bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of thymidine phosphorylase and CD163 expression on prognosis in stage II colorectal cancer
Authors: Kaidi Donia , Szeponik Louis , Yrlid Ulf , Wettergren Yvonne , Bexe Lindskog Elinor
Published: May 2022

Background

Tumor-associated macrophages (TAM) are known to facilitate colorectal cancer (CRC) growth. High macrophage infiltration in thymidine phosphorylase (TYMP) expressing CRC may correspond to poor prognosis. The prognostic impact of the expression CD163, a receptor associated with TAM, and TYMP in stroma, respectively, tumor tissue is not yet established. The aim of this study was to identify the potential associations between TYMP and CD163 expression levels and relapse-free survival (RFS) of patients with stage II CRC, and if microdissection is of importance.

Methods

Stage II CRC patients, radically resected with relapse (n = 104), were matched to patients with a 5-year relapse-free follow-up (n = 206). Gene expression of TYMP and CD163 was analyzed in snap-frozen tumor tissues and in microdissected formalin-fixed tumor tissues separated into tumor epithelium and stroma.

Results

TYMP expression was high in poorly differentiated tumors, right-sided CRC, and tumors with high microsatellite instability CD163-expressing macrophages near tumor epithelial cells had high expression in poorly differentiated and T4 tumors. High TYMP expression in tumor epithelial cells was in the multivariate analyses associated with shorter relapse-free survival (hazard ratio 1.66; 95% confidence interval: 1.09–2.56; p < 0.05).

Conclusions

TYMP expression in tumor epithelial cells was associated with RFS and emphasizes the need for tissue microdissection. Additional studies are needed to establish whether TYMP and CD163 could add clinically relevant information to identify high-risk stage II patients that could benefit from adjuvant chemotherapy.
From private digital platforms to public data spaces: implications for the digital transformation
Authors: Beverungen Daniel , Hess Thomas , Köster Antonia , Lehrer Christiane
Published: May 2022

Technological developments such as Cloud Computing, the Internet of Things, Big Data and Artificial Intelligence continue to drive the digital transformation of business and society. With the advent of platform-based ecosystems and their potential to address complex challenges, there is a trend towards greater interconnectedness between different stakeholders to co-create services based on the provision and use of data. While previous research on digital transformation mainly focused on digital transformation within organizations, it is of growing importance to understand the implications for digital transformation on different layers (e.g., interorganizational cooperation and platform ecosystems). In particular, the conceptualization and implications of public data spaces and related ecosystems provide promising research opportunities. This special issue contains five papers on the topic of digital transformation and, with the editorial, further contributes by providing an initial conceptualization of public data spaces' potential to foster innovative progress and digital transformation from a management perspective.
Assessment of new spectral indices and multi-seasonal ASTER data for gypsum mapping
Authors: Shuai Shuang , Zhang Zhi , Lv Xinbiao , Hao Lina
Published: May 2022

Advanced spaceborne thermal emission and reflection radiometer (ASTER) data and different spectral indices were employed to map gypsum minerals. However, most proposed gypsum indices are designed based on the 2.21 μm gypsum absorption, overlapping with most hydroxy-bearing minerals. Moreover, the seasonal mutual transformation between gypsum, bassanite, and anhydrite may lead to seasonal reflectance variability of gypsum formation pixels, affecting the classification accuracy of gypsum indices. In this research, the feasibility of 2.26 μm (ASTER band7) reflectance absorption for gypsum mapping was assessed, using lab and ASTER reflectance. On the basis of this, two new ASTER gypsum spectral indices (GI1: B4*B8/B6*B7; GI2: B4*B8/B7*B7) were proposed and applied to exclude the interference of hydroxyl-bearing minerals effectively. Seasonal reflectance variability of gypsum formation pixels was confirmed, and it causes the accuracy difference of gypsum indices for multi-seasonal ASTER data. The GI1 achieves the most robust accuracy for multi-seasonal ASTER data with average areas under receiver operator characteristic (ROC) curve of 98.5% and 98.7% for summer and winter ASTER data. Therefore, the GI1 can be used for gypsum mineral mapping, especially in the areas where clay minerals and other hydroxyl-containing minerals are widely distributed.
Pornography Consumption in People of Different Age Groups: an Analysis Based on Gender, Contents, and Consequences
Authors: Ballester-Arnal Rafael , García-Barba Marta , Castro-Calvo Jesús , Giménez-García Cristina , Gil-Llario Maria Dolores
Published: May 2022

Introduction

Pornography consumption has increased exponentially in recent decades. Most studies conducted so far are focused on adult samples (typically, between 18 and 30 years old), limiting the generalizability of their results. This study aims to create a taxonomy that groups various pornographic contents and thus explore different aspects of its use (e.g., preference for different pornographic content, excessive and problematic use) in people at different life stages.

Methods

Between 2016 and 2019, 8,040 individuals (71.3% men) between 12 and 85 years old (M = 33.25, SD = 14.31) completed a battery that explores pathological and non-pathological pornography use. Participants were distributed into five age groups (< 18 years old, between 18–25, 26–40, 41–60, and > 60) to perform the different analyses (ANOVA and chi-square tests for the differences between the groups, EFA for the analyses of categories of pornographic content, and hierarchical linear regressions to identify the factors related to problematic use).

