bluuebunny/crossref_metadata_2025 huggingface dataset:
Network‐based analysis using chromosomal microdeletion syndromes as a model
Authors: Corrêa Thiago , Feltes Bruno César , Schinzel Albert , Riegel Mariluce
Published: March 2021

Microdeletion syndromes (MSs) are a heterogeneous group of genetic diseases that can virtually affect all functions and organs in humans. Although systems biology approaches integrating multiomics and database information into biological networks have expanded our knowledge of genetic disorders, cytogenomic network‐based analysis has rarely been applied to study MSs. In this study, we analyzed data of 28 MSs, using network‐based approaches, to investigate the associations between the critical chromosome regions and the respective underlying biological network systems. We identified MSs‐associated proteins that were organized in a network of linked modules within the human interactome. Certain MSs formed highly interlinked self‐contained disease modules. Furthermore, we observed disease modules involving proteins from other disease groups in the MSs interactome. Moreover, analysis of integrated data from 564 genes located in known chromosomal critical regions, including those contributing to topological parameters, shared pathways, and gene–disease associations, indicated that complex biological systems and cellular networks may underlie many genotype to phenotype associations in MSs. In conclusion, we used a network‐based analysis to provide resources that may contribute to better understanding of the molecular pathways involved in MSs.
Identification ACTA2 and KDR as key proteins for prognosis of PD‐1/PD‐L1 blockade therapy in melanoma
Authors: Wang Yuchen , Li Zhaojun , Zhang Zhihui , Chen Xiaoguang
Published: March 2021

Programmed cell death protein 1 (PD‐1) /programmed cell death ligand 1 (PD‐L1) blockade is an important therapeutic strategy for melanoma, despite its low clinical response. It is important to identify genes and pathways that may reflect the clinical outcomes of this therapy in patients. We analyzed clinical dataset GSE96619, which contains clinical information from five melanoma patients before and after anti‐PD‐1 therapy (five pairs of data). We identified 704 DEGs using these five pairs of data, and then the number of DEGs was narrowed down to 286 in patients who responded to treatment. Next, we performed KEGG pathway enrichment and constructed a DEG‐associated protein‐protein interaction network. Smooth muscle actin 2 (ACTA2) and tyrosine kinase growth factor receptor (KDR) were identified as the hub genes, which were significantly downregulated in the tumor tissue of the two patients who responded to treatment. To confirm our analysis, we demonstrated similar expression tendency to the clinical data for the two hub genes in a B16F10 subcutaneous xenograft model. This study demonstrates that ACTA2 and KDR are valuable responsive markers for PD‐1/PD‐L1 blockade therapy.
Molsidomine ameliorates diabetic peripheral neuropathy complications in Wistar rats
Authors: Nayak B Pranav , Minaz Nathani , Pasha Khadar
Published: March 2021

Diabetic neuropathy is a disorder that affects various regions of the nervous system and there is no specific treatment available for it. This study evaluated the protective effect of molsidomine in diabetic neuropathy in rats. Diabetes was induced in male Wistar rats by administrating streptozotocin (52 mg/kg ip). Diabetic rats were treated with molsidomine 5 mg/kg po and 10 mg/kg po. After 8 weeks of treatment, motor coordination, mechanical allodynia, mechanical hyperalgesia, nerve conduction velocity, and glycosylated hemoglobin were assessed. Thereafter, animals were killed and the sciatic nerve was isolated for measurement of reduced glutathione and lipid peroxidation, and histopathological analysis. Treatment with molsidomine significantly improved motor coordination, paw withdrawal threshold, mechanical threshold, and nerve conduction velocity. Furthermore, molsidomine treatment also reduced malondialdehyde levels and prevented depletion of reduced glutathione in the sciatic nerve homogenate. Histopathology revealed that molsidomine treatment maintained normal architecture of the sciatic nerve. The results of our study strengthen the alternative use of molsidomine in diabetic neuropathy.
Indolo[3,2,1‐jk]carbazole Embedded Multiple‐Resonance Fluorophors for Narrowband Deep‐blue Electroluminescence with EQE≈34.7 % and CIEy≈0.085
Authors: Wei Jinbei , Zhang Chen , Zhang Dongdong , Zhang Yuewei , Liu Ziyang , Li Zhiqiang , Yu Gui , Duan Lian
Published: March 2021

Multiple‐resonance (MR) organic emitters bearing small full‐width at half‐maximum (FWHMs) are of general interest in organic light‐emitting diodes. Indolo[3,2,1‐jk]carbazole (ICz) embedded MR‐fluorophors have demonstrated extremely small FWHMs, yet in the violet region with low electroluminescence efficiency. Herein, a strategic implementation of ICz subunits into MR fluorophors is proposed by taking advantage of the synergetic effect of para‐positioned nitrogen atoms to enhance electronic coupling to decrease emitting energy gap. Deep blue emitters peaking at 441 and 447 nm with FWHMs of only 18 and 21 nm are thereof obtained, respectively, accompanied by ≈90 % photo‐luminance quantum yields. With the assistance of a thermally activated delayed fluorescence sensitizer to recycle excitons, the corresponding narrowband electroluminescent devices show unprecedent high maximum external quantum efficiencies of 32.0 % and 34.7 % with CIEy of 0.10 and 0.085, respectively.
Regio‐ and Diastereoselective Copper‐Catalyzed Carbomagnesiation for the Synthesis of Penta‐ and Hexa‐Substituted Cyclopropanes
Authors: Cohen Yair , Augustin André U. , Levy Laura , Jones Peter G. , Werz Daniel B. , Marek Ilan
Published: March 2021

