongruent) with the brand’s CO, such an artwork bestows higher perceptions of brand luxuriousness. This occurs because cultural incongruence attenuates the art infusion effect. We term this moderating effect as brand‐artwork CO congruence and show that it qualifies art infusion even if the congruent (vs. incongruent) artwork CO is stereotypically perceived as less luxurious. We further show that perceived brand authenticity underlies the effect of brand‐artwork CO congruence. Overall, the present research illustrates that cultural congruence and subsequent perception of authenticity are critical components of the art infusion effect.
Mycobacterium tuberculosis causes a leaky blood‐brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspring
Authors: Manjeese Wadzanai , Mvubu Nontobeko E. , Steyn Adrie J. C. , Mpofana Thabisile
Published: May 2021

The maternal system's exposure to pathogens influences foetal brain development through the influx of maternal cytokines and activation of the foetal immune status to a persistent inflammatory state characterised by glia cell activation. Neuroinflammation influences the blood‐brain barrier's (BBB) permeability allowing peripheral immune cell trafficking into the brain. Mycobacterium tuberculosis (Mtb) is a pathogen that causes Tuberculosis (TB), a global pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of Autism spectrum disorder (ASD), it is not known whether gestational Mtb infections also contribute to impaired foetal neurodevelopment. Here we infect pregnant Balb/c mice with Mtb H37Rv and Valproic acid (VPA) individually and in combination. Neuroinflammation was measured by assessing microglia and astrocyte population in the prefrontal cortex (PFC) and cerebellum (CER) of pups. Mtb infection increased the microglia population and caused morphological changes to a reactive phenotype in the PFC. Also, the astrocyte population was significantly increased in the PFC of Mtb pups. The BBB permeability was determined by measuring the Evans Blue (EB) dye concentration in the PFC and CER 1 hr post receiving intravenous EB‐dye injection. We found that prenatal Mtb exposure significantly increased the BBB's permeability in the PFC and CER of pups versus saline. Overall, our data demonstrate that prenatal exposure to Mtb predisposes offspring to a higher risk of BBB damage while inducing persistent neuroinflammation, which could lead to impaired neuronal development and function. These findings implicate a potential role of gestational Mtb infections in the aetiology of ASD.
Detection of the hybrid layer biodegradation initiation factor with a scanning electron microscope
Authors: Paken Gamze , Çömlekoğlu Muharrem Erhan , Sonugelen Mehmet
Published: May 2021

The purpose of this study was to elucidate the origin of initiation of hybrid layer biodegradation. Ninety caries‐free human third molars were divided into three surface groups: enamel, dentin, and NaOCl‐treated dentin. (n = 30/group) Each group was divided into three subgroups (n = 10/group) of luting resin materials with etch‐and‐rinse; self‐etch and self‐adhesive systems. Resin composite blocks and sticks were fabricated and adhered onto dentin and enamel surfaces. The bond strength values were evaluated with micro shear test and statistical analysis were made. On the other hand, teeth were sectioned with a slow‐speed saw into multiple beams. After thermocycling, samples were kept in 50% silver nitrate solution. Samples were analyzed with SEM in back‐scattered mode. According to the micro‐shear bond tests, higher bond strength values were observed in etch‐and‐rinse system. Bond strength values in self‐adhesive and etch‐and‐rinse groups were significantly higher than self‐etch groups in dentin surface and dentin surface treatment with NaOCl. Back‐scattered scanning electron microscope results showed that, different degradation mechanism was observed. The present study indicates that, due to the acid etching in dentin, collagen biodegradation was observed within the hybrid layer. On the enamel surfaces, resin degradation was related with resin monomers in adhesive systems.
Morphometric analysis of nuclear symmetry in urothelial carcinoma for predicting tumor recurrence
Authors: Klorin Geula , Halachmi Sarel , Nativ Ofer , Massalha Yamen , Stroller Leah , Amit Amnon , Sabo Edmond
Published: May 2021