Results

Pornography use was highly prevalent (> 85%) in all age groups. Using a data-driven approach, we found that the pornographic content explored in this research can be classified within four categories. Using this taxonomy, we found differences according to the age for most of the pornographic content explored (e.g., sexual intercourse with opposite-sex partners [71.6–84.5% in males and 70.2–89.5% in females]). Finally, we found that age conditions the way in which preference for different pornographic content increases the risk of excessive and problematic use.

Conclusions

Pornography consumption is frequent in different age groups, although it varies depending on age and content. In addition, some particular pornographic contents were identified that increase the risk of developing an addiction in different developmental stages.

Policy Implications

This study provides a preliminary foundation for identifying the unique characteristics of pornography use in different age groups as well as content related to increased problematic use.
Maternal Levothyroxine Treatment as an Etiologic Factor in the Development of Infantile Craniosynostosis
Authors: Block Brandon R. , Collins John J. , Rios Jose C. , Mazzola Catherine A.
Published: May 2022

Craniosynostosis (CS) is a condition characterized by premature fusion of one or more calvarial sutures. Numerous studies have demonstrated a correlation between CS and maternal hypothyroidism (MH), but research into this relationship has been scarce. A six-day-old male patient presented for initial neurosurgical consultation with trigonocephaly and prominent metopic ridging. A CT scan of the head confirmed the diagnosis of metopic CS, and it was revealed during the examination that the mother suffered from hypothyroidism during her pregnancy. Two theories provide a potential etiologic basis for the development of CS in infants born to hypothyroid mothers treated with levothyroxine. It is possible that the transplacental delivery of levothyroxine results in fetal thyrotoxicosis. Alternatively, intermittent periods of maternal hypothyroxinemia may encourage fetal thyroid hyperactivity to compensate for insufficient maternal thyroid hormones. Regardless, both theories must be formally investigated in order to elucidate the true association between CS and MH.
Am I Swede or Iranian? The question of national and ethnic identities among children of Iranian immigrants in Sweden
Authors: Ahmadi Fereshteh , Ahmadi Babak , Zandi Saeid
Published: May 2022

This article examines the impact of the host society’s social characteristics on second-generation immigrants’ understanding of their national and ethnic identities. Specifically, we studied how second-generation Iranians in Sweden identify themselves with Iranian society, with the Iranian ethnic group in Sweden, and/or with Swedish society, and then we compared second-generation Iranians in Sweden with those in the USA concerning the issue in question. To gather the data in Sweden, we used semi-structured e-mail interviews with 15 young people of Iranian background. We used secondary data to compare our results with those obtained in the USA. When comparing the results of this study with those obtained in the USA, we did not find the identity tensions and crisis reported by research on second-generation Iranians in the USA in members of the same generation in Sweden. Some policy recommendations were suggested.
The Sting of a White Flannel Moth Caterpillar (Norape ovina)
Authors: Michienzi Avery E. , Holstege Erik P. , Cole Ryan J. , Charlton Nathan P.
Published: May 2022

The purpose of this report is to describe a case of urticarial dermatitis, or erucism, caused by the white flannel moth caterpillar ( Norape ovina) in central Virginia. Many caterpillars are known to cause erucism, with the puss caterpillar ( Megalopyge opercularis) being the most reported culprit in the United States. White flannel moth caterpillars are expected to cause erucism as they belong to the same family as the puss caterpillar (Megalopygidae) and have similar venom-containing hairs, but no reports of the reaction or clinical course have been documented in the medical literature. A subject was stung by a white flannel moth caterpillar after it fell on his neck while clearing brush with a machete. The subject experienced immediate pain and developed a raised, erythematous rash where the caterpillar had fallen. The rash, referred to as erucism, was painful for 1 d and improved slowly over the course of 2 wk, but a small area of discoloration remained 2.5 mo after contact. Symptoms were managed by the subject at home and no medications were administered. The white flannel moth caterpillar inflicts erucism similar to that caused by the more commonly mentioned puss caterpillar. If only local symptoms are sustained from contact with a white flannel moth caterpillar, it can be safely and effectively managed with over-the-counter medications similar to the management for erucism induced by other caterpillar species. Irrigation and removal of urticating hairs with adhesive tape may help reduce the pain and is recommended, though not performed in this case.
Interplay of River and Tidal Forcings Promotes Loops in Coastal Channel Networks
Authors: Konkol Adam , Schwenk Jon , Katifori Eleni , Shaw John Burnham
Published: May 2022

The dense populations that inhabit global coastlines have an uncertain future due to increased flooding, storms, and human modification. The channel networks of deltas and marshes that plumb these coastlines present diverse architectures, including well‐studied dendritic topologies. However, the quasi‐stable loops that exist in nearly all coastal networks have not yet been explained. We present a model for self‐organizing networks inspired by vascular biophysics to show that loops emerge when the relative forcings between rivers and tides are comparable, resulting in interplay between hydrodynamic forcings at short time scales relative to network evolution. Using field data and satellite imaging, we confirm this control on 21 field networks. Our comparison provides compelling evidence that hydrodynamic fluctuations are capable of stabilizing loops in geophysical systems.
Platelet-derived growth factor D expression in adrenal cells is modulated by corticosteroids: putative role in adrenal suppression
Authors: Parry Christopher M. , Chan Li F. , Carr Daniel F. , Hawcutt Daniel B.
Published: May 2022

Background

Adrenal suppression is a clinically concerning side effect of inhaled corticosteroid (ICS) treatment in patients with asthma. Increased susceptibility to ICS-induced adrenal suppression has previously been identified in those with the rs591118 polymorphism in platelet-derived growth factor D (PDGFD). The mechanism underpinning this relationship is not known.

