bluuebunny/crossref_metadata_2025 huggingface dataset:
Sildenafil-evoked photoreceptor oxidative stress in vivo is unrelated to impaired visual performance in mice
Authors: Berkowitz Bruce A. , Podolsky Robert H. , Lins Childers Karen , Saadane Aicha , Kern Timothy S. , Roberts Robin , Olds Hailey , Joy Joydip , Richards Collin , Rosales Tilman , Schneider Michael , Schilling Brennan , Orchanian Arthur , Graffice Emma , Sinan Kenan , Qian Haohua , Harp Lamis
Published: March 2021

Purpose

The phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision.

Methods

In dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking.

Results

In light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil.

Conclusions

The sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.
In vitro study of Hesperetin and Hesperidin as inhibitors of zika and chikungunya virus proteases
Authors: Eberle Raphael J. , Olivier Danilo S. , Pacca Carolina C. , Avilla Clarita M. S. , Nogueira Mauricio L. , Amaral Marcos S. , Willbold Dieter , Arni Raghuvir K. , Coronado Monika A.
Published: March 2021

The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genusAlphavirus), dengue virus (DENV, genusFlavivirus), and zika virus (ZIKV, genusFlavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3proof ZIKV and nsP2proof CHIKV and, Hesperidin (HSD) against nsP2proof CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50values are in low µM range for HST against ZIKV NS2B/NS3pro(12.6 ± 1.3 µM) and against CHIKV nsP2pro(2.5 ± 0.4 µM). The IC50for HSD against CHIKV nsP2prowas 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.
Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes
Authors: Grayson Korie A. , Jyotsana Nidhi , Ortiz-Otero Nerymar , King Michael R.
Published: March 2021

Three-dimensional spheroid cultures have been shown to better physiologically mimic the cell-cell and cell-matrix interactions that occur in solid tumors more than traditional 2D cell cultures. One challenge in spheroid production is forming and maintaining spheroids of uniform size. Here, we developed uniform, high-throughput, multicellular spheroids that self-assemble using microwell plates. DU145 and PC3 cells were cultured as 2D monolayers and 3D spheroids to compare sensitization of TRAIL-resistance cancer cells to TRAIL mediated apoptosis via chemotherapy based on dimensionality. Monocultured monolayers and spheroids were treated with soluble TRAIL alone (24 hr), DTX or CBZ alone (24 hr), or a combination of taxane and TRAIL (24 + 24 hr) to determine the effectiveness of taxanes as TRAIL sensitizers. Upon treatment with soluble TRAIL or taxanes solely, monolayer cells and spheroids exhibited no significant reduction in cell viability compared to the control, indicating that both cell lines are resistant to TRAIL and taxane alone in 2D and 3D. Pretreatment with CBZ or DTX followed by TRAIL synergistically amplified apoptosis in 2D and 3D DU145 cell cultures. PC3 spheroids were more resistant to the combination therapy, displaying a more additive effect in the DTX + TRAIL group compared to 2D. There was a downregulation of DR4/5 expression in spheroid form compared to monolayers in each cell line. Additionally, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were cocultured with both PCa cell lines as spheroids to determine if CAFs confer additional resistance to chemotherapy. We determined that co-cultured spheroids show similar drug resistance to monocultured spheroids when treated with taxane plus TRAIL treatment. Collectively, these findings suggest how the third dimension and cocultures of different cell types effect the sensitization of androgen-independent prostate cancer cells to TRAIL, suggesting therapeutic targets that could overcome TRAIL-resistance in metastatic castration-resistant prostate cancer (mCRPC).
Mechanical properties and progressive failure characteristics of sandstone containing elliptical and square openings subjected to biaxial stress
Authors: Zhao Honggang , Sun Haitao , Zhang Dongming , Liu Chao
Published: March 2021

Two kinds of common tunnel shapes, i.e. elliptical opening and square opening were selected for biaxial compression tests, and the influences of two kinds of opening shapes on the mechanical properties, failure characteristics and failure modes of sandstone were compared and analyzed. The complex variable theory and mapping functions were used to obtain the analytical stress solution around elliptical and square openings. The results show that the stability of the specimen containing an elliptical opening was better than that of the specimen containing a square opening under the same lateral stress. Compared with the elliptical opening, the local damage was formed earlier in the square opening which might be caused by a higher stress concentration around the square opening. The stress distributions around openings were influenced by the opening shape and lateral stress coefficient. The top and bottom of square opening were more prone to tensile fracture, and the distribution range of tensile was larger than that of elliptical opening. When the opening failed, the intensity of square opening failure was weaker than that of elliptical opening. On the basis of the average frequency value and the rise angle value, the failure mode of specimen containing elliptical or square opening was distinguished. It was found that the mixed tension and shear failure dominated the failure of specimens with different opening shapes, and the number of shear cracks in the specimen containing a square opening was greater than that in the specimen containing an elliptical opening. The above method of judging failure mode by acoustic emission signals was well verified by the CT images of damaged specimens.
The pronounced lung lesions developing in LATY136F knock-in mice mimic human IgG4-related lung disease
Authors: Waseda Yuko , Yamada Kazunori , Mizuguchi Keishi , Ito Kiyoaki , Watanabe Satoshi , Zuka Masahiko , Ishizuka Tamotsu , Malissen Marie , Malissen Bernard , Kawano Mitsuhiro , Matsui Shoko
Published: March 2021

