bluuebunny/crossref_metadata_2025 huggingface dataset:
Opowiedzieć historię. Rola narracji w sprawozdaniu zintegrowanym – studium przypadku Novo Nordisk A/S
Authors: Kobiela-Pionnier Katarzyna
Published: September 2021

Wraz z pojawieniem się nowych trendów w sprawozdawczości przedsiębiorstw, a zwłaszcza sprawozdania zintegrowanego i strategicznego, udział narracyjnej części raportów nieustannie rośnie. Według danych Deloitte, obecnie odpowiada ona za ponad 60% objętości rocznego raportu spółki w Wielkiej Brytanii. Celem artykułu jest ukazanie roli, jaką odgrywa narracja, a zwłaszcza opowiadanie historii (ang. storytelling), w sprawozdaniu zintegrowanym. Artykuł składa się z dwóch głównych części: teoretycznej i praktycznej. W części teoretycznej na bazie studiów literaturowych przeprowadzono pogłębione rozważania na temat pojęć „narracja” i „storytelling” w kontekście sprawozdawczości przedsiębiorstw. W części praktycznej wnikliwej analizie poddano sposób prowadzenia narracji w duńskiej firmie farmaceutycznej Novo Nordisk, uznanym liderze raportowania zintegrowanego. Zdaniem autorki niewątpliwym wyzwaniem dla badaczy w najbliższej przyszłości powinno być pogłębienie wiedzy na temat narracyjnych wyborów w ramach sprawozdawczości korporacyjnej oraz ich konsekwencji w bogatym, złożonym środowisku informacyjnym.
Źródła informacji wykorzystywane w systemie wczesnego reagowania w przedsiębiorstwach
Authors: Górecka Katarzyna
Published: September 2021

W artykule przedstawiono źródła informacji wykorzystywane w analizie otoczenia przedsiębiorstwa. Kluczem do sprawnej metody przewidywania przyszłych wydarzeń jest nasłuch otoczenia, a więc wykrywanie słabych sygnałów płynących z otoczenia przedsiębiorstwa. Analiza otoczenia dalszego pomaga zidentyfikować kierunek przyszłych zmian, a analiza otoczenia bliższego – dopasować produkt do przyszłych warunków rynkowych.
Antibacterial activity of ethanol extracts of betel leaf (Piper betle L.) and areca (Areca catechu L.) nuts against food borne and oral pathogens
Authors: Khatun Masuda , Hoque Md Mahfuzul
Published: September 2021

Antimicrobial activity of ethanol extracts of betel leaf (Piper betle L.) and areca nut (Areca catechu) against six food borne enteric pathogens viz. Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (icddr,b), Salmonella typhimurium (AIM-40, icddr,b), Escherichia coli (ATCC 25922), Escherichia coli O157:H7 (ATCC 12079) and Bacillus cereus (ATCC 12079), and four oral pathogens such as isolates 1 & 2 of each of the two bacteria viz. Staphylococcus sp. and Pseudomonas sp. was investigated. Ethanol extract of betel leaf produced highest zone of inhibition (18.0 ± 1.91 mm) against Staphylococcus epidermidis (icddr,b) whereas that of areca nut produced highest zone of inhibition (15.0 ± 0.816 mm) against Staphylococcus aureus (ATCC 25923). But no inhibition was found against Salmonella typhimurium (ATCC AIM-40, icddr,b), Escherichia coli (ATCC 25922), and Escherichia coli O157:H7 (ATCC 12079) by the Ethanol extract of betel leaf. The MIC and MBC values of both ethanol extracts indicated that Gram positive organisms were more susceptible than Gram negative organisms. Highest antimicrobial activity of ethanol extracts of betel leaf was found against the isolate 1 of Staphylococcus sp. (16.5±0.5) and that of areca nut was recorded against the isolate 1 of Staphylococcus sp. (12.0±0.5) and the isolate 2 of Pseudomonas sp. (12.0±0.5). Present study reveals the potentials of both the extracts to inhibit food borne enteric and oral pathogens that could be used as food preservatives to prevent the food borne illness as well as for maintaining the oral and gut health.

Bangladesh J Microbiol, Volume 38, Number 1, June 2021, pp 15-19
Dyslipidemic profile in healthy women in relation to body fat distribution
Authors: Shubeska Stratrova Slavica , Kostova Elena
Published: September 2021

Abdominal obesity is associated with particularly adverse lipidemic profile. The aim of this study was to determine the characteristics of the dyslipidemic profile in healthy women with extreme abdominal obesity determined anthropometrically. Lipid profile and atherogenic indexes were determined in 80 healthy women, grouped in 4 groups according to their body mass index (BMI) and grouped in 3 groups according to their body fat distribution (BFD) by means of anthropometric indexes waist/hip ratio (WHR) and waist/thigh ratio circumference (WTR): group M with normal BFD (WHR<0.85 and WTR<1.45), group N with moderate (WHR 0.85-1 and WTR 1.45-1.7) and group O with extremely expressed abdominal BFD.
HDL-cholesterol (HDL-C) levels (0.84±0.26mmol/L) were significantly lowest in group O (p<0.002), and significantly lower compared to group N (1.14±0.43mmol/L) (p<0.006). Triglyceride (TG) levels were significantly higher in group O compared to group M (p<0.001) and also higher in group N compared to group M (p<0.044). Atherogenic indexes C/HDL-C, LDL/HDL-C and TG/HDL-C values in group O were significantly higher compared to the corresponding values in group M (p<0.004; p< 0.006; p<0.001), and their values were also higher in group O compared to group N, but with lower significance of the difference (p<0.05) indicating lower increase of the atherogenic indexes in moderate and significant increase in women with extreme abdominal obesity.
Dyslipidemic profile and high atherogenic indexes in women with abdominal obesity with significantly highest WHR, WTR and BMI values indicated the need to intervene earlier and more effectively in the prevention and treatment of cardiovascular and metabolic risks.