Methods

H295R cells were genotyped for rs591118 using a validated Taqman PCR allelic discrimination assay. H295R cell viability was determined after treatment with beclometasone and fluticasone (range 0–330 μM). Cortisol was measured in cell culture medium using competitive enzyme immunoassay.

Results

PDGFD protein expression in H295R cells was confirmed using Western blotting. When ACTH and forskolin were added to H295R cells, a reduction in PDGFD expression was seen, which was then restored by incubation with prochloraz, a known inhibitor of steroidogenesis. A dose-dependent, decrease in PDGFD expression was observed with beclometasone (over a 24 h incubation period) but not with beclometasone incubations beyond 24 h nor with fluticasone (at 24 or 48 h).

Conclusions

H295R cells express PDGFD protein, which can be modulated by incubation with steroidogenesis agonists and antagonists and additionally with exogenous beclometasone.

Impact

PDGFD is expressed in the human adrenal cell line, H295R, and expression can be modulated by beclometasone as well as agonists/antagonists of steroidogenesis.

This builds on previous research that identified a SNP in PDGFD (rs591118) as an independent risk factor for adrenal suppression in adults and children with obstructive airway disease treated with inhaled corticosteroids.

First in vitro experiments to support a link between the PDGF and cortisol production pathways, supporting the hypothesis that PDGFD variants can affect an individual’s sensitivity to corticosteroid-induced adrenal suppression.
Impact of antibiotics on off-target infant gut microbiota and resistance genes in cohort studies
Authors: Lebeaux Rebecca M. , Madan Juliette C. , Nguyen Quang P. , Coker Modupe O. , Dade Erika F. , Moroishi Yuka , Palys Thomas J. , Ross Benjamin D. , Pettigrew Melinda M. , Morrison Hilary G. , Karagas Margaret R. , Hoen Anne G.
Published: May 2022

Background

Young children are frequently exposed to antibiotics, with the potential for collateral consequences to the gut microbiome. The impact of antibiotic exposures to off-target microbes (i.e., bacteria not targeted by treatment) and antibiotic resistance genes (ARGs) is poorly understood.

Methods

We used metagenomic sequencing data from paired stool samples collected prior to antibiotic exposure and at 1 year from over 200 infants and a difference-in-differences approach to assess the relationship between subsequent exposures and the abundance or compositional diversity of microbes and ARGs while adjusting for covariates.

Results

By 1 year, the abundance of multiple species and ARGs differed by antibiotic exposure. Compared to infants never exposed to antibiotics, Bacteroides vulgatus relative abundance increased by 1.72% (95% CI: 0.19, 3.24) while Bacteroides fragilis decreased by 1.56% (95% CI: −4.32, 1.21). Bifidobacterium species also exhibited opposing trends. ARGs associated with exposure included class A beta-lactamase gene CfxA6. Among infants attending day care, Escherichia coli and ARG abundance were both positively associated with antibiotic use.

Conclusion

Novel findings, including the importance of day care attendance, were identified through considering microbiome data at baseline and post-intervention. Thus, our study design and approach have important implications for future studies evaluating the unintended impacts of antibiotics.

Impact

The impact of antibiotic exposure to off-target microbes and antibiotic resistance genes in the gut is poorly defined.

We quantified these impacts in two cohort studies using a difference-in-differences approach. Novel to microbiome studies, we used pre/post-antibiotic data to emulate a randomized controlled trial.

Compared to infants unexposed to antibiotics between baseline and 1 year, the relative abundance of multiple off-target species and antibiotic resistance genes was altered.

Infants who attended day care and were exposed to antibiotics within the first year had a higher abundance of Escherichia coli and antibiotic resistance genes; a novel finding warranting further investigation.
m6A methylation mediates LHPP acetylation as a tumour aerobic glycolysis suppressor to improve the prognosis of gastric cancer
Authors: Lin Jian-Xian , Lian Ning-Zi , Gao You-Xin , Zheng Qiao-Ling , Yang Ying-Hong , Ma Yu-Bin , Xiu Zhi-Song , Qiu Qing-Zhu , Wang Hua-Gen , Zheng Chao-Hui , Li Ping , Xie Jian-Wei , Lu Jun , Chen Qi-Yue , Cao Long-Long , Lin Mi , Wang Jia-Bin , Huang Chang-Ming
Published: May 2022

LHPP, a histidine phosphatase, has been implicated in tumour progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. Here, we obtained GC tissues and corresponding normal tissues from 48 patients and identified LHPP as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine LHPP levels in normal and GC tissues. The prognostic value of LHPP was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of LHPP in GC growth and metastasis were evaluated in vitro and in vivo. The results showed that LHPP expression was significantly decreased in GC tissues at both the mRNA and protein levels. Multivariate Cox regression analysis revealed that LHPP was an independent prognostic factor and effective predictor in patients with GC. The low expression of LHPP was significantly related to the poor prognosis and chemotherapy sensitivity of gastric cancer patients. Moreover, elevated LHPP expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, the m6A modification of LHPP mRNA by METTL14 represses its expression; LHPP inhibits the phosphorylation of GSK3b through acetylation and mediates HIF1A to inhibit glycolysis, proliferation, invasion and metastasis of gastric cancer cells. Together, our findings suggest that LHPP is regulated by m6A methylation and regulates the metabolism of GC by changing the acetylation level. Thus, LHPP is a potential predictive biomarker and therapeutic target for GC.
Sex differences in global metabolomic profiles of COVID-19 patients
Authors: Escarcega Rocio Diaz , Honarpisheh Pedram , Colpo Gabriela Delevati , Ahnstedt Hilda W. , Couture Lucy , Juneja Shivanki , Torres Glenda , Ortiz Guadalupe J. , Sollome James , Tabor Natalie , Ganesh Bhanu P. , Choi H. Alex , Liu Fudong , McCullough Louise D. , Tsvetkov Andrey S.
Published: May 2022

