bluuebunny/crossref_metadata_2025 huggingface dataset:
Genital powder use and risk of uterine cancer: A pooled analysis of prospective studies
Authors: O'Brien Katie M. , Tworoger Shelley S. , Harris Holly R. , Trabert Britton , Weinberg Clarice R. , Fortner Renee T. , D'Aloisio Aimee A. , Kaunitz Andrew M. , Wentzensen Nicolas , Sandler Dale P.
Published: January 2021

When powder is applied to the genital area, it has the potential to reach internal reproductive organs and promote carcinogenesis by irritating and inflaming exposed tissues. Although many studies have considered the association between genital powder use and ovarian cancer risk, the relationship between genital powder use and uterine cancer is less well‐studied. We pooled data from four large, prospective cohorts (the Nurses' Health Study, the Nurses' Health Study II, the Sister Study and the Women's Health Initiative ‐ Observational Study). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for prespecified confounders. In total, 209 185 women were included, with 37% reporting ever genital powder use. Over a mean 14.5 years of follow‐up, 3272 invasive uterine cancers were diagnosed. There was no overall association between ever genital powder use and uterine cancer (HR = 1.01, 95% CI: 0.94‐1.09), with little difference observed for frequent (≥1 times/week) vs never use (HR = 1.05, 95% CI: 0.95‐1.16; P‐for‐trend = .46). Long‐term use (>20 years; HR = 1.12, 95% CI: 0.96‐1.31; P‐for‐trend = 0.14) was associated with a small, but not statistically significant, increase in risk, compared to never use. There were not clear differences by uterine cancer histologic subtypes or across strata of relevant covariates, including race/ethnicity, follow‐up time, menopausal status and body mass index. The results of this large, pooled analysis do not support a relationship between the use of genital powder and uterine cancer, although the positive associations observed for long‐term use may merit further consideration.
The relationship between excessive lending, risk premium and risk‐taking: Evidence from European banks
Authors: Alhalabi Thaer , Castro Vitor , Wood Justine
Published: January 2021

Banks normally trade‐off the amount of loans created by the amount of risk piled up in their assets portfolios. However, their performance can induce a ‘search for yield’ or ‘gamble to survive’ behaviour. Using sample of 149 European banks during the period 2001–2016, we show that the risk management hypothesis holds for the period after the 2007–2008 financial crisis and for large banks. Contrarily, the moral hazard hypothesis, under which banks practise excessive lending to relatively risky borrowers that pay higher premium but increase their credit risk, is supported in the pre‐crisis period and for small banks. Additionally, we provide important implications to suggest that the post‐crisis regulations have restrained banks with poor performance from the ‘gamble to survive’ behaviour.
The impact of COVID‐19 on unemployment rate: An intelligent based unemployment rate prediction in selected countries of Europe
Authors: Ahmad Muneeb , Khan Yousaf Ali , Jiang Chonghui , Kazmi Syed Jawad Haider , Abbas Syed Zaheer
Published: January 2021

Unemployment remains a major cause for both developed and developing nations, due to which they lose their financial and economic impact as a whole. Unemployment rate prediction achieved researcher attention from a fast few years. The intention of doing our research is to examine the impact of the coronavirus on the unemployment rate. Accurately predicting the unemployment rate is a stimulating job for policymakers, which plays an imperative role in a country's financial and financial development planning. Classical time series models such as ARIMA models and advanced non‐linear time series methods be previously hired for unemployment rate prediction. It is known to us that mostly these data sets are non‐linear as well as non‐stationary. Consequently, a random error can be produced by a distinct time series prediction model. Our research considers hybrid prediction approaches supported by linear and non‐linear models to preserve forecast the unemployment rates much precisely. These hybrid approaches of the unemployment rate can advance their estimates by reproducing the unemployment ratio irregularity. These models' appliance is exposed to six unemployment rate statistics sets from Europe's selected countries, specifically France, Spain, Belgium, Turkey, Italy and Germany. Among these hybrid models, the hybrid ARIMA‐ARNN forecasting model performed well for France, Belgium, Turkey and Germany, whereas hybrid ARIMA‐SVM performed outclass for Spain and Italy. Furthermore, these models are used for the best future prediction. Results show that the unemployment rate will be higher in the coming years, which is the consequence of the coronavirus, and it will take at least 5 years to overcome the impact of COVID‐19 in these countries.
Duration and quality of sleep during pregnancy are associated with preterm birth and small for gestational age: A prospective study
Authors: Li Run , Zhang Ju , Gao Yan , Zhang Yiqi , Lan Xi , Dong Hongli , Wu Cheng , Yu Chengwei , Peng Min , Zeng Guo
Published: January 2021

Objective

To explore the associations of duration and quality of sleep during pregnancy with preterm birth and small for gestational age (SGA).

Methods

A prospective study was carried out on 1082 healthy women with singleton pregnancies from Chengdu, China. Self‐report questionnaires, including duration and quality of sleep and other information, were administered at 8–12, 24–28, and 32–36 weeks of pregnancy. Data on gestational age and weight and length of the neonates were recorded after delivery. After controlling the potential confounders, a multivariable logistic regression model was performed to evaluate whether duration and quality of sleep were associated with preterm birth and SGA.

