bluuebunny/crossref_metadata_2025 huggingface dataset:
Військова агресія Російської Федерації проти України як виклик і загроза міжнародному миру та безпеці людства
Authors: Voloshchuk  O. T.
Published: August 2022

Ця стаття присвячена одній із найгостріших та актуальних проблем сучасності – військовій агресії.
Автором було поставлено мету дослідити поняття, природу та сутність військової агресії як найбільшої загрози і виклику міжнародному миру та безпеці людства у XXI столітті крізь призму російсько-української війни.
До елементів наукової новизни дослідження слід віднести наступні висновки, результати та пропозиції автора: по-перше, доведено, що агресивна війна РФ спрямована проти незалежності і самостійності нашої держави, що становить загрозу не тільки Україні, а й Європі і світу, посягаючи на міжнародний правопорядок і безпеку людства, основні принципи міжнародного права, моральності та людяності; по-друге, зроблено висновок про те, що таке явище, як військова агресія, абсолютно несумісне з ідеями антропоцентризму, гуманізму, добра та справедливості, які мають бути основою основ сучасного світоустрою, аби сприяти миру, спокою та процвітанню націй та народів; по-третє, зроблено конкретні пропозиції по реформуванню ООН та головного її органу, відповідального за міжнародний мир та безпеку людства – Ради Безпеки ООН, з метою створення справді ефективного механізму міжнародної безпеки, який не дозволив би розв’язувати агресивну війну, попереджав і протидіяв цьому ганебному явищу сучасної дійсності.
Для досягнення мети використовувались такі методи, як діалектичний, формально-логічний, комунікативний та феноменологічний.
Робиться висновок про те, що нові виклики і загрози, обумовлені передусім глобалізаційними процесами та інтенсивним розвитком науки і техніки – новітній світоустрій з новими геополітичними орієнтирами, поява і застосування новітніх видів зброї, удосконалення методів та засобів ведення війни, видозмінювання основних та поява нових форм війни – диктують нові методи і засоби міжнародної безпеки. Важливим при формуванні оновленої системи міжнародної безпеки є зміцнення ідеї захисту миру в свідомості людей, що сприятиме прогресивному розвитку, мирному співіснуванню і злагоді між народами.
A Study on the Promotion of ‘Reconstruction First, Remodeling Later’ in Phase 1st New City Using Remodeling Incentives: Focused on the Bundang new city
Authors:   KOREA ASSOCIATION OF REAL ESTATE LAW, Shin Dae Sung , Lee Chun Won
Published: August 2022

housing prices have risen sharply since the Moon Jae-in administration, and in some areas of Seoul, the average apartment price has reached more than 1 billion won. Accordingly, as a real estate regulatory policy, the government introduced DSR following LTV and DTI, which are one of the financial loan regulation policies, and came up with a policy to suppress the increase in house prices through loan restraints. came up with However, the land that can supply housing on a large scale is limited and it is difficult to find suitable land at present.
Although there is a way to supply new housing through reconstruction and redevelopment, the reconstruction projects of low-rise apartment complexes that are feasible have already reached the completion stage, and the remaining middle and high-rise apartments are turning to multi-unit housing remodeling projects rather than reconstruction due to lack of business feasibility.
However, the target houses of the remodeling project are housing complexes that were built in a way that did not take into account remodeling in the past.
The Effect of Related Party Transaction, Financial Distress, and Firm Size on Tax Avoidance with Earnings Management as Intervening Variable
Authors: Dhian Mahardhika  , Surjandari Dwi Asih
Published: August 2022

This study aims to determine the effect of related party transactions, financial distress, and firm size on tax avoidance with earnings management as an intervening variable. The population in this study is manufacturing companies listed on the Indonesia Stock Exchange from 2018 - 2020, with a total of 168 companies. The sampling method used is a purposive sampling; 51 companies in the manufacturing sector are selected as samples. The analysis technique used is multiple linear regression and path analysis tests with the Eviews analysis tool. The results of this study are that related party transactions and financial distress have a negative effect on tax avoidance, while firm size has no effect on tax avoidance. Related party transactions and financial distress have no effect on earnings management, while firm size has a positive effect on earnings management. After being mediated by earnings management, firm size has a positive effect on tax avoidance, while related party transactions and financial distress have no effect on tax avoidance.
Modeling the Effects of Osmotic Dehydration Pretreatment Parameters and Lyophilization Kinetics on Mass Transfer and Selected Nutritive Parameters of Peaches
Authors: Filipović Vladimir , Filipović Jelena , Lončar Biljana , Knežević Violeta , Nićetin Milica , Vujačić Vesna
Published: August 2022