Coronavirus disease (COVID-19), caused by SARS-CoV-2, leads to symptoms ranging from asymptomatic disease to death. Although males are more susceptible to severe symptoms and higher mortality due to COVID-19, patient sex has rarely been examined. Sex-associated metabolic changes may implicate novel biomarkers and therapeutic targets to treat COVID-19. Here, using serum samples, we performed global metabolomic analyses of uninfected and SARS-CoV-2-positive male and female patients with severe COVID-19. Key metabolic pathways that demonstrated robust sex differences in COVID-19 groups, but not in controls, involved lipid metabolism, pentose pathway, bile acid metabolism, and microbiome-related metabolism of aromatic amino acids, including tryptophan and tyrosine. Unsupervised statistical analysis showed a profound sexual dimorphism in correlations between patient-specific clinical parameters and their global metabolic profiles. Identification of sex-specific metabolic changes in severe COVID-19 patients is an important knowledge source for researchers striving for development of potential sex-associated biomarkers and druggable targets for COVID-19 patients.
Endothelial ETS1 inhibition exacerbate blood–brain barrier dysfunction in multiple sclerosis through inducing endothelial-to-mesenchymal transition
Authors: Luo Yan , Yang Hang , Wan Yan , Yang Sibo , Wu Jiehong , Chen Shengcai , Li Yanan , Jin Huijuan , He Quanwei , Zhu Dong-Ya , Zhou Yifan , Hu Bo
Published: May 2022

Blood–brain barrier (BBB) dysfunction has been recognized as an early pathological feature and contributing factor in multiple sclerosis. Endothelial-to-mesenchymal transition is a process associated with endothelial dysfunction leading to the disruption of vessel stability and barrier function, yet its functional consequence in multiple sclerosis remains unclear. Here, we demonstrated that endothelial-to-mesenchymal transition accompanied the blood–brain barrier dysfunction in several neurological disorders, especially in multiple sclerosis. The activity of transcription factor ETS1, which is highly expressed in endothelial cells (ECs) and responded to an inflammatory condition, is suppressed in the central nervous system (CNS) ECs in MS and its animal model experimental autoimmune encephalomyelitis. We identify ETS1 as a central regulator of endothelial-to-mesenchymal transition (EndMT) associated with the compromise of barrier integrity. These phenotypical and functional alterations can further induce high permeability, immune infiltration, and organ fibrosis in multiple sclerosis, thus promoting disease progression. Together, these results demonstrate a functional role of EndMT in blood–brain barrier dysfunction and propose ETS1 as a potential transcriptional switch of EndMT to target the development of multiple sclerosis.
Mammalian eIF4E2-GSK3β maintains basal phosphorylation of p53 to resist senescence under hypoxia
Authors: Sun Lei , Yang He , He Dong , Chen Jian , Dong Zhiqiang , Luo Shaoxiang , Liang Huiting , Cao Yu , Cai Bingcheng , Zhang Min
Published: May 2022

Hypoxia modulates senescence, but their physiological link remains unclear. Here, we found that eIF4E2, a hypoxia-activated translation initiation factor, interacted with GSK3β to maintain phosphorylation of p53, thus resisting senescence under hypoxia. RNA-binding protein RBM38 interacted with eIF4E to inhibit the translation of p53, but GSK3β-mediated Ser195 phosphorylation disrupted the RBM38-eIF4E interaction. Through investigation of RBM38 phosphorylation, we found that the eIF4E2-GSK3β pathway specifically regulated proline-directed serine/threonine phosphorylation (S/T-P). Importantly, peptides e2-I or G3-I that blocking eIF4E2-GSK3β interaction can inhibit the basal S/T-P phosphorylation of p53 at multiple sites, therby inducing senescence through transcriptional inhibition. Additionally, a nanobody was screened via the domain where eIF4E2 bound to GSK3β, and this nanobody inhibited S/T-P phosphorylation to promote senescence. Furthermore, hypoxia inhibited eIF4E2-GSK3β pathway by mediating S-Nitrosylation of GSK3β. Blocking eIF4E2-GSK3β interaction promoted liver senescence under hypoxia, thus leading to liver fibrosis, eventually accelerating N, N-diethylnitrosamine (DEN)-induced tumorigenesis. Interestingly, eIF4E2 isoforms with GSK3β-binding motif exclusively exist in mammals, which protect zebrafish heart against hypoxia. Together, this study reveals a mammalian eIF4E2-GSK3β pathway that prevents senescence by maintaining basal S/T-P phosphorylation of p53, which underlies hypoxia adaptation of tissues.
microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis
Authors: Zhao Guifang , Yu Hongquan , Ding Lijuan , Wang Weiyao , Wang Huan , Hu Yao , Qin Lingsha , Deng Guangce , Xie Buqing , Li Guofeng , Qi Ling
Published: May 2022

