bluuebunny/crossref_metadata_2025 huggingface dataset:
Funkcjonowanie rynku obligacji komunalnych w Polsce w latach 2012-2018
Authors: Frydrych Sylwia
Published: September 2021

Niniejszy artykuł porusza tematykę funkcjonowania rynku obligacji komunalnych w Polsce. Analiza obejmuje lata 2012-2018. W opracowaniu zwrócono uwagę również na rolę Catalyst w rozwoju dłużnych papierów wartościowych. Materiałem badawczym w niniejszym artykule są: analiza literatury i aktów prawnych, metoda obserwacji, analiza dokumentów źródłowych oraz metoda dedukcji. Rezultatem rozważań jest określenie obszarów, na które należy zwrócić uwagę w celu wzrostu zainteresowania rynkiem obligacji komunalnych.

Przeprowadzona analiza wykazała, iż jednostki samorządu terytorialnego, dokonując emisji długu, przyczyniły się w niewielkim stopniu do rozwoju tego rynku. Również powstanie platformy Catalyst spowodowało nieznaczny wzrost zainteresowania emisją tego rodzaju papierów dłużnych, wyższy udział w finansowaniu zadłużenia w analizowanym okresie miały kredyty i pożyczki
Dezintegracja pozytywna przedsiębiorstwa
Authors: Gigol Tomasz
Published: September 2021

Artykuł koncentruje się na twórczym przekształceniu przedsiębiorstwa z organizacji przeciętnej do wybitnej. Czynnikiem sprawczym jest rodzaj przywództwa najwyższego kierownictwa przedsiębiorstwa. Użyto metafory organizacja - organizm G. Morgana, zawężając pojęcie organizmu do człowieka. Porównano cykl życia przedsiębiorstwa do cyklu życia i dojrzewania jednostki. Wykorzystano teorię dezintegracji pozytywnej K. Dąbrowskiego i zaadaptowano ją do teorii organizacji.
Case report of Double Valve Replacement with Coronary Artery Bypass Grafting with Supracoronary Ascending Aortic Replacement in a Single Patient - A Chimera
Authors: Gupta Saikat Das , Roy Jagadananda , Hoque Mujibul , Mandol Bhabesh C , Chanda PK
Published: September 2021

Double valve replacement is now-a-days a common procedure to treat diseased cardiac valves and the primary aim of prophylactic aortic replacement during concomitant valve replacement is to prevent dreadful complication like dissection, aortic rupture and even death. Although aortic surgeries are complex and have high morbidity and mortality rates, additional double valve procedure with coronary surgery can make it even worse. But for these patients, surgery remains the one and only treatment option for symptom relieve and prolongation of life. We herein present a case of severe aortic stenosis (AS) with severe aortic regurgitation (AR) with severe mitral regurgitation (MR) with coronary artery disease (CAD) and aortic aneurysm treated successfully by us at Square Hospitals; and to our best knowledge and according to the published articles, this is probably the first time, this type of combined cardiac procedure has been accomplished along with aortic surgery, in our country. We recommend that surgeons should perform bypass grafting along with aortic replacement and valve replacement surgery when indicated, without worrying that adding such a procedure will escalate post-operative adverse effect.
Cardiovasc j 2021; 14(1): 82-87
Incidence and Risk Factors of Acute Kidney Injury in Acute Stroke - in a Tertiary Care Hospital
Authors: Ray Nitai Chandra , Chowdhury Md Ayub Ali , Muqeet Md Abdul , Hasan Mahmud Javed , Roy Ashutosh Saha , Sarkar Santana Rani
Published: September 2021

Acute kidney injury (AKI) is a common complication after acute stroke. Multiple additional risk factors are also responsible for development of AKI during acute stroke. This cross sectional observational study was conducted with a total of 240 newly detected computed tomography (CT) confirmed acute stroke patients in Mymensingh Medical College Hospital with an aim to find out the incidence and risk factors of AKI in acute stroke. In this study, AKI developed in 15.42% of all types of acute stroke and more commonly in haemorrhagic stroke than in ischaemic stroke (23.44% vs. 12.50%, P<0.05). AKI was found more frequently (54.05%) in old >60 years age group and in male patients(17.93% vs. 11.58% & P>0.05). Again, AKI developed most commonly in chronic kidney disease (CKD) (33.33%, P<0.05) and then in diabetes mellitus (DM) (31.03%, P<0.05), in ischaemic heart disease (IHD) (28.11%, P<0.05), in hypertension (21.14%, P<0.05), in previous stroke (15.22%, P>0.05), in dyslipidaemia (13.33%, P>0.05), and in smoker (9.89%, P>0.05). Family history of (H/O) DM was present in 30.00% (P>0.05) and that of hypertension and kidney disease was present in 24.44% (P>0.05) and 25.00% (P>0.05) of stroke patients, respectively. Among the AKI patients, majority (70.27%) had hypertension and 37.84% had CKD, 29.73% had IHD. DM and smoker were 24.32%of each. Family H/O of hypertension, DM and kidney disease was present in 29.73%, 16.22% & 13.51 % of AKI patients, respectively. So, this study had identified several important risk factors of AKI, in particular age, sex, smoking, hypertension, DM, IHD, CKD and types of stroke. So, the risk score could be easily calculated to predict the risk of AKI in stroke patients. And thus to prevent the development of AKI is of utmost importance to reduce the related morbidity and mortality of acute stroke patients. A multicenter nationwide intensive research is needed to identify the precise mechanism, risk factors, their relation and actual outcome of AKI that develop in patients with acute stroke.

