bluuebunny/crossref_metadata_2025 huggingface dataset:
A standardised pre-clinical in-vitro blood-brain barrier mouse assay validates endocytosis dependent antibody transcytosis using transferrin receptor-mediated pathways
Authors: Morrison Jamie I. , Petrovic Alex , Metzendorf Nicole G. , Rofo Fadi , Yilmaz Canan U. , Stenler Sofia , Laudon Hanna , Hultqvist Greta
Published: April 2022

The presence of the blood brain barrier (BBB) creates a nigh on impenetrable obstacle for large macromolecular therapeutics that need to be delivered to the brain milieu to treat neurological disorders. To overcome this, one of the strategies used is to bypass the barrier with what is referred to as a “Trojan Horse” strategy, where therapeutics are designed to use endogenous receptor-mediated pathways to piggyback their way through the BBB. Even though in vivo methodologies are commonly used to test the efficacy of BBB penetrating biologics, comparable in vitro BBB models are in high demand, as they benefit from being an isolated cellular system devoid of physiological factors that can on occasion mask the processes behind BBB transport via transcytosis. We have developed an in vitro BBB model (In-Cell BBB-Trans assay) that helps delineate the ability of modified large bivalent IgG antibodies, conjugated to the transferrin-receptor binder scFv8D3, to cross an endothelial monolayer grown on transwell inserts. Following the administrating of bivalent antibodies to the endothelial monolayer, a highly sensitive ELISA method is used to determine the concentration in the apical (blood) and basolateral (brain) chambers of the transwell system, allowing for the evaluation of apical recycling and basolateral transcytosis respectively. Our results show that antibodies conjugated to scFv8D3 transcytose at considerably higher levels compared to unconjugated antibodies in the In-Cell BBB-Trans assay. Interestingly, we are able to show that these results mimic in vivo brain uptake studies using identical antibodies. In addition, we are able to transversely section transwell cultured cells, allowing for the identification of biomarkers pertinent to transcytosis of the antibodies. Furthermore, studies using the In-Cell BBB-Trans assay revealed transcytosis of the transferrin-receptor targeting antibodies is dependent on endocytosis. In conclusion, we have designed a simple, reproducible In-Cell BBB-Trans assay that can be used to rapidly determine the BBB penetrating capabilities of transferrin-receptor targeting antibodies. We believe the In-Cell BBB-Trans assay can be used as a powerful, pre-clinical screening platform for therapeutic neurological pathologies.
Post-stroke respiratory complications using machine learning with voice features from mobile devices
Authors: Park Hae-Yeon , Park DoGyeom , Kang Hye Seon , Kim HyunBum , Lee Seungchul , Im Sun
Published: April 2022

Background Abnormal voice may identify those at risk of post-stroke aspiration. This study was aimed to determine whether machine learning algorithms with voice recorded via a mobile device can accurately classify those at risk of tube feeding and post-stroke aspiration pneumonia and be used as digital biomarkers. Methods Voice samples from patients referred for swallowing disturbance in a university-affiliated hospital were collected prospectively using a mobile device. Subjects that required tube feeding were further classified to high risk of respiratory complication, based on the voluntary cough strength and abnormal chest x-ray images.Results A total of 449 samples were obtained, with 234 requiring tube feeding and 113 showing high risk of respiratory complications. The eXtreme gradient boosting multimodal models that included abnormal acoustic features and clinical variables showed high sensitivity levels of 88.7% (95% CI, 82.6–94.7) and 84.5% (95% CI, 76.9–92.1) in the classification of those at risk of tube feeding and at high risk of respiratory complications; respectively. In both cases, voice features proved to be the strongest contributing factors in these models.Conclusions Voice features may be considered as a viable digital biomarker in those at risk of respiratory complications related to post-stroke swallowing disturbance.
The effects of opioid policy changes on transitions from prescription opioids to heroin, fentanyl and injection drug use: A qualitative analysis
Authors: Dickson-Gomez Julia , Krechel Sarah , Spector Antoinette , Weeks Margaret , Ohlrich Jessica , Green Danielle , Li Jianghong
Published: April 2022

Background: Beginning in the 1990s, non-medical use of prescription opioids (POs) became a major public health crisis. In response to rising rates of opioid dependence and fatal poisonings, measures were instituted to decrease the prescription, diversion, and misuse of POs including prescription drug monitoring programs (PDMPs), closing “pill mills” (unethical doctors or clinics that knowingly dispensed large amounts of pain medications knowing these medications were being misused and diverted) , disciplining doctors who prescribed an excessive number of POs, and the advent of abuse deterrent formulations of POs. Methods: We conducted in-depth-interviews with people who use prescription opioids, fentanyl or heroin from a rural, urban and suburban area in three states, Connecticut, Kentucky and Wisconsin. Interviews with PWUO focused on how they initiated their opioid use and any transitions they made from prescription opioid use to heroin, fentanyl or injection drug use. Results: The majority of participants reported initiating use with prescription opioids, which they used for medical or nonmedical purposes. They described needing to take more POs or switched to heroin or fentanyl increased. As more policies were passed to limit opioid prescription, participants noticed that doctors were less likely to prescribe or refill prescription opioids. This led to scarcity of POs on the street which accelerated the switch to heroin or fentanyl. These transitions increased risk of overdose and HIV/HCV infection.Conclusions: A careful analysis of how and why people say they transitioned from PO to heroin or fentanyl reveals many unintended harms of policy changes to prevent overprescribing and diversion. They also reveal ways we can mitigate harms that have already occurred and treat people who use opioids with compassion and respect, not stigma and punishment.
A medullary hub for controlling REM sleep and pontine waves
Authors: Schott Amanda , Baik Justin , Chung Shinjae , Weber Franz
Published: April 2022