Glioblastoma (GBM) cell-derived extracellular vesicles (EVs) have been demonstrated to modulate tumor microenvironment. In the present study, we attempted to discuss the role of hsa-microRNA-27a-3p (miR-27a-3p) delivered by GBM-EVs in M2 macrophage polarization. The isolated GBM-EVs were co-cultured with macrophages. After co-culture under normoxia/hypoxia, the effect of EV-derived hsa-miR-27a-3p on GBM cell biological processes was analyzed. Additionally, the target genes of hsa-miR-27a-3p were predicted. Moreover, the binding of enhancer of zeste homologue 1 (EZH1) to lysine-specific demethylase 3A (KDM3A) promoter region and the interaction between KDM3A and connective tissue growth factor (CTGF) were analyzed. GBM mouse models were established to verify the functions of EV-derived hsa-miR-27a-3p in vivo. We found increased hsa-miR-27a-3p in GBM tissues as well as GBM-EVs, which induced M2 polarization, thus promoting proliferative, migrative and invasive potentials of GBM cells. hsa-miR-27a-3p targeted EZH1 and promoted KDM3A expression to elevate the CTGF expression. GBM-EV-delivered hsa-miR-27a-3p promoted the KDM3A-upregulated CTGF by downregulating EZH1, thereby promoting M2 macrophage polarization and development of GBM in vivo. We demonstrated that EV-derived hsa-miR-27a-3p may promote M2 macrophage polarization to induce GBM.
Ultrasound-assisted carbon ion dosimetry and range measurement using injectable polymer-shelled phase-change nanodroplets: in vitro study
Authors: Toumia Yosra , Pullia Marco , Domenici Fabio , Facoetti Angelica , Ferrarini Michele , Heymans Sophie V. , Carlier Bram , Van Den Abeele Koen , Sterpin Edmond , D’hooge Jan , D’Agostino Emiliano , Paradossi Gaio
Published: May 2022

Methods allowing for in situ dosimetry and range verification are essential in radiotherapy to reduce the safety margins required to account for uncertainties introduced in the entire treatment workflow. This study suggests a non-invasive dosimetry concept for carbon ion radiotherapy based on phase-change ultrasound contrast agents. Injectable nanodroplets made of a metastable perfluorobutane (PFB) liquid core, stabilized with a crosslinked poly(vinylalcohol) shell, are vaporized at physiological temperature when exposed to carbon ion radiation (C-ions), converting them into echogenic microbubbles. Nanodroplets, embedded in tissue-mimicking phantoms, are exposed at 37 °C to a 312 MeV/u clinical C-ions beam at different doses between 0.1 and 4 Gy. The evaluation of the contrast enhancement from ultrasound imaging of the phantoms, pre- and post-irradiation, reveals a significant radiation-triggered nanodroplets vaporization occurring at the C-ions Bragg peak with sub-millimeter shift reproducibility and dose dependency. The specific response of the nanodroplets to C-ions is further confirmed by varying the phantom position, the beam range, and by performing spread-out Bragg peak irradiation. The nanodroplets’ response to C-ions is influenced by their concentration and is dose rate independent. These early findings show the ground-breaking potential of polymer-shelled PFB nanodroplets to enable in vivo carbon ion dosimetry and range verification.
A novel approach to control Botrytis cinerea fungal infections: uptake and biological activity of antifungals encapsulated in nanoparticle based vectors
Authors: De Angelis Giulia , Simonetti Giovanna , Chronopoulou Laura , Orekhova Anastasia , Badiali Camilla , Petruccelli Valerio , Portoghesi Francesca , D’Angeli Simone , Brasili Elisa , Pasqua Gabriella , Palocci Cleofe
Published: May 2022

Botrytis cinerea, responsible for grey mold diseases, is a pathogen with a broad host range, affecting many important agricultural crops, in pre and post harvesting of fruits and vegetables. Commercial fungicides used to control this pathogen are often subjected to photolysis, volatilization, degradation, leaching, and runoff during application. In this context, the use of a delivery system, based on poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) represents an innovative approach to develop new pesticide formulations to successfully fight B. cinerea infections. In order to study NPs uptake, B. cinerea conidia and mycelium were treated with PLGA NPs loaded with the high fluorescent probe coumarin 6 (Cu6-PLGA NPs) and analyzed under ApoTome fluorescence microscopy. The observations revealed that 50 nm Cu6-PLGA NPs penetrated into B. cinerea conidia and hyphae, as early as 10 min after administration. Pterostilbene, a natural compound, and fluopyram, a synthetic antifungal, were entrapped in PLGA NPs, added to B. cinerea conidia and mycelium, and their antifungal activity was tested. The results revealed that the compounds loaded in NPs exhibited a higher activity against B. cinerea. These results lay the foundations for the use of PLGA NPs as a new strategy in plant pest management.
Modeling of cadmium(II) removal in a fixed bed column utilizing hydrochar-derived activated carbon obtained from discarded mango peels
Authors: Rind Imran Khan , Memon Najma , Khuhawar Muhammad Yar , Soomro Waheed Ali , Lanjwani Muhammad Farooque
Published: May 2022

