bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation, Identification and Quantitative Determination of Anthracene Derivatives by HPLC-UV Method in the Raw Materials of Some Representatives of the Genus Rumex of Three Vegetation Times
Authors: Poluyanov A. M. , Sokolova A. Yu. , Malashenko E. A. , Sergunova E. V. , Bobkova N. V.
Published: November 2022

Introduction. The creation of new highly effective drugs requires a thorough study of the metabolome of plant raw materials and a comparative phytochemical study of the underground organs of closely related species of Rumex, such as: R. crispus, R. obtusifolius and R. aquaticus, ubiquitous in Russia. It was noted that they have a metabolome like the official R. confertus, which in turn confirms the potential for studying these species. Of scientific and practical interest is the study of the dynamics of accumulation of the leading group of biologically active substances – anthracene derivatives, depending on the phenological phases of plant development.

Aim. Identify and quantify anthracene derivatives in the underground organs of R. confertus, R. crispus, R. obtusifolius and R. aquaticus harvested in three different phases of vegetation.

Materials and methods. Extracts from the underground organs of the studied plants obtained according to the method from the pharmacopoeial article on R. confertus were used as the analyzed solutions. The solutions were analyzed on a Nexera-i LC-2040 chromatograph (Shimadzu Corporation, Japan) equipped with a column and sample thermostat, a degasser, and an autosampler using an individually selected mobile phase elution gradient (0.1 % phosphoric acid/acetonitrile solution). Primary data were processed using LabSolutions Single LC software (Shimadzu Corporation, Japan). Compounds from the group of anthracene derivatives were identified by retention times. Detection was carried out using a UV detector with a dynamic change in the absorption wavelength during analysis from 365 ± 2 nm to 254 ± 2 nm.

Results and discussion. Alcohol-water extracts were obtained from the underground organs of Rumex. An elution gradient was selected for the simultaneous determination of 5 anthracene derivatives with a single analysis time of 40 minutes. These chromatographic conditions made it possible to identify and quantify the content of emodin, 8-O-β-D-glucoside of emodin, and chrysophanol in the underground organs of R. confertus, R. crispus, R. obtusifolius and R. aquaticus in three different vegetations. Glycosides of anthracene derivatives: glucofrangulin A and frangulin A were not found in the studied objects.

Conclusion. Anthracene derivatives were isolated from the underground organs of different vegetations, a method for the quantitative determination of anthracene derivatives in alcohol-water extracts was developed, emodin, 8-O-β-D-glucoside of emodin and chrysophanol were found and quantified.
Avoiding a Collision in Gamma Knife Radiosurgery : A Modified Mask Fixation Method
Authors: Moon Hyeong Cheol , Lee Doheui , Min Byung Jun , Kim Young Gyu , Dho Yun-Sik
Published: November 2022

Objective : The latest version of the Leksell Gamma Knife IconTM allows for mask- and frame-based fixation. Although mask fixation provides fractionated treatment and immobilization using a noninvasive method, it is not free from collision. The authors investigated the collision problem with a modified mask fixation method.Methods : This study presents a case of two meningiomas in the frontal area, where a collision occurs in the occipital area. A modified mask fixation method was introduced to avoid the collision : first, the edges of the head cushion were cut off and polystyrene beads with a diameter of approximately 5 cm were removed. Next, the head cushion was sealed using a stapler. Finally, the head cushion was flattened in the adapter. We compared the shot coordinates, 3-dimensional (3D) error, clearance distance, and vertical depth of the head cushion between the initial and modified mask fixations.Results : When comparing the initial and modified mask fixations, the difference in the shot coordinates was +10.5 mm along the y-axis, the difference in the 3D error was approximately 18 mm, and the difference in clearance was -10.2 mm. The head cushion was approximately 8 mm deeper in the modified mask fixation.Conclusion : Based on these findings, we recommend a modified mask fixation method for gamma knife radiosurgery using ICON with a collision.
Teacher’s Role in Eliminating Stereotypes in Class
Authors: Pipuš Darja
Published: November 2022

The paper Teacher’s Role in Eliminating Stereotypes in Class deals with stereotypes in education, takes a closer look at gender stereotypes in EFL, and focuses on the teacher’s role in eliminating stereotypes in the classroom. A major part of children’s socialisation occurs in schools, through formal education. School is the place where children consciously and unconsciously learn about stereotypes. This paper examines whether stereotypes exist in school, in EFL, and in what way and how to overcome them. In the beginning it describes stereotyping, sexism, gender roles and how they are present in the (EFL) classroom. It furthermore discusses the problem of stereotypes and sexism in education and the period of middle childhood in terms of the development of self-image. The central part of the paper focuses on ways of overcoming stereotypes in the EFL classroom and emphasises the role of the teacher. In terms of methodology, the paper is theoretical in nature and uses the descriptive and comparative research method as it describes some findings on the topic and comparative research method when comparing professional and scientific findings of different authors. The paper also provides some examples and is an output of the author’s ongoing personal research and work in the area of English language teaching.
MAFLD: How is it different from NAFLD?
Authors: Gofton Cameron , Upendran Yadhavan , Zheng Ming-Hua , George Jacob
Published: November 2022