Despite the highly strained nature of cyclopropanes possessing three vicinal quaternary carbon stereocenters, the regio‐ and diastereoselective copper‐catalyzed carbomagnesiation reaction of cyclopropenes provides an easy and efficient access to these novel persubstituted cyclopropyl cores with a complete regio‐ and diastereoselectivity.
Multiple‐step drawing innovative ultrahigh‐molecular‐weight polyethylene fibers modified with bacterial cellulose and scCO2‐aid
Authors: Xiang Yu , Tu Zhong‐dan , Lei Ting , Zhang Jia‐xin , Yeh Jen‐taut
Published: March 2021

Innovative supercritical carbon dioxide (scCO2)‐assisted ultrahigh‐molecular‐weight‐polyethylene (UHMWPE)/modified bacterial cellulose (MBC) as‐spun fibers were found to display substantially lower dynamic transition temperatures than those acquired for scCO2‐assisted UHMWPE or UHMWPE/MBC as‐spun fibers prepared without scCO2‐assistance or incorporation of MBC nanofibers. Multiple‐step drawing methods were first‐time applied to these finely ''relaxed'' scCO2‐assisted UHMWPE/MBC fibers and considerably improved their achievable draw ratios (Dras), orientation factor (fos), and tensile tenacities (σtts). The best five‐step drawn scCO2UHMWPE/MBC fiber displayed a particularly high σtt of 135 g d−1, which was ~35, ~3.75, and ~1.7 fold of σtts acquired for good steel fiber and the most appropriate single‐step drawn scCO2‐assisted UHMWPE and UHMWPE/MBC fibers, respectively. The particularly high Dras, fo, and σtts acquired for the best multiple‐step drawn scCO2‐assisted UHMWPE/MBC fibers is ascribed to their more ''relaxed'' UHMWPE structures, thinner lamellae, and successive increased drawing temperature in the multiple‐step drawing processes.
Favipiravir biotransformation in liver cytosol: Species and sex differences in humans, monkeys, rats, and mice
Authors: Hanioka Nobumitsu , Saito Keita , Isobe Takashi , Ohkawara Susumu , Jinno Hideto , Tanaka‐Kagawa Toshiko
Published: March 2021

Favipiravir is an antiviral agent effective against several RNA viruses that is converted into an inactive oxidative metabolite (M1), mainly by aldehyde oxidase, in humans. In the present study, the biotransformation of favipiravir into M1 in male and female humans, monkeys, rats, and mice was examined in an in vitro system using liver cytosolic fractions. The kinetics for M1 formation followed the Michaelis–Menten model in all species. The Km, Vmax, and CLint values in humans were 602 µM, 466 pmol/min/mg protein, and 776 nl/min/mg protein in males, respectively, and 713 µM, 404 pmol/min/mg protein, and 567 nl/min/mg protein in females, respectively. Species differences in CLint values were monkeys > humans > mice > rats in both males and females, and the variations for males and females were 120‐ and 96‐fold, respectively. Sex differences in CLint values were males > females in humans and mice, females > males in monkeys and rats, and marked variation (4.3‐fold) was noted in mice. This suggests that the roles of aldehyde oxidase in the hepatic metabolism of favipiravir differ extensively depending on the species and sex, and this study will aid in the assessment of the antiviral activities of favipiravir against novel and/or variant viruses.
Associations between coronary heart disease and risk of cognitive impairment: A meta‐analysis
Authors: Liang Xuan , Huang Yilin , Han Xu
Published: March 2021

Background

Several studies have demonstrated that coronary heart disease (CHD) is a high risk factor for cognitive impairment, whereas other studies showed that there was no association between cognitive impairment and CHD. The relationship between CHD and cognitive impairment is still unclear based on these conflicting results. Thus, it is of importance to evaluate the association between CHD and cognitive impairment. The present study made a meta‐analysis to explore the association between CHD and risk of cognitive impairment.

Methods

Articles exploring the association between CHD and cognitive impairment and published before November 2020 were searched in the following databases: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We used STATA 12.0 software to compute the relative risks (RRs), odds ratios (ORs), or hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

The meta‐analysis showed a positive association between CHD and risk of all‐cause cognitive impairment with a random effects model (RR = 1.27, 95% CI 1.18 to 1.36, I2 = 82.8%, p < .001). Additionally, the study showed a positive association between myocardial infraction (MI) and risk of all‐cause cognitive impairment with a random effects model (RR = 1.49, 95% CI 1.20 to 1.84, I2 = 76.0%, p < .001). However, no significant association was detected between angina pectoris (AP) and risk of all‐cause cognitive impairment with a random effects model (RR = 1.23, 95% CI 0.95 to 1.58, I2 = 79.1%, p < .001). Subgroup studies also showed that CHD patients are at higher risk for vascular dementia (VD), but not Alzheimer's disease (AD) (VD: RR = 1.34, 95% CI: 1.28–1.39; AD: RR = 0.99, 95% CI: 0.92–1.07).