Cadmium is found in many underdeveloped countries' aquatic bodies. Therefore, contaminated water should be treated before consumption; henceforth, efficient and customized point-of-use filtration is foreseeable. Traditionally, carbon-based sorbents have been utilized for such treatments, but alternative sources are also being investigated. Hydrochars made from mango peels using a thermal activation process were employed as an adsorbent instead of activated carbon in this investigation. The prepared material was porous with active surface functionalities, and the interaction of cadmium with the surface was possibly ion-exchange in nature. The performance of a material for a candle water filtering system with a 2.5 cm internal diameter and a 30.48 cm column height was determined using the parameters acquired by the Thomas model. The material was found to be highly efficient at 453.5 L/min/Filter water, whereas 31670.6 L/min/Filter can be treated if the break point and exhaustion point are considered, respectively, as the candle replacement time. These findings indicate that activated hydrochar might be a suitable sorbent for removing cadmium ions from contaminated water.
Modelling liver cancer microenvironment using a novel 3D culture system
Authors: Al Hrout Ala’a , Cervantes-Gracia Karla , Chahwan Richard , Amin Amr
Published: May 2022

The tumor microenvironment and its contribution to tumorigenesis has been a focal highlight in recent years. A two-way communication between the tumor and the surrounding microenvironment sustains and contributes to the growth and metastasis of tumors. Progression and metastasis of hepatocellular carcinoma (HCC) have been reported to be exceedingly influenced by diverse microenvironmental cues. In this study, we present a 3D-culture model of liver cancer to better mimic in vivo tumor settings. By creating novel 3D co-culture model that combines free-floating and scaffold-based 3D-culture techniques of liver cancer cells and fibroblasts, we aimed to establish a simple albeit reproducible ex vivo cancer microenvironment model that captures tumor-stroma interactions. The model presented herein exhibited unique gene expression and protein expression profiles when compared to 2D and 3D mono-cultures of liver cancer cells. Our results showed that in vivo like conditions cannot be mimicked by simply growing cancer cells as spheroids, but by co-culturing them with 3D fibroblast with which they were able to crosstalk. This was evident by the upregulation of several pathways involved in HCC, and the increase in secreted factors by co-cultured cancer cells, many of which are also involved in tumor-stroma interactions. Compared to the conventional 2D culture, the proposed model exhibits an increase in the expression of genes associated with development, progression, and poor prognosis of HCC. Our results correlated with an aggressive outcome that better mirrors in vivo HCC, and therefore, a more reliable platform for molecular understanding of HCC.
Spatial-dependent quantum dot-photon entanglement via tunneling effect
Authors: Delir Ghaleh Joughi Yaser , Sahrai Mostafa
Published: May 2022

Utilizing the vortex beams, we investigate the entanglement between the triple-quantum dot molecule and its spontaneous emission field. We present the spatially dependent quantum dot-photon entanglement created by Laguerre-Gaussian (LG) fields. The degree of position-dependent entanglement (DEM) is controlled by the angular momentum of the LG light and the quantum tunneling effect created by the gate voltage. Various spatial-dependent entanglement distribution is reached just by the magnitude and the sign of the orbital angular momentum (OAM) of the optical vortex beam.
Blood pressure and outcome after aneurysmal subarachnoid hemorrhage
Authors: Darkwah Oppong Marvin , Steinwasser Lisa , Rieß Christoph , Wrede Karsten H. , Dinger Thiemo F. , Ahmadipour Yahya , Dammann Philipp , Rauschenbach Laurèl , Gümüs Meltem , Deuschl Cornelius , Sure Ulrich , Jabbarli Ramazan
Published: May 2022

Blood pressure management is crucial in the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). Possible association between the blood pressure increase and the risk of delayed cerebral ischemia (DCI) and different systemic complications after aSAH is still a matter of debate. This study aims to elucidate the influence of blood pressure levels on the outcome of aSAH. All consecutive aSAH patients (n = 690) treated between 01/2003 and 06/2016 were included. The mean value of the mean arterial pressure (MAP) during 14 days after ictus was calculated for each individual. According to the institutional standards of vasospasm management, the mean 14 days MAP ≥ 95 mmHg was referred as increased (IMAP) and the patients with and without vasospasm were analyzed separately. Study endpoints were the occurrence of DCI on computed tomography scans, development of cardiac and nephrological complications, and poor outcome 6 months after aSAH (mRS > 2). Associations were tested in univariable/multivariable binary logistic regression analysis. IMAP was documented in 474 (68.7%) cases and was more common in individuals with poor neurological conditions at admission (p < 0.001), severe amount of intracranial blood (p = 0.001) and premorbid hypertension (p < 0.001). IMAP was independently associated with the occurrence of DCI (p = 0.014; aOR = 2.97; 95% CI 1.25–7.09) and poor functional outcome (p = 0.020; aOR = 3.14; 95% CI 1.20–8.22) in patients with vasospasm, but not in counterparts without vasospasm (p = 0.113/p = 0.086). IMAP had no influence on cardiac or nephrological complications. In aSAH individuals with cerebral vasospasm, sustained increase of blood pressure exceeding the therapeutic targets is strongly associated with the risk of DCI and poor outcome. Therefore, such an intrinsic increase of blood pressure might reflect the autoregulatory mechanisms against the impending cerebral ischemia in patients with cerebral vasospasm.