CBMJ 2019 January: vol. 08 no. 01 P: 12-18
Investigation of the Use of Underground Cold in a Tunnel-type Ventilation System
Authors: Veliyev I. , Iskenderova A. , Aliev B. , Salmanov B.
Published: September 2021

The article analyzed the main factors affecting the productivity of birds, indicating the importance of poultry production, and also studied the widespread use of two storage systems in poultry farming. As a result of the conducted analyses, the task was set to study the optimal parameters and operating modes of the installation providing tunnel-type ventilation as a working hypothesis for warm climatic zones. The aim of the study was to increase the reliability of the cooling effect inside the building in tunnel-type ventilation installations. Based on the existing methodology, an experiment was conducted and positive results were obtained. The obtained methods have shown that it is not possible to provide the treated moisture inside the building with normal ventilation. Cooling systems ensure normal humidity. But here the use of an underground cooling channel has a wider range of redundancy. In the experimental version, egg production increased by an average of 1.26%, and the weight of eggs increased by 1.5%, and the losses of birds for 5 months of the warm period were 21 heads less.
Improvement in the Hydrogenation and Dehydrogenation Features of Mg by Milling in Hydrogen with Vanadium Chloride
Authors: Song Myoung Youp , Lee Seong Ho , Kwak Young Jun
Published: September 2021

VCl3 (vanadium (III) chloride) was selected as an additive to Mg to increase the hydrogenation and dehydrogenation rates and the hydrogen storage capacity of Mg. Instead of MgH2, Mg was used as a starting material since Mg is cheaper than MgH2. Samples with a composition of 95 wt% Mg + 5 wt% VCl3 (named Mg-5VCl3) were prepared by milling in hydrogen atmosphere (reactive milling). In the first cycle (n=1), Mg-5VCl3 absorbed 5.38 wt% H for 5 min and 5.95 wt% H for 60 min at 573 K in 12 bar hydrogen. The activation of Mg-5VCl3 was completed after three hydrogenation-dehydrogenation cycles. During milling in hydrogen, β-MgH2 and γ-MgH2 were produced. The formed β-MgH2 and γ-MgH2 are considered to have made the effects of reactive milling stronger as β-MgH2 and γ-MgH2 themselves were being pulverized. The introduced defects and the interfaces between the Mg and the phases formed during the reactive milling and during hydrogenation-dehydrogenation cycling are believed to serve as heterogeneous active nucleation sites for MgH2 and Mg-H solid solution. The phases generated during hydrogenation-dehydrognation cycling are also believed to prevent the particles from coalescing during hydrogenation-dehydrognation cycling.
Recent Studies on Bimetallic Pt–M Catalyst for the Oxygen Reduction Reaction in Polymer Electrolyte Membrane Fuel Cells
Authors: Shim Yu-Jin , Jung Won Suk
Published: September 2021

Due to environmental pollution and global warming, research on new energy sources that can replace fossil fuels is important. A fuel cell is an eco-friendly energy conversion system that discharges water, and uses hydrogen as fuel. Although platinum is a widely used catalyst in PEMFCs, it has commercial limitations because of its low stability and high cost. Pt-based bimetal catalysts are being studied to improve performance and reduce the cost of fuel cell catalysts. Pt-M is excellent in terms of performance, stability, and cost, avoiding the disadvantages of the Pt catalyst. Studies on various bimetallic catalysts have been conducted, and among them, studies on Pt-Ni, Pt-Co, and Pt-Fe have been the most active. This review summarizes reports of fuel cell catalysts using Pt-M from 2014 to 2020. In recent studies, in order to improve the Pt-M performance, there have been attempts to change the pretreatment, the type of support, and the composition of Pt and M. There have also been studies that have applied new synthetic methods, which are different from traditional synthetic methods. Many Pt-M catalysts have shown better performance than commercial Pt/C, and exhibited stable performance in durability tests.
‘No Small Share of Ingenuity’: An Object-Oriented Analysis of Eighteenth-Century English Dressmaking
Authors: Dowdell Carolyn
Published: September 2021