Conclusion

In a word, CHD was significantly associated with an increased risk of developing cognitive impairment.
Prognostic value of quantitative flow ratio measured immediately after drug‐coated balloon angioplasty for in‐stent restenosis
Authors: Cai Xiaoqing , Tian Feng , Jing Jing , Jin Qinhua , Zhou Shanshan , Yin Weijun , Chen Yufang , Wu Qiang , Fu Zhenhong , Chen Yundai
Published: March 2021

Objectives

This study aimed to evaluate prognostic value of quantitative flow ratio (QFR) in drug‐coated balloon (DCB) angioplasty for in‐stent restenosis (ISR).

Background

There is a high incidence of recurrent ISR after DCB angioplasty. QFR is a novel method for fast computation of fractional flow reserve for the target vessel based on quantitative coronary angiography (QCA) and fluid dynamics algorithms.

Methods

Patients participating in the RESTORE ISR China randomized trial were enrolled and classified into the recurrent restenosis group and the non‐recurrent restenosis group. The binary classifications followed the QCA standards of ISR. Clinical and angiographic characteristics of the groups were analyzed, and the QFRs before and after lesion preparation and after final DCB angioplasty were measured and compared.

Results

A total of 208 patients who underwent follow‐up angiography were enrolled in the study, with 226 lesions measured in total. QFR value after DCB angioplasty (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.83–0.93; p < .0001 for 1 mm increase), lesion length (OR: 1.08; 95% CI: 1.01–1.15; p = .017), and vessel caliber lumen diameter (OR: 0.35; 95% CI 0.13–0.89; p = .027) were independently associated with recurrent restenosis after DCB angioplasty. The optimal QFR cut‐off value was determined to be 0.90 with a sensitivity of 0.94, specificity of 0.56, and accuracy of 0.79 in predicting recurrent restenosis.

Conclusions

The QFR value after DCB angioplasty is a promising predictor of DES ISR.
Generalized annular pustular psoriasis (Milian‐Katchoura type) induced by systemic steroids
Authors: El Jazouly Madiha , Alj Maha , Chahboun Fatimzahra , Al Bouzidi Abderrahman , Chiheb Soumiya
Published: March 2021

The aim of my clinical image is to recall this rare and benign form of pustular psoriasis and to insist on the role of the triggers of pustular psoriasis, mainly the drugs.
Invasive therapy versus conservative therapy for patients with stable coronary artery disease: An updated meta‐analysis
Authors: Vij Aviral , Kassab Kameel , Chawla Hitesh , Kaur Amandeep , Kodumuri Vamsi , Jolly Neeraj , Doukky Rami
Published: March 2021

Background

Heart disease remains the leading cause of death in the United States. Although there are clear indications for revascularization in patients with acute coronary syndromes, there is debate regarding the benefits of revascularization in stable ischemic heart disease. We sought to perform a comprehensive meta‐analysis to assess the role of revascularization compared to conservative medical therapy alone in patients with stable ischemic heart disease.

Hypothesis

There is no significant difference in all‐cause mortality or cardiovascular mortality between invasive and medical arms.

Methods

We performed a systematic literature search from January 2000 to June 2020. Our literature search yielded seven randomized controlled trials. We analyzed a total of 12 013 patients (6109 in revascularization arm and 5904 in conservative medical therapy arm). Primary outcome was all‐cause mortality. Secondary outcomes included major adverse cardiac events (MACE) (death, myocardial infarction [MI], or stroke), cardiovascular mortality, MI, and stroke. Additional subgroup analysis for all‐cause mortality was performed comparing percutaneous coronary intervention (PCI) with bare metal stent versus conservative therapy; and PCI with drug eluting stent versus conservative therapy.

Results

There was no statistically significant difference in primary outcome of all‐cause mortality between either arm (odds ratio [OR] = 0.95; 95% CI [confidence interval], 0.83 to 1.08; p = .84). There were statistically significant lower rates of MACE (death, MI or stroke) in the revascularization arm when compared to conservative arm.

Conclusions

Our analysis did not show any survival advantage of an initial invasive strategy over conservative medical therapy in patients with stable coronary artery disease (CAD).
Projections from the ventral nucleus of the lateral lemniscus to the cochlea in the mouse
Authors: Suthakar Kirupa , Ryugo David K.
Published: March 2021

Auditory efferents originate in the central auditory system and project to the cochlea. Although the specific anatomy of the olivocochlear (OC) efferents can vary between species, two types of auditory efferents have been identified based upon the general location of their cell bodies and their distinctly different axon terminations in the organ of Corti. In the mouse, the relatively small somata of the lateral (LOC) efferents reside in the lateral superior olive (LSO), have unmyelinated axons, and terminate around ipsilateral inner hair cells (IHCs), primarily against the afferent processes of type I auditory nerve fibers. In contrast, the larger somata of the medial (MOC) efferents are distributed in the ventral nucleus of the trapezoid body (VNTB), have myelinated axons, and terminate bilaterally against the base of multiple outer hair cells (OHCs). Using in vivo retrograde cell body marking, anterograde axon tracing, immunohistochemistry, and electron microscopy, we have identified a group of efferent neurons in mouse, whose cell bodies reside in the ventral nucleus of the lateral lemniscus (VNLL). By virtue of their location, we call them dorsal efferent (DE) neurons. Labeled DE cells were immuno‐negative for tyrosine hydroxylase, glycine, and GABA, but immuno‐positive for choline acetyltransferase. Morphologically, DEs resembled LOC efferents by their small somata, unmyelinated axons, and ipsilateral projection to IHCs. These three classes of efferent neurons all project axons directly to the cochlea and exhibit cholinergic staining characteristics. The challenge is to discover the contributions of this new population of neurons to auditory efferent function.
Novel action thresholds of a logistic regression model to forecast dollar spot on bentgrasses
Authors: Hempfling James W. , Ward Daniel L. , Lalancette Norman , Clarke Bruce B. , Murphy James A.
Published: March 2021