Keywords: abdominal obesity, anthropometric indexes, lipid profile, atherogenic indexes
Tubular Surfaces Around a Null Curve and Its Spherical Images
Authors: ATES Fatma
Published: September 2021

In this study, we define tubular surfaces whose center curves are null curves and their spherical images in Minkowski 3􀀀space. Firstly, we give the interior properties of the surfaces and calculate their invariant curvatures. Then, we obtain some special characterizations for the parameter curves of the surfaces. Finally, we demonstrate the theory via example and give their visualizations with the help of Mathematica.
Transpolar and bi-directional migration strategies of black-legged kittiwakes Rissa tridactyla from a colony in Novaya Zemlya, Barents Sea, Russia
Authors: Ezhov AV , Gavrilo MV , Krasnov YV , Bråthen VS , Moe B , Baranskaya AV , Strøm H
Published: September 2021

Atlantic black-legged kittiwakes Rissa tridactyla tridactyla breeding in the Barents Sea have long been considered to winter in the North Atlantic region. Here, we present the first evidence of bi-directional and transpolar migrations of kittiwakes breeding in the south-eastern Barents Sea. Using geolocators, we revealed previously unknown migration patterns of kittiwakes that breed at Yuzhny (Southern) Island of the Novaya Zemlya Archipelago. Of 27 studied individuals, 21 migrated to the North Atlantic, while 6 (22%) wintered in the North Pacific. Two birds repeated an eastward migration over 3 subsequent years, and 3 kittiwakes did so over 2 years. We hypothesize that such bi-directional migration strategies can reflect the history of the kittiwakes’ colonization of the eastern Barents Sea, where North Pacific birds may have colonized Novaya Zemlya from the east and maintained their traditional wintering grounds in the Pacific. However, we also expect that the exchange of Atlantic and Pacific (Rissa t. pollicaris) kittiwakes will increase as the sea ice barrier shrinks in the following decades, potentially having a great impact on these 2 subspecies.
What brings adolescents to the Obstetrics and Gynaecology Emergency Department of a General Hospital
Authors: Litos M. , Triantafyllidi V. , Vasileiadou D. , Papamargaritis E. , Sofoudis C. , Bakalianou K.
Published: September 2021

Introduction: Paediatric & Adolescent Gynaecology is a special field and also part of the everyday practice. This paper studies the problems adolescent females present with at the Obstetrics & Gynaecology (O&G) Emergency Department (ED). Material and Methods: Data regarding adolescent females that were examined at the O&G ED over one year (2018) were extracted from the records of Konstantiopouleio General Hospital, Athens, Greece. Results: Of the 1534 women that attended O&G ED over one year, 111 were under 19 years old (7%). Of the 83 gynaecological cases, the presenting symptom was pelvic pain in 54 (65%), irregular vaginal bleeding in 11(13%), urinary tract symptoms in 11(13%), vaginal discomfort in 3 (4%) and others in 4 (5%). In 39 (47%) no urgent gynaecological pathology was detected. There were 11 cases (13%) of ovarian cysts, 10 of urinary tract infection (12%), 7 (8%) of other surgical pathology, 6 (8%) of first trimester pregnancy complications and 10 others. Of the 28 pregnant adolescents, 10 complained of abdominal pain (36%), 6 of hyperemesis (21%), 5 of myometrial activity (18%), 4 of vaginal bleeding (14%). In 18 cases (64%) no acute medical condition was diagnosed, 4 were admitted in active labour (14%) and one with threatened delivery, two were referred to other specialties and three refused the examination. Conclusion: O&G emergency conditions in adolescent females are common and potentially serious. Healthcare professionals need to be aware and alert to the special needs of this significant and sensitive population group.
The role of epigenetic factors in descendants from Assisted Reproductive Techniques (ART)
Authors: Pergialiotis Vasilios , Prodromidou Anastasia , Dimitroulia Evangelia , Loutradis Dimitrios
Published: September 2021

Altogether, Assisted Reproductive Techniques (ART) are likely to cause some epigenetic changes in the offspring, which might consist the molecular basis of complex characteristics and diseases. The present review contributes a large biochemical dataset of a well-defined group of pre- pubertal in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) conceived children in order to detect the potential effect in the offspring’s health. Additionally, the relevant usefulness of metabolomics and proteomics are also investigated. The outcomes indicate early insulin resistance in ICSI-offspring which can set the basis for further research in the field so as to identify the respective pathophysiological pathways and mechanisms of action. The data support that metabolomics may unravel metabolic variances before they become clinically or biochemically evident, underlining its utility in the ART research.
Mixed graph colouring as scheduling multi-processor tasks with equal processing times
Authors: Sotskov Yuri N.
Published: September 2021