The effects of the osmodehydration pretreatment parameters on successive lyophilization mass transfer kinetics of the peaches, dehydrated in the combined dehydration process, were investigated and mathematically modelled. The obtained results showed the statistically significant effect of osmotic dehydration pretreatment and its parameters on the final dry matter content and water activity values of the dehydrated peaches. The maximum dry matter content and minimal water activity values of dehydrated peach samples were 84.60 % and 0.423, respectively, produced in osmodehydration pretreatment in molasses of 80 % concentration, at 50 °C, during a 5-hour process and subsequent 6-hour lyophilization. With the increase of all osmodehydration pretreatment parameters it is possible to reduce the duration of the lyophilization process, reducing the high energy demand of the dehydration method (lyophilization) and substituting it with low energy demanding dehydration method (osmodehydration) without compromising the quality of the final product, regarding the dry matter content and water activity values. Mathematical models describing the effect of the duration of the lyophilization on the dry matter content and water activity values of the fresh and dehydrated peaches were developed. They showed a good correlation between calculated and experimental values, allowing a good prediction of the investigated responses. In the combined method, protein, sugar, K and Fe content of the dehydrated peach samples were enriched and further enhanced in prolonged lyophilization stages.
Examination of the Brand Archetypes of the Hungarian Retail Banking Sector and Their Correlations with Consumer Preferences Regarding Banking Products
Authors: Gombos Nóra Julianna , Bíró-Szigeti Szilvia
Published: August 2022

The primary goal of this research is to explore the preferences of domestic consumers in relation to the brand archetypes of banks. The chosen topic fits into broader research that examines the elements of brand building in the Hungarian retail banking sector and their impact on consumer preference and behaviour. Besides defining and manufacturing products brand building includes the development of a brand personality. The basic conceptual framework examined in the present research was determined based on the Mark and Pearson brand archetype framework to enable a comparison with the findings in the USA. In the research, we were also seeking an answer to the question as to whether the consumer preference regarding the banking services, payment methods and banking marketing channels examined in research has an impact on the consumer preference regarding brand archetypes, as the exploration of such effects expands the scope for interpretation and usage of the obtained results. Knowledge of preferred brand archetypes supports the management of banks' branding tools, can help banks in their innovation activities and the results can be used to develop new products and services. It is identifiable that the most preferred archetypes by consumers among the 12 possible brand archetypes are the Sage and Caregiver archetypes. There is only a slight correlation between the consumer preference regarding the various banking services, payment methods and forms of information examined in the research and the choice of the brand archetype; however, a strong relationship can be established between the choices of brand archetypes.
Cinética y Mecanismos de Adsorción de Plomo (II) Usando Zeolita Gis-NaP Obtenida a Partir de Residuos de Ladrillo
Authors: Rodríguez Valdivia Marcelo
Published: August 2022

Este artículo reporta los resultados de una investigación efectuada para evaluar la cinética y mecanismos de adsorción de Pb2+ de una zeolita sintética del tipo Gis-NaP, que fue obtenida a partir de residuos de ladrillos y que fue caracterizada mediante diversas técnicas de análisis. El tratamiento de los resultados experimentales mostró que el modelo de pseudo-primer orden (R2 = 0,9983) describe mejor la cinética de adsorción. El mecanismo de adsorción de Pb2+ es mejor explicado por la isoterma de Freundlich que muestra ajuste perfecto (R2 = 0,980). Con un tiempo de contacto de 8 horas, se consigue la saturación del material zeolítico alcanzando una adsorción de 109,8 mg/g de Pb2+. La máxima capacidad de adsorción 124,4 mg/g (95,1%) se obtuvo para una concentración inicial de 872,0 mg/L. Según los resultados obtenidos, se concluye que la zeolita Gis-NaP tiene una alta eficiencia de remoción de Pb2+ y que se puede aplicar en el tratamiento de efluentes mineros y/o industriales.
EFFECTS OF RESTRICTION MEASURES ON MORBIDITY AND MORTALITY IMPLEMENTED DURING COVID-19 PANDEMIC IN TURKEY: A RESEARCH THROUGH NATIONAL DATA INCLUDING ONE YEAR
Authors: TÜZÜN Hakan
Published: August 2022