Dollar spot (Clarireedia jacksonii) susceptibility varies among bentgrasses (Agrostis spp.). This trial assessed the ability of five action thresholds of the risk index (RI) of a logistic regression model to forecast dollar spot incidence on bentgrass fairway turf grown on a sandy loam in North Brunswick, NJ. Dollar spot incidence was assessed over 128 observation periods (May to Nov. annually) over 3 yr and related to five action thresholds for prediction accuracy. Action thresholds included a RI threshold of 20% (RI 20%), interpreting the change in the RI over time (RI slope), adjusting the RI upwards to maximize accuracy (RImax), combining RI 20% with RI slope, and combining RImax with RI slope. The RI 20% accurately predicted disease on 63 to 66% of observation periods for highly susceptible creeping bentgrass (A. stolonifera L.) cultivars Shark, Penncross, and Independence; other action thresholds improved accuracy by only 10% or less for these cultivars. Prediction accuracy on lower susceptibility cultivars (007, Declaration, and colonial bentgrass Capri; A. capillaris L.) was substantially improved with four novel action thresholds by reducing over‐predictions compared to RI 20%. Accuracy was improved by as much as 32% when the RImax and RI slope were combined for Declaration compared to RI 20%. On low susceptibility cultivars, turf managers may be able to use action thresholds that incorporate a RI greater than 20% and/or RI slope to reduce fungicide inputs and maintain acceptable dollar spot control compared to RI 20%.
Corporate social responsibility decisions in apparel supply chains: The role of negative emotions in Bangladesh and Pakistan
Authors: Fontana Enrico , Atif Muhammad , Gull Ammar Ali
Published: March 2021

This article integrates the global value chain literature with the micro organization literature on negative emotions to explore the drivers of fear and anger among supplier factory senior managers in apparel supply chains after Rana Plaza—a major industrial disaster—and their influence on decisions on CSR practices. Based on a comparative study around Dhaka and Lahore—two key apparel manufacturing hubs—this study elucidates that supplier factory senior managers experienced similar market tensions but different social tensions after the Rana Plaza incident. Crucially, similar market tensions helped create market fear and anger, but different social tensions led to social fear and anger in Bangladesh but not in Pakistan, therefore influencing the way supplier factory senior managers take decisions regarding CSR practices. By conceptualizing communal alignment and competitive CSR, this research finally advances the global value chain literature and contributes to the current conversations on negative emotions in organizations.
Aspiration fluid cytology during single operator cholangioscopy with targeted biopsy to improves the diagnostic yield in indeterminate biliary strictures
Authors: Munot Khushboo , Raijman Isaac , Khan Vinshi , Gandle Cassandra , Shahid Marwah , Liu Yan , Patel Kalpesh , Wheeler Thomas M , Othman Mohamed O
Published: March 2021

Introduction

Sensitivities of various sampling methods to detect malignant biliary strictures remain suboptimal. Irrigation during digital single operator cholangioscopy (dSOC) is done routinely for visualization of the duct. The aim of this study was to evaluate improvement of the sensitivity for detecting malignant biliary strictures when adding aspiration fluid cytology (AFC) from the irrigated fluid during cholangioscopy to cholangioscopic biopsy (CBx).

Methods

We conducted a retrospective analysis of patients at a tertiary medical center who underwent CBx for evaluation of their biliary strictures. We included patients who had aspiration of fluid from the bile duct after CBx and were sent for cytology from January 2017 to October 2017. Diagnosis was made on the basis of final pathology or follow‐up over 9 months.

Results

Fifty‐six patients had CBx obtained, out of which 35 patients had AFC in conjunction. Twenty‐two (62%) patients were male and the average age was 65 years. Considering atypical cells as benign, the sensitivity, specificity, positive and negative predictive values (PPV, NPV) for CBx were 62.5%, 100%, 100%, and 76% respectively. When CBx combined with AFC, the above statistics went up to 81.25%, 100%, 100%, and 86.36% respectively. When atypical cells were considered malignant, the sensitivity, specificity, PPV and NPV for CBx were 81.25%, 84.21%, 81.25%, 84.21% and increased to 93.75%, 78.94%, 78.94%, and 93.75% respectively after adding AFC results.

Conclusion

For patients with biliary stricture, addition of AFC dSOC guided biopsies, significantly improves the sensitivity for detecting malignancy.
RERE deficiency causes retinal and optic nerve atrophy through degeneration of retinal cells
Authors: Kim Bum Jun , Scott Daryl A.
Published: March 2021

Background

The arginine‐glutamic acid dipeptide repeats gene (RERE) encodes a nuclear receptor coregulator that modulates gene expression through its interaction with transcriptional machinery. In humans, RERE deficiency causes neurodevelopmental disorder with or without structural defects of the brain, eye, heart, and kidney (NEDBEH). Ophthalmological defects are seen in approximately one third of individuals with NEDBEH and in RERE‐deficient mice which can serve as a useful animal model.

Results

In mice, RERE is expressed in a subset of retinal ganglion cells (RGC), the lens epithelium, and the ciliary body during the embryonic period. RERE expression expands into the outer nuclear layer and the inner nuclear layer during the postnatal period. RERE‐deficient mice have retinal and optic nerve atrophy. We show that RERE deficiency causes progressive loss of retinal cells and apoptosis of retinal cells in the ganglion cell layer as early as E17.5. The number of RGCs is also reduced in RERE‐deficient embryos and mice.