A problem of scheduling partially ordered unit-time tasks processed on dedicated machines is formulated as a mixed graph colouring problem, i. e., as an assignment of integers (colours) {1, 2, …, t} to the vertices (tasks) V {ν1, ν2, …, νn}, of the mixed graph G = (V, A, E) such that if vertices vp and vq are joined by an edge [νp, νq] ∈ E their colours have to be different. Further, if two vertices νp and νq are joined by an arc (νi, νj) ∈ A the colour of vertex νi has to be no greater than the colour of vertex νj. We prove that an optimal colouring of a mixed graph G = (V, A, E) is equivalent to the scheduling problem GcMPT|pi = 1|Cmax of finding an optimal schedule for partially ordered multi-processor tasks with unit (equal) processing times. Contrary to classical shop-scheduling problems, several dedicated machines are required to process an individual task in the scheduling problem GcMPT|pi = 1|Cmax. Moreover, along with precedence constraints given on the set V {ν1, ν2, …, νn}, it is required that a subset of tasks must be processed simultaneously. Due to the theorems proved in this article, most analytical results that have been proved for the scheduling problems GcMPT |pi = 1|Cmax so far, have analogous results for optimal colourings of the mixed graphs G = (V, A, E), and vice versa.
«The creative turn» in European social theory
Authors: Matsevich-Dukhan Iryna Ja.
Published: September 2021

The article reveals specific features of contemporary European social theory within its turn to the nature of creative practices. Different socio-philosophical methods of their cognition are demonstrated. The explication of the character of European social theory as a whole outlines the increasing interest in the formation of a theory of creative society which critically grounds the set of political programmes «Creative Europe». The author defines the concept of the creative turn within a comparative analysis of those theories of contemporary society which explore the peculiarity of social reality constituting on the basis of creative economy. Its practices become a special subject matter of social theory revealing societal limitations of their fulfillment.
A Case Series of Spontaneous Secondary Pneumothorax in Post Covid Period: A Clinical Insight
Authors: Banerjee Sayani , Das Thakur Sujoy , Nandy Aishwarya
Published: September 2021

Introduction: We are in the era of novel coronavirus pandemic. Each wave is teaching us something new about the disease pathology, long term prognosis. Nonetheless, COVID-19 is giving rise to new challenges to the clinicians every day with its new found complications, long haul Covid symptoms. Secondary spontaneous pneumothorax has been reported to be a rare complication, seen in 1%-2% of COVID-19 patients with a mean time occurrence of 24.3 days from the hospital admission during the early phase of intubation. Case discussion: We report a case series of four patients in post COVID period presented with sudden onset respiratory distress and hypoxia, diagnosed with spontaneous secondary pneumothorax. Out of three only one patient received NIV support during his past treatment for COVID-19 and others were treated with oxygen. Therefore, barotrauma secondary to positive pressure ventilation and rupture of cystic bulla cannot be a sole cause of this complication. Persistent chronic inflammatory process and ischemic damage of alveoli are other possible etiologies. Conclusion: We highlight in our case series the importance of clinical examination, especially chest auscultation, which most clinicians circumvent owing to the trepidation of contracting COVID-19. We also proposed large researches to identify causal association with pneumothorax and previous use of steroids to treat COVID-19, persistent inflammation, age, gender, comorbidity etc to prevent it, as it can be debilitating and fatal. A clinician should always keep pneumothorax as a differential in sudden deteriorating breathlessness and hypoxia in post COVID period as it may happen as late as >40 days from primary COVID diagnosis.
Development learning media of circle using android-based augmented reality for the deaf students
Authors: Andriyani Andriyani , Buliali Joko Lianto
Published: September 2021

Penelitian ini bertujuan untuk menghasilkan media pembelajaran lingkaran dengan augmented reality berbasis Android yang valid dan praktis bagi siswa tunarungu. Media pembelajaran tersebut akan dinilai kelayakannya dari segi kevalidan dan kepraktisan. Penelitian ini termasuk penelitian pengembangan (R&D) dengan menggunakan model ADDIE yang terdiri atas empat tahap yaitu analisis, pendesainan, pengembangan, implementasi dan tahap evaluasi. Subjek dalam penelitian ini adalah 17 siswa tunarungu kelas VII, VIII dan IX di SLBN 2 Bantul. Instrumen penelitian ini terdiri dari instrumen angket penilaian kevalidan dari segi materi dan media, serta lembar angket respon siswa. Analisis data skor validasi ahli dan skor respon siswa yang berbentuk skor skala lima (kategori kuantitatif), dikonversi ke dalam kategori kualitatif. Hasil penelitian berupa media lingkaran dengan augmented reality berbasis Android yang valid dan praktis. Ditinjau dari hasil penilaian ahli materi dan ahli media, kevalidan media termasuk kategori sangat baik. Sedangkan dari penilaian respon siswa, kepraktisan media termasuk kategori sangat baik. Siswa tunarungu terlihat antusias menggunakan media pembelajaran yang mengakomodir keterbatasan indra pendengarannya, melalui penyajian teks sebagai pengganti audio dalam mengilustrasikan konten visual konsep lingkaran. Meskipun sudah memenuhi kriteria kevalidan dan kepraktisan, namun media yang dikembangkan masih memiliki keterbatasan yang memerlukan adanya penelitian lebih lanjut menurut penilaian guru.
Constructing Age for Young Readers
Authors: Joosen Vanessa
Published: September 2021

Children's literature studies has been relatively slow in adopting techniques from digital humanities. This article explains a method for digitising, annotating, and analysing texts in xml to investigate the implicit age norms that children's books convey. The case studies are seventeen books by Bart Moeyaert and La Belle Sauvage by Philip Pullman. The analysis of speech distribution, topic modelling, syntactic parsing, and lexical analysis with digital tools adds information about implicit age norms that can support and inspire narrative analyses with close reading.
Jill Craigie, Post-war British Film Culture and the British Film Academy
Authors: Tasker Yvonne
Published: September 2021

This article seeks to locate the socialist feminist film-maker Jill Craigie in the British film culture of the post-war period. Long regarded in scholarly accounts as something of an outsider, a woman who was effectively shut out of the industry during the 1950s, this article seeks to position Craigie rather differently. While acknowledging the obstacles she undoubtedly faced, it details aspects of her achievements and her visibility in the British film culture of the immediate post-war period. Craigie's politically driven documentaries and realist film practice accorded with prevailing discourses of ‘quality’ and she acquired the status of what would today be termed a media personality who worked across film, radio, television and print media. Considering Craigie as a figure embedded in the British film establishment, this article gives particular emphasis to her role in the British Film Academy (BFA), arguing that the significance of this practitioner-led organisation has yet to be fully recognised in British film history. The argument draws on archives held at the British Academy of Film and Television Arts (BAFTA) to begin a discussion of how the BFA, and Craigie as the first woman to be elected to its Management Council, played its part in the development of British film culture.
Independent Miss Craigie: Narration and the Archive in a Documentary Biopic
Authors: Thynne Lizzie
Published: September 2021

This article explores the process of making a documentary about Jill Craigie which drew, in particular, on the collection of her papers at the Women's Library and on documents belonging to Craigie and her family. Independent Miss Craigie (2021) seeks to examine the scope and synergies of film-making and politics in a career which encompassed independent production, journalism, broadcasting, television and writing. Our documentary aims to evoke the tensions between Craigie's own (rather diverse) accounts of her career, the evidence of it in her papers and in the contemporary reception of her work. This article about the making of the film provides space to reflect on how archival materials can be used to construct a narrative of a woman director's career. In doing so, it highlights the inevitable gaps and elisions in archival sources and, indeed, in the interpretation of Craigie's films and come to some conclusions about Craigie's disparaging attitude to her own work in later life.
Differential Interactome Based Drug Repositioning Unraveled Abacavir, Exemestane, Nortriptyline Hydrochloride, and Tolcapone as Potential Therapeutics for Colorectal Cancers
Authors: Beklen Hande , Arslan Sema , Gulfidan Gizem , Turanli Beste , Ozbek Pemra , Karademir Yilmaz Betul , Arga Kazim Yalcin
Published: September 2021

There is a critical requirement for alternative strategies to provide the better treatment in colorectal cancer (CRC). Hence, our goal was to propose novel biomarkers as well as drug candidates for its treatment through differential interactome based drug repositioning. Differentially interacting proteins and their modules were identified, and their prognostic power were estimated through survival analyses. Drug repositioning was carried out for significant target proteins, and candidate drugs were analyzed via in silico molecular docking prior to in vitro cell viability assays in CRC cell lines. Six modules (mAPEX1, mCCT7, mHSD17B10, mMYC, mPSMB5, mRAN) were highlighted considering their prognostic performance. Drug repositioning resulted in eight drugs (abacavir, ribociclib, exemestane, voriconazole, nortriptyline hydrochloride, theophylline, bromocriptine mesylate, and tolcapone). Moreover, significant in vitro inhibition profiles were obtained in abacavir, nortriptyline hydrochloride, exemestane, tolcapone, and theophylline (positive control). Our findings may provide new and complementary strategies for the treatment of CRC.
The Role of Cutaneous Microcirculatory Responses in Tissue Injury, Inflammation and Repair at the Foot in Diabetes
Authors: Balasubramanian Gayathri Victoria , Chockalingam Nachiappan , Naemi Roozbeh
Published: September 2021

Diabetic foot syndrome is one of the most costly complications of diabetes. Damage to the soft tissue structure is one of the primary causes of diabetic foot ulcers and most of the current literature focuses on factors such as neuropathy and excessive load. Although the role of blood supply has been reported in the context of macro-circulation, soft tissue damage and its healing in the context of skin microcirculation have not been adequately investigated. Previous research suggested that certain microcirculatory responses protect the skin and their impairment may contribute to increased risk for occlusive and ischemic injuries to the foot. The purpose of this narrative review was to explore and establish the possible link between impairment in skin perfusion and the chain of events that leads to ulceration, considering the interaction with other more established ulceration factors. This review highlights some of the key skin microcirculatory functions in response to various stimuli. The microcirculatory responses observed in the form of altered skin blood flow are divided into three categories based on the type of stimuli including occlusion, pressure and temperature. Studies on the three categories were reviewed including: the microcirculatory response to occlusive ischemia or Post-Occlusive Reactive Hyperaemia (PORH); the microcirculatory response to locally applied pressure such as Pressure-Induced Vasodilation (PIV); and the interplay between microcirculation and skin temperature and the microcirculatory responses to thermal stimuli such as reduced/increased blood flow due to cooling/heating. This review highlights how microcirculatory responses protect the skin and the plantar soft tissues and their plausible dysfunction in people with diabetes. Whilst discussing the link between impairment in skin perfusion as a result of altered microcirculatory response, the review describes the chain of events that leads to ulceration. A thorough understanding of the microcirculatory function and its impaired reactive mechanisms is provided, which allows an understanding of the interaction between functional disturbances of microcirculation and other more established factors for foot ulceration.
Porous Geometry Guided Micro-mechanical Environment Within Scaffolds for Cell Mechanobiology Study in Bone Tissue Engineering
Authors: Zhao Feihu , Xiong Yi , Ito Keita , van Rietbergen Bert , Hofmann Sandra
Published: September 2021

Mechanobiology research is for understanding the role of mechanics in cell physiology and pathology. It will have implications for studying bone physiology and pathology and to guide the strategy for regenerating both the structural and functional features of bone. Mechanobiological studies in vitro apply a dynamic micro-mechanical environment to cells via bioreactors. Porous scaffolds are commonly used for housing the cells in a three-dimensional (3D) culturing environment. Such scaffolds usually have different pore geometries (e.g. with different pore shapes, pore dimensions and porosities). These pore geometries can affect the internal micro-mechanical environment that the cells experience when loaded in the bioreactor. Therefore, to adjust the applied micro-mechanical environment on cells, researchers can tune either the applied load and/or the design of the scaffold pore geometries. This review will provide information on how the micro-mechanical environment (e.g. fluid-induced wall shear stress and mechanical strain) is affected by various scaffold pore geometries within different bioreactors. It shall allow researchers to estimate/quantify the micro-mechanical environment according to the already known pore geometry information, or to find a suitable pore geometry according to the desirable micro-mechanical environment to be applied. Finally, as future work, artificial intelligent – assisted techniques, which can achieve an automatic design of solid porous scaffold geometry for tuning/optimising the micro-mechanical environment are suggested.
Circular RNA CircPPP1CB Suppresses Tumorigenesis by Interacting With the MiR-1307-3p/SMG1 Axis in Human Bladder Cancer
Authors: Wang Feifan , Zhang Yan , Zhou Xuejian , Chen Xianwu , Xiang Jiayong , Fan Mengjing , Yu Yanlan , Cai Yueshu , Wu Hongshen , Huang Shihan , He Ning , Hu Zhenghui , Ding Guoqing , Jin Xiaodong
Published: September 2021

Circular RNA (circRNA) is a newly discovered endogenous non-coding RNA (ncRNA), which is characterized with a closed circular structure. A growing body of evidence has verified the vital roles of circRNAs in human cancer. In this research, we selected circPPP1CB as a study object by circRNA sequencing and quantitative real-time PCR (qRT-PCR) validation in human bladder cancer (BC). CircPPP1CB is downregulated in BC and is negatively correlated with clinical stages and histological grades. Functionally, circPPP1CB modulated cell growth, metastasis, and epithelial-to-mesenchymal transition (EMT) process in vitro and in vivo. Mechanically, we performed various experiments to verify the circPPP1CB/miR-1307-3p/SMG1 regulatory axis. Taken together, our results demonstrated that circPPP1CB participates in tumor growth, metastasis, and EMT process by interacting with the miR-1307-3p/SMG1 axis, and that circPPP1CB might be a novel therapeutic target and diagnostic biomarker in human BC.
Characterization of the Primary Human Trophoblast Cell Secretome Using Stable Isotope Labeling With Amino Acids in Cell Culture
Authors: Rosario Fredrick J. , Pardo Sammy , Michelsen Trond M. , Erickson Kathryn , Moore Lorna , Powell Theresa L. , Weintraub Susan T. , Jansson Thomas
Published: September 2021

The placental villus syncytiotrophoblast, the nutrient-transporting and hormone-producing epithelium of the human placenta, is a critical regulator of fetal development and maternal physiology. However, the identities of the proteins synthesized and secreted by primary human trophoblast (PHT) cells remain unknown. Stable Isotope Labeling with Amino Acids in Cell Culture followed by mass spectrometry analysis of the conditioned media was used to identify secreted proteins and obtain information about their relative rates of synthesis in syncytialized multinucleated PHT cells isolated from normal term placental villus tissue (n = 4/independent placenta). A total of 1,344 proteins were identified, most of which have not previously been reported to be secreted by the human placenta or trophoblast. The majority of secreted proteins are involved in energy and carbon metabolism, glycolysis, biosynthesis of amino acids, purine metabolism, and fatty acid degradation. Histone family proteins and mitochondrial proteins were among proteins with the slowest synthesis rate whereas proteins associated with signaling and the plasma membrane were synthesized rapidly. There was a significant overlap between the PHT secretome and proteins known be secreted to the fetal circulation by the human placenta in vivo. The generated data will guide future experiments to determine the function of individual secreted proteins and will help us better understand how the placenta controls maternal and fetal physiology.
Skeletal Muscle Deconditioning in Breast Cancer Patients Undergoing Chemotherapy: Current Knowledge and Insights From Other Cancers
Authors: Mallard Joris , Hucteau Elyse , Hureau Thomas J. , Pagano Allan F.
Published: September 2021

Breast cancer represents the most commonly diagnosed cancer while neoadjuvant and adjuvant chemotherapies are extensively used in order to reduce tumor development and improve disease-free survival. However, chemotherapy also leads to severe off-target side-effects resulting, together with the tumor itself, in major skeletal muscle deconditioning. This review first focuses on recent advances in both macroscopic changes and cellular mechanisms implicated in skeletal muscle deconditioning of breast cancer patients, particularly as a consequence of the chemotherapy treatment. To date, only six clinical studies used muscle biopsies in breast cancer patients and highlighted several important aspects of muscle deconditioning such as a decrease in muscle fibers cross-sectional area, a dysregulation of protein turnover balance and mitochondrial alterations. However, in comparison with the knowledge accumulated through decades of intensive research with many different animal and human models of muscle atrophy, more studies are necessary to obtain a comprehensive understanding of the cellular processes implicated in breast cancer-mediated muscle deconditioning. This understanding is indeed essential to ultimately lead to the implementation of efficient preventive strategies such as exercise, nutrition or pharmacological treatments. We therefore also discuss potential mechanisms implicated in muscle deconditioning by drawing a parallel with other cancer cachexia models of muscle wasting, both at the pre-clinical and clinical levels.
Targeting Histone Modifications in Breast Cancer: A Precise Weapon on the Way
Authors: Li Wei , Wu Hao , Sui Shiyao , Wang Qin , Xu Shouping , Pang Da
Published: September 2021

Histone modifications (HMs) contribute to maintaining genomic stability, transcription, DNA repair, and modulating chromatin in cancer cells. Furthermore, HMs are dynamic and reversible processes that involve interactions between numerous enzymes and molecular components. Aberrant HMs are strongly associated with tumorigenesis and progression of breast cancer (BC), although the specific mechanisms are not completely understood. Moreover, there is no comprehensive overview of abnormal HMs in BC, and BC therapies that target HMs are still in their infancy. Therefore, this review summarizes the existing evidence regarding HMs that are involved in BC and the potential mechanisms that are related to aberrant HMs. Moreover, this review examines the currently available agents and approved drugs that have been tested in pre-clinical and clinical studies to evaluate their effects on HMs. Finally, this review covers the barriers to the clinical application of therapies that target HMs, and possible strategies that could help overcome these barriers and accelerate the use of these therapies to cure patients.
Super-Resolution Microscopy: Shedding New Light on In Vivo Imaging
Authors: Jing Yingying , Zhang Chenshuang , Yu Bin , Lin Danying , Qu Junle
Published: September 2021

Over the past two decades, super-resolution microscopy (SRM), which offered a significant improvement in resolution over conventional light microscopy, has become a powerful tool to visualize biological activities in both fixed and living cells. However, completely understanding biological processes requires studying cells in a physiological context at high spatiotemporal resolution. Recently, SRM has showcased its ability to observe the detailed structures and dynamics in living species. Here we summarized recent technical advancements in SRM that have been successfully applied to in vivo imaging. Then, improvements in the labeling strategies are discussed together with the spectroscopic and chemical demands of the fluorophores. Finally, we broadly reviewed the current applications for super-resolution techniques in living species and highlighted some inherent challenges faced in this emerging field. We hope that this review could serve as an ideal reference for researchers as well as beginners in the relevant field of in vivo super resolution imaging.
Unilateral Intervention in the Sinuses of Rabbits Induces Bilateral Inflammatory and Microbial Changes
Authors: Lux Christian A. , Johnston James J. , Waldvogel-Thurlow Sharon , Dassi Camila , Douglas Richard G. , Cho Do-Yeon , Taylor Michael W. , Biswas Kristi
Published: September 2021

Background

Chronic rhinosinusitis (CRS) is a globally prevalent inflammatory condition of the paranasal sinuses which severely impairs patients’ quality of life. An animal model of unilateral sinusitis by transient sinus occlusion has been described previously in rabbits. The aim of this study was to characterise the sinusitis rabbit model by investigating temporal and bilateral changes in the bacterial community and mucosal inflammation.

Methods

Development of sinusitis was achieved by endoscopically placing Merocel®, a sterile nasal packing material, in the left middle meatus of six New Zealand white rabbits for four weeks. After a total period of 14 weeks, rabbits were assessed for sinusitis by endoscopic examination, magnetic resonance imaging (MRI) and histology. Swabs from the left and right middle meatus were obtained for bacterial community analysis at three time points (week 0, week 4, week 14) during the study.

Results

Endoscopic evaluation showed unilateral inflammation in all animals examined after the 4-week blocking period and at week 14. Notably, inflammatory changes were also seen in the contralateral sinus of all animals at week 4. MRI images demonstrated unilateral sinus opacification at week 4 in two rabbits, and partial unilateral sinus opacification at week 14 in one rabbit only. Histological analyses revealed substantial spatial heterogeneity of mucosal inflammation with inconsistent findings across all animals. No significant differences in mucosal inflammatory markers (such as goblet cell hyperplasia, epithelial denudation and oedema) could be identified between nostrils at week 14. The bacterial community in the rabbit sinuses was heavily dominated by Helicobacter at week 0 (baseline). At the end of the blocking period (week 4), bacterial alpha and beta diversity were significantly increased in both nostrils. The bacterial community composition at week 14 had primarily returned to baseline, reflecting the endoscopic and radiological results.

Conclusion

This study reaffirmed the ability for development of sinusitis without inoculation of any pathogens in a rabbit model. We were able to demonstrate bilateral sinonasal mucosal inflammation, by inducing unilateral sinus blockage, which resulted in significant changes to the sinonasal bacterial community. These findings may explain some of the clinical observations seen in CRS and warrant further research to reveal potential implications for its therapeutic management.
Protective Immunity Induced by TgMIC5 and TgMIC16 DNA Vaccines Against Toxoplasmosis
Authors: Zhu Yu-Chao , Ma Li-Juan , Zhang Ji-Li , Liu Jian-Fa , He Yong , Feng Ji-Ye , Chen Jia
Published: September 2021

Toxoplasma gondii is an obligate intracellular parasite, which is responsible for a widely distributed zoonosis. Effective vaccines against toxoplasmosis are necessary to protect the public health. The aim of this study is to evaluate the immune efficacy of DNA vaccines encoding TgMIC5 and TgMIC16 genes against T. gondii infection. The recombinant plasmid pVAX-MIC5 and pVAX-MIC16 were constructed and injected intramuscularly in mice. The specific immune responses and protection against challenge with T. gondii RH tachyzoites were evaluated by measuring the cytokine levels, serum antibody concentrations, lymphocyte proliferation, lymphocyte populations, and the survival time. The protection against challenge with the T. gondii RH tchyzoites and PRU cysts was examined by evaluation of the reduction in the brain cyst burden. The results indicated that immunized mice showed significantly increased levels of IgG, IFN-γ, IL-2, IL-12p70, and IL-12p40 and percentages of CD4+ and CD8+ T cells. Additionally, vaccination prolonged the mouse survival time and reduced brain cysts compared with controls. Mouse groups immunized with a two-gene cocktail of pVAX-MIC5 + pVAX-MIC16 were more protected than mouse groups immunized with a single gene of pVAX-MIC5 or pVAX-MIC16. These results demonstrate that TgMIC5 and TgMIC16 induce effective immunity against toxoplasmosis and may serve as a good vaccine candidate against T. gondii infection.
The Role of Tricarboxylic Acid Cycle Metabolites in Viral Infections
Authors: Sánchez-García Francisco Javier , Pérez-Hernández Celia Angélica , Rodríguez-Murillo Miguel , Moreno-Altamirano María Maximina Bertha
Published: September 2021

Host cell metabolism is essential for the viral replication cycle and, therefore, for productive infection. Energy (ATP) is required for the receptor-mediated attachment of viral particles to susceptible cells and for their entry into the cytoplasm. Host cells must synthesize an array of biomolecules and engage in intracellular trafficking processes to enable viruses to complete their replication cycle. The tricarboxylic acid (TCA) cycle has a key role in ATP production as well as in the synthesis of the biomolecules needed for viral replication. The final assembly and budding process of enveloped viruses, for instance, require lipids, and the TCA cycle provides the precursor (citrate) for fatty acid synthesis (FAS). Viral infections may induce host inflammation and TCA cycle metabolic intermediates participate in this process, notably citrate and succinate. On the other hand, viral infections may promote the synthesis of itaconate from TCA cis-aconitate. Itaconate harbors anti-inflammatory, anti-oxidant, and anti-microbial properties. Fumarate is another TCA cycle intermediate with immunoregulatory properties, and its derivatives such as dimethyl fumarate (DMF) are therapeutic candidates for the contention of virus-induced hyper-inflammation and oxidative stress. The TCA cycle is at the core of viral infection and replication as well as viral pathogenesis and anti-viral immunity. This review highlights the role of the TCA cycle in viral infections and explores recent advances in the fast-moving field of virometabolism.
Unraveling the Complexity of Imported Malaria Infections by Amplicon Deep Sequencing
Authors: He Xi , Zhong Daibin , Zou Chunyan , Pi Liang , Zhao Luyi , Qin Yucheng , Pan Maohua , Wang Siqi , Zeng Weiling , Xiang Zheng , Chen Xi , Wu Yanrui , Si Yu , Cui Liwang , Huang Yaming , Yan Guiyun , Yang Zhaoqing
Published: September 2021

Imported malaria and recurrent infections are becoming an emerging issue in many malaria non-endemic countries. This study aimed to determine the molecular patterns of the imported malaria infections and recurrence. Blood samples were collected from patients with imported malaria infections during 2016–2018 in Guangxi Zhuang Autonomous Region, China. Next-generation amplicon deep-sequencing approaches were used to assess parasite genetic diversity, multiplexity of infection, relapse, recrudescence, and antimalarial drug resistance. A total of 44 imported malaria cases were examined during the study, of which 35 (79.5%) had recurrent malaria infections within 1 year. The majority (91.4%) had one recurrent malaria episode, whereas two patients had two recurrences and one patient had three recurrences. A total of 19 recurrence patterns (the species responsible for primary and successive clinical episodes) were found in patients returning from malaria epidemic countries. Four parasite species were detected with a higher than usual proportion (46.2%) of non-falciparum infections or mixed-species infections. An increasing trend of recurrence infections and reduced drug treatment efficacy were observed among the cases of imported malaria. The high recurrence rate and complex patterns of imported malaria from Africa to non-endemic countries have the potential to initiate local transmission, thereby undermining efforts to eliminate locally acquired malaria. Our findings highlight the power of amplicon deep-sequencing applications in molecular epidemiological studies of the imported malaria recurrences.
Using a Two-Sample Mendelian Randomization Method in Assessing the Causal Relationships Between Human Blood Metabolites and Heart Failure
Authors: Wang Zixian , Chen Shiyu , Zhu Qian , Wu Yonglin , Xu Guifeng , Guo Gongjie , Lai Weihua , Chen Jiyan , Zhong Shilong
Published: September 2021

Background: Heart failure (HF) is the main cause of morbidity and mortality worldwide, and metabolic dysfunction is an important factor related to HF pathogenesis and development. However, the causal effect of blood metabolites on HF remains unclear.

Objectives: Our chief aim is to investigate the causal relationships between human blood metabolites and HF risk.

Methods: We used an unbiased two-sample Mendelian randomization (MR) approach to assess the causal relationships between 486 human blood metabolites and HF risk. Exposure information was obtained from Sample 1, which is the largest metabolome-based genome-wide association study (mGWAS) data containing 7,824 Europeans. Outcome information was obtained from Sample 2, which is based on the results of a large-scale GWAS meta-analysis of HF and contains 47,309 cases and 930,014 controls of Europeans. The inverse variance weighted (IVW) model was used as the primary two-sample MR analysis method and followed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis.

Results: We observed that 11 known metabolites were potentially related to the risk of HF after using the IVW method (P < 0.05). After adding another four MR models and performing sensitivity analyses, we found a 1-SD increase in the xenobiotics 4-vinylphenol sulfate was associated with ~22% higher risk of HF (OR [95%CI], 1.22 [1.07–1.38]).

Conclusions: We revealed that the 4-vinylphenol sulfate may nominally increase the risk of HF by 22% after using a two-sample MR approach. Our findings may provide novel insights into the pathogenesis underlying HF and novel strategies for HF prevention.
Association Between Metabolic Syndrome and an Increased Risk of Hospitalization for Heart Failure in Population of HFpEF
Authors: Zhou Ying , Fu Liyao , Sun Jiaxing , Zhu Zhaowei , Xing Zhenhua , Zhou Shenghua , Tai Shi , Wang Yongjun
Published: September 2021

Background: The association between metabolic syndrome and the development of heart failure (HF) with preserved ejection fraction (HFpEF) has not been completely clarified.

Aim: To evaluate the association between metabolic syndrome and the risk of HF hospitalization for patients with HFpEF.

Methods: Patient data were obtained from the American cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial database. Data for the primary outcome (hospitalization for HF) and secondary outcomes (all-cause mortality, cardiovascular mortality, and all-cause hospitalization) were collected, and hazard ratios (HRs) for the patients with and without metabolic syndrome were analyzed by applying a multivariable Cox proportional hazard model.

Results: Among the 1,548 total participants, 1,197 had metabolic syndrome. The patients with metabolic syndrome exhibited worse heart function and a lower quality of life than those without metabolic syndrome. During the 3.3 years of follow-up, 351 patients were hospitalized for HF. After a multivariable adjustment, the risk of hospitalization for HF and all-cause hospitalization (adjusted HR = 1.42, 95% CI: 1.01–2.00; p = 0.042 and adjusted HR = 1.27; 95% CI: 1.04–1.54; p = 0.017, respectively) were independently associated with HFpEF for the patients with metabolic syndrome. In addition, the risks of HF hospitalization and all-cause hospitalization among 267 propensity score-matched patients were higher for patients with metabolic syndrome (HR = 1.53, 95% CI = 1.05–2.23, and p = 0.025 and HR = 1.34, 95% CI = 1.08–1.67, and p = 0.009, respectively).

Conclusion: The risks of HF hospitalization and all-cause hospitalization were higher for patients with HFpEF having metabolic syndrome than for those without metabolic syndrome.
The Potential Role of Cardiac CT in the Evaluation of Patients With Known or Suspected Cardiomyopathy: From Traditional Indications to Novel Clinical Applications
Authors: Conte Edoardo , Mushtaq Saima , Muscogiuri Giuseppe , Formenti Alberto , Annoni Andrea , Mancini Elisabetta , Ricci Francesca , Melotti Eleonora , Gigante Carlo , Lorenza Zanotto , Guglielmo Marco , Baggiano Andrea , Maragna Riccardo , Giacari Carlo Maria , Carbucicchio Corrado , Catto Valentina , Pepi Mauro , Andreini Daniele , Pontone Gianluca
Published: September 2021

After 15 years from its advent in the clinical field, coronary computed tomography (CCTA) is now widely considered as the best first-step test in patients with low-to-moderate pre-test probability of coronary artery disease. Technological innovation was of pivotal importance for the extensive clinical and scientific interest in CCTA. Recently, the advent of last generation wide-coverage CT scans paved the way for new clinical applications of this technique beyond coronary arteries anatomy evaluation. More precisely, both biventricular volume and systolic function quantification and myocardial fibrosis identification appeared to be feasible with last generation CT. In the present review we would focus on potential applications of cardiac computed tomography (CCT), beyond CCTA, for a comprehensive assessment patients with newly diagnosed cardiomyopathy, from technical requirements to novel clinical applications.