“Metabolic dysfunction-associated fatty liver disease (MAFLD)” is the term suggested in 2020 to refer to fatty liver disease related to systemic metabolic dysregulation. The name change from nonalcoholic fatty liver disease (NAFLD) to MAFLD comes with a simple set of criteria to enable easy diagnosis at the bedside for the general medical community, including primary care physicians. Since the introduction of the term, there have been key areas in which the superiority of MAFLD over the traditional NAFLD terminology has been demonstrated, including for the risk of liver and extrahepatic mortality, disease associations, and for identifying high-risk individuals. Additionally, MAFLD has been adopted by a number of leading pan-national and national societies due to its concise diagnostic criterion, removal of the requirement to exclude concomitant liver diseases, and reduction in the stigma associated with this condition. The current article explores the differences between MAFLD and NAFLD diagnosis, areas of benefit, some potential limitations, and how the MAFLD terminology has opened up new fields of research.
The Need for Greater Reporting of Medical Device Incidents
Authors: Craig Amanda , O’Meley Patrick , Carter Pamela
Published: November 2022

Post-market monitoring of medical devices by manufacturers and regulatory agencies aids the identification of novel hazards or increasing trends in the risks associated with devices. This narrative review estimates the rates of under-reporting of medical device adverse events and explores the reasons and possible solutions. Incident reports may be presented to the manufacturer or the regulatory agency spontaneously by consumers, patients, clinicians, or distributors of medical devices. However, it is evident that reporting does not occur to a great extent, with the rate of reporting estimated to be as low as 0.5% of all occurrences. The programmes and processes to increase and support the reporting of adverse events need to be reviewed, with consideration given to the cost-benefit of increased reporting in relation to the regulator, regulated entities, healthcare facilities, and professionals, as well as the public.
Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies: Adverse Effects. What Do We Really Know? A Literature Review
Authors: Mavridis Theodoros , Koniari Chrysa , Fakas Nikolaos , Mitsikostas Dimos D.
Published: November 2022

Migraine is a chronic and disabling disorder affecting >1 billion individuals worldwide.
Current treatments for the prevention of migraine include antihypertensives, antiepileptics, and antidepressants, and all share limited tolerability and adherence, highlighting the need for the development of new disease-specific and mechanism-based agents. In this context, four novel anti-calcitonin gene-related peptide monoclonal antibodies have been investigated in a large Phase II–III clinical programme and showed similar efficacy to the currently used drugs for migraine prevention but with a significantly improved safety profile, as highlighted in this review. It is expected that patient compliance with treatment will increase with the use of these therapies, improving the long-term overall outcome of migraine. However, real-world evidence is needed to confirm the tolerability and safety of anti-calcitonin gene-related peptide monoclonal antibodies before the drugs can be established as first-line agents in the prophylactic treatment of migraine.
A Snapshot of Webinars’ Usage and Disruptive Potential in B2B Sales
Authors: Fauser Prof. Dr. Simon , Schmaeh Prof. Dr. Marco , Beck Luca , Karman Leon , Stackelies Lisa , Ziegler Nils , Tran Linh Chi , Jana Tran Nhat Thanh
Published: November 2022

The usage of webinars is witnessing a resurgence in popularity, especially since the COVID-19 pandemic. It is now revealing itself to be an actual shift in how buyers and sellers do business in the future. Therefore, this study aims to investigate whether webinars will continue to be a valuable tool in B2B sales in the future. Specifically, it aims to gain a deeper understanding of how the role of webinars evolved in recent years and analyze its future potential.
Webinars are an essential tool for a wide variety of different use cases. While they have been around for over a decade, webinars recently have seen a resurgence in popularity. As the COVID-19 pandemic strictly limited contact between people and made them work from home as an only option, hosting and participating in webinars has become more common than ever - whether in business, education, or leisure.
Webinars can be effective for various purposes as they are held in real-time and allow multiple engagement opportunities between attendees and hosts. Moreover, because of their remote nature, webinars are more cost-effective and time-saving in organizing and supervising. Consequently, it is cheaper and more convenient to reach your desired target group as a webinar host than to hold a seminar in physical form. Among other reasons, convenience and interaction seem to be the most potent aspects of cementing webinars as a tool in the digital world. Nevertheless, where exactly are they used, and how do they create value in their respective usage fields?
Evaluation and Prediction of Formation of Heat-Affected Zone and Mechanical Properties According to Welding Method of STS 316L/A516-70N Clad Plates
Authors: Hwang Cheolhong , Joe Myungwoo , Kim Sunhwan , Han Doohee , Yoo Kyunghoon , Kim Sungwoong , Kim Youngjoo , Lee Sangyeob , Park Joonsik
Published: November 2022

Two welding methods of FCAW (Flux-cored arc welding) + FCAW, and FCAW + GTAW (Gas tungsten arc welding) were compared to identify effective routes for STS 316L/A516-70N clad stainless steel. Since the welding speed of the FCAW + GTAW welding method is slower than that of the FCAW + FCAW welding method, the amount of heat input is large, the size of the heat-affected zone formed is larger, and the amount of angular deformation is also large. The microstructure and deformation of the welding specimens were investigated by computational simulation, and the results were compared with calculated results for actual specimens. The results were very similar, thus confirming the high accuracy of the calculation. After measuring the hardness value of the actual welded specimens, the specimen welded by the FCAW + FCAW welding method was found to have a higher hardness value. The hardness of the welded portion of the FCAW + GTAW specimen tests tended to remain at nearly the same value throughout the specimen, indicating that the FCAW + GTAW hardness profile is desirable. In the computer simulation, butt welding was used to set the optimal heat source conditions for the two welding methods, and the effect of heat formed during welding was confirmed using the thermal analysis results according to the conditions. Based on the butt welding conditions, the residual stress and strain for the two welding methods are discussed, using calculations for the welding of C-seam (circumferential seam) and L-seam (longitudinal seam) used in the manufacture of pressure vessels.
Electrical, Thermal, and Thermoelectric Transport Properties of Se-doped Polycrystalline Re2Te5
Authors: Lee Se Woong , Park Okmin , Kim Hyun-Sik , Seo Won-Seon , Kim Sang-il
Published: November 2022