Results

Participants with short duration of sleep during the third trimester were more likely to report preterm birth (odds ratio [OR] 2.16, 95% confidence interval [CI] 1.26–4.81) and SGA (OR 2.67, 95% CI 1.18–6.54). Participants with poor quality of sleep during the third trimester were at high risk for preterm birth (OR 2.26, 95% CI 1.29–5.84) and SGA (OR 2.08, 95% CI 1.19–5.38).

Conclusion

Short duration and poor quality of sleep during pregnancy are associated with an increased risk of preterm birth and SGA. Sleep characteristics should be assessed during prenatal evaluations to decrease adverse maternal and fetal outcomes.
Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish
Authors: Du Zheng‐Cai , Xia Zhong‐Shang , Huang Yan‐Feng , Peng Yi , Cao Bing‐Bing , Li Chun‐Qi , Liang Yun‐Fei , Zhao Fang‐Hui , Zhang Ming‐Zhe , Chen Zhang‐Mei , Hou Xiao‐Tao , Hao Er‐Wei , Deng Jia‐Gang
Published: January 2021

Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti‐ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE‐induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose‐dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.
Continuous assessment of metabolic activity of mitochondria using resonance Raman microspectroscopy
Authors: Lalonde Joshua W. , Noojin Gary D. , Pope Nathaniel J. , Powell Samantha M. , Yakovlev Vladislav V. , Denton Michael L.
Published: January 2021

Dysfunctional mitochondrial activity can lead to a variety of different diseases. As such, there exists a need to quantify changes in mitochondria function as it relates to these specific diseased states. Here, we present the use of resonance Raman (RR) spectroscopy as a tool to determine changes in isolated mitochondrial activity. RR spectroscopy, using 532 nm as the excitation source, specifically provides information on the reduction and oxidation (RedOx) state of cytochrome c, which is determined by the activity of protein complexes in the electron transport chain (ETC). In this model, injection of the substrate succinate into the mitochondrial sample is used to drive the ETC, which causes a subsequent change in cytochrome c RedOx state. This change in RedOx state is tracked by RR spectroscopy. This tool gives real‐time information on the rise and fall of the amount of reduced cytochrome c within the mitochondrial sample, providing a method for rapid assessment of mitochondrial metabolism that has broad applications in both basic science and medical research.
Noninvasive measurement of the 308nm LED‐basedUVBprotection factor of sunscreens
Authors: Kobylinski Susanna , Reble Carina , Schanzer Sabine , Gersonde Ingo , Wiora Georg , Lobo Ploch Neysha , Karrer Hans , Kolbe Ludger , Khazaka Georg , Lademann Jürgen , Meinke Martina C.
Published: January 2021

The current method for determining the sun protection factor (SPF) requires erythema formation. Noninvasive alternatives have recently been suggested by several groups. Our group previously developed a functional sensor based on diffuse reflectance measurements with one UVB LED, which was previously evaluated on pig ear skin. Here we present the results of a systematic in vivo study using 12 sunscreens on 10 volunteers (skin types [ST] I‐III). The relationship of the UVB‐LED reflectance of unprotected skin and melanin index was determined for each ST. The spatial variation of the reflectance signal of different positions was analyzed and seems to be mainly influenced by sample inhomogeneity except for high‐protection factors (PFs) where signal levels are close to detection noise. Despite the low‐signal levels, a correlation of the measured LED‐based UVB PF with SPF reference values from test institutes with R2= 0.57 is obtained, suggesting a strong relationship of SPF and LED‐based UVB‐PF. Measured PFs tend to be lower for increasing skin pigmentation. The sensor design seems to be suitable for investigations where a fast measurement of relative changes of PFs, such as due to inhomogeneous application, bathing and sweating, is of interest.
The protective effects of trelagliptin on high‐fat diet‐induced nonalcoholic fatty liver disease in mice
Authors: Wang Guang , Wu Bing , Zhang Lening , Jin Xuefei , Wang Kun , Xu Wenzhou , Zhang Bo , Wang Heyuan
Published: January 2021

Nonalcoholic fatty liver disease (NAFLD) occurs in patients with type 2 diabetes mellitus (T2DM). Trelagliptin is an important member of the Gliptins family, which has been recently licensed for the treatment of T2DM. However, the pharmacological function of trelagliptin in NAFLD has not been previously reported. In this study, we aimed to investigate the roles of trelagliptin in the development of NAFLD in a mouse model. To induce NAFLD disease, C57BL/6 mice were fed a high‐fat diet for 10 weeks. Our results indicate that trelagliptin reduced plasma lipid levels in NAFLD mice by reducing triglycerides, total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. Treatment with trelagliptin exhibited an improvement in insulin resistance. More important, trelagliptin improved liver function by reducing alanine transaminase, aspartate transaminase, lactate dehydrogenase, and total bile acid. In addition, trelagliptin ameliorated oxidative stress in the liver of NAFLD mice by reducing malondialdehyde and increasing the levels of reduced glutathione and superoxide dismutase activity. Also, the enzyme‐linked immunosorbent assay results indicate that trelagliptin‐treated mice displayed anti‐inflammatory properties by reducing the levels of interleukin 1β (IL‐1β), IL‐6, and tumor necrosis factor‐α. Hematoxylin and eosin and Oil red O staining show that trelagliptin treatment ameliorates liver tissue damage and hepatic lipid deposition. Mechanistically, we found that the administration of trelagliptin reduced the activity of hepatic nuclear factor‐κB but increased the activity of AMP‐activated protein kinase. These findings suggest that trelagliptin might become a promising therapeutic agent for the treatment of NAFLD.
The existence of r‐golf designs
Authors: Li Xiangqian , Chang Yanxun , Zhou Junling
Published: January 2021