Rapid-eye-movement (REM) sleep is a distinct behavioral state associated with vivid dreaming and memory processing. Phasic bursts of electrical activity, measurable as spike-like pontine (P)-waves, are a hallmark of REM sleep implicated in memory consolidation. However, the brainstem circuits regulating P-waves, and their interactions with circuits generating REM sleep, remain largely unknown. Here, we show that an excitatory population of dorsomedial medulla (dmM) neurons expressing corticotropin-releasing-hormone (CRH) regulates both REM sleep and P-waves. Calcium imaging showed that dmM CRH neurons are selectively activated during REM sleep and recruited during P-waves, and opto- and chemogenetic experiments revealed that this population promotes REM sleep. Chemogenetic manipulation also induced prolonged changes in P-wave frequency, while brief optogenetic activation reliably triggered P-waves along with transiently accelerated theta oscillations in the electroencephalogram (EEG). Together, these findings anatomically and functionally delineate a common medullary hub for the regulation of both REM sleep and P-waves.
Suicide attempt-related emergency department visits among adolescents: a nationwide population-based study in Korea, 2016–2019
Authors: Lee Kyung-Shin , Lim Daesung , Paik Jong-Woo , Choi Youn Young , Jeon Jaehyun , Sung Ho Kyung
Published: April 2022

BackgroundThe incidence of adolescent suicide in Korea is increasing; however, nationwide data regarding short-term prediction of suicide attempts (SAs) is still limited. Therefore, this study aimed to investigate the incidence of SA-related annual emergency department (ED) visits among adolescents in Korea from 2016 to 2019 and to summarize the corresponding demographic and clinical characteristics based on the dispositions of SA-related ED visits.MethodsMost referral hospitals provide relevant essential ED information to the National Emergency Medical Center through the National Emergency Department Information System (NEDIS). We analyzed NEDIS data on adolescent visits (aged <20 years) for a 4-year period from 2016 to 2019. Patients were classified into the discharge and hospitalization groups for comparison, and jointpoint regression analysis was used to identify the years in which there was a change in annual percentage change (APC) in age- and sex-standardized incidence rates of SA-related ED visits. The characteristics of patients in the discharge group and hospitalization group subgroups were also compared.ResultsThe APC in the incidence rate of SA-related ED visits in the 4-year study period revealed a 35.61% increase. The incidence rate increase was higher among females (APC: 46.26%) than among males (APC: 17.95%). Moreover, the incidence rate increased faster in mid-adolescence patients (APC: 51.12%) than in late-adolescence patients (APC: 26.98%). The proportion of poisoning as the SA method was 69.7% in the hospitalization group and 34.5% in the discharge group (p < 0.001).DiscussionOur findings suggest that an increase in the number of SA-related ED visits among female and mid-adolescent patients represented the largest increase in SA-related ED visits from 2016 to 2019. Accordingly, evidence-based suicide prevention programs need to be customized based on sex and age, and further diversification of health care systems is needed through analysis of the characteristics of the dispositions of SA-related ED visits.
Larvicidal property of the extracts of the seaweeds; Sargassum wightii, S. ilicifolium and Gelidiella acerosa vis-a-vis Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus
Authors: Perumal Pachiappan , Dhanasundaram Sundaramoorthy , Aravinth Annamalai , Amutha Vadivel , Santhanam Perumal
Published: April 2022

Toxicity potential of the 3-solvent extracts of Sargassum wightii, S. ilicifolium and Gelidiella acerosa – seaweeds against the 4th larval-stage of 3 mosquitos was evaluated. The ethyl acetate extracts of the brown seaweeds (S. wightii & S. ilicifolium) and the red seaweed (G. acerosa) exerted the highest larvicidal effect. The S. wightii-ethyl acetate extract (SW-EA) exerted the huge death-rates of Anopheles stephensi with the lethal concentrations of (μg/mL);3.98 - LC50 and 12.17- LC90 followed by 4.43 & 24.44 on Culex quinquefasciatus and 9.26 & 52.00 on Aedes aegypti, respectively. The S. ilicifolium - ethyl acetate (SI-EA) caused the deaths of Anopheles stephensi with the lethal (LC-50&LC-90) doses (μg/mL) of; 18.934 & 371.753, followed by 34.104 & 423.012 on Aedes aegypti, and 40.728 & 683.813 on Culex quinquefasciatus respectively. Corresponding values for the G. acerosa-ethyl acetate-extract (GA-EA) (that caused maximum death-toll of Anopheles stephensi were); 4.59& 15.91, followed by 14.18& 78.77 on Culex quinquefasciatus and 23.261& 354.903 for Aedes aegypti. The algal-analyses showed the common phytochemical - constituents, aliphatic amines, alkynes and alkenes - groups and predominantly the Phytol acetate, OCTADECANOIC ACID and n-Hexadecanoic acid. The generated data form important basis for further investigation towards antimalarial drug development.
Independently Tunable Triple Fano Resonances in Plasmonic Waveguide Structure and Its Applications for Sensing
Authors: Wu Qiaohua , Zhang Yingqiu , Qu Desheng , Li Chunlei
Published: April 2022