Re2Te5 is considered a potential thermoelectric material because of its intrinsically low thermal conductivity, due to its complex crystal structure. Herein, a series of Se-doped Re2Te5 (Re2Te5-xSex,x = 0, 0.2, 1, and 2) samples were synthesized, and their electrical and thermal transport properties were investigated. Pure orthorhombic Re2Te5 phases were successfully synthesized without any impurities for all compositions, and the continuous decrease in the calculated lattice parameters confirmed the substitution of Se atoms at the Te sites. A maximum power factor of 0.135 mW/mK2 was achieved for the sample withx = 0.2 at 880 K, mainly due to the increase in carrier concentration and electrical conductivity. The lattice thermal conductivity significantly decreased for all doped samples, which was attributed to the point defect phonon scattering caused by Se doping. The thermoelectric figure of merit,zT reached a maximum value of 0.20 at 880 K for Re2Te4.8Se0.2 (x = 0.2) sample, which was approximately 22% higher than that of the pristine Re2Te5 sample. The weighted mobility, quality factor, and expectedzT were calculated to evaluate the optimization of the power factor andzT.
An Investigation of the Relationship Between Gender Roles Attitudes and Self-Esteem of Married
Authors: ERCAN Merve , KOÇAK Orhan , ERCAN Fatümatü Zehra
Published: November 2022

This study aimed to investigate the relationship between the gender roles attitudes (GRA) and self-esteem of married women. The study has a quantitative design. GRAS, Self-Esteem Scale, and the Demographic Questionnaire were used to collect data. Correlation, regression, and ANOVA analyses were performed to analyze the data. The correlation analysis performed to understand the relationship between GRA and self-esteem has revealed a positive and weak relationship between the sub-dimensions of GRA and income and education status; while a weak negative relationship has found between the sub-dimensions of GRA and years of marriage and the number of children. The hierarchical regression analysis carried out to understand the predictive power of GRAS sub-dimensions and demographic characteristics on self-esteem showed that two dimensions of GRAS, namely TGR and egalitarian gender roles, significantly and moderately predicted self-esteem of married women in marriage, while the variables of years of marriage, number of children, education status and income were ound to predict self-esteem significantly at a low level.
Kronik Hepatit B Enfeksiyonu, Siroz ve Antiviral Tedavi İlişkili Sarı Ürtiker Olgusu
Authors: DUYAN Ayser , KILIÇ Arzu
Published: November 2022

Ürtiker; mast hücre degranülasyonuna bağlı olarak kaşıntılı eritemli plaklar ile seyreden yaygın görülen inflamatuar deri hastalığıdır. Klinikte eritemli ve ödemli papül ve plaklar ile seyreder. Serumda hiperbilirubinemi tespit edilen ürtikerli hastalarda ise deride sarımsı plaklar görülebilir. Literatürde kronik karaciğer hastalığı, akut karaciğer yetmezliği, biliyer hastalıklar, transfüzyon ve antiviral tedaviler ile ilişkili sarı ürtiker vakalarının ortaya çıktığı bildirilmiştir. Biz de bu olguda hepatit B enfeksiyonuna bağlı karaciğer sirozu tanısıyla takipli ve antiviral tedavi alan, sarı ürtikeryal plak ve papülleri ortaya çıkan bir hasta sunmayı ve ürtikerli hastalarda hiperbilirubinemiye bağlı olarak sarı ürtikeryal makül, papül ve plakların görülebileceğinin farkındalığını oluşturmayı amaçladık.
Methadone alters the peripheral inflammatory and central immune landscape following prenatal exposure in rats
Authors: Madurai Nethra K. , Kitase Yuma , Hamimi Sarah , Kirk Shannon E. , Sevensky Riley , Ramachandra Sindhu , Muthukumar Sankar , Vasan Vikram , Ozen Maide , Gerner Gwendolyn , Robinson Shenandoah , Jantzie Lauren L.
Published: November 2022