Rationale

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by an elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. Pathological changes are most frequently seen in the pancreas, lacrimal glands, and salivary glands, but pathological changes in the lung also exist. Linker for activation of T cell (LAT)Y136F knock-in mice show Th2-dominant immunoreactions with elevated serum IgG1 levels, corresponding to human IgG4. We have reported that LATY136F knock-in mice display several characteristic features of IgG4-RD and concluded that they constitute an appropriate model of human IgG4-RD in salivary glands, pancreas, and kidney lesions.

Objectives

The aim of this study is to evaluate whether lung lesions in LATY136F knock-in mice can be a model of IgG4-related lung disease.

Methods

Lung tissue samples from LATY136F knock-in mice (LAT) and wild-type mice (WT) were immunostained for IgG1 and obtained for pathological evaluation, and cell fractions and cytokine levels in broncho-alveolar lavage fluid (BALF) were analyzed.

Results

In the LAT group, IgG1-positive inflammatory cells increased starting at 4 weeks of age and peaked at 10 weeks of age. The total cell count and percentage of lymphocytes increased significantly in BALF in the LAT group compared to the WT group. In BALF, Th2-dominant cytokines and transforming growth factor-β were also increased. In the LAT group, marked inflammation around broncho-vascular bundles peaked at 10 weeks of age. After 10 weeks, fibrosis around broncho-vascular bundles and bronchiectasis were observed in LATY136F knock-in mice but not WT mice.

Conclusions

LATY136F knock-in mice constitute an appropriate model of lung lesions in IgG4-RD.
Limited evidence for executive function load impairing selective copying in a win-stay lose-shift task
Authors: Dunstone Juliet , Atkinson Mark , Grainger Catherine , Renner Elizabeth , Caldwell Christine A.
Published: March 2021

The use of ‘explicitly metacognitive’ learning strategies has been proposed as an explanation for uniquely human capacities for cumulative culture. Such strategies are proposed to rely on explicit, system-2 cognitive processes, to enable advantageous selective copying. To investigate the plausibility of this theory, we investigated participants’ ability to make flexible learning decisions, and their metacognitive monitoring efficiency, under executive function (EF) load. Adult participants completed a simple win-stay lose-shift (WSLS) paradigm task, intended to model a situation where presented information can be used to inform response choice, by copying rewarded responses and avoiding those that are unrewarded. This was completed alongside a concurrent switching task. Participants were split into three conditions: those that needed to use a selective copying, WSLS strategy, those that should always copy observed information, and those that should always do the opposite (Expt 1). Participants also completed a metacognitive monitoring task alongside the concurrent switching task (Expt 2). Conditions demanding selective strategies were more challenging than those requiring the use of one rule consistently. In addition, consistently copying was less challenging than consistently avoiding observed stimuli. Differences between selectively copying and always copying were hypothesised to stem from working memory requirements rather than the concurrent EF load. No impact of EF load was found on participants’ metacognitive monitoring ability. These results suggest that copying decisions are underpinned by the use of executive functions even at a very basic level, and that selective copying strategies are more challenging than a combination of their component parts. We found minimal evidence that selective copying strategies relied on executive functions any more than consistent copying or deviation. However, task experience effects suggested that ceiling effects could have been masking differences between conditions which might be apparent in other contexts, such as when observed information must be retained in memory.
Independent predictors of acute kidney injury in patients with acute coronary syndrome after percutaneous coronary intervention
Authors: Zhunuspekova Aisulu , Mansurova Jamilya , Karazhanova Lyudmila
Published: March 2021

Introduction

High residual platelet reactivity (RPR) in patients after percutaneous coronary intervention (PCI) receiving antiplatelet agents has been associated with a high risk of developing acute kidney injury (AKI).

Study aim

This study aimed at identification of independent prognostic predictors of AKI risk in patients with acute coronary syndrome (ACS) after PCI.

Study design, setting and patients

This was a prospective single-center clinical trial that included 155 patients (n = 119 without AKI, n = 36 with AKI, mean age 64.0±10.6 years, of whom 74.2% were males), who underwent PCI with stenting. We prospectively evaluated RPR using optical aggregometry. Development of AKI was the primary endpoint.