Trial registration number: German clinical trial registry (DRKS, Unique identifier: DRKS00008749, 06/09/2015).
Soil and landscape factors influence geospatial variation in maize grain zinc concentration in Malawi
Authors: Botoman L. , Chagumaira C. , Mossa A. W. , Amede T. , Ander E. L. , Bailey E. H. , Chimungu J. G. , Gameda S. , Gashu D. , Haefele S. M. , Joy E. J. M. , Kumssa D. B. , Ligowe I. S. , McGrath S. P. , Milne A. E. , Munthali M. , Towett E. , Walsh M. G. , Wilson L. , Young S. D. , Broadley M. R. , Lark R. M. , Nalivata P. C.
Published: May 2022

Dietary zinc (Zn) deficiency is widespread globally, and in particular among people in sub-Saharan Africa (SSA). In Malawi, dietary sources of Zn are dominated by maize and spatially dependent variation in grain Zn concentration, which will affect dietary Zn intake, has been reported at distances of up to ~ 100 km. The aim of this study was to identify potential soil properties and environmental covariates which might explain this longer-range spatial variation in maize grain Zn concentration. Data for maize grain Zn concentrations, soil properties, and environmental covariates were obtained from a spatially representative survey in Malawi (n = 1600 locations). Labile and non-labile soil Zn forms were determined using isotopic dilution methods, alongside conventional agronomic soil analyses. Soil properties and environmental covariates as potential predictors of the concentration of Zn in maize grain were tested using a priori expert rankings and false discovery rate (FDR) controls within the linear mixed model (LMM) framework that informed the original survey design. Mean and median grain Zn concentrations were 21.8 and 21.5 mg kg−1, respectively (standard deviation 4.5; range 10.0–48.1). A LMM for grain Zn concentration was constructed for which the independent variables: soil pH(water), isotopically exchangeable Zn (ZnE), and diethylenetriaminepentaacetic acid (DTPA) extractable Zn (ZnDTPA) had predictive value (p < 0.01 in all cases, with FDR controlled at < 0.05). Downscaled mean annual temperature also explained a proportion of the spatial variation in grain Zn concentration. Evidence for spatially dependent variation in maize grain Zn concentrations in Malawi is robust within the LMM framework used in this study, at distances of up to ~ 100 km. Spatial predictions from this LMM provide a basis for further investigation of variations in the contribution of staple foods to Zn nutrition, and where interventions to increase dietary Zn intake (e.g. biofortification) might be most effective. Other soil and landscape factors influencing spatially dependent variation in maize grain Zn concentration, along with factors operating over shorter distances such as choice of crop variety and agronomic practices, require further exploration beyond the scope of the design of this survey.
Fibrin-coated collagen fleece versus absorbable dural sealant for sellar closure after transsphenoidal pituitary surgery: a comparative study
Authors: Spitaels Julien , Moore Justin , Zaidman Nathalie , Arroteia Isabel Fernandes , Appelboom Geoffrey , Barrit Sami , Carlot Sébastien , De Maertelaer Viviane , Hassid Sergio , De Witte Olivier
Published: May 2022

Various surgical methods to prevent postoperative cerebrospinal fluid (CSF) leaks during transsphenoidal surgery have been reported. However, comparative studies are scarce. We aimed to compare the efficacy of a fibrin-coated collagen fleece (TachoSil) versus a dural sealant (DuraSeal) to prevent postoperative CSF leakage. We perform a retrospective study comparing two methods of sellar closure during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenoma resection: TachoSil patching versus DuraSeal packing. Data concerning diagnosis, reconstruction technique, and surgical outcomes were analyzed. The primary endpoint was postoperative CSF leak rate. We reviewed 198 consecutive patients who underwent 219 EETS for pituitary adenoma from February 2007 and July 2018. Intraoperative CSF leak occurred in 47 cases (21.5%). A total of 33 postoperative CSF leaks were observed (15.1%). A reduction of postoperative CSF leaks in the TachoSil application group compared to the conventional technique using Duraseal was observed (7.7% and 18.2%, respectively; p = 0.062; Pearson exact test) although non-statistically significant. Two patients required lumbar drainage, and no revision repair was necessary to treat postoperative CSF rhinorrhea in Tachosil group. Fibrin-coated collagen fleece patching may be a valuable method to prevent postoperative cerebrospinal fluid (CSF) leaks during EETS for pituitary adenoma resection.
Evaluation of the α-casein (CSN1S1) locus as a potential target for a site-specific transgene integration
Authors: Smirnov A. V. , Kontsevaya G. V. , Shnaider T. A. , Yunusova A. M. , Feofanova N. A. , Gerlinskaya L. A. , Serova I. A. , Serov O. L. , Battulin N. R.
Published: May 2022

Transgenic animals are an important tool in biotechnology, including the production of recombinant proteins in the milk. Traditionally, expression constructs are based on hybrid vectors bearing mammary gland specific regulatory elements from the α-casein (Csn1s1), β-casein (Csn2), whey acidic protein (WAP), or β-lactoglobulin (BLG) genes. Overexpression from the randomly integrated vectors typically provides high levels of expression, but has drawbacks due to unpredictable genome localization. CRISPR-Cas9 targeted transgene integration into the endogenous casein locus could alleviate the need for extensive animal screening to achieve high and reproducible expression levels. We decided to evaluate such a “precise” integration approach, placing the human granulocyte–macrophage colony-stimulating factor (hGMCSF) gene under control of the mouse endogenous alpha-S1-casein (Csn1s1) promoter. We designed two types of transgene integrations: a knock-in in the second exon of the Csn1s1 (INS-GM) and a full-size Csn1s1 replacement with hGMCSF (REP-GM) which was never tested before. The INS-GM approach demonstrated low transgene expression and milk protein levels (0.4% of Csn2 transcripts; 2–11 µg/ml hGMCSF). This was probably caused by the absence of the 3’-polyadenylation signal in the hGMCSF transgene. REP-GM animals displayed high transgene expression, reaching and slightly exceeding the level of the endogenous Csn1s1 (30–40% of Csn2 transcripts), but yielded less hGMCSF protein than expected (0.2–0.5 mg/ml vs 25 mg/ml of Csn1s1), indicating that translation of the protein is not optimal. Homozygous inserts leading to the Csn1s1 knock-out did not have any long standing effects on the animals’ health. Thus, in our experimental design, site-specific transgene integration into the casein locus did not provide any significant advantage over the overexpression approach.
EGFR inhibition reverses resistance to lenvatinib in hepatocellular carcinoma cells
Authors: He Xiaoping , Hikiba Yohko , Suzuki Yoshimasa , Nakamori Yoshinori , Kanemaru Yushi , Sugimori Makoto , Sato Takeshi , Nozaki Akito , Chuma Makoto , Maeda Shin
Published: May 2022