Conclusions

We conclude that RERE is required to control the apoptosis of retinal cells in the developing retina, and that RERE deficiency results in the retina atrophy through degeneration of the retinal cells and optic nerve atrophy through the loss of RGCs.
Genetically diverse populations spread faster in benign but not in challenging environments
Authors: Mortier Frederik , Masier Stefano , Bonte Dries
Published: March 2021

Population spread from a limited pool of founding propagules is at the basis of biological invasions. The size and genetic variation of these propagules eventually affect whether the invasion is successful or not. The inevitable bottleneck at introduction decreases genetic diversity, and therefore should affect population growth and spread. However, many heavily bottlenecked invasive populations have been successful in nature. Negative effects of a genetic bottleneck are typically considered to be relaxed in benign environments because of a release from stress. Despite its relevance to understand and predict invasions, empirical evidence on the role of genetic diversity in relation to habitat quality is largely lacking. We use the mite Tetranychus urticae Koch as a model to experimentally assess spread rate and size of genetically depleted inbred populations vs. enriched mixed populations. This was assessed in replicated linear patch systems consisting of benign (bean), challenging (tomato), or a gradient (bean to tomato) habitat. As expected, we found no effect of genetic diversity on population size in benign habitat but found that it increased population size in challenging habitat. However, we found that population spread rates were increased due to genetic diversity in the benign but not in the challenging habitat. Additionally, variance in spread was consistently higher in genetically poor populations and highest in the challenging habitat. Our experiment challenges the general view that a bottleneck in genetic variation decreases invasion success in challenging but not benign environments.
Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice
Authors: Pieronne‐Deperrois Marie , Guéret Alexandre , Djerada Zoubir , Crochemore Clément , Harouki Najah , Henry Jean‐Paul , Dumesnil Anaïs , Larchevêque Marine , do Rego Jean‐Claude , do Rego Jean‐Luc , Nicol Lionel , Richard Vincent , Jaisser Frédéric , Kolkhof Peter , Mulder Paul , Monteil Christelle , Ouvrard‐Pascaud Antoine
Published: March 2021

Aims

In post‐menopausal women, incidence of heart failure with preserved ejection fraction is higher than in men. Hormonal replacement therapies did not demonstrate benefits. We tested whether the non‐steroidal mineralocorticoid receptor antagonist finerenone limits the progression of heart failure in ovariectomized (OVX) mice with metabolic disorders.

Methods and results

Ovariectomy was performed in 4‐month‐old mice, treated or not at 7 months old for 1 month with finerenone (Fine) 1 mg/kg/day. Left ventricular (LV) cardiac and coronary endothelial functions were assessed by echocardiography, catheterization, and myography. Blood pressure was measured by plethysmography. Insulin and glucose tolerance tests were performed. Exercise capacity and spontaneous activity were measured on treadmill and in combined indirect calorimetric cages equipped with voluntary running wheel. OVX mice presented LV diastolic dysfunction without modification of ejection fraction compared with controls (CTL), whereas finerenone improved LV filling pressure (LV end‐diastolic pressure, mmHg: CTL 3.48 ± 0.41, OVX 6.17 ± 0.30**, OVX + Fine 3.65 ± 0.55†, **P < 0.01 vs. CTL, †P < 0.05 vs. OVX) and compliance (LV end‐diastolic pressure–volume relation, mmHg/RVU: CTL 1.65 ± 0.42, OVX 4.77 ± 0.37***, OVX + Fine 2.87 ± 0.26††, ***P < 0.001 vs. CTL, ††P < 0.01 vs. OVX). Acetylcholine‐induced endothelial‐dependent relaxation of coronary arteries was impaired in ovariectomized mice and improved by finerenone (relaxation, %: CTL 86 ± 8, OVX 38 ± 3**, OVX + Fine 83 ± 7††, **P < 0.01 vs. CTL, ††P < 0.01 vs. OVX). Finerenone improved decreased ATP production by subsarcolemmal mitochondria after ovariectomy. Weight gain, increased blood pressure, and decreased insulin and glucose tolerance in OVX mice were improved by finerenone. The exercise capacity at race was diminished in untreated OVX mice only. Spontaneous activity measurements in ovariectomized mice showed decreased horizontal movements, reduced time spent in a running wheel, and reduced VO2 and VCO2, all parameters improved by finerenone.

Conclusions

Finerenone improved cardiovascular dysfunction and exercise capacity after ovariectomy‐induced LV diastolic dysfunction with preserved ejection fraction.
Neprilysin inhibition does not alter dynamic of proenkephalin‐A 119‐159 and pro‐substance P in heart failure
Authors: Arfsten Henrike , Goliasch Georg , Bartko Philipp E. , Prausmüller Suriya , Spinka Georg , Cho Anna , Novak Johannes , Mascherbauer Julia , Haslacher Helmuth , Strunk Guido , Hülsmann Martin , Pavo Noemi
Published: March 2021

Aims

As NEP degrades many substrates, the specific therapeutic mechanism of NEP inhibition with angiotensin receptor neprilysin inhibitor (ARNi) in heart failure with reduced ejection fraction (HFrEF) is not entirely evident. The aim of this study was to investigate the response of two substrates of NEP—the tachykinin and enkephalin systems—to the initiation of ARNi therapy in HFrEF.