Results

Acute renal dysfunction was observed in 36 patients (23.2%) after PCI, the risk factors of which according to univariate regression analysis were: age (p = 0.040), low diastolic blood pressure (DBP) (p = 0.001), having severe heart failure (HF) according to Killip (p<0.001), low level of hemoglobin (p = 0.026) and erythrocytes (p = 0.005), increased creatinine (p<0.001), low baseline glomerular filtration rate (GFR) (p<0.001), low left ventricular ejection fraction (LV EF) (p = 0.003), high residual platelet reactivity (RPR) (p<0.001) and platelet aggregation area under the curve (AUC) with 10 μg/mL ADP (p<0.001), as well as dose of X-ray contrast medium (XCM) (p = 0.008). As a result of multivariate regression analysis the following independent predictors of AKI were established with the inclusion of the above factors: baseline creatinine level [OR 1.033 at 95% CI from 1.017 to 1.049; p<0.001], RPR with 10 μg/mL ADP [OR 1.060 at 95% CI from 1.027 to 1.094; p = 0.001], dose of an XCM [ОR 1.005 at 95% CI from 1.001 to 1.008; р = 0.014], diastolic blood pressure (DBP) [OR 0.926 at 95% CI from 0.888 to 0.965; p<0.001].

Conclusion

ADP-induced high residual platelet reactivity, baseline creatinine level, X-ray contrast medium, low diastolic blood pressure were independent predictors of AKI in patients with ACS after PCI.
Prevalence of sleep disturbances in Chinese adolescents: A systematic review and meta-analysis
Authors: Liang Mengjiao , Guo Ling , Huo Jing , Zhou Guoliang
Published: March 2021

Objectives

To review cross-sectional studies on the prevalence of sleep disturbance in Chinese adolescents and use a meta-analysis to explore the factors that may explain the heterogeneity between estimates of the prevalence.

Methods

We followed the Preferred Reporting Items for Systematic Review and Meta-analysis and searched the PubMed, Embase, Cochrane Library, PsycINFO, Scopus, Web of Science, SinoMed, Chinese National Knowledge Infrastructure (CNKI), WanFang, and VIP Database for Chinese Technical Periodicals databases from their inception through June 30, 2020. Analysis of the abstract, full-text, and data were conducted independently with uniform standards. Sub-group analyses and meta-regression analyses were performed to explore the associations between prevalence and gender, sex ratio, mean age, area, studying stage, sample size, survey time, response rate, assessment tools, PSQI cut-off, and quality score of the study.

Results

A total of 63 studies (64 groups of outcomes) were included in our analysis, covering 430,422 adolescents across China, of which 104,802 adolescents had sleep disturbances. The overall pooled prevalence was 26% (95% CI: 24–27%). Adolescents in senior high school (28%, 95% CI: 24–31%, p<0.001) had a higher prevalence of sleep disturbances than those in junior high school (20%, 95% CI: 15–24%, p<0.001). Studies with effective sample size of more than 1,000 and less than 3,000 had the highest prevalence of 30% (95% CI: 24–35%, p<0.001). The prevalence of sleep disturbances was not affected by other factors.

Conclusion

This systematic review and meta-analysis revealed that sleep disturbances are common in Chinese adolescents, and effective psychological and behavior intervention may be needed to help adolescents solve their sleep problems.
Incidence and risk factors for major bleeding among patients undergoing percutaneous coronary intervention: Findings from the Norwegian Coronary Stent Trial (NORSTENT)
Authors: Samuelsen Per-Jostein , Eggen Anne Elise , Steigen Terje , Wilsgaard Tom , Kristensen Andreas , Skogsholm Anne , Holme Elizabeth , van den Heuvel Christian , Nordrehaug Jan Erik , Bendz Bjørn , Nilsen Dennis W. T. , Bønaa Kaare Harald
Published: March 2021

Introduction

Bleeding is a concern after percutaneous coronary intervention (PCI) and subsequent dual antiplatelet therapy (DAPT). We herein report the incidence and risk factors for major bleeding in the Norwegian Coronary Stent Trial (NORSTENT).

Materials and methods

NORSTENT was a randomized, double blind, pragmatic trial among patients with acute coronary syndrome or stable coronary disease undergoing PCI during 2008–11. The patients (N = 9,013) were randomized to receive either a drug-eluting stent or a bare-metal stent, and were treated with at least nine months of DAPT. The patients were followed for a median of five years, with Bleeding Academic Research Consortium (BARC) 3–5 major bleeding as one of the safety endpoints. We estimated cumulative incidence of major bleeding by a competing risks model and risk factors through cause-specific Cox models.

Results

The 12-month cumulative incidence of major bleeding was 2.3%. Independent risk factors for major bleeding were chronic kidney disease, low bodyweight (< 60 kilograms), diabetes mellitus, and advanced age (> 80 years). A myocardial infarction (MI) or PCI during follow-up increased the risk of major bleeding (HR = 1.67, 95% CI 1-29-2.15).