Urothelial carcinoma is the ninth most common cancer in the world. Cytological analysis of the urine is used for screening, as well as for cases suspected for neoplasia of the urinary tract. However, the sensitivity of urine cytology examination is low. The golden standard for diagnosing bladder cancer relies upon cystoscopy followed by a biopsy, which is microscopically assessed by the pathologist. Treatment decisions are based on the histological grade and stage of the tumor. Posttreatment tumor recurrence is 50%. The purpose of this study is to predict recurrence of urothelial carcinoma using a novel morphometric method of nuclear symmetry analysis. This method may help tailor the appropriate treatment and may reduce the need of invasive surgical procedures in patients. Computerized morphometry was applied to develop multiple symmetry indices of the nuclei of the tumor cells as follows: each nucleus was physically divided along its digital axis in two segments that were separately analyzed for their shape, size, optical density, and texture. Subsequently, ratios were obtained by mathematically dividing between the morphometric values of the two nuclear segments where the denominator contained the largest value of the two. These ratios were named symmetry indices and were included as variables to predict the recurrence time of the tumors. The change in the symmetry indices (loss of symmetry) of the nuclear roundness, fractal dimension and margination were the only independent predictors of recurrence time. Computerized morphometry of nuclear symmetry indices may help to predict tumor recurrence in urothelial carcinomas.
Anatomical, histological, and surface ultrastructural evaluation of the palatal mucosa of domestic rabbit (Oryctolagus cuniculus)
Authors: Mahdy Mohamed A. A. , Mohammed Elsayed S. I.
Published: May 2021

The present study investigated the morphology of the palate of rabbit (Oryctolagus cuniculus). Samples from 12 healthy adult rabbits were examined by gross observation, morphometry, scanning electron and light microscopy. The hard palate was elongated and narrowed rostrally. The incisive papilla appeared as a diamond‐shaped prominence flanked on both sides by a groove on which a slit‐like opening of the nasopalatine duct opened. The palatine raphe was in the form of a groove. On either side of the raphe, 14–16 palatine ridges were present. The direction of these ridges differed according to their position. An incomplete (short) palatine ridge was occasionally present at the caudal part of the hard palate. Several gland openings were scattered on the surface of the palatine ridges. The soft palate extended to about the middle of epiglottis caudally. Its ventral surface had numerous thin transverse mucosal folds separated by furrows, and several openings of glands. Histologically, the incisive papilla, palatine ridges, and soft palate were lined by a parakeratinized stratified squamous epithelium resting on a dense connective layer of lamina propria. The degree of keratinization and the thickness of the lamina propria decreased caudally. Seromucoid glands were present in the rostral and caudal parts of the hard palate, as well as in the soft palate. In conclusion, the palate of rabbit presented characteristic features suggesting functional adaptations for their herbivores diet. Studying the morphological characteristics of the hard and soft palate of rabbits will help veterinary practitioners to investigate pathology malformations and diseases of the oral cavity.
Physician awareness, preparedness, and opinions toward consumer‐initiated genetic testing in Thailand: Views from a changing landscape
Authors: Kittikoon Siraphob , Pithukpakorn Manop , Pramyothin Pornpoj
Published: May 2021

Consumer‐initiated genetic tests have captured public interest in recent years, including in low‐to‐middle‐income countries (LMICs) such as Thailand. Due to limited resources and personnel, physicians will most likely bear the burden of increasing service needs from the public as consumer‐initiated genetic tests become popularized. The primary objective of this study was to describe (a) awareness, (b) preparedness to provide counseling about the consumer‐initiated genetic test, and (c) opinions on the usefulness of consumer‐initiated genetic tests among physicians at an academic hospital in Bangkok, Thailand. The secondary objective was to describe factors that were associated with the awareness, preparedness, and opinion of the participants. Paper questionnaires were sent out to participants which included internal medicine residents, fellows, and faculty staff members. The questionnaires assessed awareness, preparedness to discuss consumer‐initiated genetic test results, and opinion on the usefulness of consumer‐initiated genetic tests and included both closed‐ and open‐ended questions. Responses were anonymous. Among 308 participants, there were 223 (72.4%) residents, 14 (4.5%) fellows, and 71 (23.1%) staff members. Only 15% of participants were aware of consumer‐initiated genetic tests, mostly from the internet, and only 7% were prepared to provide counseling regarding consumer‐initiated genetic tests. However, 60% agreed that consumer‐initiated genetic tests may be clinically useful. Many participants, including trainees, expressed concerns about the interpretation of consumer‐initiated genetic test results, application into clinical practice, appropriate counseling, and patient referral to geneticists. Multivariate logistic regression revealed that years of work experience was independently associated with awareness of consumer‐initiated genetic tests, while male gender and less work experience were independently associated with favorable opinion toward the usefulness of consumer‐initiated genetic tests. Our results pointed to an urgent need for genetic counselors in Thailand. Also, physicians, particularly trainees, need appropriate training to prepare them for a rapidly evolving environment where consumer‐initiated genetic tests become commonplace.
IgG4‐related sclerosing cholangitis may be a risk factor for cancer
Authors: Kurita Yusuke , Fujita Yuji , Sekino Yusuke , Watanabe Seitaro , Iwasaki Akito , Kagawa Koichi , Tanida Emiko , Yagi Shin , Hasegawa Sho , Sato Takamitsu , Hosono Kunihiro , Kato Shingo , Kobayashi Noritoshi , Ichikawa Yasushi , Endo Itaru , Nakajima Atsushi , Kubota Kensuke
Published: May 2021