An r‐golf design of order , briefly by r‐G(v), is a large set of idempotent Latin squares of order (ILSs) which contains symmetric ILSs and transposed pairs of ILSs. In this paper, we mainly consider the existence problem of r‐G(v)s. We present several recursive constructions and also display some direct constructions. As an application, several infinite classes of r‐G(v)s are determined, including the existence of 0‐G(v)s for more than half of admissible parameters and the existence of r‐G(v)s where and is any admissible integer ( odd and ).
Clinical evaluation of a laboratory‐developed test using clone E1L3N for the detection of PD‐L1 expression status in non‐small cell lung cancer
Authors: Xu Hanyan , Dong Xidan , Zhao Hanxin , Hou Tongtong , Chen Chengshui , Chen Guorong , Ye Junru , Li Yuping
Published: January 2021

Background

Programmed death ligand 1 (PD‐L1) has been used as a diagnostic marker to identify patients that will benefit from immune checkpoint inhibitors in non‐small cell lung cancer (NSCLC). Immunohistochemistry with E1L3N clone is one of the most widely used and inexpensive laboratory‐developed tests for PD‐L1, but still need to be compared and validated with standard methods for clinical application.

Methods

We investigated the performance of E1L3N clone for PD‐L1 testing in 299 tumor tissues of NSCLC patients and its comparability with FDA‐approved 22C3 clone.

Results

The results show that the negative coincidence rate, weak positive coincidence rate, and positive coincidence rate were 97.4%, 92.2%, and 97.6% using the E1L3N assay relative to the 22C3 assay, respectively. An overall agreement of 96.3% was achieved between these two assays. We also found that the overall concordances were 97.8% and 93.9% for PD‐L1 detection in large and small specimens, respectively, and no significant difference was obtained between these two assays (p = 0.076). In addition, the expression of PD‐L1 was not detected in tumor tissues of benign lung disease using both the E1L3N and 22C3 assays.

Conclusion

E1L3N can be used as a reliable alternative antibody clone to evaluate PD‐L1 expression status for NSCLC patients.
Overexpression of GLUT3 promotes metastasis of triple‐negative breast cancer by modulating the inflammatory tumor microenvironment
Authors: Tsai Tai‐Hua , Yang Ching‐Chieh , Kou Tai‐Chih , Yang Chang‐En , Dai Jia‐Zih , Chen Chia‐Ling , Lin Cheng‐Wei
Published: January 2021

Triple‐negative breast cancer (TNBC) exhibits a higher level of glycolytic capacity and are commonly associated with an inflammatory microenvironment, but the regulatory mechanism and metabolic crosstalk between the tumor and tumor microenvironment (TME) are largely unresolved. Here, we show that glucose transporter 3 (GLUT3) is particularly elevated in TNBC and associated with metastatic progression and poor prognosis in breast cancer patients. Expression of GLUT3 is crucial for promoting the epithelial‐to‐mesenchymal transition and enhancing invasiveness and distant metastasis of TNBC cells. Notably, GLUT3 is correlated with inflammatory gene expressions and is associated with M1 tumor‐associated macrophages (TAMs), at least in part by C‐X‐C Motif Chemokine Ligand 8 (CXCL8). We found that expression of GLUT3 regulates CXCL8 production in TNBC cells. Secretion of CXCL8 participates in GLUT3‐overexpressing TNBC cells‐elicited activation of inflammatory TAMs, which further enhances GLUT3 expression and mobility of TNBC cells. Our findings demonstrate that aerobic glycolysis in TNBC not only promotes aggressiveness of tumor cells but also initiates a positive regulatory loop for enhancing tumor progression by modulating the inflammatory TME.
The antithetic role of ceramide and sphingosine‐1‐phosphate in cardiac dysfunction
Authors: Cirillo Federica , Piccoli Marco , Ghiroldi Andrea , Monasky Michelle M. , Rota Paola , La Rocca Paolo , Tarantino Adriana , D'Imperio Sara , Signorelli Paola , Pappone Carlo , Anastasia Luigi
Published: January 2021

Cardiovascular diseases (CVDs) are the leading cause of death globally and the number of cardiovascular patients, which is estimated to be over 30 million in 2018, represent a challenging issue for the healthcare systems worldwide. Therefore, the identification of novel molecular targets to develop new treatments is an ongoing challenge for the scientific community. In this context, sphingolipids (SLs) have been progressively recognized as potent bioactive compounds that play crucial roles in the modulation of several key biological processes, such as proliferation, differentiation, and apoptosis. Furthermore, SLs involvement in cardiac physiology and pathophysiology attracted much attention, since these molecules could be crucial in the development of CVDs. Among SLs, ceramide and sphingosine‐1‐phosphate (S1P) represent the most studied bioactive lipid mediators, which are characterized by opposing activities in the regulation of the fate of cardiac cells. In particular, maintaining the balance of the so‐called ceramide/S1P rheostat emerged as an important novel therapeutical target to counteract CVDs. Thus, this review aims at critically summarizing the current knowledge about the antithetic roles of ceramide and S1P in cardiomyocytes dysfunctions, highlighting how the modulation of their metabolism through specific molecules, such as myriocin and FTY720, could represent a novel and interesting therapeutic approach to improve the management of CVDs.
Development and functional characterization of novel fully human anti‐CD19 chimeric antigen receptors for T‐cell therapy
Authors: Dai Zhenyu , Hu Xuelian , Jia Xiangyin , Liu Jianwei , Yang Yongkun , Niu Panpan , Hu Guang , Tan Taochao , Zhou Jianfeng
Published: January 2021