Conclusions

The 12-month cumulative incidence of major bleeding in NORSTENT was higher than reported in previous, explanatory trials. This analysis strengthens the role of chronic kidney disease, advanced age, and low bodyweight as risk factors for major bleeding among patients receiving DAPT after PCI. The presence of diabetes mellitus or recurrent MI among patients is furthermore a signal of increased bleeding risk.

Clinical trial registration

Unique identifier NCT00811772; http://www.clinicaltrial.gov.
DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis
Authors: Noto Davide , Giammanco Antonina , Spina Rossella , Fayer Francesca , Cefalù Angelo B. , Averna Maurizio R.
Published: March 2021

SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from TF Immunoprecipitation (TF ChIP) experiments. The CNN is trained with several 100 bp sequences containing both SRE and NF-Y. Once trained, the model is used to predict the presence of SRE-NFY in the first 500 bp of all the known gene promoters. Finally, genes are grouped according to biological process and the processes enriched in genes containing SRE-NFY in their promoters are analyzed in details. This workflow allowed to identify biological processes enriched in SRE containing genes not directly linked to cholesterol metabolism and possible novel DNA patterns able to fill in for missing classical SRE sequences.
Assessment of dream-related aspects and beliefs in a large cohort of French students using a validated French version of the Mannheim Dream questionnaire
Authors: Napias Alice , Denechere Emilie , Mayo Willy , Ghorayeb Imad
Published: March 2021

Focusing on a specific population when studying dream characteristics can shed light on underlying mechanisms and correlates of dreaming. The aim of this study is to establish a clearer description of specific dream aspects and beliefs in a large cohort of students using a validated questionnaire, and to further investigate the role of sociodemographic variables such as age, gender and field of study. Participants were 1137 students aged from 18 to 34 (mean age: 22.2) who responded to an online version of the questionnaire. Our results showed a difference between humanities and science students, and a differential effect of gender on dream variables. Our results are discussed in light of previous investigations using the same questionnaire or focusing on the same population.
The gap of water supply—Demand and its driving factors: From water footprint view in Huaihe River Basin
Authors: An Min , Fan Lijuan , Huang Jin , Yang Wenjing , Wu Hailin , Wang Xiao , Khanal Ribesh
Published: March 2021

Climate change, population growth, the development of industrialization and urbanization are increasing the demand for water resources, but the water pollution is reducing the limited water supply. In recent years, the gap between water supply and demand which shows water scarcity situation is becoming more serious. Clear knowing this gap and its main driving factors could help us to put forward water protection measures correctly. We take the data of Huaihe River Basin from 2001 to 2016 as an example and use ecological water footprint to describe the demand, with the water carrying capacity representing the supply. We analyze the water supply-demand situation of Huaihe River Basin and its five provinces from footprint view in time and space. Then we apply the Logarithmic Mean Divisia Index model to analyze the driving factors of the ecological water footprint. The results show that: (1) the supply and demand balance of Huaihe River Basin was only achieved in year 2003 and 2005. There is also a large difference between Jiangsu province and other provinces in Huaihe River basin, most years in Jiangsu province per capital ecological footprint of water is more than 1 hm2/person except the years of 2003, 2015, and 2016. But other provinces are all less than 1 hm2/person. (2) Through the decomposition of water demand drivers, we concluded that economic development is the most important factor, with an annual contribution of more than 60%. Our study provides countermeasures and suggestions for the management and optimal allocation of water resources in Huaihe River Basin, and also provides reference for the formulation of water-saving policies in the world.
Validation of the loop-mediated isothermal amplification method for rapid and sensitive detection of Ureaplasma species in respiratory tracts of preterm infants
Authors: Mikami Yuta , Fuwa Kazumasa , Arima Eriko , Suda Yasuo , Yanagihara Itaru , Ibara Satoshi
Published: March 2021

Introduction

A simple and rapid diagnosis of Ureaplasma spp. is required for the choice of the appropriate antibiotic. However, an ideal detection method has not been available. This study examines the efficacy of the loop-mediated isothermal amplification (LAMP) assay, which provides rapid and sensitive results, to detect Ureaplasma spp. in respiratory tract samples of preterm infants.

Methods

The study included preterm infants born before 32 weeks of gestation admitted Kagoshima City Hospital from June 2018 to March 2020. Nasopharyngeal swabs and/or tracheal aspirates were obtained in the first seven postnatal days. One hundred sixty-seven nasopharyngeal swabs and 101 tracheal aspirates were analyzed by LAMP, culture, and quantitative real-time polymerase chain reaction.

Results

All 167 infants had a median (range) gestational age of 28.7 weeks (22.3–30.9) and birthweight 1030g (322–1828). One hundred sixty-seven nasopharyngeal swabs and 101 tracheal aspirates were obtained. In the results of nasopharyngeal swabs, the sensitivity and specificity of LAMP were 73.9% (17/23) and 97.2% (140/144), whereas those of quantitative real-time polymerase chain reaction were 73.9% (17/23) and 95.8% (138/144), compared to culture. In the results of tracheal aspirates, the sensitivity and specificity of LAMP were 89.5% (17/19) and 92.7% (76/82), whereas those of quantitative real-time polymerase chain reaction were 89.5% (17/19) and 93.9% (77/82), compared to culture.