Opioid use during pregnancy continues to rise at alarming rates with a parallel trend in the number of infants and children exposed to opioid medications each year. Prenatal opioid exposure (POE) occurs at a critical timepoint in neurodevelopment disrupting intricate pathways essential for neural-immune maturation with the potential for devastating long-term consequences. Understanding the mechanisms underlying injury associated with POE is essential to address long-term outcomes and identify diagnostic and therapeutic biomarkers in this vulnerable patient population. Using an established preclinical model of POE, we investigated changes in cerebral and peripheral inflammation and peripheral blood mononuclear cell (PBMC) activity. We hypothesized that neuroinflammation, as defined by changes in specific cerebral immune cell populations, would exist in adult rats following POE concomitant with sustained peripheral immune hyperreactivity (SPIHR). Our data demonstrated alterations in cerebral immune cells at postnatal day 60 (P60) typified by increased regulatory T cells (p < 0.01) and neutrophils (p < 0.05) in rats with POE compared to controls. Evaluation of serum revealed increased levels of IL-6 (p < 0.05) and CXCL1 (p < 0.05) at P21 in rats with POE compared to controls with no significant difference in cytokine or chemokine levels between the two groups at P60. Additionally, PBMCs isolated from rats with POE at P21 demonstrated baseline hypersecretion of IL-6 (p < 0.01) and SPIHR with increased levels of TNF-α (p < 0.05) and CXCL1 (p < 0.05) following stimulation with LPS. At P60, however, there was no significant difference found in cytokine or chemokine levels secreted by PBMCs isolated from rats with POE at baseline or with LPS stimulation when compared to controls. Taken together, these data demonstrate cerebral inflammation months after prenatal opioid exposure and long after the resolution of systemic inflammation and SPIHR seen at toddler age equivalent. Chronic alterations in the cerebral immune cell populations secondary to prenatal opioid exposure may underly long-term consequences of developmental brain injury including deficits in cognition and attention. These findings may be invaluable to further investigations of precise biomarkers of injury and targeted therapeutics for this vulnerable population.
Emerging role of mesenchymal stem cell-derived extracellular vesicles in oral and craniomaxillofacial tissue regenerative medicine
Authors: Liu Meng , Liu Xin , Su Yuting , Li Shijie , Chen Yuan , Liu Anqi , Guo Jing , Xuan Kun , Qiu Xinyu
Published: November 2022

Mesenchymal stem cells (MSCs) are multipotent stem cells with differentiation potential and paracrine properties, drawing significant attention in the field of regenerative medicine. Extracellular vesicles (EVs), mainly including exosomes, microvesicles and apoptotic bodies (ABs), are predominantly endosomal in origin and contain bioactive molecules, such as miRNAs, mRNAs, and proteins, which are transferred from their original cells to target cells. Recently it has emerged that MSC-derived EVs (MSC-EVs) combine the advantages of MSCs and EVs, which may be used as a promising MSC-based therapy in tissue repair and regeneration. Oral and craniomaxillofacial diseases are clinically complications containing the soft and hard tissues in craniofacial and dental arches. These diseases are often induced by various factors, such as chemical, microbiological, physical factors, and systemic disorders. For decades, tissue repair and regeneration in oral and craniomaxillofacial regions provide substantial improvements in the prevention and treatment of some severe diseases. In this review we discuss MSC-EVs and their therapeutic potential in oral and craniomaxillofacial tissue regenerative medicine.
Microbial (E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate reductase (IspH) and its biotechnological potential: A mini review
Authors: Huang Shiyong , Xue Yanfen , Ma Yanhe , Zhou Cheng
Published: November 2022

(E)-4-hydroxy-3-methylbut-2-enyl pyrophosphate (HMBPP) reductase (IspH) is a [4Fe-4S] cluster-containing enzyme, involved in isoprenoid biosynthesis as the final enzyme of the methylerythritol phosphate (MEP) pathway found in many bacteria and malaria parasites. In recent years, many studies have revealed that isoprenoid compounds are an alternative to petroleum-derived fuels. Thus, ecofriendly methods harnessing the methylerythritol phosphate pathway in microbes to synthesize isoprenoid compounds and IspH itself have received notable attention from researchers. In addition to its applications in the field of biosynthesis, IspH is considered to be an attractive drug target for infectious diseases such as malaria and tuberculosis due to its survivability in most pathogenic bacterium and its absence in humans. In this mini-review, we summarize previous reports that have systematically illuminated the fundamental and structural properties, substrate binding and catalysis, proposed catalytic mechanism, and novel catalytic activities of IspH. Potential bioengineering and biotechnological applications of IspH are also discussed.
Compact automated culture machine for human induced pluripotent stem cell maintenance and differentiation
Authors: Bando Kazunori , Yamashita Hiromi , Tsumori Motomu , Minoura Hayase , Okumura Koji , Hattori Fumiyuki
Published: November 2022

The technologies used to generate human induced pluripotent stem cell (iPSC) from somatic cells potentially enable the wide application of iPSC-derived differentiated cells in industrial research fields as a replacement for animals. However, as highly trained individuals are required to obtain reproducible results, this approach has limited social implementation. In the research field of iPSC, it is believed that documentable information is not enough for reproducing the quality of the differentiated cells. Therefore, automated culture machines for cell processing should make the starting of iPSC-using researches easier. We developed a programmable all-in-one automated culture machine, with dense and compact constitution that fits within a normal biosafety cabinet (200 mm wide, 233 mm height, and 110 mm depth). This instrument was fabricated using novel x-y-z-axes-rail-system, such as an overhead traveling crane, in a factory, which served as the main handling machinery. This machine enabled stable and efficient expansion of human iPSC under the feeder-free condition, without karyotype alterations, and simultaneously differentiated the cells into various cell types, including cardiomyocytes, hepatocytes, neural progenitors, and keratinocytes. Overall, this machine would facilitate the social implementation of human pluripotent stem cells and contribute to the accumulation of sharable knowledge for the standardization of the entire handling processes of iPSC in pharmaceutical, food, and cosmetic research.
Extracellular matrix: Brick and mortar in the skeletal muscle stem cell niche
Authors: Schüler Svenja C. , Liu Yuguo , Dumontier Simon , Grandbois Michel , Le Moal Emmeran , Cornelison DDW , Bentzinger C. Florian
Published: November 2022