This research is aimed to determine effects of restriction measures implemented in Turkey during COVID 19 pandemic throughout detecting variations in the “number of cases daily”, “test positivity rate daily”, and “number of death daily” according to different restriction periods. In order to be able to analyze on the basis of cases declared as standard, the periods of restriction measures between November 18, 2020 and November 17, 2021 were included in the research. The data of the Ministry of Health was used as the source. When making statistical assessment for the "number of cases per day" and the "test positivity rate per day", we evaluated each restriction period to cover the first 10 days after the end of this period. When comparing the “daily death numbers”, we evaluated each restriction period to include the daily death numbers for the first 21 days after the end of that period. The highest means were seen for all three parameters examined during “revised local decision-making phase”. These mean are 57,396 for number of cases per day, 18.4 for test positivity rate per day, 351 for number of deaths per day. This period is the only period in which the means for "number of cases" and "number of deaths" are higher than the first period, which is the reference period, and for these parameters, a statistically significant difference is detected with the reference period (p
Comparison of survival outcomes among patients with uterine carcinosarcoma and those with grade 3 uterine carcinoma: A systematic review of the literature
Authors: Pergialiotis Vasilios , Thomakos Nikolaos , Armata Nikol-Natalia , Gkotsi Efthimia Eirini , Gousias Andreas Konstantinos , Kaisari Ioanna , Marra Marianna , Rodolakis Alexandros , Haidopoulos Dimitrios
Published: August 2022

Introduction: Endometrial carcinosarcoma is an aggressive form of cancer that has been classified in type II endometrial carcinomas. However, survival outcomes seem to differ considerably compared to grade 3 endometrioid adenocarcinoma, the predominant form of cancer in this group of patients. The purpose of the present systematic review is to investigate overall and progression free survival in patients with endometrial carcinosarcoma to those of patients with grade 3 endometrioid adenocarcinoma. Methods: We used Medline, Scopus, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, Clinicaltrials.gov and Google Scholar databases. Statistical analysis was performed using the Sidik-Jonkman random effect model (REM) in Rstudio. Findings: Overall, 10.121 patients from 8 studies were investigated. The results of the present meta-analysis indicate that patients with Gr3EC had better overall survival rates HR 2.41 (95% CI 1.29, 4.51). However, this effect might be influenced by selection bias and underpowered studies as following adjustment of the aggregated estimate for small study effects we observed that it was not significant (HR 1.00, 95%CI 0.96, 1.05, p=.858). Although it was not possible to accumulate data concerning the progression free survival, individual studies reported worse outcomes in patients with carcinosarcoma. Conclusions: Carcinosarcoma is a particularly aggressive form of endometrial cancer and deserves further attention from researchers as current treatment alternatives do not seem to reach survival outcomes of patients suffering from grade 3 endometrioid adenocarcinoma.
Botryoid Rhabdomyosarcoma of the cervix: A systematic review of the literature from 1937 to 2017 – all registered cases
Authors: Zachariou Eleftherios , Bellos Ioannis , Papadatou Konstantina , Rodolaki Kalliopi , Thomakos Nikolaos , Haidopoulos Dimitrios , Rodolakis Alexandros , Pergialiotis Vasilios
Published: August 2022

Purpose: Embryonal rhabdomyosarcoma of the cervix (RMS) is a rare malignancy and occurs mainly in the first two decades of life. Botryoid rhabdomyosarcoma is a subtype of embryonal rhabdomyosarcoma and is an aggressive malignancy that arises from embryonal rhabdomyoblasts. It is often found in the genital tract of infants and young children. Study design: we conducted a systematic review to accumulate the available evidence in the international literature. We searched Medline (1966–2021), Scopus (2004–2021), Clinicaltrials.gov (2008–2021), EMBASE (1980-2021), Cochrane Central Register of Controlled Trials CENTRAL (1999-2021), and Google Scholar (2004-2021) for relevant observational studies and case reports. Results: We retrieved 156 cases with a mean age of 24.4 years with the oldest patient at the age of 89 years and the youngest 67-day-old infant. Twenty-four patients died. Ninety-seven patients were free of disease (85%). Of those 11 (11.3%) patients died. Fifteen patients (15%) developed relapse and 13 (86.6%) of them died. In 42 cases we could not extract information concerning their survival. Discussion: The findings of our study are mainly limited to case reports and small case series, and there are no standard treatment guidelines available and no consensus on how to manage these cases. Surgery should be guided by the response to initial chemotherapy and should attempt to conserve the function of the bladder, rectum, vagina, and ovaries. As this is a disease of adolescence, fertility preservation in well-selected cases is of paramount importance.
Perinatal outcomes following assisted reproductive technology: A Review of the Literature
Authors: Papadatou Konstantina , Zachariou Eleftherios , Pergialiotis Vasilios , Daskalakis George
Published: August 2022