This article details eighteenth-century English dressmaking through an in-depth, object-oriented exploration of garment construction practices and techniques from a maker's perspective. Building upon prior scholarship of women's work and aspects of pre-industrial English garment trades, this article employs primary and secondary source materials in conjunction with extensive object-based research of extant garments. The research findings outline exactly how pre-industrial English dressmakers’ skills were nuanced, sophisticated and adaptive to making and remaking, as well as the personal, haptic connections they cultivated with their work.
The Clothing of a Regency Poet, Lord Byron (1788–1824)
Authors: Wilcox David
Published: September 2021

Byron was a best-selling poet and a celebrity with a notorious reputation. This article seeks to examine how his public image and private person were related, the part clothing played in the projection of his public image, and the degree of control he exerted over his body and his self-image. The article examines a number of sources relating to Lord Byron — his journals and letters, his poetry and public output, biographies, bills and accounts, paintings and illustrations, and the surviving clothing associated with the poet. From these a clothing narrative of the poet's early life, up until the time of his departure for Europe in 1816, can be constructed and examined in relation to the fashions of his era and the idiosyncrasies of the poet. Some of the surviving clothes are examined for their cut and construction and discussed in relation to others of the period. A companion article, dealing with his life abroad until the time of his death in 1824, will follow at a later date.
Tajuro's Jacket: A Story of Japanese Castaways, Russian Ambassadors and a Remarkable Early Nineteenth-Century Sailor's Jacket
Authors: Rudd Putman Tyler , Brenckle Matthew
Published: September 2021

This article examines the historical and material context of a rare sailor's jacket, c. 1804, probably produced in England and worn by a Japanese castaway named Tajuro (among the first Japanese men to circumnavigate the globe) during a Russian expedition to Japan. We place Tajuro's jacket in the longer history of garments worn by sailors and labourers. Because it is the only surviving example definitively used at sea by an identified seaman on a particular voyage, from the long eighteenth century, Tajuro's jacket provides a glimpse into what European, Russian, and American sailors wore in this era. It is an invaluable addition to the scanty material archive of common sailors’ clothing with a story that shows the global possibilities of early modern travel.
EXPERIMENTAL RESEARCH OF RE-EQUIPMENT A WHEELED VEHICLE INTO A ELECTROMOBILE
Authors: Hladchenko Volodymyr
Published: September 2021

The article presents the results of the carried out road tests of a wheeled vehicle of category M1, which was re-equipment into a electromobile. The electromobile is equipped with a traction electric motor Balkankar DS 3.6/7.5/14, a power storage battery on lithium cells with a maximum voltage of 100.8 V and a capacity of 6.45 kW∙h. The traction motor control system is impulse with electronic power switches. As a result of the road tests carried out, the maximum speed of movement, the acceleration time on a given path, the acceleration time to the given speed, the “acceleration – coasting” speed characteristic were determined and acceleration was carried out in gears that ensure the maximum speed. Comparison of the results of theoretical and experimental studies testifies to the adequacy of the developed mathematical model and the initial data that form the basis for calculating the indicators of re-equipped wheeled vehicle into electromobile.
REDUCTION OF EXTERNAL NOISE VEHICLE of SPAI “BOHDANA” ON THE BASIS OF THE KrAZ-63221 IMPROVED TWO-CHAMBER REACTIVE NOISE SILENCER
Authors: Fedorov Volodymyr , Filipova Halyna , Yanovsky Vasyl
Published: September 2021

High-quality military equipment is a vital necessity for the independent state of Ukraine, especially in the conditions of aggravation of the situation at the front. One of the parameters that determines the quality of military vehicles is the level of external noise. The external noise of this type of car, in addition to the negative impact on human health (including the crew), is also an unmasking factor. In order to reduce the level of external noise of SPAI “Bogdan” on the basis of the chassis KrAZ-63221, the use of an advanced two-chamber jet muffler of the exhaust gases of the internal combustion engine is proposed. The known two-chamber jet muffler of exhaust gases has a fixed internal partition. Its acoustic efficiency is described by a known formula. It is proposed to make the inner partition of the muffler movable. This need arises from the fact of constant changes in the speed of the engine crankshaft during the movement of the car. The change in the position of the inner partition is consistent with the change in the speed of the crankshaft, because these two processes are synchronized. The mathematical package IDL was used to analyze the known formula for the efficiency of a two-chamber jet exhaust muffler of an engine with a movable inner partition. Given the need to show the dependence of the efficiency of the muffler simultaneously on two parameters – the speed of the crankshaft and the position of the movable inner partition of the muffler – the method of color coding was chosen. The design of a two-chamber jet noise muffler developed for ACS “Bogdan” is given. As a result of introduction of the developed muffler noise reduction of level of external noise of the SPAI “Bogdan” on the basis of the chassis KrAZ-63221 car on 2–3,5 dBA in the range of speeds of movement of 45–85 km/h is forecasted.
Effect of Gambogic Acid–Loaded Porous-Lipid/PLGA Microbubbles in Combination With Ultrasound-Triggered Microbubble Destruction on Human Glioma
Authors: Wang Feng , Dong Lei , Wei Xixi , Wang Yongling , Chang Liansheng , Wu Hongwei , Liu Shuyuan , Chang Yuqiao , Yin Yaling , Luo Xiaoqiu , Jia Xiaojian , Yan Fei , Li Nana
Published: September 2021