The extracellular matrix (ECM) is an interconnected macromolecular scaffold occupying the space between cells. Amongst other functions, the ECM provides structural support to tissues and serves as a microenvironmental niche that conveys regulatory signals to cells. Cell-matrix adhesions, which link the ECM to the cytoskeleton, are dynamic multi-protein complexes containing surface receptors and intracellular effectors that control various downstream pathways. In skeletal muscle, the most abundant tissue of the body, each individual muscle fiber and its associated muscle stem cells (MuSCs) are surrounded by a layer of ECM referred to as the basal lamina. The core scaffold of the basal lamina consists of self-assembling polymeric laminins and a network of collagens that tether proteoglycans, which provide lateral crosslinking, establish collateral associations with cell surface receptors, and serve as a sink and reservoir for growth factors. Skeletal muscle also contains the fibrillar collagenous interstitial ECM that plays an important role in determining tissue elasticity, connects the basal laminae to each other, and contains matrix secreting mesenchymal fibroblast-like cell types and blood vessels. During skeletal muscle regeneration fibroblast-like cell populations expand and contribute to the transitional fibronectin-rich regenerative matrix that instructs angiogenesis and MuSC function. Here, we provide a comprehensive overview of the role of the skeletal muscle ECM in health and disease and outline its role in orchestrating tissue regeneration and MuSC function.
Cyclins and CDKs in the regulation of meiosis-specific events
Authors: Palacios-Blanco Inés , Martín-Castellanos Cristina
Published: November 2022

How eukaryotic cells control their duplication is a fascinating example of how a biological system self-organizes specific activities to temporally order cellular events. During cell cycle progression, the cellular level of CDK (Cyclin-Dependent Kinase) activity temporally orders the different cell cycle phases, ensuring that DNA replication occurs prior to segregation into two daughter cells. CDK activity requires the binding of a regulatory subunit (cyclin) to the core kinase, and both CDKs and cyclins are well conserved throughout evolution from yeast to humans. As key regulators, they coordinate cell cycle progression with metabolism, DNA damage, and cell differentiation. In meiosis, the special cell division that ensures the transmission of genetic information from one generation to the next, cyclins and CDKs have acquired novel functions to coordinate meiosis-specific events such as chromosome architecture, recombination, and synapsis. Interestingly, meiosis-specific cyclins and CDKs are common in evolution, some cyclins seem to have evolved to acquire CDK-independent functions, and even some CDKs associate with a non-cyclin partner. We will review the functions of these key regulators in meiosis where variation has specially flourished.
Early administration of ivabradine in patients admitted for acute decompensated heart failure
Authors: Yang Teng-Yao , Tsai Meng-shu , Jan Jeng-Yu , Chang Jung-Jung , Chung Chang-Ming , Lin Ming-Shyan , Chen Hui-Ming , Lin Yu-Sheng
Published: November 2022

Background

Heart rate (HR) control is important in heart failure (HF) patients with reduced ejection fraction, and ivabradine is indicated for patients with chronic HF and sinus rhythm. However, ivabradine is limited in initiation of ivabradine at acute stage of HF.

Materials and methods

This multi-institutional retrospective study enrolled 30,639 patients who were admitted for HF from January 01, 2013 to December 31, 2018 at Chang Gung Memorial Hospitals. After applying selection criteria, the eligible patients were divided into ivabradine and non-ivabradine groups according to the initiation of ivabradine at the index hospitalization. HR, clinical outcomes including HF hospitalization, all-cause hospitalization, mortality, the composite of cardiovascular (CV) death or HF hospitalization and newly developed atrial fibrillation, and left ventricular ejection fraction (LVEF) and left atrium size were compared between the ivabradine and non-ivabradine groups after inverse probability of treatment weighting (IPTW) analysis after 12 months.

Results

The HR at admission in the ivabradine group (n = 433) was 99.04 ± 20.69/min, compared to 86.99 ± 20.34/min in the non-ivabradine group (n = 9,601). After IPTW, HR was lower in the ivabradine group than that in the non-ivabradine group after 12 months (74.14 ± 8.53 vs. 81.23 ± 16.79 bpm, p = 0.079). However, there were no significant differences in HF hospitalization (HR = 1.02; 95% CI, 0.38–2.79), all-cause hospitalization (HR = 0.95; 95% CI, 0.54–1.68), mortality (HR = 0.87; 95% CI, 0.69–1.08), the composite of CV death or HF hospitalization (HR = 0.87; 95% CI, 0.69–1.08) and newly developed AF between the two groups. In addition, LVEF increased with time in both groups, but there were no significant differences during the observation period.

Conclusion

Ivabradine was beneficial in controlling HR when initiated in patients with acute stage of HF, but it did not seem to provide any benefits in reducing HF hospitalization, all-cause hospitalization, and mortality in 1 year after discharge.
Tibio-pedal arterial pressure assessment during endovascular intervention to improve quality-of-life in patients with intermittent claudication
Authors: Kwan Tak W. , Lee Samuel , Lin Patricia , Liou Michael , Siu Henry , Patel Apurva , Ruzsa Zoltan
Published: November 2022

Objective

The aim of this study is to compare the quality-of-life (QOL) outcomes and the tibio-pedal arterial pressure post-endovascular intervention.

Background

Physiological assessment of peripheral arterial lesions is infrequently performed during endovascular interventions.

Materials and methods

We retrospectively reviewed all 343 patients with intermittent claudication who underwent an endovascular intervention via tibio-pedal artery access from October 2018 to May 2021. The baseline and post-intervention tibio-pedal arterial pressures from the pedal sheaths were measured. QOL was assessed using a pre-validated Walking Impairment Questionnaire (WIQ) score before and at 30-day after intervention. We compared the baseline tibio-pedal arterial pressure, post-intervention tibio-pedal arterial pressure, delta pressure (post-intervention minus baseline), baseline WIQ scores, 30-day WIQ scores, and delta score (30-day minus baseline).

Results

All 343 patients had successful tibio-pedal accesses. The average tibio-pedal arterial pressure at baseline was 87.0 ± 1.8 mmHg vs. 135.5 ± 1.7 mmHg post-intervention (p < 0.001). Average baseline and 30-day WIQ scores were summation (99.8 ± 3.3 vs. 115.0 ± 3.1, p < 0.001), walking distance (35.7 ± 1.3 vs. 42.5 ± 1.3, p < 0.001), walking speed (21.1 ± 0.9 vs. 23.6 ± 0.8, p = 0.036), stair climbing (4.7 ± 1.4 vs. 24.2 ± 1.4, p = 0.019), and symptoms (18.8 ± 0.2 vs. 20.1 ± 0.2, p < 0.001), respectively. When comparing the increased post-intervention tibio-pedal arterial pressure <60 mmHg vs. ≥60 mmHg, the average delta WIQ scores were all significantly improved with summation (10.0 ± 3.9 to 25.8 ± 5.5, p = 0.01), walking distance (4.1 ± 1.7 to 9.8 ± 2.5, p = 0.02), walking speed (1.5 ± 1.1 to 4.3 ± 1.5, p = 0.02), stair climbing (2.3 ± 1.8 to 9.4 ± 2.5, p = 0.02), and symptoms (1.0 ± 0.3 to 1.8 ± 0.4, p = 0.04), respectively.

Conclusion

Increasing the post-intervention tibio-pedal arterial pressure by 60 mmHg can enhance QOL as suggested by improvement of WIQ scores.
Augmented detection of septal defects using advanced optical coherence tomography network-processed phonocardiogram
Authors: Huang Po-Kai , Yang Ming-Chun , Wang Zi-Xuan , Huang Yu-Jung , Lin Wei-Chen , Pan Chung-Long , Guo Mei-Hui
Published: November 2022

Background

Cardiac auscultation is a traditional method that is most frequently used for identifying congenital heart disease (CHD). Failure to diagnose CHD may occur in patients with faint murmurs or obesity. We aimed to develop an intelligent diagnostic method of detecting heart murmurs in patients with ventricular septal defects (VSDs) and atrial septal defects (ASDs).

Materials and methods

Digital recordings of heart sounds and phonocardiograms of 184 participants were obtained. All participants underwent echocardiography by pediatric cardiologists to determine the type of CHD. The phonocardiogram data were classified as normal, ASD, or VSD. Then, the phonocardiogram signal was used to extract features to construct diagnostic models for disease classification using an advanced optical coherence tomography network (AOCT-NET). Cardiologists were asked to distinguish normal heart sounds from ASD/VSD murmurs after listening to the electronic sound recordings. Comparisons of the cardiologists’ assessment and AOCT-NET performance were performed.

Results

Echocardiography results revealed 88 healthy participants, 50 with ASDs, and 46 with VSDs. The AOCT-NET had no advantage in detecting VSD compared with cardiologist assessment. However, AOCT-NET performance was better than that of cardiologists in detecting ASD (sensitivity, 76.4 vs. 27.8%, respectively; specificity, 90 vs. 98.5%, respectively).

Conclusion

The proposed method has the potential to improve the ASD detection rate and could be an important screening tool for patients without symptoms.
Environmental and social determinants of thyroid cancer: A spatial analysis based on the Geographical Detector
Authors: Huo Shirui , Liu Ying , Sun Anyi , Zhang Bo
Published: November 2022

Introduction

Thyroid cancer has increased sharply in China in recent years. This change may be attributable to multiple factors. The current study aimed to explore the environmental and social determinants of thyroid cancer.

Methods

Incidence data from 487 cancer registries in 2016 were collected. Eight factors were considered, namely, air pollution, green space, ambient temperature, ultraviolet radiation, altitude, economic status, healthcare, and education level. A geographical detector (measured by q statistic) was used to evaluate the independent and interactive impact of the eight factors on thyroid cancer.

Results

Social factors, especially economic status and healthcare level (q > 0.2), were most influential on thyroid cancer.Ultraviolet radiation, air pollution, and temperature had more impact on women, while green space and altitude had more influence on men. Enhanced effects were observed when two factors interacted. Spatially, economic status, healthcare, and air pollution were positively associated with thyroid cancer, while education level, green space, and altitude were negatively related to thyroid cancer.

Conclusion

The socio-environmental determinants and spatial heterogeneity of thyroid cancer were observed in this study. These findings may improve our understanding of thyroid cancer epidemiology and help guide public health interventions.
Analysis of the key ligand receptor CADM1_CADM1 in the regulation of thyroid cancer based on scRNA-seq and bulk RNA-seq data
Authors: He Hui , Cong Shan , Wang Yu , Ji Qinghai , Liu Weiyan , Qu Ning
Published: November 2022

Introduction

Advanced papillary thyroid cancer (PTC) has a poor prognosis, 60~70% of which become radio iodine refractory (RAI-R), but the molecular markers that assess PTC progress to advanced PTC remain unclear. Meanwhile, current targeted therapies are badly effective due to drug resistance and adverse side effects. Ligand-receptor pairs (L/R pairs) play an important role in the interactions between tumor cells and other cells in the tumor microenvironment (TME). Nowadays, therapies targeting ligand-receptor pairs in the TME are advancing rapidly in the treatment of advanced cancers. However, therapies targeting L/R pairs applied to advanced PTC remains challenging because of limited knowledge about L/R pairs in PTC.