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Lenvatinib is approved as a first-line treatment for unresectable HCC. The therapeutic duration of lenvatinib is limited by resistance, but the underlying mechanism is unclear. To establish lenvatinib-resistant cells, Hep3B cells were initially treated with 3 µM lenvatinib. The concentration was gradually increased by 1 µM or 0.5 µM per week and it reached to 7.5 µM 2 months after the initial exposure to lenvatinib. The biological characteristics of these cells were analyzed by ERK activation in the MAPK signaling pathway and a human phospho‐receptor tyrosine kinase (RTK) antibody array. Factors possibly related to lenvatinib resistance were analyzed using inhibitors, and cell proliferation was analyzed. We established lenvatinib-resistant HCC cells (LR cells) by long-term exposure to lenvatinib. Lenvatinib reduced ERK activation in the parent cells, but not in the LR cells. RTK array analysis showed that the activities of EGFR and insulin-like growth factor 1 receptor (IGF1R)/insulin receptor (INSR) were significantly increased in LR cells, whereas the activities of other RTKs were unchanged. Erlotinib, a widely used EGFR inhibitor, downregulated ERK activation in LR cells. The proliferation of LR cells will also be affected when lenvatinib is combined with erlotinib to treat LR cells. In contrast, inhibition of IGFR/INSR did not affect ERK activation or cell proliferation. Scavenging of reactive oxygen species (ROS) ameliorated the enhanced EGFR activation in LR cells. Lenvatinib resistance was induced by enhanced EGFR activation, possibly via ROS accumulation, in lenvatinib- resistant cells. These findings may enable the development of lenvatinib combination therapies for HCC.
TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2
Authors: Egawa Naohiro , Izumi Yuishin , Suzuki Hidefumi , Tsuge Itaru , Fujita Koji , Shimano Hitoshi , Izumikawa Keiichi , Takahashi Nobuhiro , Tsukita Kayoko , Enami Takako , Nakamura Masahiro , Watanabe Akira , Naitoh Motoko , Suzuki Shigehiko , Seki Tsuneyoshi , Kobayashi Kazuhiro , Toda Tatsushi , Kaji Ryuji , Takahashi Ryosuke , Inoue Haruhisa
Published: May 2022

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.
One-year outcomes of intravitreal brolucizumab injections in patients with polypoidal choroidal vasculopathy
Authors: Ito Arisa , Maruyama-Inoue Maiko , Kitajima Yoko , Ikeda Shoko , Inoue Tatsuya , Kadonosono Kazuaki
Published: May 2022

To evaluate the 1-year visual outcomes and anatomic responses of Japanese patients who received intravitreal brolucizumab (IVBr) injections for polypoidal choroidal vasculopathy (PCV). This was a retrospective study of 17 treatment-naïve eyes with PCV that were treated with IVBr. We evaluated the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT) and number of injections for 1 year. The eradication of polypoidal lesions was also evaluated using by indocyanine green angiography during the 1-year follow-up. Non-infectious intraocular inflammation developed in two (11.8%) eyes; 15 eyes were assessed at the 1-year follow-up examination. The mean BCVA improved significantly from 0.28 at baseline to 0.13 (P < 0.05) at 1 year. The CMT and CCT decreased significantly after 1 year. The mean number of injections was 6.4 ± 0.13. The rate of complete resolution of polypoidal lesions at 1 year was 93.3%. A dry macula was achieved in 13 eyes (86.6%) after the loading phase and in 11 eyes (73.3%) at 1 year. The IVBr injections appeared to be effective for improving both functional and anatomic outcomes in Japanese patients with PCV, with a high regression rate of polypoidal lesions.
Synthesis of two-dimensional ultrathin photocatalytic materials towards a more sustainable environment
Authors: Zhao Chengxiao , Han Chenhui , Yang Xiaofei , Xu Jingsan
Published: May 2022

The latest progress in 2D ultrathin nanomaterials used for photocatalysis has been summarized from a sustainable synthesis perspective. Various synthetic strategies and approaches have been discussed and compared.
Orienting dilute thin films of non-planar spin-1/2 vanadyl–phthalocyanine complexes
Authors: Xu Zhewen , Romankov Vladyslav , Doll Andrin , Dreiser Jan
Published: May 2022

We have found that in dilute films of VOPc in a TiOPc host the molecular orientation can be tailored using a PTCDA layer. An analytical model allows to extract the molecular orientation from the angle-dependent X-ray linear dichroism.