Background/Purpose

The relationship between autoimmune pancreatitis (AIP) and malignancy has been reported. However, the potential risk for cancer in patients with immunoglobulin 4 (IgG4)‐related sclerosing cholangitis (IgG4‐SC) is unclear. The present study aimed to evaluate the incidence of cancer in IgG4‐SC patients.

Methods

We retrospectively collected clinical data for 121 patients diagnosed with IgG4‐SC from 7 hospitals. We calculated the standardized incidence ratio (SIR) of cancer in IgG4‐SC patients based on the national cancer rates. The SIR of the period after the diagnosis of IgG4‐SC were calculated.

Results

The mean follow‐up period was 6.4 years, with 121 IgG4‐SC patients. During the follow‐up period, 26 patients had cancer, and 29 cancers were diagnosed. The SIR of cancer after the diagnosis of IgG4‐SC was 1.90 (95% confidence interval [CI] 1.67‐2.21). The SIR of pancreatic and bile duct cancer was 10.30 and 8.88, respectively. The SIR of cancer in <1 year, 1‐5 years, and >5 years after diagnosis of IgG4‐SC were 2.58, 1.01, and 2.44, respectively.

Conclusions

IgG4‐SC patients have a high risk of cancer including pancreatic and bile duct cancer. The risk of cancer was high less <1 year and >5 years after diagnosis of IgG4‐SC. Therefore, IgG4‐SC patients may require careful long‐term follow‐up.
Investigation of mass‐scale drift effects in the milli‐mass range: Influence on high mass resolution mode multicollector‐inductively coupled plasma mass spectrometer isotope ratio measurements
Authors: Pramann Axel , Noordmann Janine , Rienitz Olaf
Published: May 2021

The consequences, possible origins, and prevention of mass‐scale drifts in the high mass resolution mode (HR, M/ΔM ≈ 8000) under constant conditions were investigated and simulated in case of a multicollector‐inductively coupled plasma mass spectrometer (MC‐ICP‐MS) using silicon enriched in 28Si as the main element in this survey. A drifting mass scale strongly impairs the precise and accurate determination of isotope ratios, depending especially on the peak/plateau width. For example, 29Si+ in Si highly enriched in 28Si has an extremely small mass plateau width of ΔM ≤ 4 × 10−3 u, compare ΔM(56Fe+) ≈ 18 × 10−3 u, which is to our knowledge one of the smallest plateaus routinely investigated in isotope ratio measurements, thus requiring extreme stability. During warm‐up of the double‐focusing sector field mass spectrometer, a mass drift up to ΔM/Δt ≥ 0.006 u/hr has been observed. Long‐term studies on mass scale stability and simulations concerning fluctuations of the magnetic field B, acceleration voltage Uacc and ESA voltage UESA are reported. A change of one of these quantities of 0.01% induces changes of the mass scale of 6 × 10−3 u, 3 × 10−3u, and 1 × 10−3 u in the case of B, Uacc, and UESA, respectively. After identifying electrical charging/discharging effects in the mass spectrometer affecting the mass scale stability, the instrument was completely dismantled and carefully reinstalled. Additional stability tests using silicon, strontium, and lead finally yielded a mass drift of ΔM/Δt ≤ 0.001 u/8 h in the case of silicon. This enhanced stability guarantees measurements of isotope ratios on smallest plateaus with lowest uncertainty. The importance of a stable mass scale is pointed out and the relevant quantities of a typical magnetic sector field mass spectrometer are discussed.
SARS‐CoV‐2 antibodies: IgA correlates with severity of disease in early COVID‐19 infection
Authors: Zervou Fainareti N. , Louie Ping , Stachel Anna , Zacharioudakis Ioannis M. , Ortiz‐Mendez Yadira , Thomas Kristen , Aguero‐Rosenfeld Maria E.
Published: May 2021