Impressive outcomes have been achieved by chimeric antigen receptor (CAR)‐T cell therapy using murine‐derived single‐chain variable fragment (scFv) FMC63 specific for CD19 in patients with B cell malignancies. However, evidence suggests that human anti‐mouse immune responses might be responsible for poor persistence and dysfunction of CAR‐T cells, leading to poor outcomes or early tumor recurrence. Substituting a fully human scFv for murine‐derived scFv may address this clinically relevant concern. In this study, we discovered two human anti‐CD19 scFv candidates through an optimized protein/cell alternative panning strategy and evaluated their function in CAR‐T cells and CD19/CD3 bispecific antibody formats. The two clones exhibited excellent cytotoxicity in CAR‐T cells and bispecific antibodies in vitro compared with the benchmarks FMC63 CAR‐T cells and blinatumomab. Furthermore, Clone 78‐BBz CAR‐T cells exhibited similar in vivo antitumor activity to FMC63‐BBz CAR‐T cells. Our results indicate that Clone 78‐BBz CAR has excellent efficacy and safety profile and is a good candidate for clinical development.
Melatonin maintains inner blood‐retinal barrier via inhibition of p38/TXNIP/NF‐κB pathway in diabetic retinopathy
Authors: Tang Lei , Zhang Chaoyang , Yang Qian , Xie Hai , Liu Dandan , Tian Haibin , Lu Lixia , Xu Jing‐Ying , Li Weiye , Xu Guoxu , Qiu Qinghua , Liu Kun , Luo Dawei , Xu Guo‐Tong , Zhang Jingfa
Published: January 2021

The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti‐inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood–retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF‐α, IL‐1β, ICAM‐1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO‐1, occludin, JAM‐A, and claudin‐5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF‐κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF‐κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin‐based DR therapy.
Advanced purification platform using circularly permuted caspase‐2 for affinity fusion‐tag removal to produce native fibroblast growth factor 2
Authors: Lingg Nico , Cserjan‐Puschmann Monika , Fischer Andreas , Engele Petra , Kröß Christina , Schneider Rainer , Brocard Cécile , Berkemeyer Matthias , Striedner Gerald , Jungbauer Alois
Published: January 2021

BACKGROUND

Recombinant proteins produced for use as biopharmaceuticals need to harbor their native N‐terminus. A drawback in expression of recombinant proteins as fusion proteins with an affinity fusion‐tag is that enzymatic or chemical processing is required to trim the artificial tag and release the true protein of interest. In many cases, however, this processing step generates an incorrect N‐terminus.

RESULTS

Human fibroblast growth factor 2 (FGF2) was expressed as a fusion protein in Escherichia coli fed‐batch cultivations. The protein of interest (POI) carried an N‐terminal affinity fusion‐tag which enabled purification via affinity chromatography. After enzymatic removal of the affinity fusion‐tag with a circularly permuted human caspase‐2 (cpCasp2), the POI was further purified using subtractive affinity chromatography. Mass spectrometric analysis confirmed the authentic N‐terminus of the POI. The generated POI was highly pure with 42 ppm host cell protein, 3.7 μg mL−1 dsDNA and ~ 1000 EU mL−1 endotoxin. Only a small number of E. coli host cell proteins were co‐purified with the POI. Because of the high specificity of the novel protease cpCasp2, no off‐target cleavage could be observed.

CONCLUSION

Our findings demonstrate that cpCasp2 can be used for the production of native proteins using a fusion‐protein process. This represents a first case study at large laboratory scale for the production of an industrially relevant protein. This technology constitutes the basis of a highly scalable cpCasp2‐based platform fusion protein process (CASPON technology) purification platform. © 2021 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Fe doped CeO2 nanocubes with the exposure of active (100) facets for photocatalytic ozonation of 4‐chlorophenol under solar irradiation
Authors: Xu Shiting , Chen Xixi , Zhan Shujuan , Tian Shuanghong , Xiong Ya
Published: January 2021

BACKGROUND

To strengthen the treatment efficiency of photocatalytic ozonation, it is necessary to develop a stable bifunctional catalyst active in both processes of photocatalysis and catalytic ozonation.