Gambogic acid (GA) is a highly effective antitumor agent, and it is used for the treatment of a wide range of cancers. It is challenging to deliver drugs to the central nervous system due to the inability of GA to cross the blood–brain barrier (BBB). Studies have shown that ultrasound-targeted microbubble destruction can be used for transient and reversible BBB disruption, significantly facilitating intracerebral drug delivery. We first prepared GA–loaded porous-lipid microbubbles (GA porous-lipid/PLGA MBs), and an in vitro BBB model was established. The cell viability was detected by CCK-8 assay and flow cytometry. The results indicate that U251 human glioma cells were killed by focused ultrasound (FUS) combined with GA/PLGA microbubbles. FUS combined with GA/PLGA microbubbles was capable of locally and transiently enhancing the permeability of BBB under certain conditions. This conformational change allows the release of GA to extracellular space. This study provides novel targets for the treatment of glioma.
Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content
Authors: Burchat Natalie , Sharma Priyanka , Ye Hong , Komakula Sai Santosh Babu , Dobrzyn Agnieszka , Vartanian Vladimir , Lloyd R. Stephen , Sampath Harini
Published: September 2021

Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese (Ay/a) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in Ay/a mice (Ay/aTg) prevents increased body weight, without reducing food intake. Instead, obesity resistance in Ay/aTg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the Ay/a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring.
Automated High-Pressure Atline Analysis of Photo-High-P,T Vitamin D3 Microfluidic Synthesis
Authors: Escribà-Gelonch Marc , Tran Nghiep Nam , Hessel Volker
Published: September 2021

Process analytical technology has become a relevant topic in both industry and academia as a mechanism to control process quality by measuring critical parameters; being mainly applied in pharmaceutical industry. An emerging topic is process monitoring with subsequent process automation in flow chemistry using inline, online and atline analyzers. Flow chemistry often deliberately and favorably uses harsh conditions (termed Novel Process Windows) to achieve process intensification which raises the need for sampling under these conditions. This demands for setting in place a stabilization of the sample before exposing it to the processing. Ignoring this may result in being unable to use inline/online analytics and posing the need for a separation step before quantitative analysis, leaving atline analysis as the only feasible option. That means that sampling and connected operations need also to be automated. This is where this study sets in, and this is enabled by a modified high-performance liquid chromatography (HPLC) autosampler coupled to the photo-high-p,T flow synthesis of vitamin D3. It shows that sampling variables, such as decompression speed, can be even more critical in terms of variability of results than process variables such as concentration, pressure, and temperature. The modification enabled the autosampler fully automated and unattended sampling from the reactor and enabled pressure independent measurements with 89% accuracy, >95% reproducibility, and >96% repeatability, stating decompression speed as the primary responsibility for measurements’ uncertainty.
The Evolutionary Dynamics of Negative Existentials in Indo-European
Authors: Shirtz Shahar , Talamo Luigi , Verkerk Annemarie
Published: September 2021

Where in earlier work diachronic change is used to explain away exceptions to typologies, linguistic typologists have started to make use of explicit diachronic models as explanations for typological distributions. A topic that lends itself for this approach especially well is that of negation. In this article, we assess the explanatory value of a specific hypothesis, the Negative Existential Cycle (NEC), on the distribution of negative existential strategies (“types”) in 106 Indo-European languages. We use Bayesian phylogenetic comparative methods to infer posterior distributions of transition rates and parameters, thus applying rational methods to construct and evaluate a set of different models under which the attested typological distribution could have evolved. We find that the frequency of diachronic processes that affect negative existentials outside of the NEC cannot be ignored—the unidirectional NEC alone cannot explain the evolution of negative existential strategies in our sample. We show that non-unidirectional evolutionary models, especially those that allow for different and multiple transitions between strategies, provide better fit. In addition, the phylogenetic modeling is impacted by the expected skewed distribution of negative existential strategies in our sample, pointing out the need for densely sampled and family-based typological research.
Words Matter: An Analysis of the Content and Readability of COVID-19 Information on Clinic Websites
Authors: Sakhuja Mayank , Yelton Brooks , Arent Michelle A. , Noblet Samuel , Macauda Mark M. , Fedrick Delores , Friedman Daniela B.
Published: September 2021

Objective: To examine content and readability of COVID-19 information on outpatient clinic websites in South Carolina.