Timing of detection of immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), and their use to support the diagnosis are of increasing interest. We used the Gold Standard Diagnostics ELISA to evaluate the kinetics of SARS‐CoV‐2 IgG, IgA, and IgM antibodies in sera of 82 hospitalized patients with polymerase chain reaction (PCR)‐confirmed coronavirus disease 2019 (COVID‐19). Serum samples were collected 1–59 days post‐onset of symptoms (PoS) and we examined the association of age, sex, disease severity, and symptoms' duration with antibody levels. We also tested sera of 100 ambulatory hospital employees with PCR‐confirmed COVID‐19 and samples collected during convalescence, 35–57 days PoS. All but four of the admitted patients (95.1%) developed antibodies to SARS‐CoV‐2. Antibodies were detected within 7 days PoS; IgA in 60.0%, IgM in 53.3%, and IgG in 46.7% of samples. IgG positivity increased to 100% on Day 21. We did not observe significant differences in the rate of antibody development in regard to age and sex. IgA levels were highest in patients with a severe and critical illness. In multiple regression analyses, only IgA levels were statistically significantly correlated with critical disease (p = .05) regardless of age, sex, and duration of symptoms. Among 100 ambulatory hospital employees who had antibody testing after 4 weeks PoS only 10% had positive IgA antibodies. The most frequently isolated isotype in sera of employees after 30 days PoS was IgG (88%). IgA was the predominant immunoglobulin in early disease and correlated independently with a critical illness. IgG antibodies remained detectable in almost 90% of samples collected up to two months after infection.
Substantial decrease in concurrent meteorological droughts and consecutive cold events in Huai River Basin, China
Authors: Zhang Yuqing , Yang Xiuqin , Chen Changchun
Published: May 2021

Concurrent meteorological droughts and consecutive cold events can significantly impact local ecosystems, socio‐economies, and human health. The respective characteristics of droughts and cold extremes have been extensively studied, however, their concurrent extremes have received very little attention. In this study, we used the Huai River Basin as a case to build a magnitude index of concurrent meteorological droughts and consecutive cold events (CDCMI) based on daily minimum temperature data and a 1‐month standardized precipitation evapotranspiration index (SPEI) from 1961 to 2018. Results show that the magnitude of meteorological droughts increased over the observation period, while consecutive cold events significantly decreased. CDCMI showed a significant downward trend at a rate of −0.14 per decade. Large differences were observed between 1990–2018 and 1961–1989—especially in the southern parts of the basin (around −50%). The frequency of mild and moderate concurrent meteorological droughts and consecutive cold events showed no significant upward or downward trends, but severe and extreme concurrent events showed pronounced decreasing trends at rates of −0.03 events/decade and − 0.036 events/decade, respectively. Under the same return period, high CDCMI values are present in the southeastern part of the basin, indicating that the concurrent events in this region are more serious. When CDCMI = 1.79 (extreme grade), the return period in the southeastern part of the basin (5–10 years) is much lower than that in the northwestern part of the basin (>100 years), indicating that this part is harmed to a greater extent by the concurrent extremes than elsewhere in the basin. The spatial pattern of maximum CDCMI again indicates that the southeastern part of the basin is at a high risk for concurrent events. The proposed magnitude index may be a useful tool for analysing concurrent (compound) droughts and cold events as well as their potential impacts.
Using information‐theoretic approaches for model selection in meta‐analysis
Authors: Cinar Ozan , Umbanhowar James , Hoeksema Jason D. , Viechtbauer Wolfgang
Published: May 2021

Meta‐regression can be used to examine the association between effect size estimates and the characteristics of the studies included in a meta‐analysis using regression‐type methods. By searching for those characteristics (i.e., moderators) that are related to the effect sizes, we seek to identify a model that represents the best approximation to the underlying data generating mechanism. Model selection via testing, either through a series of univariate models or a model including all moderators, is the most commonly used approach for this purpose. Here, we describe alternative model selection methods based on information criteria, multimodel inference, and relative variable importance. We demonstrate their application using an illustrative example and present results from a simulation study to compare the performance of the various model selection methods for identifying the true model across a wide variety of conditions. Whether information‐theoretic approaches can also be used not only in combination with maximum likelihood (ML) but also restricted maximum likelihood (REML) estimation was also examined. The results indicate that the conventional methods for model selection may be outperformed by information‐theoretic approaches. The latter are more often among the set of best methods across all of the conditions simulated and can have higher probabilities for identifying the true model under particular scenarios. Moreover, their performance based on REML estimation was either very similar to that from ML estimation or at times even better depending on how exactly the REML likelihood was computed. These results suggest that alternative model selection methods should be more widely applied in meta‐regression.