RESULTS

A series of Fe doped CeO2 nanocubes with the main exposure of active (100) crystal facets were simply synthesized by a one‐pot hydrothermal method and applied in photocatalytic ozonation for the first time. It was found that doping did not change the morphology of nanocubes but it decreased the crystal size, induced abundant defects of oxygen vacancies and Ce3+, and shifted the optical absorption edge to the visible region. Due to these structure modifications, Fe doped CeO2 nanocubes enhanced the mineralization rate of 4‐chlorophenol by 55.4–74.7% and reduced the formation of carcinogenic bromate by 60.2–85.4%, depending on the doping content. Due to the simultaneous occurrence of photocatalysis, catalytic ozonation, and their synergy in 5%Fe‐CeO2 mediated photocatalytic ozonation under solar irradiation, 4‐chlorophenol almost completely degraded within 9 min, 74.7% of mineralization rate was achieved within 45 min, and the first order kinetics reaction constant reached 2.97 × 10−2·min−1, about 4.1 times that of photo ozonation without any catalysts. Moreover, the introduction of 5%Fe‐CeO2 to the ozonation, photolysis, and photo ozonation decreased the corresponding energy consumption by 60.2%, 84.2%, and 62.5%, respectively.

CONCLUSION

In this study, an efficient and economical Fe doped CeO2 nanocubes‐mediated photocatalytic ozonation process was successfully developed for the refractory organics‐containing wastewater treatment under solar light irradiation. © 2021 Society of Chemical Industry
Cell cycle during neuronal migration and neocortical lamination
Authors: Wu Shanshan , Wei Tingting , Fan Wenjuan , Wang Yanli , Li Chaojie , Deng Jinbo
Published: January 2021

Objectives

In order to understand the relationships between neocortical lamination and cell cycle, various cells, such as neural stem cell, migrating postmitotic neuron, Cajal‐Retzius (CR) cell, and mature pyramidal cell in various cell phases were investigated in mouse cortices.

Methods

With mouse neocortex and hippocampus, the immunofluorescent labeling, BrdU assay, and DiI tracing technique were implemented in the study.

Results

(1) During mouse development, the neocortex expressed different proteins, such as FOXP2, CDP, and Nestin, which could be used as the markers for cortical lamination. (2) The neural stem cells were mainly located in the subventricular zone, with the expressions of Nestin, Cyclin A2, Cyclin E1, and CDT1, suggesting that they were in the repeated cell cycle. Furthermore, the migrating neurons in the neocortex were Cyclin D1‐ (G1 phase‐specific marker) positive, suggesting that they were in the G1 phase. However, Pyramidal cells that developed from postmitotic migrating neurons and settled in the cortical plate were Cyclin D1‐ negative, suggesting that they were in the G0 phase. (3) Reelin positive CR cells appeared in the molecular layer of the neocortex in early embryonic day (E10), which could express Cyclin A2, Cyclin E1, and CDT1 as pyramidal cells, but not Cyclin D1, suggesting that they may have exited the cell cycle and entered the G0 phase.

Conclusion

The neural migration, neural proliferation, and cell cycle alterations play an important role during cortical lamination. During the cortical development and lamination, the neural stem cells and migrating postmitotic neurons are in different cell cycle phases, but pyramidal cells and CR cells have exited the cell cycle.
Ultra‐structural and physico‐chemical characterization of eggs and egg hairs (setae) of the new invasive pest, fall armyworm,Spodoptera frugiperda(J. E. Smith) in India: A first report
Authors: Kannan Malaichamy , Elango Kolanthasamy , Kalyanasundaram Manickavasagam , Govindaraju Kasivelu
Published: January 2021

In this study, we report first time in India on the morphology, ultra‐architectural pattern of the chorion in the egg and egg hair (setae). Further, physico‐chemical characterizations of egg hairs (setae) were studied in the new invasive pest, fall armyworm,Spodoptera frugiperda. The egg is dome shaped with flattened base and curves upward to a broadly rounded point at the apex. HR‐SEM micrographs revealed the surface ultrastructure of eggs chorion and shows structural elements of a marked rosette of petals surround the micropyle followed by micropylar rosette region around the micropyle plate. There was a small single micropylar opening along with 9 micropylar rosette cells and 13 micropylar rosette zones present near to the micropylar pit. In the egg the first order ribs were absent, but around 58–60 numbers of second order ribs were present. All the ventral and lateral cells of the eggs are connected by 19–22 cross striae and not forming a grid pattern, but joints with the longitudinal ribs at several of angles and totally 1,277–1,495 convex cells present at the egg's surface. The physico‐chemical characteristics of egg hairs were studied using Fourier transform infrared (FT‐IR) and thermogravimetric analysis (TGA) analysis. TGA results show that three weight losses occurred at 142, 418, and 880°C, respectively. FT‐IR confirms the presence of amides, sulfoxide, and nitro compounds in egg hairs (setae).
Comprehensive evaluation of methods for small extracellular vesicles separation from human plasma, urine and cell culture medium
Authors: Dong Liang , Zieren Richard C. , Horie Kengo , Kim Chi‐Ju , Mallick Emily , Jing Yuezhou , Feng Mingxiao , Kuczler Morgan D. , Green Jordan , Amend Sarah R. , Witwer Kenneth W. , de Reijke Theo M. , Cho Yoon‐Kyoung , Pienta Kenneth J. , Xue Wei
Published: January 2021