Conclusions

The LAMP assay showed similar sensitivity and specificity with quantitative real-time polymerase chain reaction in the respiratory tracts of preterm infants including extremely preterm infants during the immediate postnatal period. Therefore, the LAMP is a practical alternative for the early detection so that appropriate antibiotics can be administered for preventing BPD.
A convenient approach to synthesize substituted 5-Arylidene-3-m-tolyl thiazolidine-2, 4-diones by using morpholine as a catalyst and its theoretical study
Authors: Jahan Khorshada , Khan Kaif Rashid , Akhter Kawsari , Romman Umme Kulsum Rowzatur , Halim Ershad
Published: March 2021

Thiazolidinediones are very important and used as a drug for the treatment of type 2 diabetes. Here, we report a convenient approach to synthesis 3-m-tolyl-5-arylidene-2,4-thiazolidinediones (TZDs) derivatives7a-ein two steps with moderate to good yield using morpholine as a catalyst. All the structures were confirmed by their spectral IR,1H NMR and13C NMR data. The anti-diabatic activity of all synthesized molecules is evaluated by docking with peroxisome proliferator-activated receptor-γ (PPARγ). Preliminary flexible docking studies reveals that our compounds7a,7dand7eshowed better binding affinity with the protein and could be a potential candidate for the treatment of type 2 diabetes in near future.
Presence of antibody-dependent cellular cytotoxicity (ADCC) against SARS-CoV-2 in COVID-19 plasma
Authors: Tso For Yue , Lidenge Salum J. , Poppe Lisa K. , Peña Phoebe B. , Privatt Sara R. , Bennett Sydney J. , Ngowi John R. , Mwaiselage Julius , Belshan Michael , Siedlik Jacob A. , Raine Morgan A. , Ochoa Juan B. , Garcia-Diaz Julia , Nossaman Bobby , Buckner Lyndsey , Roberts W. Mark , Dean Matthew J. , Ochoa Augusto C. , West John T. , Wood Charles
Published: March 2021

Background

Neutralizing-antibody (nAb) is the major focus of most ongoing COVID-19 vaccine trials. However, nAb response against SARS-CoV-2, when present, decays rapidly. Given the myriad roles of antibodies in immune responses, it is possible that antibodies could also mediate protection against SARS-CoV-2 via effector mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), which we sought to explore here.

Methods

Plasma of 3 uninfected controls and 20 subjects exposed to, or recovering from, SARS-CoV-2 infection were collected from U.S. and sub-Saharan Africa. Immunofluorescence assay was used to detect the presence of SARS-CoV-2 specific IgG antibodies in the plasma samples. SARS-CoV-2 specific neutralizing capability of these plasmas was assessed with SARS-CoV-2 spike pseudotyped virus. ADCC activity was assessed with a calcein release assay.

Results

SARS-CoV-2 specific IgG antibodies were detected in all COVID-19 subjects studied. All but three COVID-19 subjects contained nAb at high potency (>80% neutralization). Plasma from 19/20 of COVID-19 subjects also demonstrated strong ADCC activity against SARS-CoV-2 spike glycoprotein, including two individuals without nAb against SARS-CoV-2.

Conclusion

Both neutralizing and non-neutralizing COVID-19 plasmas can mediate ADCC. Our findings argue that evaluation of potential vaccines against SARS-CoV-2 should include investigation of the magnitude and durability of ADCC, in addition to nAb.
Development and validation of a predictive model of in-hospital mortality in COVID-19 patients
Authors: Velasco-Rodríguez Diego , Alonso-Dominguez Juan-Manuel , Vidal Laso Rosa , Lainez-González Daniel , García-Raso Aránzazu , Martín-Herrero Sara , Herrero Antonio , Martínez Alfonzo Inés , Serrano-López Juana , Jiménez-Barral Elena , Nistal Sara , Pérez Márquez Manuel , Askari Elham , Castillo Álvarez Jorge , Núñez Antonio , Jiménez Rodríguez Ángel , Heili-Frades Sarah , Pérez-Calvo César , Górgolas Miguel , Barba Raquel , Llamas-Sillero Pilar
Published: March 2021