Methods and results

Between 2016 and 2018, 141 consecutive patients with stable HFrEF [74 with initiation of ARNi and 67 controls on continuous angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) therapy] were prospectively enrolled. Plasma proenkephalin‐A 119‐159 (PENK) and pro‐substance P (pro‐SP) were serially determined. Proenkephalin‐A 119‐159 and pro‐SP correlated strongly with each other (rs = 0.67, P < 0.001) and kidney function (rs = −0.66, P < 0.001 and rs = −0.54, P < 0.001) and modestly with NT‐proBNP (rs = 0.32, P < 0.001 and rs = 0.24, P = 0.006, respectively). Concentrations of circulating PENK were slightly elevated after 1 and 2 year follow‐up compared with baseline (BL) [BL median: 67.4 pmol/L (IQR: 57.3–89.8), 1 year: 83.5 pmol/L (IQR: 62.4–111.6), 2 years: 92.3 pmol/L (IQR: 63.1–101.9); BL vs. 1 year: P = 0.017 and BL vs. 2 years: P = 0.019] in the overall analysis, but lost significance at 2 year follow‐up when assessed in paired subanalysis (P = 0.116). Plasma pro‐SP levels remained comparable during the entire follow‐up [BL median: 78.3 pmol/L (IQR: 67.9–90.6), 1 year: 75.9 pmol/L (IQR: 58.6–96.3), 2 years: 79.7 pmol/L (IQR: 59.9–105.3); P = ns for both timepoints]. Biomarker patterns of ARNi patients were independent from baseline therapy, that is, ACEi or ARB (P > 0.05 between groups).

Conclusions

Although enkephalins and SP are known substrates of NEP, NEP inhibition by ARNi does not clearly affect the circulating precursors PENK and pro‐SP in HFrEF.
A Novel Sensitive and Selective Amperometric Detection Platform for the Vanillin Content in Real Samples
Authors: Karakaya Serkan , Kaya İsmet
Published: March 2021

Accurate and sensitive determination of vanillin in commercial samples is significant for food safety & quality. In the proposed study, copper particles were coated on an indium tin oxide electrode (ITO) by cyclic voltammetry (CV) for the determination of vanillin in food samples. CV studies indicated that the electrodeposition of Cu particles provides a good electrocatalytic effect towards the oxidation of vanillin. The fabricated sensor determines vanillin linearly between 0.50 μM–2.0 mM (Limit of detection: 0.15 μM). The Cu/ITO was successfully tested on vanillin samples and the recommended method provides accurate and selective determination of vanillin in daily samples.
Promotion effect of metal phosphides towards electrocatalytic and photocatalytic water splitting
Authors: Han Yanling , Chen Yong , Fan Rongli , Li Zhaosheng , Zou Zhigang
Published: March 2021

Hydrogen evolution from water splitting over semiconductors has been considered one of the most promising ways to address energy shortages and environmental pollution. Searching for low‐cost, highly efficient, and durable catalysts is the key to improve the hydrogen production rate. Expensive noble metals, such as Pt and Au, are generally loaded onto semiconductors to promote photocatalytic activity. Metal phosphides are promising candidates to replace noble metals in hydrogen generation via electrocatalytic or photocatalytic water splitting due to their low hydrogen‐producing overpotential, tunable electronic structure, high electrical conductivity, and low price. In this review article, the characteristics and synthetic methods of metal phosphides are briefly introduced, and the development of metal phosphides for electrocatalytic or photocatalytic water splitting is presented. Finally, the challenges and future directions of metal phosphides are discussed.

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Generalization of the Neville–Aitken interpolation algorithm on Grassmann manifolds: Applications to reduced order model
Authors: Mosquera Rolando , El Hamidi Abdallah , Hamdouni Aziz , Falaize Antoine
Published: March 2021

An extension of the well‐known Neville–Aitken's algorithm for interpolation on the Grassmann manifold in the framework of parametric model order reduction is presented. Interpolation points on are the subspaces spanned by bases obtained by Proper Orthogonal Decomposition of available solutions associated with the chosen parameter sampling. The Neville–Aitken's algorithm is performed recursively via the geodesic barycenter of two points. Three CFD applications are presented: (i) the Von Karman vortex shedding street, (ii) the lid‐driven cavity with inflow and (iii) the flow induced by a rotating solid. Numerical results are relevant with respect to accuracy while the asymptotic complexity is comparable to the state of the art.
Out with the New And In With the Old: Reviving a Traditional Makah Halibut Hook for Modern Fisheries Management Challenges
Authors: Stewart Ian J , Scordino Jonathan J (Čibuqsus) , Petersen Joseph R , Wise Alex W , Svec Cole I , Buttram Reginald H , L Monette Joshua , Gonzales Maria R , Svec Russell , Scordino Joe , Butterfield Kaeden , Parker William , Buzzell Laurence A
Published: March 2021