One of the challenges that restricts the evolving extracellular vesicle (EV) research field is the lack of a consensus method for EV separation. This may also explain the diversity of the experimental results, as co‐separated soluble proteins and lipoproteins may impede the interpretation of experimental findings. In this study, we comprehensively evaluated the EV yields and sample purities of three most popular EV separation methods, ultracentrifugation, precipitation and size exclusion chromatography combined with ultrafiltration, along with a microfluidic tangential flow filtration device, Exodisc, in three commonly used biological samples, cell culture medium, human urine and plasma. Single EV phenotyping and density‐gradient ultracentrifugation were used to understand the proportion of true EVs in particle separations. Our findings suggest Exodisc has the best EV yield though it may co‐separate contaminants when the non‐EV particle levels are high in input materials. We found no 100% pure EV preparations due to the overlap of their size and density with many non‐EV particles in biofluids. Precipitation has the lowest sample purity, regardless of sample type. The purities of the other techniques may vary in different sample types and are largely dependent on their working principles and the intrinsic composition of the input sample. Researchers should choose the proper separation method according to the sample type, downstream analysis and their working scenarios.
The impact of oral diseases in cirrhosis on complications and mortality
Authors: Ladegaard Grønkjær Lea , Holmstrup Palle , Jepsen Peter , Vilstrup Hendrik
Published: January 2021

Background and Aim

The aims of this study were to describe the prevalence of various oral diseases and to examine the association of the oral diseases with complications and mortality of cirrhosis.

Methods

A total of 184 cirrhosis patients were enrolled and were followed up for 2 years. They underwent oral clinical and radiographic examination. At study entry, the associations between oral diseases with nutrition, inflammation, and cirrhosis complication status were examined. Then, the associations of oral diseases with all‐cause and cirrhosis‐related mortality were examined using Cox regression to adjust for confounding by age, gender, smoking, alcohol use, alcoholic cirrhosis, cirrhosis complications, comorbidity, Child‐Pugh, and Model of End‐Stage Liver Disease (MELD) score.

Results

At entry, 26% of the patients had gross caries, 46% periapical lesions, 27% oral mucosal lesions, and 68% periodontitis. Having one or more oral diseases was associated with a higher prevalence of cirrhosis complications (46.7 vs 20.5%), higher C‐reactive protein (28.5 mg/L vs 10.4 mg/L), and higher nutritional risk score (4 vs 3). Two‐thirds of the patients died during follow‐up. The patients with more than one oral disease had an increasingly higher all‐cause mortality (two diseases: hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.02–1.98; three and four diseases: HR 1.75, 95% CI 1.05–3.24) and even higher cirrhosis‐related mortality (two diseases: HR 1.60, 95% CI 1.01–2.40; three and four diseases: HR 2.04, 95% CI 1.05–8.83) compared to those with no oral disease.

Conclusion

In cirrhosis, having more than one oral disease was associated with more complications and with higher mortality.
Domestic revenue mobilisation in developing countries: An exploratory analysis of sub‐Saharan Africa and Latin America
Authors: Gwaindepi Abel
Published: January 2021

This study compares taxation trends, volatility and tax effort between sub‐Saharan Africa (SSA) and Latin American and the Caribbean (LAC) countries since 1980. It finds that the LAC countries lead on revenue collection and revenue stability, but richer SSA countries outperform their LAC counterparts. Since 2010, there has been a divergence on personal income taxes, which have grown in SSA but declined in the LAC. The panel analysis shows that tax determinants are sensitive to income levels. The study shows the importance of exploring diversity and cross‐regional variations on income levels. Additionally, it shows that room exists for peer‐to‐peer lessons on tax reforms.
Dual‐labeled prostate‐specific membrane antigen (PSMA)‐targeting agent for preoperative molecular imaging and fluorescence‐guided surgery for prostate cancer
Authors: Kim Myoung Hyoun , Kim Seul‐Gi , Kim Dae‐Weung
Published: January 2021

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc‐99m GRFLTGGTGRLLRIS‐GHEG‐ECG‐K(‐5‐carboxy‐X‐rhodamine)‐NH2 (GRFLT‐ECG‐ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT‐ECG‐ROX was synthesized using Fmoc solid‐phase peptide synthesis. Radiolabeling of GRFLT‐ECG‐ROX with Tc‐99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC‐3 tumor‐bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc‐99m, Tc‐99m GRFLT‐ECG‐ROX complexes were prepared in high yield (>96%). The binding affinity value (Kd) of Tc‐99m GRFLT‐ECG‐ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc‐99m GRFLT‐ECG‐ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real‐time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc‐99m GRFLT‐ECG‐ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal.
Preparation, quality control, and biodistribution assessment of [111In]In‐DOTA‐PR81 in BALB/c mice bearing breast tumors
Authors: Abbas Abadi Sareh , Alirezapour Behrouz , Kertész István , Rasaee Mohammad Javad , Mohammadnejad Javad , Paknejad Malihe , Yousefnia Hassan , Zolghadri Samaneh
Published: January 2021

In this study, [111In]In‐DOTA‐PR81 was developed, and its preliminary preclinical qualifications were assessed for single photon emission computed tomography (SPECT) imaging of breast cancer. DOTA‐NHS‐ester was practiced and successively purified by molecular filtration. The chelate:mAb ratio was determined by spectrophotometry. DOTA‐PR81 was radiolabeled with In‐111 and its radiochemical yield, in vitro stability, in vitro internalization, and immunoreactivity tests were performed. SPECT imaging and tissue counting were applied to evaluate the tissue distribution of [111In]In‐DOTA‐hIgG and [111In]In‐DOTA‐PR81 in BALB/c mice bearing breast tumors. The radiochemical yield of [111In]In‐DOTA‐PR81 complex was >95.0 ± 0.5% (ITLC), and the specific activity was 170 ± 44 MBq/mg. Conjugation reaction resulted in the average number of chelators attached to a mAb (c/a) of 3.4 ± 0.3:1. The radioimmunoconjugate showed immunoreactivity towards MCF7 cell line and MUC1 antigen while its significant in vitro and in vivo stability were investigated over 48 h, respectively (93.0 ± 1.2% in phosphate‐buffered saline (PBS) and 84.0 ± 1.3% in human serum). The peak concentration of internalized activity of [111In]In‐DOTA‐PR81 was between 4 to 6 h. In comparison with control probes, the complex was accumulated with high specificity and sensitivity at the tumor site. Achieved results indicated that [111In]In‐DOTA‐PR81 could be contemplated as an appropriate radiotracer for prognostic imaging of antigens in oncology.
Cine MRI detects elevated left heart pressure in pulmonary hypertension
Authors: Lin Kai , Sarnari Roberto , Pathrose Ashitha , Gordon Daniel , Blaisdell Julie , Markl Michael , Carr James C.
Published: January 2021

Cine magnetic resonance imaging (MRI) is an emerging modality for evaluating left ventricular (LV) motion/deformation patterns, which may have potential to identify LV dysfunctions underlying postcapillary pulmonary hypertension (PH). The aim of this study was to test the hypothesis that cine MRI‐derived LV motion/deformation indices can be used to identify an elevated left heart pressure in PH. This was a retrospective study, which included 26 precapillary and 28 postcapillary PH patients (23 males, 58.9 ± 13.5 years old). All patients underwent right heart catheterization (the “reference standard”) and cardiac MRI. Balanced steady‐state free precession cine sequence acquired at 1.5 T was used. Cine MRI datasets were analyzed by using heart deformation analysis. LV motion/deformation indices were measured through 25 phases within a cardiac cycle. Peak LV displacement, velocity, strain, and strain rates at systole, early and late diastole were compared between the two patient groups using t‐tests. The Pearson correlation coefficient (r) was used to investigate the association between cine MRI‐derived indices and pulmonary capillary wedge pressure (PCWP). Multivariable linear and logistic regression models were applied to assess the ability of MRI‐derived parameters to predict PCWP and postcapillary PH. Compared to 26 precapillary PH patients, the 28 postcapillary PH patients had lower peak late radial diastolic displacement (0.43 ± 0.19 cm vs. 0.64 ± 0.18 cm) and velocity (12.2 ± 5.8 mm/s vs. 18.9 ± 5.6 mm/s) and peak late radial (52.1 ± 32.7%/s vs. 97.1 ± 38%/s) and circumferential (38 ± 19.8%/s vs. 63.1 ± 22.9%/s) strain rates. PCWP was correlated with peak late radial diastolic displacement (r = −0.54) and velocity (r = −0.57) and peak late radial (r = −0.63) and circumferential diastolic (r = −0.63) strain rates. Peak late radial strain rate could predict PCWP (β = −0.09) and postcapillary PH (β = −0.036). All p < 0.05. Cine MRI‐derived LV late diastolic motion/deformation properties can be used to estimate elevated left heart pressure in PH.

Level of Evidence

3

Technical Efficacy Stage

1
Investigating metabolism by mass spectrometry: From steady state to dynamic view
Authors: Audano Matteo , Pedretti Silvia , Ligorio Simona , Giavarini Flavio , Caruso Donatella , Mitro Nico
Published: January 2021

Metabolism is the set of life‐sustaining reactions in organisms. These biochemical reactions are organized in metabolic pathways, in which one metabolite is converted through a series of steps catalyzed by enzymes in another chemical compound. Metabolic reactions are categorized as catabolic, the breaking down of metabolites to produce energy, and/or anabolic, the synthesis of compounds that consume energy. The balance between catabolism of the preferential fuel substrate and anabolism defines the overall metabolism of a cell or tissue. Metabolomics is a powerful tool to gain new insights contributing to the identification of complex molecular mechanisms in the field of biomedical research, both basic and translational. The enormous potential of this kind of analyses consists of two key aspects: (i) the possibility of performing so‐called targeted and untargeted experiments through which it is feasible to verify or formulate a hypothesis, respectively, and (ii) the opportunity to run either steady‐state analyses to have snapshots of the metabolome at a given time under different experimental conditions or dynamic analyses through the use of labeled tracers. In this review, we will highlight the most important practical (e.g., different sample extraction approaches) and conceptual steps to consider for metabolomic analysis, describing also the main application contexts in which it is used. In addition, we will provide some insights into the most innovative approaches and progress in the field of data analysis and processing, highlighting how this part is essential for the proper extrapolation and interpretation of data.
Determination of substituent effects on the proton affinities of natural nucleosides by the kinetic method
Authors: Liguori Angelo , Napoli Anna , Sindona Giovanni
Published: January 2021

The kinetics of the unimolecular dissociations of proton‐bound dimers produced by fast‐atom bombardment from nucleosides and reference amines enables the evaluation of the proton affinities (PAs) of ribonucleosides. The PAs of cytosine, guanosine, adenosine, uridine, and deoxyuridine have been thus determined. These values and those already available for the corresponding DNA homologues allow the evaluation of the effect of the hydroxyl group in position 2′ of the sugar moiety, which lowers the PAs of RNA nucleosides by 0.6–1 kcal/mol, and of the methyl group in position 5 of the thymine ring, which enhances the basicity of deoxythymidine over deoxyuridine by 0.6 kcal/mol.
SARS‐CoV‐2 RNA detection in stool samples from acute gastroenteritis cases, Brazil
Authors: Fumian Tulio M. , Malta Fábio C. , dos Santos Débora R. L. , Pauvolid‐Corrêa Alex , Fialho Alexandre M. , Leite José P. G. , Miagostovich Marize P.
Published: January 2021

We described the detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in stool samples from patients presenting only acute gastroenteritis (AGE) symptoms. From January to July 2020, 121 AGE stool samples were screened by quantitative reverse‐transcription polymerase chain reaction. We detected SARS‐CoV‐2 in 27.5% of samples received during the epidemic period. No infectious viruses were observed in Vero E6 cells.
It matters how old we feel in organizations: Testing a multilevel model of organizational subjective‐age diversity on employee outcomes
Authors: Kunze Florian , Boehm Stephan A. , Bruch Heike
Published: January 2021

This study contributes to the emerging literature on age diversity effects at the organizational level of analysis by comparing the role of chronological‐age diversity versus subjective‐age diversity. We hypothesize a multilevel model in which organizational‐level subjective‐age diversity is negatively related to bonding social capital within organizations, which, in turn, contributes to heightened employee engagement and lowered turnover intentions. The assumed relationships are tested in a multilevel sample of 96 German small‐ and medium‐sized companies with 16,274 employees participating. We gathered data from four different sources to circumvent common source problems and received support for most of the proposed relationships. Given the potentially detrimental effects of high subjective‐age diversity in the workplace, the paper concludes with practical recommendations on how to manage subjective‐age diversity in companies proactively.
Nitrospira as versatile nitrifiers: Taxonomy, ecophysiology, genome characteristics, growth, and metabolic diversity
Authors: Vijayan Ardhra , Vattiringal Jayadradhan Rejish Kumar , Pillai Devika , Prasannan Geetha Preena , Joseph Valsamma , Isaac Sarojini Bright Singh
Published: January 2021

The global nitrogen cycle is of paramount significance as it affects important processes like primary productivity and decomposition. Nitrification, the oxidation of ammonia to nitrate via nitrite, is a key process in the nitrogen cycle. The knowledge about nitrification has been challenged during the last few decades with inventions like anaerobic ammonia oxidation, ammonia‐oxidizing archaea, and recently the complete ammonia oxidation (comammox). The discovery of comammox Nitrospira has made a paradigm shift in nitrification, before which it was considered as a two‐step process, mediated by chemolithoautotrophic ammonia oxidizers and nitrite oxidizers. The genome of comammox Nitrospira equipped with molecular machineries for both ammonia and nitrite oxidation. The genus Nitrospira is ubiquitous, comes under phylum Nitrospirae, which comprises six sublineages consisting of canonical nitrite oxidizers and comammox. The single‐step nitrification is energetically more feasible; furthermore, the existence of diverse metabolic pathways in Nitrospira is critical for its establishment in various habitats. The present review discusses the taxonomy, ecophysiology, isolation, identification, growth, and metabolic diversity of the genus Nitrospira; compares the genomes of canonical nitrite‐oxidizing Nitrospira and comammox Nitrospira, and analyses the differences of Nitrospira with other nitrifying bacteria.
Principal component analysis of the biological characteristics of entomopathogenic fungi in nutrient‐limited and cuticle‐based media
Authors: Montesinos‐Matías Roberto , Ordaz‐Hernández Armando , Angel‐Cuapio Alejandro , Colin‐Bonifacio Yazmin , Garcia‐Garcia Rosa E. , Ángel‐Sahagún Cesar A. , Arredondo‐Bernal Hugo C.
Published: January 2021

Media formulated with insect cuticle (0.5% and 1%; Sphequit Sph®), with a reduction in nutrients (¼ Sabouraud dextrose agar + yeast [SDAY]) and commercial media (potato dextrose agar, Sabouraud dextrose agar) were evaluated for the cultivation of Beauveria bassiana, Cordyceps javanica (Isaria javanica [Bally] Samson & Hywel‐Jones), and Metarhizium robertsii. By using principal component analysis, it was determined that the ¼ SDAY and Sph formulations have greater advantages than commercial media for the development of fungi. The ¼ SDAY and Sph (0.5% and 1%) improved hydrophobicity, radial growth rate, germination, conidia yield, and virulence in B. bassiana; in M. robertsii, they favored conidia yield, germination, and virulence, and in C. javanica, the ¼ SDAY and Sph 0.5% media enhanced conidia yield, germination, radial growth rate, and virulence. We suggest that these formulations are an alternative to commercial culture media as they are cheaper and appropriate to improve the growth characteristics and virulence of the three strains evaluated. Some applications of culture media are suggested, and the importance of multivariate analysis as an exploratory tool to carry out the choice of culture media in a suitable way for the development of mycoinsecticides is also discussed.