Participants: Thirty-three outpatient clinic websites.

Methods: Using a multi-step search strategy, we located three COVID-19 information content sections from each website. Descriptive statistics were calculated for content section characteristics (focus, information source, target population/race, presence of graphics, mobilizing information). Flesch Reading Ease (FRE), Flesch Kincaid Grade Level (FKGL), and Simple Measure of Gobbledygook (SMOG) were used to calculate reading levels. Mann Whitney U and Kruskal Wallis tests were performed to examine readability levels by clinic type (primary care vs. specialty) and content section characteristics.

Results: Twenty-six clinics offered COVID-19 information; 70 content sections across all 26 clinics were analyzed. Sections focused on COVID-19 clinic policies (48.4%), prevention (22.6%), testing (19.4%), and symptoms (9.7%). 93.5% lacked target population, 41.9% provided no information source, 38.7% had no graphics, and none mentioned racial/ethnic groups. MFRE = 54.3, MFKGL = 9.9, MSMOG = 9.5.

Conclusion: COVID-19 information focused mainly on clinic policy and was written at a ninth-grade skill level. Findings suggest there is opportunity for clinics to update their online content to convey more plain language and sourced information, especially for high-risk groups.
Efficiency Power Plant Implementation Decision-Making Based on the Profit Function and Its Numerical Simulation
Authors: Zhu Yiping , Jin Yue
Published: September 2021

The efficiency power plant (EPP) is a kind of virtual power plant with zero emission, zero pollution, and low cost and exhibits a high-quality low-carbon production behavior in input-output analysis. In the process of implementing EPP, enterprises not only save electricity but also reduce carbon emissions, while increasing the cost of R&D and equipment. Therefore, it is very necessary to study relationships between carbon quota and EPP implementation decision. In this paper, we build the profit functions of three different types of enterprises implementing EPP and analyze the relationship of main parameters, such as the probability of implementing EPP, electricity saving, income, cost, and carbon quota, and obtain nine relative results. Then, we use ‘Maple’ software to simulate the results by drawing images of parameters, and all the above nine results passed the simulation test verification. At last, we collect the actual survey data and use VC++ programming to carry out an empirical study in China to prove the practicability of the model and the results. The results show that, under the carbon quota trading system, enterprises should tend to implement EPPs and increase investment in R&D and acquisition of EPPs and are needed to adjust the intensity of implementing EPPs according to the change of carbon quota and unit carbon quota income, to obtain higher income.
The Output Consensus Problem of DC Microgrids With Dynamic Event-Triggered Control Scheme
Authors: Geng Yan , Ji Jianwei , Hu Bo
Published: September 2021

In this paper, the output consensus problem of DC microgrids with dynamic event-triggered control scheme is investigated. According to the properties of DC microgrids and multi-agent systems, the multi-agent systems function model for DC microgrids is provided. For making the multi-agent systems achieve output consensus, the non-periodic and periodic dynamic event-triggered control schemes are provided, respectively, which are classified according to the style of receiving information. By using a series of analysis, it can be proved that these two control schemes not only can make systems achieve output consensus, but also can avoid the Zeno-behavior successfully. Moreover, the periodic dynamic event-triggered control scheme does not need the continuous information transfer. Finally, a numerical example is provided to support our conclusions.
Design Method of Differential Cascading for Dual-Stator Brushless Doubly-Fed Induction Wind Generator With Staggered Dual Cage Rotor
Authors: Zeng Yu , Cheng Ming , Yan Xiaoming , Zhang Changguo
Published: September 2021

This article proposes a new differential-cascading-based dual-stator brushless doubly-fed induction machine with a staggered dual cage rotor. Conventional differential mode of the brushless doubly-fed machine with cage rotor suffers from the low number of rotor bars because of the low equivalent synchronous pole pairs of |p1-p2|, and thus, severe rotor flux leakage, low capacity of magnetic field conversion of the rotor and low efficiency. To overcome the obstacle of the excessive harmonics of the rotor, a design method based on the differential cascading is proposed which enables the cage rotor with a high number of conductor bars even in the case of low pole pairs of |p1-p2|, hence the greatly reduced rotor leakage inductance and enhanced performance of the machine. The rotating magneto-motive force theory is applied to derive the interconnection rule of the staggered dual cage rotor, and meanwhile, the corresponding examples are illustrated. The performance comparisons between the differential cascading and the sum cascading based on the proposed machine are carried out. The results show that the proposed machine based on the differential cascading obtains higher power densities comparing to the sum cascading at the region of sub-natural synchronous speed, while its drawback is the increment of the loss due to the high rotor frequency, gaining lower efficiencies at the region of super-natural synchronous speed.
Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis
Authors: Sato Hiroki , Saito Takeshi , Horii Hiroshi , Kajiura Mami , Kikuchi Noriaki , Takada Nobuhisa , Taguchi Koichi , Yoshida Mika , Hasegawa Masakazu , Taguchi Hiroyuki , Yoshida Yukinori , Ando Katsuyoshi , Fujiya Mikihiro , Omori Yuko , Hank Thomas , Liss Andrew S. , Gala Manish K. , Makita Yoshio , Ono Yusuke , Mizukami Yusuke , Okumura Toshikatsu
Published: September 2021

Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.
Heterogeneous Genetic Diversity Estimation of a Promising Domestication Medicinal Motherwort Leonurus Cardiaca Based on Chloroplast Genome Resources
Authors: Sun Jiahui , Wang Yiheng , Garran Thomas Avery , Qiao Ping , Wang Mengli , Yuan Qingjun , Guo Lanping , Huang Luqi
Published: September 2021

Leonurus cardiaca has a long history of use in western herbal medicine and is applied for the treatment of gynaecological conditions, anxiety, and heart diseases. Because of its botanical relationship to the primary Chinese species, L. japonicus, and extensive medical indications that go beyond the traditional indications for the Chinese species, it is a promising medicinal resource. Therefore, the features of genetic diversity and variability in the species have been prioritized. To explore these issues, we sequenced the chloroplast genomes of 22 accessions of L. cardiaca from different geographical locations worldwide using high-throughput sequencing. The results indicate that L. cardiaca has a typical quadripartite structure and range from 1,51,236 bp to 1,51,831 bp in size, forming eight haplotypes. The genomes all contain 114 distinct genes, including 80 protein-coding genes, 30 transfer RNA genes and four ribosomal RNA genes. Comparative analysis showed abundant diversity of single nucleotide polymorphisms (SNPs), indels, simple sequence repeats (SSRs) in 22 accessions. Codon usage showed highly similar results for L. cardiaca species. The phylogenetic and network analysis indicated 22 accessions forming four clades that were partly related to the geographical distribution. In summary, our study highlights the advantage of chloroplast genome with large data sets in intraspecific diversity evaluation and provides a new tool to facilitate medicinal plant conservation and domestication.
Inhibition of IP3R/Ca2+ Dysregulation Protects Mice From Ventilator-Induced Lung Injury via Endoplasmic Reticulum and Mitochondrial Pathways
Authors: Ye Liu , Zeng Qi , Ling Maoyao , Ma Riliang , Chen Haishao , Lin Fei , Li Zhao , Pan Linghui
Published: September 2021

Rationale

Disruption of intracellular calcium (Ca2+) homeostasis is implicated in inflammatory responses. Here we investigated endoplasmic reticulum (ER) Ca2+ efflux through the Inositol 1,4,5-trisphosphate receptor (IP3R) as a potential mechanism of inflammatory pathophysiology in a ventilator-induced lung injury (VILI) mouse model.

Methods

C57BL/6 mice were exposed to mechanical ventilation using high tidal volume (HTV). Mice were pretreated with the IP3R agonist carbachol, IP3R inhibitor 2-aminoethoxydiphenyl borate (2-APB) or the Ca2+ chelator BAPTA-AM. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected to measure Ca2+ concentrations, inflammatory responses and mRNA/protein expression associated with ER stress, NLRP3 inflammasome activation and inflammation. Analyses were conducted in concert with cultured murine lung cell lines.

Results

Lungs from mice subjected to HTV displayed upregulated IP3R expression in ER and mitochondrial-associated-membranes (MAMs), with enhanced formation of MAMs. Moreover, HTV disrupted Ca2+ homeostasis, with increased flux from the ER to the cytoplasm and mitochondria. Administration of carbachol aggravated HTV-induced lung injury and inflammation while pretreatment with 2-APB or BAPTA-AM largely prevented these effects. HTV activated the IRE1α and PERK arms of the ER stress signaling response and induced mitochondrial dysfunction-NLRP3 inflammasome activation in an IP3R-dependent manner. Similarly, disruption of IP3R/Ca2+ in MLE12 and RAW264.7 cells using carbachol lead to inflammatory responses, and stimulated ER stress and mitochondrial dysfunction.

Conclusion

Increase in IP3R-mediated Ca2+ release is involved in the inflammatory pathophysiology of VILI via ER stress and mitochondrial dysfunction. Antagonizing IP3R/Ca2+ and/or maintaining Ca2+ homeostasis in lung tissue represents a prospective treatment approach for VILI.
Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture
Authors: Carriquiriborde Francisco , Martin Aispuro Pablo , Ambrosis Nicolás , Zurita Eugenia , Bottero Daniela , Gaillard María Emilia , Castuma Celina , Rudi Erika , Lodeiro Aníbal , Hozbor Daniela F.
Published: September 2021

Outer membrane vesicles (OMV) derived from Bordetella pertussis—the etiologic agent of the resurgent disease called pertussis—are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/Th17 profile, but even more interestingly, they may induce a tissue-resident memory immune response. This immune response is recommended for the new generation of pertussis-vaccines that must be developed to overcome the weaknesses of current commercial acellular vaccines (second-generation of pertussis vaccine). The third-generation of pertussis vaccine should also deal with infections caused by bacteria that currently circulate in the population and are phenotypically and genotypically different [in particular those deficient in the expression of pertactin antigen, PRN(-)] from those that circulated in the past. Here we evaluated the protective capacity of OMV derived from bacteria grown in biofilm, since it was observed that, by difference with older culture collection vaccine strains, circulating clinical B. pertussis isolates possess higher capacity for this lifestyle. Therefore, we performed studies with a clinical isolate with good biofilm-forming capacity. Biofilm lifestyle was confirmed by both scanning electron microscopy and proteomics. While scanning electron microscopy revealed typical biofilm structures in these cultures, BipA, fimbria, and other adhesins described as typical of the biofilm lifestyle were overexpressed in the biofilm culture in comparison with planktonic culture. OMV derived from biofilm (OMVbiof) or planktonic lifestyle (OMVplank) were used to formulate vaccines to compare their immunogenicity and protective capacities against infection with PRN(+) or PRN(-) B. pertussis clinical isolates. Using the mouse protection model, we detected that OMVbiof-vaccine was more immunogenic than OMVplank-vaccine in terms of both specific antibody titers and quality, since OMVbiof-vaccine induced antibodies with higher avidity. Moreover, when OMV were administered at suboptimal quantity for protection, OMVbiof-vaccine exhibited a significantly adequate and higher protective capacity against PRN(+) or PRN(-) than OMVplank-vaccine. Our findings indicate that the vaccine based on B. pertussis biofilm-derived OMV induces high protection also against pertactin-deficient strains, with a robust immune response.
The Impact of IgA and the Microbiota on CNS Disease
Authors: Pu Annie , Lee Dennis S. W. , Isho Baweleta , Naouar Ikbel , Gommerman Jennifer L.
Published: September 2021

Although anatomically distant from the central nervous system (CNS), gut-derived signals can dynamically regulate both peripheral immune cells and CNS-resident glial cells to modulate disease. Recent discoveries of specific microbial taxa and microbial derived metabolites that modulate neuroinflammation and neurodegeneration have provided mechanistic insight into how the gut may modulate the CNS. Furthermore, the participation of the gut in regulation of peripheral and CNS immune activity introduces a potential therapeutic target. This review addresses emerging literature on how the microbiome can affect glia and circulating lymphocytes in preclinical models of human CNS disease. Critically, this review also discusses how the host may in turn influence the microbiome, and how this may impact CNS homeostasis and disease, potentially through the production of IgA.
The Effects of COVID-19 on the Placenta During Pregnancy
Authors: Rad Habib Sadeghi , Röhl Joan , Stylianou Nataly , Allenby Mark C. , Bazaz Sajad Razavi , Warkiani Majid E. , Guimaraes Fernando S. F. , Clifton Vicki L. , Kulasinghe Arutha
Published: September 2021

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.
Effects of LaNiO3 Seed Layer on the Microstructure and Electrical Properties of Ferroelectric BZT/PZT/BZT Thin Films
Authors: Ruan Jinyu , Yin Chao , Zhang Tiandong , Pan Hao
Published: September 2021

Ferroelectric multilayer films attract great attention for a wide variation of applications. The synergistic effect by combining different functional layers induces distinctive electrical properties. In this study, ferroelectric BaZr0.2Ti0.8O3/PbZr0.52Ti0.48O3/BaZr0.2Ti0.8O3 (BZT/PZT/BZT) multilayer thin films are designed and fabricated by using the magnetron sputtering method, and a LaNiO3 (LNO) seed layer is introduced. The microstructures and electrical properties of the BZT/PZT/BZT films with and without the LNO seed layer are systematically studied. The results show that the BZT/PZT/BZT/LNO thin film exhibits much lower surface roughness and a preferred (100)-orientation growth, with the growth template and tensile stress provided by the LNO layer. Moreover, an enhanced dielectric constant, decreased dielectric loss, and improved ferroelectric properties are achieved in BZT/PZT/BZT/LNO thin films. This work reveals that the seed layer can play an important role in improving the microstructure and properties of ferroelectric multilayer films.
CFTR Rescue in Intestinal Organoids with GLPG/ABBV-2737, ABBV/GLPG-2222 and ABBV/GLPG-2451 Triple Therapy
Authors: de Poel Eyleen , Spelier Sacha , Korporaal Ricardo , Lai Ka Wai , Boj Sylvia F. , Conrath Katja , van der Ent Cornelis K. , Beekman Jeffrey M.
Published: September 2021