We retrospectively evaluated 2879 hospitalized COVID-19 patients from four hospitals to evaluate the ability of demographic data, medical history, and on-admission laboratory parameters to predict in-hospital mortality. Association of previously published risk factors (age, gender, arterial hypertension, diabetes mellitus, smoking habit, obesity, renal failure, cardiovascular/ pulmonary diseases, serum ferritin, lymphocyte count, APTT, PT, fibrinogen, D-dimer, and platelet count) with death was tested by a multivariate logistic regression, and a predictive model was created, with further validation in an independent sample. A total of 2070 hospitalized COVID-19 patients were finally included in the multivariable analysis. Age 61–70 years (p<0.001; OR: 7.69; 95%CI: 2.93 to 20.14), age 71–80 years (p<0.001; OR: 14.99; 95%CI: 5.88 to 38.22), age >80 years (p<0.001; OR: 36.78; 95%CI: 14.42 to 93.85), male gender (p<0.001; OR: 1.84; 95%CI: 1.31 to 2.58), D-dimer levels >2 ULN (p= 0.003; OR: 1.79; 95%CI: 1.22 to 2.62), and prolonged PT (p<0.001; OR: 2.18; 95%CI: 1.49 to 3.18) were independently associated with increased in-hospital mortality. A predictive model performed with these parameters showed an AUC of 0.81 in the development cohort (n = 1270) [sensitivity of 95.83%, specificity of 41.46%, negative predictive value of 98.01%, and positive predictive value of 24.85%]. These results were then validated in an independent data sample (n = 800). Our predictive model of in-hospital mortality of COVID-19 patients has been developed, calibrated and validated. The model (MRS-COVID) included age, male gender, and on-admission coagulopathy markers as positively correlated factors with fatal outcome.
The effect of familiarity on infants’ social categorization capacity
Authors: Ferera Matar , Pun Anthea , Baron Andrew Scott , Diesendruck Gil
Published: March 2021

Recent studies indicate that a preference for people from one’s own race emerges early in development. Arguably, one potential process contributing to such a bias has to do with the increased discriminability of own- vs. other-race faces–a process commonly attributed to perceptual narrowing of unfamiliar groups’ faces, and analogous to the conceptual homogenization of out-groups. The present studies addressed two implications of perceptual narrowing of other-race faces for infants’ social categorization capacity. In Experiment 1, White 11-month-olds’ (N= 81) looking time at a Black vs. White face was measured under three between-subjects conditions: a baseline “preference” (i.e., without familiarization), after familiarization to Black faces, or after familiarization to White faces. Compared to infants’ a priori looking preferences as revealed in the baseline condition, only when familiarized to Black faces did infants look longer at the "not-familiarized-category" face at test. According to the standard categorization paradigm used, such longer looking time at the novel (i.e., "not-familiarized-category") exemplar at test, indicated that categorization of the familiarized faces had ensued. This is consistent with the idea that prior to their first birthday, infants already tend to represent own-race faces as individuals and other-race faces as a category. If this is the case, then infants might also be less likely to form subordinate categories within other-race than own-race categories. In Experiment 2, infants (N= 34) distinguished between an arbitrary (shirt-color) based sub-categories only when shirt-wearers were White, but not when they were Black. These findings confirm that perceptual narrowing of other-race faces blurs distinctions among members of unfamiliar categories. Consequently, infants: a) readily categorize other-race faces as being of the same kind, and b) find it hard to distinguish between their sub-categories.
Validation of a new automated chemiluminescent anti-SARS-CoV-2 IgM and IgG antibody assay system detecting both N and S proteins in Japan
Authors: Yokoyama Rin , Kurano Makoto , Morita Yoshifumi , Shimura Takuya , Nakano Yuki , Qian Chungen , Xia Fuzhen , He Fan , Kishi Yoshiro , Okada Jun , Yoshikawa Naoyuki , Nagura Yutaka , Okazaki Hitoshi , Moriya Kyoji , Seto Yasuyuki , Kodama Tatsuhiko , Yatomi Yutaka
Published: March 2021

PCR methods are presently the standard for the diagnosis of Coronavirus disease 2019 (COVID-19), but additional methodologies are needed to complement PCR methods, which have some limitations. Here, we validated and investigated the usefulness of measuring serum antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using the iFlash3000 CLIA analyzer. We measured IgM and IgG titers against SARS-CoV-2 in sera collected from 26 PCR-positive COVID-19 patients, 53 COVID-19-suspected but PCR-negative patients, and 20 and 100 randomly selected non-COVID-19 patients who visited our hospital in 2020 and 2017, respectively. The repeatability and within-laboratory precision were obviously good in validations, following to the CLSI document EP15-A3. Linearity was also considered good between 0.6 AU/mL and 112.7 AU/mL for SARS-CoV-2 IgM and between 3.2 AU/mL and 55.3 AU/mL for SARS-CoV-2 IgG, while the linearity curves plateaued above the upper measurement range. We also confirmed that the seroconversion and no-antibody titers were over the cutoff values in all 100 serum samples collected in 2017. These results indicate that this measurement system successfully detects SARS-CoV-2 IgM/IgG. We observed four false-positive cases in the IgM assay and no false-positive cases in the IgG assay when 111 serum samples known to contain autoantibodies were evaluated. The concordance rates of the antibody test with the PCR test were 98.1% for SARS-CoV-2 IgM and 100% for IgG among PCR-negative cases and 30.8% for SARS-CoV-2 IgM and 73.1% for SARS-CoV-2 IgG among PCR-positive cases. In conclusion, the performance of this new automated method for detecting antibody against both N and S proteins of SARS-CoV-2 is sufficient for use in laboratory testing.
Real-time dispersal of malaria vectors in rural Africa monitored with lidar
Authors: Jansson Samuel , Malmqvist Elin , Mlacha Yeromin , Ignell Rickard , Okumu Fredros , Killeen Gerry , Kirkeby Carsten , Brydegaard Mikkel
Published: March 2021