Although fisheries challenges evolve rapidly, historical approaches may provide “new” tools for managers. In the state of Washington, the Makah Tribe have used čibu·d, their traditional fishhook, to target Pacific Halibut Hippoglossus stenolepis long before the advent of modern fisheries. We describe our experience in rediscovering this historical harvesting method, testing the species selectivity, refining the approach, and producing a tool ready for application in modern fisheries management. Over nearly a decade, we were able to uncover substantial traditional knowledge in the community. Turning this knowledge into a reproducible and consistent product for testing proved difficult. Initial attempts to deploy the gear using commercial longlines encountered a range of challenges, but suggested refinements for further research. Subsequent experiments in recreational fisheries were successful due to the lessons learned during initial work. Our experience may be of value to others hoping to investigate historical methods with potential for addressing modern problems.
Synthesis of middle–long–middle structured intralipids by biological catalysis and the evaluation of intralipids’ protective effect on liver injury rats
Authors: Liu Changsheng , Chen An’nan , Xu Li , Wang Tianqi , Zhang Renwei , Xu Juntao , Yu Yue , Nie Kaili , Deng Li , Wang Fang
Published: March 2021

Intralipids are widely used to provide energy and necessary fatty acids for the patients. The structure of lipids may affect their function. We developed a bio‐catalyzed route to prepare various intralipids and investigated the protective effect of intralipids against α‐naphthylisothiocyanate (ANIT) induced liver injury rats, further discussing the structure–function relationship. The middle–long–middle (MLM) structural intralipid was synthesized through alcoholysis‐esterification, and the influence factors were investigated. ANIT treatment caused liver injury, further making hepatocyte damage, and increasing related biochemical indexes, like aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and total bilirubin (TBIL). Especially, MLM‐based and structoglyceride (STG) intralipids worked better in the early stage, to reduce the AST, ALT, and TBIL (p < .05). MLM showed a comparative advantage over other intralipids to accelerate the reduction of ALT (1st day) and AST (3rd day). MLM intralipid might be a promising next‐generation intralipid than the current STG intralipid liver‐injury patients. The biological catalysis MLM‐based intralipids can make the maximum utilization of fatty acids for the liver regeneration, where middle‐chain fatty acid (MCFA) in sn‐1,3 position can be metabolized directly to provide energy and long‐chain fatty acid (LCFA) in sn‐2 position can be delivered effectively for cell membrane repairing.
Methylphenidate use in geriatric depression: A systematic review
Authors: Smith Kristin R. , Kahlon Christie H. , Brown Jamie N. , Britt Rachel B.
Published: March 2021

Objectives

Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression.

Methods

PubMed (1946–December 2020) and Embase (1947–December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late‐life depression, and MPH. Studies were included if they were a randomized‐controlled trial or open‐label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older.

Results

After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day.

Conclusions

Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short‐term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long‐term trials are needed to further define the role of MPH in this population.
Factors associated with the severity of delirium
Authors: Tachibana Masako , Inada Toshiya , Ichida Masaru , Kojima Shihori , Shioya Mayumi , Wakayama Kazuki , Ozaki Norio
Published: March 2021

Background

Various factors affecting the development of delirium have been identified. However, the associations between the severity of delirium and potentially related factors have not been adequately investigated. The aim of the present study was to explore factors associated with the severity of delirium and to identify the reversible contributing factors.

Methods

A total of 577 patients with delirium referred to the Department of Psychiatry during the 5 years from May 2015 to April 2020 at a general hospital were included. The Delirium Rating Scale‐revised‐98 (DRS‐R‐98) was used to measure the severity of delirium. Multiple regression analysis was used to determine whether individual factors were associated with the severity of delirium.

Results

Intensive care unit admission (p = 0.003), use of benzodiazepines (p = 0.01), dementia (p = 0.02), and older age (p = 0.045) were all positively associated the severity of delirium, while use of β‐blockers (p = 0.001) was negatively associated with the severity of delirium.

Conclusions

Reversible contributing factors, that is use of benzodiazepines, should be avoided as much as possible, especially in elderly patients or patients with dementia or patients who need critical care in ICU. Reducing the dose of benzodiazepines or switching them to other drugs should be a priority.
Generalized–ensemble method study: A helix‐mimetic compound inhibits protein–protein interaction by long‐range and short‐range intermolecular interactions
Authors: Higo Junichi , Takashima Hajime , Fukunishi Yoshifumi , Yoshimori Atsushi
Published: March 2021

A heterocyclic compound mS‐11 is a helix‐mimetic designed to inhibit binding of an intrinsic disordered protein neural restrictive silence factor/repressor element 1 silencing factor (NRSF/REST) to a receptor protein mSin3B. We apply a generalized ensemble method, multi‐dimensional virtual‐system coupled molecular dynamics developed by ourselves recently, to a system consisting of mS‐11 and mSin3B, and obtain a thermally equilibrated distribution, which is comprised of the bound and unbound states extensively. The lowest free‐energy position of mS‐11 coincides with the NRSF/REST position in the experimentally‐determined NRSF/REST‐mSin3B complex. Importantly, the molecular orientation of mS‐11 is ordering in a wide region around mSin3B. The resultant binding scenario is: When mS‐11 is distant from the binding site of mSin3B, mS‐11 descends the free‐energy slope toward the binding site maintaining the molecular orientation to be advantageous for binding. Then, finally a long and flexible hydrophobic sidechain of mS‐11 fits into the binding site, which is the lowest‐free‐energy complex structure inhibiting NRSF/REST binding to mSin3B.
Seeking Stability: Consumer Motivations for Communal Nostalgia
Authors: Han Minju , Newman George E.
Published: March 2021