Methods

We screened the critical L/R pair: CADM1-CADM1 using 65311 single-cell RNA sequencing (scRNA-seq) samples from 7 patients in different stage of PTC and bulk RNA-seq datasets containing data from 487 tumor samples and 58 para-carcinoma samples. Moreover, the expression levels of CADM1-CADM1 was assessed by quantitative real time polymerase chain reaction (qRT-PCR) and the function was analyzed using Transwell immigration assay.

Results

We found that CADM1_CADM1 could be regarded as a biomarker representing a good prognosis of PTC. In addition, the high expression of CADM1_CADM1 can strongly increase the sensitivity of many targeted drugs, which can alleviate drug resistance. And the results of qRT-PCR showed us that the expression of CADM1_CADM1 in PTC was down-regulated and overexpression of CADM1 could suppresses tumor cell invasion migration.

Conclusion

Our study identified that CADM1_CADM1 played an essential role in the progression of PTC for the first time and our findings provide a new potential prognostic and therapeutic ligand-receptor pair for advanced PTC.
Prognostic analysis of m6A-related genes as potential biomarkers in idiopathic pulmonary fibrosis
Authors: Wang Zhiqiang , Shen Lanyu , Wang Junjie , Huang Jiaqian , Tao Huimin , Zhou Xiumin
Published: November 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease with limited treatment options. N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, there are few studies on m6A in IPF. This project mainly explores the prognostic value of m6A-related genes as potential biomarkers in IPF, in order to establish a set of accurate prognostic prediction model. In this study, we used GSE28042 dataset in GEO database to screen out 218 m6A-related candidate genes with high IPF correlation and high differential expression through differentially expressed gene analysis, WGCNA and m6A correlation analysis. The genes associated with the prognosis of IPF were screened out by univariate Cox regression analysis, LASSO analysis, and multivariate Cox regression analysis, and the multivariate Cox model of prognostic risk of related genes was constructed. We found that RBM11, RBM47, RIC3, TRAF5 and ZNF14 were key genes in our model. Finally, the prognostic prediction ability and independent prognostic characteristics of the risk model were evaluated by survival analysis and independent prognostic analysis, and verified by the GSE93606 dataset, which proved that the prognostic risk model we constructed has a strong and stable prediction efficiency.
Recent advances and current challenges in population genomics of structural variation in animals and plants
Authors: Pokrovac Ivan , Pezer Željka
Published: November 2022

The field of population genomics has seen a surge of studies on genomic structural variation over the past two decades. These studies witnessed that structural variation is taxonomically ubiquitous and represent a dominant form of genetic variation within species. Recent advances in technology, especially the development of long-read sequencing platforms, have enabled the discovery of structural variants (SVs) in previously inaccessible genomic regions which unlocked additional structural variation for population studies and revealed that more SVs contribute to evolution than previously perceived. An increasing number of studies suggest that SVs of all types and sizes may have a large effect on phenotype and consequently major impact on rapid adaptation, population divergence, and speciation. However, the functional effect of the vast majority of SVs is unknown and the field generally lacks evidence on the phenotypic consequences of most SVs that are suggested to have adaptive potential. Non-human genomes are heavily under-represented in population-scale studies of SVs. We argue that more research on other species is needed to objectively estimate the contribution of SVs to evolution. We discuss technical challenges associated with SV detection and outline the most recent advances towards more representative reference genomes, which opens a new era in population-scale studies of structural variation.
TSSNote-CyaPromBERT: Development of an integrated platform for highly accurate promoter prediction and visualization of Synechococcus sp. and Synechocystis sp. through a state-of-the-art natural language processing model BERT
Authors: Mai Dung Hoang Anh , Nguyen Linh Thanh , Lee Eun Yeol
Published: November 2022

Since the introduction of the first transformer model with a unique self-attention mechanism, natural language processing (NLP) models have attained state-of-the-art (SOTA) performance on various tasks. As DNA is the blueprint of life, it can be viewed as an unusual language, with its characteristic lexicon and grammar. Therefore, NLP models may provide insights into the meaning of the sequential structure of DNA. In the current study, we employed and compared the performance of popular SOTA NLP models (i.e., XLNET, BERT, and a variant DNABERT trained on the human genome) to predict and analyze the promoters in freshwater cyanobacterium Synechocystis sp. PCC 6803 and the fastest growing cyanobacterium Synechococcus elongatus sp. UTEX 2973. These freshwater cyanobacteria are promising hosts for phototrophically producing value-added compounds from CO2. Through a custom pipeline, promoters and non-promoters from Synechococcus elongatus sp. UTEX 2973 were used to train the model. The trained model achieved an AUROC score of 0.97 and F1 score of 0.92. During cross-validation with promoters from Synechocystis sp. PCC 6803, the model achieved an AUROC score of 0.96 and F1 score of 0.91. To increase accessibility, we developed an integrated platform (TSSNote-CyaPromBERT) to facilitate large dataset extraction, model training, and promoter prediction from public dRNA-seq datasets. Furthermore, various visualization tools have been incorporated to address the “black box” issue of deep learning and feature analysis. The learning transfer ability of large language models may help identify and analyze promoter regions for newly isolated strains with similar lineages.
The sweet potato B-box transcription factor gene IbBBX28 negatively regulates drought tolerance in transgenic Arabidopsis
Authors: Dong Jingjing , Zhao Cailiang , Zhang Jie , Ren Yuchao , He Liheng , Tang Ruimin , Wang Wenbin , Jia Xiaoyun
Published: November 2022

B-box (BBX) which are a class of zinc finger transcription factors, play an important role in regulating of photoperiod, photomorphogenesis, and biotic and abiotic stresses in plants. However, there are few studies on the involvement of BBX transcription factors in response to abiotic stresses in sweet potato. In this paper, we cloned the DNA and promoter sequences of IbBBX28. There was one B-box conserved domain in IbBBX28, and the expression of IbBBX28 was induced under drought stress. Under drought stress, compared to wild type Arabidopsis, the protective enzyme activities (SOD, POD, and CAT) were all decreased in IbBBX28-overexpression Arabidopsis but increased in the mutant line bbx28, while the MDA content was increased in the IbBBX28-overexpression Arabidopsis and decreased in the bbx28. Moreover, the expression levels of the resistance-related genes showed the same trend as the protective enzyme activities. These results showed that IbBBX28 negatively regulates drought tolerance in transgenic Arabidopsis. Additionally, the yeast two-hybrid and BiFC assays verified that IbBBX28 interacted with IbHOX11 and IbZMAT2. The above results provide important clues for further studies on the role of IbBBX28 in regulating the stress response in sweet potato.
Development and performance evaluation of an artificial intelligence algorithm using cell-free DNA fragment distance for non-invasive prenatal testing (aiD-NIPT)
Authors: Lee Junnam , Lee Sae-Mi , Ahn Jin Mo , Lee Tae-Rim , Kim Wan , Cho Eun-Hae , Ki Chang-Seok
Published: November 2022

With advances in next-generation sequencing technology, non-invasive prenatal testing (NIPT) has been widely implemented to detect fetal aneuploidies, including trisomy 21, 18, and 13 (T21, T18, and T13). Most NIPT methods use cell-free DNA (cfDNA) fragment count (FC) in maternal blood. In this study, we developed a novel NIPT method using cfDNA fragment distance (FD) and convolutional neural network-based artificial intelligence algorithm (aiD-NIPT). Four types of aiD-NIPT algorithm (mean, median, interquartile range, and its ensemble) were developed using 2,215 samples. In an analysis of 17,678 clinical samples, all algorithms showed >99.40% accuracy for T21/T18/T13, and the ensemble algorithm showed the best performance (sensitivity: 99.07%, positive predictive value (PPV): 88.43%); the FC-based conventional Z-score and normalized chromosomal value showed 98.15% sensitivity, with 40.77% and 36.81% PPV, respectively. In conclusion, FD-based aiD-NIPT was successfully developed, and it showed better performance than FC-based NIPT methods.
Intranasal inoculation of IFN-λ resolves SARS-CoV-2 lung infection via the rapid reduction of viral burden and improvement of tissue damage
Authors: Shin Haeun , Kim Sujin , Jo Ara , Won Jina , Gil Chan Hee , Yoon So Yeon , Cha Hyunkyung , Kim Hyun Jik
Published: November 2022

Introduction

The innate immune responses of upper airway could further our understanding toward antiviral strategies against SARS-CoV-2. We characterize the potential of interferon (IFN)-λ as an innate immune inducer for the rapid clearance of SARS-CoV-2 in the lung and the therapeutic efficacy of intranasal inoculation of IFN-λ to resolve acute lung infection.

Methods

Syrian golden hamsters were infected with SARS-CoV-2 and the dynamics of SARS-CoV-2 infection depending on IFN-λ inoculation were tested.

Results

SARS-CoV-2-infected Syrian golden hamsters exhibited a significant decrease in body weight and high viral mRNA level at 3 days post-infection (dpi). Although viral replication was reduced completely from 7 dpi, the pathologic findings remained prominent until 14 dpi in the lung of hamsters. The transcription of IFN-λ was significantly induced in response to SARS-CoV-2 infection with the increase of IFN-stimulated genes. Intranasal inoculation of IFN-λ restricted SARS-CoV-2 replication in the lungs of infected completely from 3 dpi with markedly reduction of inflammatory cytokines. The transcriptional phenotypes were altered to the direction of damage repair and tissue remodeling in the lungs of SARS-CoV-2-infected hamsters following intranasal inoculation of IFN-λ, which improved SARS-CoV-2-caused lung damage.

Conclusion

Collectively, our findings suggest that IFN-λ might be a potent innate immune inducer in the lung and intranasal inoculation of IFN-λ resolves SARS-CoV-2 infection with rapid viral clearance and improvement of lung damage.
Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia
Authors: Pereda Maria A. , Hosahalli Vasanna Smitha , Desai Neha J. , Deng Victoria , Owusu-Ansah Amma , Dallas Mari H. , Pateva Irina , Dalal Jignesh
Published: November 2022

Daratumumab, a CD38 monoclonal antibody that has been FDA-approved to treat multiple myeloma, has acquired popularity and is used off-label for both auto- and alloantibody mediated disorders, particularly in refractory/resistant circumstances. Much of the published data for its use in pediatric blood disorders has been in post-transplant autoimmune cytopenias. Here we describe three patients in whom daratumumab was used outside of post-transplant autoimmune cytopenias, highlighting further potential uses of this medication.