A surface plasmon polaritons (SPPs) waveguide structure composed of a metal-insulator-metal (MIM) waveguide with a baffle, a special square cavity (SSC) and a ring cavity (RC), is proposed to realize independent tuning of triple Fano resonances. Using the finite element method (FEM), the magnetic field distributions and optical transmission spectra of the structure are analyzed in detail. The simulation results show that the structure achieves triple Fano resonances originated from two different mechanics. One of Fano resonances occurs in the RC, and the others occur in SSC. By regulating the structural parameters of the SSC and RC, respectively, these Fano resonances can be well tuned independently, which provides flexibility for the structure to be applied to optical devices. In addition, the structure exhibits great performances in refractive index sensing and bio-sensing. The maximum sensitivity of refractive index sensing achieves 2350 nm/RIU, and there is a good linear relationship between resonance wavelength and refractive index. Due to great sensitivity and independent tunability, the SPPs waveguide structure may be potentially used in micro-nano optical devices, especially in optical on-chip sensor.
Bubbles as a feeding predictor improves the welfare of farmed fish
Authors: Kleiber Aude , Le-Calvez Jean-Michel , Kerneis Thierry , Batard Axel , Goardon Lionel , Labbé Laurent , Brunet Valentin , Ferreira Vitor Hugo Bessa , Guesdon Vanessa , Calandreau Ludovic , Colson Violaine
Published: April 2022

Occupational enrichment emerges as a promising strategy for improving the welfare of farmed animals. This form of enrichment aims to stimulate cognitive abilities of animals by providing them with more opportunities to interact with and control their environment. Predictability (i.e., having information about the regularity of salient daily events), and in particular predictability of feeding, is currently one of the most studied occupational enrichment strategies and can take several forms. In fish, while temporal predictability (based on the time of day) of feeding has been widely investigated, signalled predictability (based on a signal, such as light or sound) has received little attention. Depending on the type of predictability used and the ecology of the species, the effects on fish welfare often differ. The present study aimed to determine which feeding predictability would be most appropriate for rainbow trout, the main continental farmed fish in Europe, and what the consequences might be for their welfare. We tested four feeding predictability conditions: temporal (based on time of day), signalled (based on bubble diffusion), temporal + signalled (based on time and bubble diffusion), and unpredictable (random feeding times). Behavioural and zootechnical outcomes recorded were swimming activity, aggressive and stereotypic behaviours, emotional reactivity, and growth. Our results showed that rainbow trout could predict daily feedings relying on time and/or bubbles as predictors as early as two weeks of conditioning. Temporal predictability alone resulted in an increase in pre-feeding aggressive and stereotypic behaviours, suggesting that the use of time as the sole predictor of feedings in husbandry practices may be detrimental to fish welfare. The combination of temporal and signalled predictability elicited the highest conditioned response and the level of pre-feeding aggression and stereotypy tended to be lower than for temporal predictability alone. Signalled predictability with bubbles alone resulted in fewer pre-feeding agonistic and stereotypic behaviours than in the temporal predictability condition. Interestingly, we also found that bubbles were highly attractive regardless of the condition considered. We conclude, therefore, that the use of bubbles as a feeding predictor could represent an interesting approach to improve rainbow trout welfare in farms, by acting as both an occupational and physical enrichment.
CuO-based materials for thermochemical CO2 capture cycles: The influence of the formation of a CuO percolation network on oxygen release and oxidation kinetics
Authors: Imtiaz Qasim , Armutlulu Andac , Donat Felix , Müller Christoph
Published: April 2022

Thermochemical CO2 capture cycles such as chemical looping combustion (CLC) are an economically promising CO2 capture technology that rely on the combustion of a hydrocarbon fuel with lattice oxygen that is derived from a solid oxygen carrier. The oxygen carrier is typically regenerated with air. To increase the agglomeration resistance and redox stability of the oxygen carriers, the active phase is often stabilized with high Tammann temperature ceramics, resulting in the formation of so-called cermet structures. It has been hypothesized that the redox performance of the cermets depends critically on the conduction pathways for solid-state ionic diffusion and the activation energy for charge transport. Here, we investigate the influence of the formation of a percolation network on the electrical conductivity and the rate of oxidation for CeO2-stabilized Cu. We found that for oxygen carriers that contained 60 wt. % CuO, the charge transport occurred predominately via Cu/CuO conduction pathways. Below the percolation threshold of CuO, the conduction of charge carriers took place via CeO2 grains, which formed a continuous network. The measurements of charge transport and redox characteristics confirmed that the activation energy for charge transport through the cermet increased with decreasing Cu content. This indicates that the solid-state diffusion of charge carriers plays an important role during re-oxidation.
An APPSO-SVM approach building the monitoring model of dam safety
Authors: WEN Zhiping , FAN Zhendong , SU Huaizhi
Published: April 2022

The measured data-based dam monitoring model could be used to analyze and predict the dam's operational behavior providing a scientific basis for risk assessment and decision-making of dam management. The traditional dam safety monitoring models established by multiple regression, stepwise regression, time series, gray theory, and other statistical methods have poor robustness and generalization. For this reason, an optimized support vector machine (SVM) whose novelty lies in simple execution procedure, self-adaptive hyperparameter selection from adaptive position particle swarm optimization (APPSO), user-friendly implementation and retention of influence factor combination, is presented for constructing the dam safety monitoring model.
Vibrational and fluorescence spectroscopy mapping structural rearrangement in edible Samia ricini (Eri) pupae proteins during ultrasound assisted extraction and their in-depth proteome profiling
Authors: Sarkar Preeti , Haokip Nemnunhoi , Mahanta Charu Lata , Duary Raj Kumar
Published: April 2022

The present study initially investigated the optimum conditions for maximum protein separation from edible Eri pupae using 150-400W ultrasound power within 5–30 min having a protein yield of > 50% for establishing any significant conformational and physico-chemical alterations. Results showed that 5 min of ultrasonic treatment was feasible to improve extraction yield with increasing power value, best of 250-300W with 20 min treatment. Ultrasound assisted extracted protein at 67.5, 71.4 and 76.4 J mL− 1 exhibited maximum secondary structural changes with an increase in varied disorganized structures. The temperature factor was more evident above 75°C, causing significant shifts in a Fourier transform infrared (FTIR) region of 1620–1642 cm− 1, particularly with a deviation of intermolecular β-sheets. The Raman band intensity pattern at 2929 and 1440–1465 cm− 1 was highest in sonicated treatment at 67.5 J mL− 1 and then significantly declined. Thus, indicating cross-linkage due to the formation of new unstable intermolecular S-S bond in samples treated at 71.4 and 76.4 J mL− 1, which explains the polarity of the microenvironment nearby hydrogen bonds, consistent with particle size and thermal characterization data. The peaks at 2014, 2168, and 2420 cm− 1 gradually disappeared with increased in ultrasonic energy input, probably depicting the development of firm 3-D network-like structures. Around 107 distinct proteins in Eri pupae assigned to 26 insect protein families were deduced via MS/MS investigation of pellet and supernatant. The outcomes will later facilitate in identifying the protein-protein interrelations accountable for functional aspects of product developed with Eri pupae protein isolate.
Geophysical and anthropogenic drivers for global and regional fire emission trends from 2001 to 2019
Authors: Wu Sifeng , Smith Stuart William , Lee Janice Ser Huay
Published: April 2022

Fire plays an important role in the earth system. Carbon emissions from fires affect the global carbon budget and consequently climate change. Biome-specific qualities such as vegetation, climate and human land-use change are altering long-term trends in carbon emissions from fires. Whilst some biomes and continents seem to witness increasing fire-derived carbon emissions, others see decreasing trends. Yet, currently a biome-wide perspective on fire-derived carbon emission trends is lacking. We used total carbon emissions from the Global Fire Emissions Database (version 4 with small fires) to investigate the spatial and temporal dynamics of fire emissions from 2001 to 2019 across the world. While the global trend for fire emissions stayed relatively unchanged (non-significant trend), this was due to contrasting trends in two geographical biomes. Specifically, a decreasing trend in tropical savannas and grasslands, notably across the African continent and an increasing trend in boreal forests, especially a dense cluster in the east Siberian taiga in Boreal Asia. The decrease in emissions in African savannas and grasslands was driven by a decline in vegetation, and thus fuel, and an increase in anthropogenic intervention, especially agricultural expansion. Increase in fire emissions from boreal forests in Boreal Asia was driven by agricultural activities and climate change towards a drier climate (e.g., lower humidity). For many biomes, fire-derived carbon emissions are driven by several anthropogenic activities, vegetation and climate drivers, likely due to the complex feedback governing emissions. This global and biome-wide study highlights that anthropogenic activities in relatively small regions can shape global fire-derived carbon emission trends. Monitoring and management interventions are needed to address increasing fire-derived carbon emission areas, particularly the east Siberian taiga, and other forested biomes where deforestation contributes to rising carbon emission trends.
CFTR, one membrane protein, inhibits proliferation and metastasis of hepatocellular carcinoma through new pathways
Authors: Xu Yijia , Yang Liying , Zhang Mengying , Sun Jianfang , Wen Ruojin , Liu Xin , Lv Kaikai , Wang Qi , Zhao Shangfeng , Teng Ying , Qiu Yingxin , Su Yang , Liu Yanfeng , Zhang Jinghai , Zhao Mingyi
Published: April 2022

Background: CFTR, a chloride channel protein expressed on cell membrane, plays an important role in the transdermal transport of salt and the regulation of intracellular ion concentration, and may be closely related to the occurrence and development of cancer. Methods: In this study, the expression level of CFTR in hepatocellular carcinoma (HCC) and its correlation with metastasis and prognosis were predicted by TGCA, GEPIA and GTEx databases. By constructing MHCC97H with stable overexpression of CFTR and HepG2 with stable interference expression of CFTR cell lines, the expression level of CFTR and its correlation with proliferation and metastasis of HCC cells were preliminarily verified by Western Blot, MTT, Transwell and PI staining. In order to further clarify the potential related mechanism, it was predicted through String and Genecards databases, and the expression level of related proteins was verified by Western Blot. And it was further verified by orthotopic HCC transplanted tumor models combined with in vivo imaging system, western blot and immunohistochemical. Finally, CLUE Command database and autodock was used to predict the potential anti-HCC drugs targeting CFTR.Results: The results showed that the expression of CFTR was significantly lower in human HCC tissues (predicted by clinical data) and HCC cells (HepG2, MHCC97L, MHCC97H), and the expression level was negatively correlated with clinical stage, prognosis (predicted by clinical data) and metastatic potency of HCC cells. CFTR could regulate the metastasis and proliferation of HCC by regulating the expression of MMP2, MMP9, E-cadherin, N-cadherin, and CyclinB1 proteins in vitro and in vivo. CFTR could regulate the expression of HSP90, TERT, and DNAJC6, which meant that HSP90, TERT, and DNAJC6 might build a bridge for CFTR to regulate proliferation and metastasis proteins. Parecoxib might be one potential anti-HCC drug by targeting CFTR.Conclusions: The above studies further clarify a potential new mechanism of HCC occurrence and metastasis, and provide potential new targets and treatment schemes for the diagnosis and treatment of HCC.
Effects of thiostrepton alone or in combination with selumetinib on triple-negative breast cancer metastasis
Authors: KORKMAZ FUNDA DEMIRTAS , Turacli Irem Dogan , ESENDAGLI Guldal , EKMEKCİ Abdullah
Published: April 2022

Objective FoxM1 transcription factor contributes to tumor metastasis and poor prognosis in many cancers including triple-negative breast cancer (TNBC). In this study, we examined the effects of FoxM1 inhibitor Thiostrepton (THIO) alone or in combination with MEK inhibitor Selumetinib (SEL) on metastatic parameters in vitro and in vivo.Methods Cell viability was determined by MTT assay. Immunoblotting and immunohistochemistry was used to assess metastasis-related protein expressions in 4T1 cells and its allograft tumor model in Balb/C mice. In vivo uPA activity was determined by enzymatic methods.Results Both inhibitors were effective on the expressions of FoxM1, ERK, p-ERK, Twist, E-cadherin, and Vimentin alone or in combination in vitro. THIO significantly decreased 4T1 cell migration and changed the cell morphology from mesenchymal-like to epithelial-like structure. THIO was more effective than in combination with SEL in terms of metastatic protein expressions in vivo. THIO alone significantly inhibited mean tumor growth, decreased lung metastasis rate and tumor foci, however, no significant changes in these parameters were observed in the combined group. Immunohistochemically, FoxM1 expression intensity was decreased with THIO and its combination with SEL in the tumors.Conclusion This study suggests that inhibiting FoxM1 as a single target is more effective than combined treatment with MEK in that TNBC allograft model, and targeting FoxM1 via THIO may provide therapeutic benefits in the subset of TNBC tumors with high metastatic capacity.
Explaining the factors affecting women's Life during covid 19: A Qualitative Study among Women in Southern Iran
Authors: Shahabi Nahid , Hosseini Zahra , Homayuni Atefeh , Rad Roghayeh Ezati , Gharibzadeh Abdollah
Published: April 2022

BackgroundThe long-term impact of covid-19 on women's health can cause serious damage to the family and society. In addition to the fear of disease and death, Corona has raised other concerns for women. The present study aims to explain the lockdown experiences among southern Iranian women during Covid-19 pandemic.MethodsIn this qualitative study, which was conducted from November 2020 to March 2021, 20 women who referred to Bandar Abbas health centers were included in the study based on purposive sampling with maximum variation (in terms of age, educational status, marital status, employment). In-depth individual interviews were continued until data saturation, the data were analyzed through conventional content analysis and constant comparison by MAXQDA10 software. ResultsSeven major categories were extracted. they included family-social relations, occupational challenges, financial challenges, leisure time, access to services, psychological reactions, and physical problems. ConclusionThe results showed that lockdown in Covid-19 had a range of positive to negative affecting on women's life. learning new lifestyles and how to live under threat can help manage the negative effects of lockdown.
Crocin Inhibit the Metastasis of MDA-MB-231 cell line by Suppressing Epithelial to Mesenchymal Transition through WNT/β-catenin Signaling Pathway
Authors: Dariushnejad Hassan , ALJAF Karwan Anwar Hassan , Wasman Hunar Mustafa , Pirzeh Lale , Ghorbanzadeh Vajihe
Published: April 2022

Breast cancer is divided into different subtypes based on molecular characteristics, among these subtypes, Triple-negative breast cancer, has the poorest prognosis and survival with invasive. In this study, TNBC cell line was used to explore crocin anti-metastatic effect on the Wnt/β-catenin pathway. Cell proliferation assessed by MTT assay and effects of crocin on migration monitored by transwell and wound healing experiments. Expression of certain epithelial-mesenchymal transition (EMT) markers genes was evaluated by real-time PCR. β-catenin expression also examined by real-time PCR. Findings revealed crocin significantly inhibits cell proliferation and migration of tumor cells in a dose-dependent manner. Moreover, crocin decreased the expression of Vimentin, Snail, Zeb-1 and β-catenin. Also, crocin increased the expression of E-cadherin in MDA-MB-231 cell line. Results showed an association between crocin and Wnt/β-catenin signaling pathway. In conclusion, this study establishes that crocin can be a promising therapeutic for triple-negative breast cancer.
Association of xenobiotic-metabolizing genes polymorphisms with cervical cancer risk in the Tunisian population
Authors: helaoui ahlem , Sfar Sana , Boudhiba Najet , Dehghanian Fariba , Dehbashi Moein , Bouchahda Haifa , Hojati Zohra , KENANI Abderraouf
Published: April 2022