Existing research has examined why consumers are drawn to things from their past (personal nostalgia). However, little empirical work has examined why consumers prefer products that were never a part of their personal history (communal nostalgia). For example, a consumer may purchase vinyl records even though she grew up listening to mp3 files. Here, we find that one reason why consumers may be drawn to communal nostalgia is that it can provide a sense of social stability. Drawing on System Justification Theory (Jost & Banaji, British Journal of Social Psychology, 33, 1994 and 1–27), we demonstrate that perceived threats to the social system increase consumer demand for communal nostalgia and enhance the pleasure consumers get from certain retro products. We further show that a retro product’s ability to provide a sense of stability to consumers mediates the effect of system justification on communal nostalgia. Together, these findings suggest that communal nostalgia may be driven by its own unique motivational antecedents that are distinct from personal nostalgia, as individuals seek to connect to aspects of society that are perceived as stable and unchanging.
Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology
Authors: Wei Lai , Singh Rajan , Ro Seungil , Ghoshal Uday C
Published: March 2021

Functional gastrointestinal disorders (FGIDs), currently known as disorders of gut–brain interaction, are emerging microbiota–gut–brain abnormalities that are prevalent worldwide. The pathogenesis of FGIDs is heterogeneous and is intertwined with gut microbiota and its derived molecule‐modulated mechanisms, including gut dysmotility, visceral hypersensitivity, gut immune abnormalities, abnormal secretion, and impaired barrier function. There has been phenomenal progress in understanding the role of gut microbiota in FGIDs by underpinning the species alternations between healthy and pathological conditions such as FGIDs. However, the precise gut microbiota‐directed cellular and molecular pathogeneses of FGIDs are yet enigmatic. Determining the mechanistic link between the gut microbiota and gastrointestinal (GI) diseases has been difficult due to (i) the lack of robust animal models imitating the various aspects of human FGID pathophysiology; (ii) the absence of longitudinal human and/or animal studies to unveil the interaction of the gut microbiota with FGID‐relevant pathogenesis; (iii) uncertainty about connections between human and animal studies; and (iv) insufficient data supporting a holistic view of disease‐specific pathophysiological changes in FGID patients. These unidentified gaps open possibilities to explore pathological mechanisms directed through gut microbiota dysbiosis in FGIDs. The current treatment options for dysbiotic gut microbiota are limited; dietary interventions, antibiotics, probiotics, and fecal microbiota transplantation are the front‐line clinical options. Here, we review the contribution of gut microbiota and its derived molecules in gut homeostasis and explore the possible pathophysiological mechanisms involved in FGIDs leading to potential therapeutics options.
Advances in immunotherapy for pancreatic ductal adenocarcinoma
Authors: Miyazawa Motoki , Katsuda Masahiro , Kawai Manabu , Hirono Seiko , Okada Ken‐ichi , Kitahata Yuji , Yamaue Hiroki
Published: March 2021

Advances in immunotherapy against advanced cancers can be considered stunning and epoch‐making. Meanwhile, efficacy of immune‐based therapies, especially immune checkpoint inhibitors, remains insufficient in pancreatic ductal adenocarcinoma, differing from other immunogenic cancers. To date, neither immunotherapies targeting immune system acceleration nor release of immunologic brakes have been able to overcome the robust immune barrier in the pancreatic tumor microenvironment, which is characterized by rich fibrotic stroma and accumulation of immunosuppressive myeloid cells. However, by receiving an immune checkpoint blockade, patients with abundant tumor‐infiltrating lymphocytes in pancreatic ductal adenocarcinoma clearly have better prognosis, and patients with mismatch repair deficiency have achieved better outcomes, albeit in a small population of pancreatic ductal adenocarcinoma. We overview recent preclinical and clinical studies that have been concerned with immune‐based therapies including cancer vaccine and immune checkpoint inhibitors. By providing a deep insight into the immunosuppressive tumor microenvironment, we suggest the possibility of comprehensive immune intensification that could reverse the tumor microenvironment, making it conducive to cytotoxic T lymphocyte activity for overcoming pancreatic ductal adenocarcinoma.
Female labour force participation and dowries in Pakistan
Authors: Makino Momoe
Published: March 2021

Dowries are prevalent in South Asian countries, despite legal bans. Theoretical studies suggest that increasing women's financial contribution to households is the key to effectively abolishing this practice. To empirically examine this proposition, we conducted a unique survey in rural Pakistan and gathered contemporaneous information about the expected amount of dowry for unmarried daughters. The estimation results show a negative association between female labour force participation and the expected amount of dowry, whereas no negative association is observed with other marriage expenses. These findings suggest that the negative association derives from appreciation of working women rather than their stigmatization.
Finding the right fit: Mock victims' preferences for police interviewer characteristics
Authors: Snow Mark D. , Akca Davut , Connors Christina J. , Crough Quintan , Eastwood Joseph
Published: March 2021

Victims can provide details necessary to resolve criminal investigations but may be reluctant to come forward and fully disclose an incident to law enforcement. Although evidence‐based interviewing techniques such as rapport‐building have shown promise in increasing cooperation, the potential impact of interviewers' inherent characteristics (e.g., age and gender) on information disclosure has been relatively under examined. We investigated mock sexual assault victims' preferences for various police interviewer characteristics and the impact of these preferences on hypothetical reporting behaviour. Participants rated interviewers' interpersonal skills as highly important. Gender differences were observed, with only female participants consistently reporting that having a same‐gender interviewer was important. Participants also indicated that if they were provided with their preferred interviewer, they would feel more comfortable, provide more detail, and would be more willing to report the offence to police. Our findings suggest that matching interviewees with their preferred interviewers may improve interviewing and investigative outcomes.