Lack of tools for detailed, real-time observation of mosquito behavior with high spatio-temporal resolution limits progress towards improved malaria vector control. We deployed a high-resolution entomological lidar to monitor a half-kilometer static transect positioned over rice fields outside a Tanzanian village. A quarter of a million in situ insect observations were classified, and several insect taxa were identified based on their modulation signatures. We observed distinct range distributions of male and female mosquitoes in relation to the village periphery, and spatio-temporal behavioral features, such as swarming. Furthermore, we observed that the spatial distributions of males and females change independently of each other during the day, and were able to estimate the daily dispersal of mosquitoes towards and away from the village. The findings of this study demonstrate how lidar-based monitoring could dramatically improve our understanding of malaria vector ecology and control options.
LncRNA LINC00857 strengthens the malignancy behaviors of pancreatic adenocarcinoma cells by serving as a competing endogenous RNA for miR-340-5p to upregulate TGFA expression
Authors: Li Tingfu , Zhao Hongbo , Zhou Hua , Geng Tingting
Published: March 2021

Background

Pancreatic adenocarcinoma (PAAD) is a pancreatic disease with a high mortality rate in the world. This present research intends to identify the function of lncRNA LINC00857/miR-340-5p/Transforming growth factor alpha (TGFA) in the progression of PAAD.

Methods

Bioinformatics analysis was used to explore the differentially expressed lncRNA/miRNA/mRNA and analyze the relationship between lncRNA/miRNA/mRNA expression and prognosis of PAAD by enquiring TCGA, GEO and GTEX. KEGG pathway analysis and GO enrichment analysis were implemented to annotate the crucial genes regulated by LINC00857. The biological behaviors of PAAD cells were detected by CCK-8, colony formation and transwell assays. Interactive associations between LINC00857 and miR-340-5p, as well as miR-340-5p and TGFA were analyzed by dual luciferase assay.

Results

By enquiring TCGA database, we got that LINC00857 was highly expressed in patients with PAAD and positively associated with worse prognosis in PAAD patients. Moreover, LINC00857 upregulation promoted the proliferation and clone formation abilities of PAAD cells. Afterwards, the downstream miRNA and mRNA targets of LINC00857 were picked up to construct a ceRNA network. Further study revealed that TGFA expression was positively regulated by LINC00857 and negatively regulated by miR-340-5p. Besides that, the inhibitory effect of miR-340-5p on PAAD cells growth and movement can be blocked by LINC00857 upregulation. While, the malignant behavior of PAAD cells induced by TGFA overexpression can be eliminated by LINC00857 knockdown.

Conclusions

Upregulation of LINC00857 improved growth, invasion and migration abilities of PAAD cells by modulation of miR-340-5p/TGFA, affording potential targets and biomarkers for the clinical diagnosis and treatment.
Cuba’s cardiovascular risk factors: International comparison of levels and education gradients
Authors: Dieci Maria , Llibre-Rodriguez Juan J. , Acosta Daisy , Dow William H.
Published: March 2021

Background

Cuba’s life expectancy at 79 is third highest in Latin America. Many attribute this to social investments in health and education, but comparative research is sparse, thus we compare Cuba with neighboring Dominican Republic, Costa Rica due to its strong social protections, and the U.S. Given high cardiovascular mortality, we focus on cardiovascular risk factor levels. To assess the role of health care, we distinguish medically amenable biomarkers from behavioral risk factors. To assess the role of Cuba’s focus on equity, we compare education gradients in risk factors.

Methods

We analyze Cuban data from the 10/66 Dementia Research Group baseline survey of urban adults ages 65 plus. Comparison samples are drawn from the Dominican Republic 10/66 survey, the Costa Rican CRELES, and U.S. NHANES. We analyze cross-country levels and education gradients of medically amenable (hypertension, diabetes, hypercholesterolemia, access to health care) and behavioral (smoking, obesity) risk factors,–using sex-stratified weighted means comparisons and age-adjusted logistic regression.