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have transformed the treatment of cystic fibrosis (CF) by targeting the basis of the disease. In particular, treatment regimen consisting of multiple compounds with complementary mechanisms of action have been shown to result in optimal efficacy. Here, we assessed the efficacy of combinations of the CFTR modulators ABBV/GLPG-2222, GLPG/ABBV-2737 and ABBV/GLPG-2451, and compared it to VX-770/VX-809 in 28 organoid lines heterozygous for F508del allele and a class I mutation and seven homozygous F508del organoid lines. The combination ABBV/GLPG-2222/ABBV-2737/ABBV/GLPG-2451 showed increased efficacy over VX-770/VX-809 for most organoids, despite considerable variation in efficacy between the different organoid cultures. These differences in CFTR restoration between organoids with comparable genotypes underline the relevance of continuing to optimize the ABBV/GLPG‐Triple therapy, as well as the in vitro characterization of efficacy in clinically relevant models.
Control of Newly-Designed Wearable Robotic Hand Exoskeleton Based on Surface Electromyographic Signals
Authors: Li Ke , Li Zhengzhen , Zeng Haibin , Wei Na
Published: September 2021

The human hand plays a role in a variety of daily activities. This intricate instrument is vulnerable to trauma or neuromuscular disorders. Wearable robotic exoskeletons are an advanced technology with the potential to remarkably promote the recovery of hand function. However, the still face persistent challenges in mechanical and functional integration, with real-time control of the multiactuators in accordance with the motion intentions of the user being a particular sticking point. In this study, we demonstrated a newly-designed wearable robotic hand exoskeleton with multijoints, more degrees of freedom (DOFs), and a larger range of motion (ROM). The exoskeleton hand comprises six linear actuators (two for the thumb and the other four for the fingers) and can realize both independent movements of each digit and coordinative movement involving multiple fingers for grasp and pinch. The kinematic parameters of the hand exoskeleton were analyzed by a motion capture system. The exoskeleton showed higher ROM of the proximal interphalangeal and distal interphalangeal joints compared with the other exoskeletons. Five classifiers including support vector machine (SVM), K-near neighbor (KNN), decision tree (DT), multilayer perceptron (MLP), and multichannel convolutional neural networks (multichannel CNN) were compared for the offline classification. The SVM and KNN had a higher accuracy than the others, reaching up to 99%. For the online classification, three out of the five subjects showed an accuracy of about 80%, and one subject showed an accuracy over 90%. These results suggest that the new wearable exoskeleton could facilitate hand rehabilitation for a larger ROM and higher dexterity and could be controlled according to the motion intention of the subjects.
Association Between Alcohol Consumption and Risk of Bladder Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Lao Yongfeng , Li Xiaolong , He Lijuan , Guan Xin , Li Rongxin , Wang Yanan , Li Yanyou , Wang Yunchang , Li Xu , Liu Shuai , Dong Zhilong
Published: September 2021

Background

Controversial results of the association between alcohol consumption and risk of bladder cancer were reported by the previous meta-analyses.

Objective

To quantitatively investigate the association between alcohol consumption and risk of bladder cancer based on prospective cohort studies, and explore whether there is potential dose-response relation.

Method

PubMed, EMBASE, the Cochrane Library databases, China Biology Medicine disc (CBM), and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant studies. Categorical meta-analysis was performed for risk estimates of any alcohol consumers versus non-drinkers as well as different drinking degrees (light, moderate, and heavy) versus none. And two-stage generalized least-squares regression and restricted cubic spline, as well as fixed-effects dose-response models, were used for linear and nonlinear dose-response relation exploration.

Results

9 prospective cohort studies including 1,971,396 individuals were finally included. We did not observe a significant association between alcohol intake and the risk of bladder cancer in the entire population. Linear association was detected in those who consumed alcohol from liquor or spirits (P linear=0.02). One drink increment each day of alcohol could elevate the risk of bladder cancer by 9% (RR=1.09; 95%CI: 1.01-1.17). Alcohol was a risk factor of bladder cancer for male drinkers (RR=1.23; 95%CI: 1.13-1.35; I2=3.7%), while none linear or nonlinear relation was found.

Conclusion

No significant association between alcohol consumption and bladder cancer risk was found in the entire population, but there was a linear dose-response relation in those who consume alcohol from liquor or spirits. Alcohol may elevate the risk of bladder cancer in males in a dose-independent way.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42020216195).