Background: Host genetic characteristics and environmental factors interactions may play a crucial role in cervical carcinogenesis. We investigated the impact of functional genetic variants of four xenobiotic-metabolizing genes (AhR, CYP1A1, GSTM1, and GSTT1) on cervical cancer development in Tunisian women. Methods: The AhR gene polymorphism was analyzed using the tetra-primer ARMS-PCR, whereas the CYP1A1 polymorphism genotypes were identified by PCR-RFLP. A multiplex ligation-dependent polymerase chain reaction approach was applied for the analysis of GSTM1 and GSTT1 polymorphisms. Results: The homozygous A/A genotype of the AhR gene (rs2066853) and the heterozygous T/C genotype of the CYP1A1 SNP (CYP1A1-MspI) appeared to be associated with an increased risk of cervical tumorigenesis (ORa = 2.81; ORa = 5.52, respectively). Furthermore, a significantly increased risk of cervical cancer was associated with the GSTT1 null genotype (ORa = 2.65). However, the null GSTM1 genotype showed any significant association with the risk of cervical cancer compared to the wild genotype (ORa = 1.18; p = 0.784). Considering the combined effect, we noted a significantly higher association with cancer risk for individuals with at least two high-risk genotypes of CYP1A1/GSTT1 (ORa = 4.2), individuals with at least two high-risk genotypes of CYP1A1/GSTT1/AhR (ORa = 11.3) and individuals with at least two high-risk genotypes of CYP1A1/GSTM1/GSTT1/AhR exploitation low-risk genotype as a reference. Conclusion: This study indicated that the single-gene contribution and the combined effect of xenobioticmetabolizing gene polymorphisms (AhR, CYP1A1-MspI, GSTM1, and GSTT1) may have a considerable association with increased cervical cancer risk.
Identification of molecular subtypes of chronic obstructive pulmonary disease by gene expression profiling
Authors: zhangpingan 张平安 , Gao Na , Li Xiaoning , Ji Guochao , Wu Jianjun
Published: April 2022

BackgroundChronic obstructive pulmonary disease (COPD) has become the fourth most lethal disease in the world and is expected to rise to the third most lethal disease in the world after 2030.COPD is complex and has clinical heterogeneity. However, identifying the subgroup characteristics of chronic obstructive pulmonary disease has become a challenge.ObjectivesThe ultimate goal of studying these different subgroups is to find patients with unique treatment goals and formulate targeted treatment plans to improve the prognosis of the disease and improve the quality of life of patients.MethodsWe obtained the relevant gene chip by searching the gene expression omnibus (GEO) database. According to the gene expression profile, 151patients with chronic obstructive pulmonary disease were divided into three subgroups, which showed different expression patterns. Therefore, we used weighted gene coexpression analysis (WGCNA) to identify the differences between different subgroups and identified five subgroup specific weighted gene coexpression analysis modules.ResultsThe characteristics of WGCNA module showed that subjects in subgroup I showed airway remodeling characteristics; Subjects in subgroup II showed metabolic activity; Subjects in subgroup III showed inflammatory characteristics.ConclusionsThis study obtained the clinical subgroup classification of chronic obstructive pulmonary disease through consensus clustering, and found that patients in different subgroups may have unique gene expression patterns, which can help researchers explore new treatment strategies for COPD according to the characteristics of clinical subgroups.
Effects of phosphorus fertiliser use redistribution on crop calorie production and equal availability
Authors: Ma Lin , Bai Zhaohai , Liu Ling , Kroeze Carolien , Maryna Strokal , Chen Xinping
Published: April 2022

There are large regional differences in the use of phosphorus (P) in global food production. Likewise, the access of people to food calories and exposure to water pollution differ largely among world regions. Redistribution of P use is needed to meet the planetary boundary (PB) and to improve P-related inequalities. We present a global redistribution of P according to four principles: responsibility, capability, equality and food security, and under strict and loose PB targets. These principles yield contrasting results for the geographical distribution of P fertiliser use, crop calorie production and equal availability. Redistributing P fertiliser use under PB without improvement of P management may pose a threat to global food security: 3–43% of the current global crop calorie production may be threatened. The impact is smaller under the loose PB targets and equality redistribution principle. There is a tradeoff between low crop calorie losses and equal availability for people to crop calories. Overall, the negative impacts on food security could remain limited but would likely be achieved at the cost of increased inequality in per capita food calorie distributions, which implies an increasing need for free international trading of agricultural products.
Prevalence of Tibia Valga Morphology in Valgus Knees and its Implications for Primary Total Knee Arthroplasty
Authors: Sobhi Salar , Khan Riaz J.K. , Fick Daniel P. , Finsterwald Michael A.
Published: April 2022

IntroductionTibia valga, an extra-articular valgus deformity of the tibia, is common in valgus knees and can result in component misplacement and early total knee arthroplasty (TKA) failure. However, the prevalence and importance of tibia valga in TKA has been seldom reported. This study aims to describe the prevalence and characteristics of tibia valga morphology in valgus knees and describes implications for surgical planning in primary TKA.MethodsWe prospectively examined pre-operative weightbearing whole-body EOS digital radiographs of patients with knee osteoarthritis listed for TKA between December 2018 and December 2020. Hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), joint line convergence angle (JLCA) and tibial morphology with centre of rotation of angulation of tibia (CORA-tibia) were measured and analysed.ResultsIn 830 knees, 253 (30%) and 577 (70%) were classified as valgus and varus respectively. In valgus knees, 89 knees (35%) had tibia valga. Median CORA-tibia was 2.8o (range 0.2-10.9o). Tibia valga knees had no difference in mLDFA, higher HKA (5.0o versus 3.0o, p=0.002) and mMPTA (89.6o versus 88.1o, p<0.01), and lower JLCA (2.1o versus 2.3o, p<0.01) compared to non-tibia valga knees. Tibia valga deformity was weakly positively correlated with valgus HKA (ρ=0.23, p<0.001) and mMPTA (ρ=0.38, p<0.001). In varus knees, there were 52 cases of tibia valga (9%) with median CORA-tibia of 3.0o (range 0.5-5.5o). Tibia valga knees had higher mMPTA (87.0o versus 85.2o, p<0.05) and no difference in HKA, mLDFA and JLCA. CORA-tibia was weakly positively correlated with mMPTA.ConclusionsTibia valga is common in valgus knees, occurring in 35% of this population. Extra-articular tibial rather than distal femoral anatomy contributes most to valgus HKA. To detect the deformity, full leg-length radiographs should be acquired pre-operatively. Intramedullary instrumentation should be used cautiously in knees with tibia valga when performing TKA.
The Impact of Incorporating Lactobacillus Acidophilus Bacteriocin with Inulin and FOS on Yogurt Quality
Authors: Hussien Heba , Abd-Rabou Hagar Saeed , Saad Marwa A.
Published: April 2022

This study determined the quality of yogurt fortified with 2% inulin, 2% Fructo-oligo-saccharides (FOS), and Lactobacillus acidophilus with their bacteriocins. The results indicated that coagulation time increased by 3.29–22.75% in yogurts prepared with Lactobacillus acidophilus and their bacteriocins compared to the control also titratable acidity increased gradually in all groups during storage. The sensorial properties showed the superiority of inulin, FOS, and Lactobacillus acidophilus bacteriocin groups. Lactobacillus bulgaricus, Streptococcus thermophiles, and Lactobacillus acidophilus count increased in the treatments compared to the control group incorporated with an extended shelf life to 39 days of storage in the treatments containing lactobacillus acidophilus bacteriocin. Coliforms, Moulds, and yeasts did not detect in the group containing 2% inulin, 2% FOS, and lactobacillus acidophilus bacteriocin for 21 days of refrigerated storage. This study proved that 2% inulin, 2% FOS, and Lactobacillus acidophilus bacteriocin fortification extended the shelf life for 6 weeks.
Fabrication of near-invisible solar cell with monolayer WS2
Authors: He Xing , Iwamoto Yuta , Kaneko Toshiro , Kato Toshiaki
Published: April 2022

Herein, we developed a near-invisible solar cell through a precise control of the contact barrier between an indium tin oxide (ITO) electrode and a monolayer tungsten disulfide (WS2), grown by chemical vapor deposition (CVD). The contact barrier between WS2 and ITO was controlled by coating various thin metals on top of ITO (Mx/ITO) and inserting a thin layer of WO3 between Mx/ITO and the monolayer WS2, which resulted in a drastic increase in the Schottky barrier height (up to 220 meV); this could increase the efficiency of the charge carrier separation in our Schottky-type solar cell. The power conversion efficiency (PCE) of the solar cell with the optimized electrode (WO3/Mx/ITO) was more than 1000 times that of a device using a normal ITO electrode. Large-scale fabrication of the solar cell was also investigated, which revealed that a simple size expansion with large WS2 crystals and parallel long electrodes could not improve the total power (PT) obtained from the complete device even with an increase in the device area; this can be explained by the percolation theory. This problem was addressed by reducing the aspect ratio (width/channel length) of the unit device structure to a value lower than a critical threshold. By repeating the experiments on this optimized unit device with an appropriate number of series and parallel connections, PT could be increased up to 420 pW from a 1-cm2 solar cell with a very high value (79 %) of average visible transmission (AVT).
A nomogram based on contrast-enhanced MRI and margin to identify lung metastasis in soft-tissue sarcoma
Authors: Hu Yue , Wang Xiaoyu , Yue Zhibin , Wang Hongbo , Wang Yan , Luo Yahong , Jiang Wenyan
Published: April 2022

Purpose
To develop a multi-modality MRI-based radiomics nomogram for predicting the lung metastasis (LM) in soft-tissue sarcoma (STS).
Methods
We enrolled 122 patients who clinicopathologically confirmed STS from our hospital to form a primary cohort. Thirty-two patients from another hospital were included as an external validation cohort. All patients underwent pretreatment T1-weighted contrast-enhanced (T1-CE) MRI scans. Radiomics features were calculated and selected from the T1-CE MRI sequence, and used to build the radiomics signature. Clinical factors were evaluated by the logistic regression. Multivariable logistic regression analysis was applied to construct a radiomics nomogram incorporating the radiomics signature with the important clinical factor. Receiver operating characteristic (ROC), calibration and decision curve analysis (DCA) curves were plotted to assess the radiomics methods.
Results
A total of 5 features were finally identified highly related to the LM status to develop the radiomics signature. A clinical-radiomics nomogram integrating the radiomics signature and margin achieved the best prediction performance in the training (AUCs, nomogram vs. radiomics signature vs. margin, 0.918 vs. 0.864 vs. 0.609), internal validation (AUCs, nomogram vs. radiomics signature vs. margin, 0.864 vs. 0.841 vs. 0.666) and external validation (AUCs, nomogram vs. radiomics signature vs. margin, 0.843 vs. 0.800 vs. 0.643) cohort. DCA indicated potential usefulness of the nomogram.
Conclusions
This study evaluated predictive values of T1-CE MRI for the prediction of lung metastasis in STSs, and proposed a nomogram model to potentially facilitate the preoperative individualized treatment decision making for STSs.
Differentiation of Gelsemium elegans-containing toxic honeys and non-toxic honeys by near infrared spectroscopy combine with aquaphotomics
Authors: Su Yuancui , Yang Chuanmei , Tan Chengsen , Li Yuanpeng , Tu Shan , Zhu Siqi , Wang Yongmei , Wang Lihu , Hu Junhui , Mo Yuxiang , Zhao Hongxia , Huang Furong
Published: April 2022

This work proposes a fast and accurate method based on near-infrared (NIR) spectroscopy with partial least-squares discriminant analysis (PLS-DA) and aquaphotomics to identify toxic honeys. PLS-DA was used to construct an optimal model for distinguishing toxic honey from non-toxic honey. The models based on preprocessed NIR spectra have an accuracy of 92.73% and were more accurate than the model based on raw NIR spectra. Based on the aquaphotomics analysis of the first overtone of water (1300–1600 nm), we found that the 1398 nm, 1440 nm, and 1472 nm bands can be used as markers to distinguish toxic honeys. Compared to non-toxic honeys, G. elegans-containing toxic honeys have a significantly smaller number of water molecules with multiple hydrogen bonds, due to the hydrogen bonding of the C-O-C, C = O, and NH2 groups of gelsemine and koumine. These groups replace hydrogen bonds between glucose/polysaccharide molecules and water.
Prevalence and factors associated with possible cases of familial hypercholesterolemia in Brazilian adults: a cross-sectional study
Authors: de Sá Ana Carolina Micheletti Gomide Nogueira , Gomes Crizian Saar , Prates Elton Junio Sady , Brant Luisa Campos Caldeira , Malta Deborah Carvalho
Published: April 2022

This study aimed to estimate the prevalence of possible cases of FH and analyze associated factors in the adult Brazilian population. Cross-sectional study with laboratory data from the Brazilian National Health Survey, with 8,521 participants. Possible cases of FH were defined according to the Dutch Lipid Clinic Network criteria. The prevalence and 95% confidence intervals (95%CI) of possible cases of FH were estimated according to sociodemographic variables, lifestyle, diabetes, hypertension, altered tests, treatment and self-rated health. Logistic regression was used to analyze the associations. The prevalence of possible cases of FH was 0.96%, higher in women, between 45 and 59 years, white race/skin color and others, less education, people with diabetes, hypertension and total cholesterol ≥ 310 mg/dL. The presence of FH was positively associated with regular self-rated health (OR 1.96; 95%CI 0.99–3.84), poor/very poor (OR 3.02; 95%CI 1.30–7.03) and negatively with black race/skin color (OR 0.10; 95%CI 0.02–0.46) and complete elementary school, incomplete high school (OR 0.47; 95%CI 0.23–0.98) and complete high school and more (OR 0.45; 95%CI 0.21–0.95). FH affects 1:104 Brazilian adults, these findings contribute to mitigate the burden of disease. Due to the scarcity of studies on FH in low- and middle-income countries, further studies are desirable.
Genome Sequencing-Based Evolutionary Prediction of Glycan-Adhering Lectins and Experimental Evaluation of a Lectin (FimH) Inhibitor Using an Enterohemorrhagic Escherichia coli Strain Isolated in Korea
Authors: Park Junyoung , Kim Cheorl-Ho , Cho Seung-Hak
Published: April 2022

We analyzed the evolutionary characteristics of the predicted lectin-like adhesins to construct a lectin-glycan interaction network (LGI). A total of 20,603 assembled Esherichia. coli sequences were retrieved from NCBI, including 2,240 strains with Shiga toxin in their genome. A strain isolated from a Korean patient with diarrhea, EHEC NCCP14539, was also sequenced. The outer-membrane embedded proteins which could be adhesins were predicted from the annotated genes of E. coli strains. In addition, we performed a phylogenetic analysis using the fimH gene, a well-known adhesin of enterohemorrhagic E. coli (EHEC). Multiple sequence alignment of the 2,204 E. coli strains yielded an evolutionary tree. Multi-locus sequence typing-based phylogenetic analysis revealed that NCCP14539 is the ancestor of 70 EHEC strains. An experiment was conducted to find an FimH inhibitor using NCCP14539 strain. Using a T7 phage display method, FimH was selected as an adherent lectin from the GM1- and Gb3- attached lectins. Through simulation docking, we then confirmed that Gb3 has a stronger binding ability to FimH and inferred the binding site sequence. Thus, our results provide evidence that Gb3-derived peptides can act as novel agents to block FimH binding and prevent infection by EHEC.