Results

Neither medically amenable nor behavioral risk factors are uniformly better in Cuba than comparison countries. Obesity is lower in Cuba, but male smoking is higher. Hypertension, diabetes, and hypercholesterolemia levels are high in all countries, though Cuba’s are lower than Costa Rica. Hypertension awareness in Cuba is similar to Costa Rica. Cuba has a higher proportion of hypertensives on treatment than Costa Rica, though lower than the U.S. Comparative gradients by education are similarly mixed. For behavioral factors, Cuba shows the strongest gradients (primarily for men) among the countries compared: smoking improves, but obesity worsens with education. Hypertension awareness also improves with education in Cuba, but Cuba shows no significant differences by education in hypertension treatment.

Conclusion

Smoking is comparatively high in Cuba, but obesity is low, and the resulting biomarkers show comparatively mixed patterns. Cuba’s social protections have not eliminated strong educational gradients in behavioral risk factors, but the healthcare system appears to have eliminated disparities such as in hypertension treatment.
Genome editing to model and reverse a prevalent mutation associated with myeloproliferative neoplasms
Authors: Baik Ron , Wyman Stacia K. , Kabir Shaheen , Corn Jacob E.
Published: March 2021

Myeloproliferative neoplasms (MPNs) cause the over-production of blood cells such as erythrocytes (polycythemia vera) or platelets (essential thrombocytosis). JAK2 V617F is the most prevalent somatic mutation in many MPNs, but previous modeling of this mutation in mice relied on transgenic overexpression and resulted in diverse phenotypes that were in some cases attributed to expression level. CRISPR-Cas9 engineering offers new possibilities to model and potentially cure genetically encoded disorders via precise modification of the endogenous locus in primary cells. Here we develop “scarless” Cas9-based reagents to create and reverse the JAK2 V617F mutation in an immortalized human erythroid progenitor cell line (HUDEP-2), CD34+ adult human hematopoietic stem and progenitor cells (HSPCs), and immunophenotypic long-term hematopoietic stem cells (LT-HSCs). We find no overt in vitro increase in proliferation associated with an endogenous JAK2 V617F allele, but co-culture with wild type cells unmasks a competitive growth advantage provided by the mutation. Acquisition of the V617F allele also promotes terminal differentiation of erythroid progenitors, even in the absence of hematopoietic cytokine signaling. Taken together, these data are consistent with the gradually progressive manifestation of MPNs and reveals that endogenously acquired JAK2 V617F mutations may yield more subtle phenotypes as compared to transgenic overexpression models.
Abstinence-related motivational engagement for smoking cessation: Longitudinal patterns and predictive validity
Authors: Palmer Amanda M. , Sutton Steven K. , Correa John B. , Simmons Vani N. , Brandon Thomas H.
Published: March 2021

The Abstinence-Related Motivational Engagement (ARME) scale was developed to assess motivation to remain abstinent after a smoking cessation attempt. The ARME demonstrated reliability and validity among a small sample of ex-smokers. This study expands the psychometric evaluation of the ARME and tests the ARME as a predictor of smoking status among a sample of participants quitting smoking. The parent trial tested the efficacy of a self-help smoking cessation intervention (N = 1874), with assessments every 6 months. Internal consistency and factor structure of the ARME was evaluated at each assessment to confirm use of the measure as designed. Discriminant validity was assessed by comparing the ARME to the Situation-specific Abstinence Self-Efficacy (SSE) scale via inter-correlations and prediction of future smoking status. Finally, the trajectories of both the ARME and SSE were compared among continuous abstainers and continuous smokers. A single-factor structure was observed at each assessment. Cronbach’s alphas ranged from 0.88–0.91 for the total sample. Correlations between the ARME and the SSE ranged from 0.38–0.47 (ps <0.001) among smokers; and from 0.09–0.15 (most ps > 0.05) among abstainers. Among current smokers, the ARME and SSE were independent positive predictors of subsequent abstinence (AORs 1.28–2.29, ps <0.001). For those currently abstinent, only the SSE predicted subsequent abstinence (AORs 1.69–2.60, ps <0.05). GEE analyses showed different trajectories for the two measures, as well as between abstainers and smokers. In conclusion, the ARME is a reliable, valid measure with unique predictive utility for current smokers and a distinct trajectory among those who have successfully quit.
A prospective study of the adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers
Authors: El Alam Molly B. , Sims Travis T. , Kouzy Ramez , Biegert Greyson W. G. , Jaoude Joseph A. B. I. , Karpinets Tatiana V. , Yoshida-Court Kyoko , Wu Xiaogang , Delgado-Medrano Andrea Y. , Mezzari Melissa P. , Ajami Nadim J. , Solley Travis , Ahmed-Kaddar Mustapha , Lin Lilie L. , Ramondetta Lois , Jazaeri Amir , Jhingran Anuja , Eifel Patricia J. , Schmeler Kathleen M. , Wargo Jennifer , Klopp Ann H. , Colbert Lauren E.
Published: March 2021

Background

A diverse and abundant gut microbiome can improve cancer patients’ treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT.

Materials and methods

Rectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. 42 of these patients received antibiotics during the study period. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size.

Results

Gut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species.

Conclusion

After CRT, the diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers.