bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Domain States in Rhombohedral Lead Zirconate Titanate Films via Misfit Strains and Surface Charges
Authors: Vorotiahin Ivan S. , Morozovska Anna N. , Eliseev Eugene A. , Genenko Yuri A.
Published: July 2021

Using the Landau–Ginzburg–Devonshire approach and numerical modeling, an influence of the misfit strain and surface screening charges as well as the role of the flexoelectric effect have been studied in the case of a rhombohedral lead zirconate titanate ferroelectric/ferroelastic thin film with an anisotropic misfit caused by a substrate. The magnitude and sign of the misfit strain influence the domain structure, providing misfit‐dependent phases with different favorable polarization components. Whilst strong enough compressive misfit strains favor a phase with orthorhombic‐like polarization directions, strong tensile misfits only yield in‐plane polarization components. The strength of surface screening conditions the existence of closure domain structures and, by increasing, supports the single‐domain state. The flexoelectric effect exhibits a weak influence on the phase diagram of multi‐domain states when compared with the phase diagram of single‐domain states. Its effect, however, becomes significant in the case of skyrmion topological states spontaneously formed near the film surface when compressive misfit strains are applied. Cooperative influence of the misfit strain, surface screening charges, and temperature can set a thin rhombohedral ferroelectric film into a number of different polar and structural states, whereby the role of the flexoelectric effect is pronounced for topologically nontrivial structures.
Mixed‐methods exploration of students' motivation in using augmented reality in neuroanatomy education with prosected specimens
Authors: Bölek Kerem A. , De Jong Guido , Van der Zee Catharina E. E. M. , van Cappellen van Walsum Anne‐Marie , Henssen Dylan J. H. A.
Published: July 2021

The use of augmented reality (AR) in teaching and studying neuroanatomy has been well researched. Previous research showed that AR‐based learning of neuroanatomy has both alleviated cognitive load and was attractive to young learners. However, how the attractiveness of AR effects student motivation has not been discovered. Therefore, the motivational effects of AR were investigated in this research by the use of quantitative and qualitative methods. Motivation elicited by the GreyMapp‐AR, an AR application, was investigated in medical and biomedical sciences students (n = 222; mean age: 19.7 ± 1.4 years) using the instructional measure of motivation survey (IMMS). Additional components (i.e., attention, relevance, confidence, and satisfaction) were also evaluated with motivation as measured by IMMS. Additionally, 19 students underwent audio‐recorded individual interviews which were transcribed for qualitative analysis. Males regarded the relevance of AR significantly higher than females (P < 0.024). Appreciation of the GreyMapp‐AR program was found to be significantly higher in students studying biomedical sciences as compared to students studying medicine (P < 0.011). Other components and scores did not show significant differences between student groups. Students expressed that AR was beneficial in increasing their motivation to study subcortical structures, and that AR could be helpful and motivating for preparing an anatomy examination. This study suggests that students are motivated to study neuroanatomy by the use of AR, although the components that make up their individual motivation can differ significantly between groups of students.
Musculoskeletal anatomy knowledge in Australian chiropractors
Authors: Giuriato Rosemary , Štrkalj Goran , Prvan Tania , Hulme Anneliese , Pather Nalini
Published: July 2021

Anatomy is a key knowledge area in chiropractic and is formally offered in the undergraduate component of chiropractic education. There is the potential for loss of anatomy knowledge before the opportunity to apply it in a clinical setting. This study aimed to determine whether chiropractic clinicians retain a level of anatomy knowledge comparable to that of chiropractic students and to compare chiropractors' self‐rating of their anatomical knowledge against an objective knowledge assessment tool. A previously validated multiple‐choice test was utilized to measure retention of limb musculoskeletal (MSK) knowledge in Australian chiropractors. One hundred and one registered chiropractors completed the questionnaire and responses were scored, analyzed, and compared to scores attained by undergraduate and postgraduate chiropractic students who had previously completed the same questionnaire. The results indicated that practitioners retained their anatomy knowledge, with a significantly higher total mean score than the undergraduate group [total mean score = 36.5% (±SD 13.6%); P < 0.01] but not significantly different to the postgraduate group [total mean score = 52.2% (±SD 14.1%); P = 0.74]. There was a weak positive correlation between chiropractors' self‐rated knowledge and test performance scores indicating the effectiveness of this Australian chiropractic group in self‐assessing their anatomy knowledge. This study found that Australian chiropractors' knowledge of MSK anatomy was retained during the transition from university to clinical practice and they accurately evaluated their own test performance.
Breaking barriers: The landscape of human and veterinary medical anatomy education and the potential for collaboration
Authors: McNulty Margaret A. , Mussell Jason C. , Lufler Rebecca S.
Published: July 2021

Despite human (HUM) and veterinary (VET) medical institutions sharing the goal of educating future clinicians, there is little collaboration between them regarding curricular and pedagogical practices during the preclinical/basic science training years. This may be, at least in part, due to a lack of understanding of each type of curriculum. This study presents data about curricula, student populations, pedagogical methodologies applied, and anatomy educators' training at both HUM and VET institutions. Preclinical curricula, admissions criteria, and student demographics were analyzed for 21 institutions in the United States having both HUM and VET schools. This dataset was augmented by a questionnaire sent to anatomists internationally, detailing anatomy curricula, pedagogies applied, and anatomy educators' training. Many curricular similarities between both training programs were identified, including anatomy education experiences. However, VET programs were found to include more preclinical coursework than HUM programs. Students who matriculate to VET or HUM schools have similar academic records, including prerequisite coursework and grade point average. Median HUM class size was significantly larger, and the percentage of women enrolled in VET institutions was significantly higher. Training of anatomy educators was identical with one exception: VET educators are far more likely to hold a clinical degree. This study elucidates the substantial similarities between VET and HUM programs, particularly in anatomy education, underscoring the potential for collaboration between both types of programs in areas such as interprofessional education, bioethics, zoonotic disease management, and postgraduate training.
How signaling pathways link extracellular mechano‐environment to proline biosynthesis: A hypothesis
Authors: Chen Keng , Guo Ling , Wu Chuanyue
Published: July 2021

We propose a signaling pathway in which cell‐extracellular matrix (ECM) adhesion components PINCH‐1 and kindlin‐2 sense mechanical signals from ECM and link them to proline biosynthesis, a vital metabolic pathway for macromolecule synthesis, redox balance, and ECM remodeling. ECM stiffening promotes PINCH‐1 expression via integrin signaling, which suppresses dynamin‐related protein 1 (DRP1) expression and mitochondrial fission, resulting in increased kindlin‐2 translocation into mitochondria and interaction with Δ1‐pyrroline‐5‐carboxylate (P5C) reductase 1 (PYCR1). Kindlin‐2 interaction with PYCR1 protects the latter from proteolytic degradation, leading to elevated PYCR1 level. Additionally, PINCH‐1 promotes P5C synthase (P5CS) expression and P5C synthesis, which, together with increased PYCR1 level, support augmented proline biosynthesis. This signaling pathway is frequently activated in fibrosis and cancer, resulting in increased proline biosynthesis and excessive collagen matrix production, which in turn further promotes ECM stiffening. Targeting this signaling pathway, therefore, may provide an effective strategy for alleviating fibrosis and cancer progression.
Parallel and large‐scale antitumor investigation using stable chemical gradient and heterotypic three‐dimensional tumor coculture in a multi‐layered microfluidic device
Authors: Liu Wenming , Hu Rui , Han Kai , Sun Meilin , Liu Dan , Zhang Jinwei , Wang Jinyi
Published: July 2021

Background

Cancer has been responsible for a large number of human deaths in the 21st century. Establishing a controllable, biomimetic, and large‐scale analytical platform to investigate the tumor‐associated pathophysiological and preclinical events, such as oncogenesis and chemotherapy, is necessary.

Methods and Results

This study presents antitumor investigation in a parallel, large‐scale, and tissue‐mimicking manner based on well‐constructed chemical gradients and heterotypic three‐dimensional (3D) tumor cocultures using a multifunction‐integrated device. The integrated microfluidic device was engineered to produce a controllable and steady chemical gradient by manipulative optimization. Array‐like and size‐homogeneous production of heterotypic 3D tumor cocultures with in vivo‐like features, including similar tumor‐stromal composition and functional phenotypic gradients of metabolic activity and viability, was successfully established. Furthermore, temporal, parallel, and high‐throughput analyses of tumor behaviors in different antitumor stimulations were performed in a device based on the integrated operations involving gradient generation and coculture.

Conclusion

This achievement holds great potential for applications in the establishment of multifunctional tumor platforms to perform tissue‐biomimetic neoplastic research and therapy assessment in the fields of oncology, bioengineering, and drug discovery.
Contribution of a DNA Nick to DNA Bendability Depending on the Bending Force
Authors: Yeou Sanghun , Lee Nam Ki
Published: July 2021

A DNA nick plays a pivotal role in the bending and release of mechanical stress for double‐stranded DNA (dsDNA). However, it remains unclear how a DNA nick modulates the bendability of dsDNA. Here, we report that a single nick in 30 base‐pair dsDNA decreases the bending stiffness of dsDNA by 20%–30% and that the bendability of dsDNA depends on the applied bending force. To achieve this, we used D‐shaped DNA nanostructures and single‐molecule fluorescence resonance energy transfer for measurement of the bending angle of dsDNA. We found that a nick in dsDNA under a bending force increases the bendability of dsDNA and the bending stiffness of dsDNA decreases further as the applied bending force is increased. Our results provide a new perspective for the effect of a nick on dsDNA mechanics, and the methods introduced here will be useful for investigating various biological processes involving DNA nicks.
A cross‐linked anti‐TNF‐α aptamer for neutralization of TNF‐α‐induced cutaneous Shwartzman phenomenon: A simple and novel approach for improving aptamers' affinity and efficiency
Authors: Mashayekhi Kazem , Sankian Mojtaba , Haftcheshmeh Saeed Mohammadian , Taheri Ramezan Ali , Hassanpour Kazem , Farnoosh Gholamreza
Published: July 2021

To increase the efficiency of aptamers to their targets, a simple and novel method has been developed based on aptamer oligomerization. To this purpose, previously anti‐human TNF‐α aptamer named T1–T4 was trimerized through a trimethyl aconitate core for neutralization of in vitro and in vivo of TNF‐α. At first, 54 mer T1–T4 aptamers with 5′‐NH2 groups were covalently coupled to three ester residues in the trimethyl aconitate. In vitro activity of novel anti‐TNF‐α aptamer and its dissociation constant (Kd) was done using the L929 cell cytotoxicity assay. In vivo anti‐TNF‐α activity of new oligomerized aptamer was assessed in a mouse model of cutaneous Shwartzman. Anchoring of three T1–T4 aptamers to trimethyl aconitate substituent results in formation of the 162 mer fragment, which was well revealed by gel electrophoresis. In vitro study indicated that the trimerization of T1–T4 aptamer significantly improved its anti‐TNF‐α activity compared to non‐modified aptamers (P < 0.0001) from 40% to 60%. The determination of Kd showed that trimerization could effectively enhance Kd of aptamer from 67 nM to 36 nM. In vivo study showed that trimer aptamer markedly reduced mean scar size from 15.2 ± 1.2 mm to 1.6 ± 0.1 mm (P < 0.0001), which prevent the formation of skin lesions. In vitro and in vivo studies indicate that trimerization of anti‐TNF‐α aptamer with a novel approach could improve the anti‐TNF‐α activity and therapeutic efficacy. According to our findings, a new anti‐TNF‐α aptamer described here could be considered an appropriate therapeutic agent in treating several inflammatory diseases.
Difference in the airway luminal area between the standing and supine positions using upright and conventional computed tomography
Authors: Matsumoto Shunsuke , Yamada Yoshitake , Yamada Minoru , Chubachi Shotaro , Yokoyama Yoichi , Matsuoka Shiho , Tanabe Akiko , Niijima Yuki , Murata Mitsuru , Fukunaga Koichi , Jinzaki Masahiro
Published: July 2021

No clinical studies to date have compared the airway luminal area between supine and standing positions. Our aim was therefore to compare the airway luminal area between these two positions on computed tomography (CT) and to determine its correlation with forced expiratory volume in 1 s (FEV1). Thirty‐two asymptomatic volunteers underwent both conventional (supine position) and upright (standing position) CT during deep inspiration breath‐holding. Pulmonary function tests were conducted on the same day. We measured the airway luminal area on CT in each position. Paired t‐tests and Pearson's correlation coefficients were used for statistical analysis. The average luminal areas of the trachea, right and left main bronchi, and average third‐generation airway were greater in the standing than the supine position by 3.4%, 6.1%, 5.5%, and 5.2%, respectively. The correlation coefficients between airway luminal areas and FEV1 tended to be higher in the standing than the supine position; this correlation was highest for the average third‐generation airway (r = 0.70, P < 0.0001). The airway luminal areas of the trachea, bilateral main bronchi, and average third‐generation airway were greater in the standing than the supine position. The average third‐generation airway area in the standing position had the highest correlation with FEV1.
What's your name again? A review of the superior longitudinal and arcuate fasciculus evolving nomenclature
Authors: Porto de Oliveira João Vítor Miranda , Raquelo‐Menegassio Antônio Felipe , Maldonado Igor Lima
Published: July 2021

Studies of the superior longitudinal fasciculus (SLF) have multiplied in recent decades owing to methodological advances, but the absence of a convention for nomenclature remains a source of confusion. Here, we have reviewed existing nomenclatures in the context of the research studies that generated them and we have identified their agreements and disagreements. A literature search was conducted using PubMed/MEDLINE, Web‐of‐Science, Embase, and a review of seminal publications, without restrictions regarding publication date. Our search revealed that diffusion imaging, autoradiography, and fiber dissection have been the main methods contributing to tract designation. The first two have been particularly influential in systematizing the horizontal elements distant from the lateral sulcus. Twelve approaches to naming were identified, eight of them differing considerably from each other. The terms SLF and arcuate fasciculus (AF) were often used as synonyms until the second half of the 20th century. During the last 15 years, this has ceased to be the case in a growing number of publications. The term AF has been used to refer to the assembly of three different segments, or exclusively to long frontotemporal fibers. Similarly, the term SLF has been employed to denote the whole superior longitudinal associative system, or only the horizontal frontoparietal parts. As only partial correspondence can be identified among the available nomenclatures, and in the absence of an official designation of all anatomical structures that can be encountered in clinical practice, a high level of vigilance regarding the effectiveness of every oral or written act of communication is mandatory.
Performance of glucoamylase self‐producing eBOOST™ GT yeast on ethanol production
Authors: Viswanathan Mothi Bharath , Bhatia Gitanshu , Jansen Mickel , Basu Rahul , Singh Vijay
Published: July 2021

Background and objectives

This study demonstrates ethanol production using a new yeast strain called eBOOST™ GT, that can self‐produce glucoamylase and reduce glycerol production. The advanced yeast’s potential with added glucoamylase expression was investigated by observing and comparing its final ethanol and glycerol concentration against granular starch hydrolyzing enzyme (GSHE) catalyzed Ethanol Red fermentation.

Findings

The ethanol concentration in advanced yeast fermentation with self‐produced glucoamylase was measured at 10.03% v/v, which is 40% less than GSHE catalyzed Ethanol Red fermentation. However, upon externally providing additional glucoamylase (at 50% of the recommended dosage), eBOOST™ GT was able to produce similar ethanol concentration, compared to Ethanol Red fermentation catalyzed with GSHE enzyme. Furthermore, in this scenario, the glycerol concentration at the end of fermentation was 31% less than observed concentrations in operating with only self‐produced glucoamylase and 72% less than conventional GSHE fermentation.

Conclusions

The newly engineered yeast strain proves its capability to meet GSHE catalyzed ethanol yield at reduced enzyme consumption, and therefore, reduction in enzyme costs. The rate of substrate consumption and process economics are areas of future research for eBOOST™ GT ethanol fermentation.

Significance and novelty

This study provides important information on enzyme reduction and ethanol production, while using a self‐enzyme producing yeast.
FFNet: A simple image dedusting network with feature fusion
Authors: Huang Jiayan , Li Zuoyong , Wang Chuansheng , Yu Zhaochai , Cao Xinrong
Published: July 2021

Dust is a common air pollution source. The color of images captured under dusty weather is usually yellow even brown, which reduces scene visibility and causes the loss of image details. To remove the dust and make image scene clear, this article presents a simple and effective image dedusting network called FFNet. In the process of image feature extraction, the FFNet uses several residual blocks with smoothed dilated convolution, that is, common dilated convolution followed by separable and shared (SS) blockwise fully connected operation to extend the receptive field and reduce gridding artifacts caused by common dilated convolution. Furthermore, the FFNet fuses image features from different layers via an adaptive weighting scheme. Due to the difficulty of collecting real dusty images, we used our proposed dusty image synthesis scheme to achieve data augmentation for better network training. Experiments on a series of synthetic and real dusty images demonstrate that the FFNet obtains better image dedusting performance than several state‐of‐the‐art image restoration methods.
A computational model for investigating the evolution of colonic crypts during Lynch syndrome carcinogenesis
Authors: Haupt Saskia , Gleim Nils , Ahadova Aysel , Bläker Hendrik , von Knebel Doeberitz Magnus , Kloor Matthias , Heuveline Vincent
Published: July 2021

Lynch syndrome (LS), the most common inherited colorectal cancer (CRC) syndrome, increases the cancer risk in affected individuals. LS is caused by pathogenic germline variants in one of the DNA mismatch repair (MMR) genes, complete inactivation of which causes numerous mutations in affected cells. As CRC is believed to originate in colonic crypts, understanding the intra‐crypt dynamics caused by mutational processes is essential for a complete picture of LS CRC and may have significant implications for cancer prevention.

We propose a computational model describing the evolution of colonic crypts during LS carcinogenesis. Extending existing modeling approaches for the non‐Lynch scenario, we incorporated MMR deficiency and implemented recent experimental data demonstrating that somaticCTNNB1mutations are common drivers of LS‐associated CRCs, if affecting both alleles of the gene. Further, we simulated the effect of different mutations on the entire crypt, distinguishing non‐transforming and transforming mutations.

As an example, we analyzed the spread of mutations in the genesAPCandCTNNB1, which are frequently mutated in LS tumors, as well as of MMR deficiency itself. We quantified each mutation's potential for monoclonal conversion and investigated the influence of the cell location and of stem cell dynamics on mutation spread.

Thein silicoexperiments underline the importance of stem cell dynamics for the overall crypt evolution. Further, simulating different mutational processes is essential in LS since mutations without survival advantages (the MMR deficiency‐inducing second hit) play a key role. The effect of other mutations can be simulated with the proposed model. Our results provide first mathematical clues towards more effective surveillance protocols for LS carriers.
Rebalancing TGF‐β/Smad7 signaling via Compound kushen injection in hepatic stellate cells protects against liver fibrosis and hepatocarcinogenesis
Authors: Yang Yang , Sun Mayu , Li Weida , Liu Chaobao , Jiang Zheshun , Gu Pengfei , Li Jingquan , Wang Wei , You Rongli , Ba Qian , Li Xiaoguang , Wang Hui
Published: July 2021

Background

Liver fibrosis and fibrosis‐related hepatocarcinogenesis are a rising cause for morbidity and death worldwide. Although transforming growth factor‐β (TGF‐β) is a critical mediator of chronic liver fibrosis, targeting TGF‐β isoforms and receptors lead to unacceptable side effect. This study was designed to explore the antifibrotic effect of Compound kushen injection (CKI), an approved traditional Chinese medicine formula, via a therapeutic strategy of rebalancing TGF‐β/Smad7 signaling.

Methods

A meta‐analysis was performed to evaluate CKI intervention on viral hepatitis‐induced fibrosis or cirrhosis in clinical randomized controlled trials (RCTs). Mice were given carbon tetrachloride (CCl4) injection or methionine‐choline deficient (MCD) diet to induce liver fibrosis, followed by CKI treatment. We examined the expression of TGF‐β/Smad signaling and typical fibrosis‐related genes in hepatic stellate cells (HSCs) and fibrotic liver tissues by qRT‐PCR, Western blotting, RNA‐seq, immunofluorescence, and immunohistochemistry.

Results

Based on meta‐analysis results, CKI improved the liver function and relieved liver fibrosis among patients. In our preclinical studies by using two mouse models, CKI treatment demonstrated promising antifibrotic effects and postponed hepatocarcinogenesis with improved liver function and histopathologic features. Mechanistically, we found that CKI inhibited HSCs activation by stabilizing the interaction of Smad7/TGF‐βR1 to rebalance Smad2/Smad3 signaling, and subsequently decreased the extracellular matrix formation. Importantly, Smad7 depletion abolished the antifibrotic effect of CKI in vivo and in vitro. Moreover, matrine, oxymatrine, sophocarpine, and oxysophocarpine were identified as material basis responsible for the antifibrosis effect of CKI.

Conclusions

Our results unveil the approach of CKI in rebalancing TGF‐β/Smad7 signaling in HSCs to protect against hepatic fibrosis and hepatocarcinogenesis in both preclinical and clinical studies. Our study suggests that CKI can be a candidate for treatment of hepatic fibrosis and related oncogenesis.
Fcγ receptor activation mediates vascular inflammation and abdominal aortic aneurysm development
Authors: Lopez‐Sanz Laura , Bernal Susana , Jimenez‐Castilla Luna , Prieto Ignacio , La Manna Sara , Gomez‐Lopez Sergio , Blanco‐Colio Luis Miguel , Egido Jesus , Martin‐Ventura Jose Luis , Gomez‐Guerrero Carmen
Published: July 2021

Background

Abdominal aortic aneurysm (AAA), a degenerative vascular pathology characterized by permanent dilation of the aorta, is considered a chronic inflammatory disease involving innate/adaptive immunity. However, the functional role of antibody‐dependent immune response against antigens present in the damaged vessel remains unresolved. We hypothesized that engagement of immunoglobulin G (IgG) Fc receptors (FcγR) by immune complexes (IC) in the aortic wall contributes to AAA development. We therefore evaluated FcγR expression in AAA lesions and analysed whether inhibition of FcγR signaling molecules (γ‐chain and Syk kinase) influences AAA formation in mice.

Methods

FcγR gene/protein expression was assessed in human and mouse AAA tissues. Experimental AAA was induced by aortic elastase perfusion in wild‐type (WT) mice and γ‐chain knockout (γKO) mice (devoid of activating FcγR) in combination with macrophage adoptive transfer or Syk inhibitor treatment. To verify the mechanisms of FcγR in vitro, vascular smooth muscle cells (VSMC) and macrophages were stimulated with IgG IC.

Results

FcγR overexpression was detected in adventitia and media layers of human and mouse AAA. Elastase‐perfused γKO mice exhibited a decrease in AAA incidence, aortic dilation, elastin degradation, and VSMC loss. This was associated with (1) reduced infiltrating leukocytes and immune deposits in AAA lesions, (2) inflammatory genes and metalloproteinases downregulation, (3) redox balance restoration, and (4) converse phenotype of anti‐inflammatory macrophage M2 and contractile VSMC. Adoptive transfer of FcγR‐expressing macrophages aggravated aneurysm in γKO mice. In vitro, FcγR deficiency attenuated inflammatory gene expression, oxidative stress, and phenotypic switch triggered by IC. Additionally, Syk inhibition prevented IC‐mediated cell responses, reduced inflammation, and mitigated AAA formation.

Conclusion

Our findings provide insight into the role and mechanisms mediating IgG‐FcγR‐associated inflammation and aortic wall injury in AAA, which might represent therapeutic targets against AAA disease.
CB1R and iNOS are distinct players promoting pulmonary fibrosis in Hermansky–Pudlak syndrome
Authors: Cinar Resat , Park Joshua K. , Zawatsky Charles N. , Coffey Nathan J. , Bodine Steven P. , Abdalla Jasmina , Yokoyama Tadafumi , Jourdan Tony , Jay Lindsey , Zuo Mei Xing G. , O'Brien Kevin J. , Huang Junfeng , Mackie Ken , Alimardanov Asaf , Iyer Malliga R. , Gahl William A. , Kunos George , Gochuico Bernadette R. , Malicdan May Christine V.
Published: July 2021

Hermansky–Pudlak syndrome (HPS) is a rare genetic disorder which, in its most common and severe form, HPS‐1, leads to fatal adult‐onset pulmonary fibrosis (PF) with no effective treatment. We evaluated the role of the endocannabinoid/CB1R system and inducible nitric oxide synthase (iNOS) for dual‐target therapeutic strategy using human bronchoalveolar lavage fluid (BALF), lung samples from patients with HPS and controls, HPS‐PF patient‐derived lung fibroblasts, and bleomycin‐induced PF in pale ear mice (HPS1ep/ep). We found overexpression of CB1R and iNOS in fibrotic lungs of HPSPF patients and bleomycin‐infused pale ear mice. The endocannabinoid anandamide was elevated in BALF and negatively correlated with pulmonary function parameters in HPSPF patients and pale ear mice with bleomycin‐induced PF. Simultaneous targeting of CB1R and iNOS by MRI‐1867 yielded greater antifibrotic efficacy than inhibiting either target alone by attenuating critical pathologic pathways. Moreover, MRI‐1867 treatment abrogated bleomycin‐induced increases in lung levels of the profibrotic interleukin‐11 via iNOS inhibition and reversed mitochondrial dysfunction via CB1R inhibition. Dual inhibition of CB1R and iNOS is an effective antifibrotic strategy for HPSPF.
The human melanoma proteome atlas—Defining the molecular pathology
Authors: Betancourt Lazaro Hiram , Gil Jeovanis , Kim Yonghyo , Doma Viktória , Çakır Uğur , Sanchez Aniel , Murillo Jimmy Rodriguez , Kuras Magdalena , Parada Indira Pla , Sugihara Yutaka , Appelqvist Roger , Wieslander Elisabet , Welinder Charlotte , Velasquez Erika , de Almeida Natália Pinto , Woldmar Nicole , Marko‐Varga Matilda , Pawłowski Krzysztof , Eriksson Jonatan , Szeitz Beáta , Baldetorp Bo , Ingvar Christian , Olsson Håkan , Lundgren Lotta , Lindberg Henrik , Oskolas Henriett , Lee Boram , Berge Ethan , Sjögren Marie , Eriksson Carina , Kim Dasol , Kwon Ho Jeong , Knudsen Beatrice , Rezeli Melinda , Hong Runyu , Horvatovich Peter , Miliotis Tasso , Nishimura Toshihide , Kato Harubumi , Steinfelder Erik , Oppermann Madalina , Miller Ken , Florindi Francesco , Zhou Qimin , Domont Gilberto B. , Pizzatti Luciana , Nogueira Fábio C. S. , Horvath Peter , Szadai Leticia , Tímár József , Kárpáti Sarolta , Szász A. Marcell , Malm Johan , Fenyö David , Ekedahl Henrik , Németh István Balázs , Marko‐Varga György
Published: July 2021

The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in‐depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma. The data generated by global proteomic experiments covered 72% of the proteins identified in the recently reported high stringency blueprint of the human proteome. This study contributes to the NIH Cancer Moonshot initiative combining detailed histopathological presentation with the molecular characterization for 505 melanoma tumor samples, localized in 26 organs from 232 patients.
A structured seabird population model reveals how alternative forage fish control rules benefit seabirds and fisheries
Authors: Koehn Laura E. , Siple Margaret C. , Essington Timothy E.
Published: July 2021

Fisheries for forage fish may affect the survival and reproduction of piscivorous predators, especially seabirds. However, seabirds have evolved life history strategies to cope with natural fluctuations in prey and it is difficult to separate effects of fishing on seabirds from impacts of natural variability. To date, potential impacts of forage fisheries on seabirds have mainly been explored using ecosystem models that simplify seabird–forage‐fish dynamics. We sought to explore how different forage fish harvest policies affect seabirds, accounting for structured population dynamics, life history specifics, and variation in forage fish dependencies across life stages; and how impacts vary across seabird and forage fish life histories. To explore these impacts, we developed an age‐stage structured seabird model that incorporates seabird diet specialization, foraging behavior, and reproductive strategy, as well as different functional responses between prey availability and adult survival, juvenile survival, reproductive success, and breeder propensity. We parameterized this model for two contrasting seabird life histories: (1) a low fecundity, limited foraging range, diet specialist (“restricted”); and (2) a high fecundity, wide ranging, diet generalist (“flexible”). Each was paired with two different forage fish prey archetypes that were fished under various control rules. The restricted seabird population was expectedly less robust to constant fishing pressure than the flexible seabird, and this sensitivity was mainly due to functional response parameterization, rather than other life history parameters. Particularly, the restricted seabird was highly sensitive to the relationship between prey availability and adult survival but was not sensitive to the relationship between prey and reproductive success. An adaptive biomass‐limit harvest rule for forage fish resulted in substantially higher seabird abundance compared to constant fishing across all scenarios, with minimal trade‐offs to the fishery (depending on fishery management objectives). However, mechanisms governing the impact of the forage fish fishery on the seabird varied by forage fish type. Therefore, tailoring forage fish management strategies to forage fish life history can lead to mutually acceptable outcomes for fisheries and seabirds. If data or time are limited, an adaptive control rule is likely a safe bet for meeting seabird conservation objectives with limited impacts to fisheries.
Extraordinary Compatibility to Mass Loading and Rate Capability of Hierarchically Porous Carbon Nanorods Electrode Derived from the Waste Tire Pyrolysis Oil
Authors: Li Shengping , Yang Zipan , Wu Mingzhen , Xu Chenggen , Zhang Xilu , Lin Rundan , Wang Xuejie , Zhao Lu , Sun Dong , Ma Xinlong , Gao Jinsen
Published: July 2021

The conversion of waste tire pyrolysis oil (WTPO) into S‐doped porous carbon nanorods (labeled as WPCNs) with hierarchical pore structure is realized by a simple template‐directed approach. The specific surface area of as‐obtained porous carbon nanorods can reach up to 1448 m2 g−1 without the addition of any activating agent. As the capacitive electrode, WPCNs possess the extraordinary compatibility to capacitance, different electrolyte systems as well as long‐term cycle life even at a commercial‐level areal mass loading (10 mg cm−2). Besides, only an extremely small capacitance fluctuation is observed under the extreme circumstance (−40 to 80 °C), reflecting the excellent high‐ and low‐temperature performance. The relationship between the pore structure and capacitive behavior is analyzed by comparing WPCNs with mesopores‐dominated asphalt‐derived porous carbon nanorods (APCNs) and micropores‐dominated activated carbon. The molecular dynamics simulation further reveals the ion diffusion and transfer ability of the as‐prepared carbon materials under different pore size distribution. The total ion flow (NT) of WPCNs calculated by the simulation is obviously larger than APCNs and the NT ratio between them is similar with the experimental average capacitance ratio. Furthermore, this work also provides a valuable strategy to prepare the electrode material with high capacitive energy storage ability through the high value‐added utilization of WTPO.
Musicogenic reflex seizure with positive antiglutamic decarboxylase antibody: A case report
Authors: Al‐Attas Alawi A. , Al Anazi Riyam F. , Swailem Saleh K.
Published: July 2021

The association of musicogenic epilepsy (ME) with antibodies against glutamic decarboxylase (GAD) supports autoimmune workups for these patients. No appropriate treatment has been established for ME; therefore, immunotherapy should be considered for patients who become drug‐resistant. The connection between neurological manifestations and antibodies against GAD, a rate‐limiting enzyme that helps create the inhibitory neurotransmitter gamma‐aminobutyric acid, has been well established. Furthermore, a strong correlation has been found between ME and the temporal lobe. However, its connection with anti‐GAD antibodies is still unclear. This paper reports on a 50‐year‐old right‐handed female who has had ME symptoms for 14 years and been found to be anti‐GAD antibody–positive. Therefore, we will elaborate on the relation between ME and anti‐GAD antibodies.
Hybrid testing of capacity designed RC structural walls for the determination of nonlinear seismic shear amplification
Authors: Fatemi Hassan , Lamarche Charles‐Philippe , Paultre Patrick
Published: July 2021

Hybrid testing is an effective experimental method to study the dynamic behavior of structural elements under various types of loads. The hybrid testing method enables the seismic responses of large structural elements to be reproduced, such as the responses of reinforced concrete (RC) shear walls in a laboratory environment without needing to include the large masses typically encountered in multistory buildings. In this study, a test specimen corresponding to the base plastic hinge zone of an eight‐story RC structural wall was tested in a laboratory environment, whereas the remainder of the wall was modeled numerically to evaluate the seismic shear amplification due to nonlinear higher mode effects. A method is presented for controlling three degrees of freedom of a specimen with high axial stiffness and high lateral stiffness at the beginning of the test and the substantially reduced stiffness after cracking and yielding of the specimen. Because the duration of an uninterrupted test would have been very long, a method was used to stop and restart the test at will so that the whole test could be performed over several days. Seismic shear amplification due to nonlinear higher mode effects in a structural wall with yielding occurring at the base is measured for the first time in a hybrid test . The test results clearly present seismic shear amplification that is larger than building codes recommended values.
Widespread cryptic variation in genetic architecture between the sexes
Authors: van der Bijl Wouter , Mank Judith E.
Published: July 2021

The majority of the genome is shared between the sexes, and it is expected that the genetic architecture of most traits is shared as well. This common architecture has been viewed as a major source of constraint on the evolution of sexual dimorphism (SD). SD is nonetheless common in nature, leading to assumptions that it results from differential regulation of shared genetic architecture. Here, we study the effect of thousands of gene knockout mutations on 202 mouse phenotypes to explore how regulatory variation affects SD. We show that many traits are dimorphic to some extent, and that a surprising proportion of knockouts have sex-specific phenotypic effects. Many traits, regardless whether they are monomorphic or dimorphic, harbor cryptic differences in genetic architecture between the sexes, resulting in sexually discordant phenotypic effects from sexually concordant regulatory changes. This provides an alternative route to dimorphism through sex-specific genetic architecture, rather than differential regulation of shared architecture.
Income gradient of pharmaceutical panic buying at the outbreak of the COVID‐19 pandemic
Authors: Elek Péter , Bíró Anikó , Fadgyas‐Freyler Petra
Published: July 2021

We analyze the timing, magnitude, and income dependence of pharmaceutical panic buying around the outbreak of the COVID‐19 pandemic in Hungary. We use district‐level monthly and daily administrative data on detailed categories of pharmaceutical purchases, merge them to income statistics, and estimate multilevel panel models. Our main results are as follows. First, the days of therapy (DOT) of pharmaceutical purchases increased by more than 30% in March 2020, when major lockdown measures were announced. This pattern holds for almost all categories of pharmaceuticals. Second, shortly after the panic reactions, the aggregate amount of pharmaceutical purchases returned to their preshock levels; however, the frequency of pharmacy visits decreased. Third, the panic buying reaction was significantly stronger in richer geographical areas, where—according to the daily data—people also reacted earlier to the pandemic‐related news. Overall, the results suggest that panic buying of pharmaceuticals can have detrimental effects on vulnerable populations.
Households' out‐of‐pocket expenditure for healthcare in Bangladesh: A health financing incidence analysis
Authors: Sarker Abdur Razzaque , Sultana Marufa , Alam Khorshed , Ali Nausad , Sheikh Nurnabi , Akram Raisul , Morton Alec
Published: July 2021

Background

Despite improvements in many health indicators, providing access to affordable healthcare remains a considerable challenge in Bangladesh. Financing incidence analysis will enable an evaluation of how well the healthcare system performs to achieve equity in health financing. The objective of this study is to assess the burden of out‐of‐pocket (OOP) cost on different socio‐economic groups by assessing the health financing incidence because OOP cost dominates household expenditure on health in Bangladesh.

Methods

The study was conducted using latest Household Income and Expenditure Survey (HIES) 2016. We focused mainly on four specific indicators: level of monthly household OOP cost on in‐patient care, urban‐rural differences in OOP cost, socio‐economic status differences in different payment mechanisms and the Kakwani index. Descriptive statistics were employed to analyse and summarise the selected variables based on the SES and location of residence (e.g., rural and urban).

Results

The study showed the overall OOP healthcare expenditure was 7.7% of the household monthly income while the poorer income group suffered more and spent up to 35% of their household income on healthcare. The Kakwani index indicated that the poorest quintile spends a greater share of their income on healthcare services than the richest quintile.

Conclusions

This study observed that OOP cost in Bangladesh is regressive, that is, poorer members of society contribute a greater share of their income. Therefore, policymakers should initiate health reforms for developing and implementing risk‐pooling financing mechanisms such as social health insurance to achieve the Universal Health Coverage in Bangladesh.
Bioremediation of textile dye wastewater using microalgae: current trends and future perspectives
Authors: Premaratne Malith , Nishshanka GKSH , Liyanaarachchi VC , Nimarshana PHV , Ariyadasa Thilini U
Published: July 2021

Wastewater generated from the textile industry contains numerous pollutants, most notably dyes, which can cause adverse effects, including negative impact on aesthetics, eutrophication, decrease of photosynthetic activity and bioaccumulation of toxins in aquatic ecosystems, if discharged without adequate treatment. The cultivation of microalgae in the textile dye effluent has been identified as a promising alternative to conventional methods of wastewater treatment. During microalgae cultivation, dyes present in effluent are remediated through bioconversion/biodegradation or biosorption. Thus, treatment using microalgae reduces the color and nutrient load of textile effluent, which mitigates numerous negative environmental impacts caused by its discharge into the natural environment. Furthermore, compared to conventional treatment processes, use of microalgae for bioremediation of textile effluent provides the added advantage of generating valuable biomass that can be processed into bioproducts, biofuels and bioenergy. Wastewater‐integrated cultivation would enhance the sustainability of microalgal biomass production by reducing the freshwater footprint and recovery of waste nutrients from effluent, thereby promoting the concept of a biobased economy. In this mini‐review, the current status and future perspectives of using microalgae for bioremediation of textile dye wastewater were analyzed, with focus on various strategies reported in the literature. A critical review of the literature showed that most studies focused on wastewater treatment, while exploring applications for concomitantly generated biomass was a secondary consideration. Hence, the requirement of a paradigm shift in current research for valorization of microalgal biomass was highlighted. Moreover, it was concluded that comprehensive feasibility studies are necessary prior to industrial‐scale bioremediation of textile dye effluent. © 2021 Society of Chemical Industry (SCI).
First mathematics course in college and graduating in engineering: Dispelling the myth that beginning in higher‐level mathematics courses is always a good thing
Authors: Wilkins Jesse L. M. , Bowen Bradley D. , Mullins Sara Brooke
Published: July 2021

Background

Graduation rates in engineering programs continue to be a concern in higher education. Prior research has documented an association between students' experiences in first‐year mathematics courses and graduation rates, but the influences of the mathematics courses completed and the grades earned are not fully understood.

Purpose

The purpose of this study was to investigate the relationship among the first undergraduate mathematics course a student completes, the grade they earn in this course, and the likelihood of graduating with a degree in engineering within six years.

Method

The study involved 1504 students from five consecutive cohorts of first‐year students enrolled in an engineering degree program at a medium‐sized Midwestern public university. Logistic regression was used to model the interrelationship between course and grade in predicting the relative likelihood of graduation for students enrolled in 16 different mathematics courses.

Results

Overall, students who take Calculus I or a more advanced mathematics course as their first mathematic course and who are more successful in their first mathematics course are more likely to graduate with a degree in engineering. However, considering grade and course together, some groups of students who are more successful in lower‐level mathematics courses are as likely to graduate as students who are less successful in upper‐level mathematics courses.

Conclusions

Evidence from this study helps to dispel the myth that beginning with higher‐level mathematics courses is the optimal course‐taking strategy when pursuing an engineering degree. Findings have implications for student advising, curriculum and instruction, high school course‐taking, and broadening participation in engineering.
Extracellular vesicle‐mediated endothelial apoptosis and EV‐associated proteins correlate with COVID‐19 disease severity
Authors: Krishnamachary Balaji , Cook Christine , Kumar Ashok , Spikes Leslie , Chalise Prabhakar , Dhillon Navneet K.
Published: July 2021

Coronavirus disease‐2019 (COVID‐19), caused by the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has lead to a global pandemic with a rising toll in infections and deaths. Better understanding of its pathogenesis will greatly improve the outcomes and treatment of affected patients. Here we compared the inflammatory and cardiovascular disease‐related protein cargo of circulating large and small extracellular vesicles (EVs) from 84 hospitalized patients infected with SARS‐CoV‐2 with different stages of disease severity. Our findings reveal significant enrichment of proinflammatory, procoagulation, immunoregulatory and tissue‐remodelling protein signatures in EVs, which remarkably distinguished symptomatic COVID‐19 patients from uninfected controls with matched comorbidities and delineated those with moderate disease from those who were critically ill. Specifically, EN‐RAGE, followed by TF and IL‐18R1, showed the strongest correlation with disease severity and length of hospitalization. Importantly, EVs from COVID‐19 patients induced apoptosis of pulmonary microvascular endothelial cells in the order of disease severity. In conclusion, our findings support a role for EVs in the pathogenesis of COVID‐19 disease and underpin the development of EV‐based approaches to predicting disease severity, determining need for patient hospitalization and identifying new therapeutic targets.