Nowadays, infertility affects approximately 8-12% of the population. Μultiple causative factors are leading to the failure of subfertile couples to achieve a normal pregnancy, as well as various types of assisted reproductive techniques that have developed globally in order to confront infertility. Over the past few years, especially after the birth of the world’s first baby to be conceived by In Vitro Fertilization (IVF) in 1978, numerous studies have been conducted concerning the risk of obstetric and perinatal complications. In this review, we aimed to detail the perinatal outcomes in relation to the ART procedures routinely applied. Consequently, the above-mentioned procedures have been associated with the presentation of hypertensive disorders and gestational diabetes mellitus in women, multiple pregnancy, preterm birth and low birth weight. Furthermore, studies indicate that infants born from assisted reproductive technologies appear to suffer much more frequently not only by congenital or epigenetic abnormalities, but also by neurodevelopmental disorders and specific types of cancer. Indisputably, artificial fertilization methods still continue growing worldwide with new medical technologies’ evolvement. It becomes, therefore, evident that the possible long-term, adverse neonatal outcomes have not been completely clarified yet. Taking into consideration that the number of the couples that undergo fertility treatments is constantly rising, more research is of vital importance so that their potential impact of such exposure on maternal and neonatal health can be understood.
Development of augmented reality applications as a medium for learning mathematics
Authors: Lia Rahmawati  , Sulisworo Dwi
Published: August 2022

Penelitian ini adalah penelitian pengembangan dengan hasil media pembelajaran matematika berbasis augmented reality, yaitu sebuah aplikasi augmented reality. Aplikasi augmented reality merupakan aplikasi yang dapat mengubah gambar 2D menjadi 3D, sehingga tepat digunakan dalam materi bangun ruang. Penggunaan animasi 3D menjadi lebih menarik bagi siswa sehingga diharapkan siswa lebih termotivasi dalam belajar matematika. Metode dalam penelitian ini, yaitu pengembangan dengan hasil akhir yaitu media pembelajaran matematika. Instrumen yang digunakan dalam penelitian  ini adalah instrumen uji beta dengan menggunakan model ARCS. Langkah-langkah pengembangan dalam penelitian ini yaitu peneliti melakukan analisis kebutuhan, kemudian desain awal, dan pengujian dengan item-item yang dinilai dalam instrumen penelitian. Aspek-aspek yang dinilai dengan media pembelajaran yang dihasilkan dalam penelitian meliputi relevansi, perhatian, keyakinan, dan kepuasan. Model pembelajaran yang digunakan dalam penelitian ini, yaitu model pembelajaran Project Based Learning (PjBL). Peneliti menggunakan subjek penelitian siswa SD kelas 6 dari berbagai sekolah.
Creation Myth: The Imagining of the Gothic Imagination in the Diodati Triptych: Gothic (1986), Haunted Summer (1988), and Remando al viento (1988)
Authors: O’Brien Harvey
Published: August 2022

This article argues that amid the slasher carnage, three 1980s gothic films representing the literary imagination of Frankenstein attempted to proffer a vision of horror rooted in creation rather than death. In so doing they reinvigorate the radical roots of horror as a challenge to the status quo: a reconfiguration of life into forms which awaken fears as characters face precarious destinies haunted by their past. Ken Russell’s Gothic (1986), Ivan Passer’s Haunted Summer (1988), and Gonzalo Suárez’s Remando al viento / Rowing with the Wind (1988) all depict Mary Shelley facing personal and social challenges from her (male) peers including Percy Shelley, Lord Byron, and John Polidori. Arguably it is Mary who will in time emerge as an even more enduring literary voice, evinced by the fact of her being the protagonist of these films. During the Summer at Villa Diodati on the shores of Lake Geneva where each of these authors sought to create stories of horror, the films imagine the psychosexual power games and intellectual debates which surrounded these literary conjurations. All three films also depict an intrusion of the supernatural as Mary’s monster actually manifests in the liminal space between waking and dreaming. Though wildly different in tone and affect, all three films represent a Gothicism (or an adjacent Gothic allusion) distinct from either the nostalgic or the dismissive deployment of its tropes in other genre films at the time and in so doing raise questions about 1980s cinema and culture more broadly.
Sounds Like Murder: Early 1980s Gothic on North American Radio
Authors: McMurtry Leslie
Published: August 2022

Horror and the Gothic have long been staple genres of radio drama, including the radio drama revival series of the late 1970s–early 1980s , CBS Radio Mystery Theater (1974–82). During the same time period, the Canadian government, recognising an emergent national-identity crisis in relation to its southern neighbour, invested heavily in original programming on the Canadian Broadcasting Corporation (CBC). This resulted in the popular horror series Nightfall (1980–3), which Danielle Hancock argues presented ‘murder as a Canadian national narrative’ (2018). While CBSRMT occasionally adapted existing stories from other media, the majority of the output for both series were original, written-for-the-air dramas. Embodying Gothic returns of the past upon the present and the effects of transgressive conduct in society, murder is examined as a Gothic trait in episodes of Nightfall and CBSRMT. Radio’s ambiguities and intimacies provoke listeners of these programmes to confront disjunction. The differing worldviews – American masculine nationalism and neoconservatism subverted; Canadian polite and tolerant masculinity turned upside down by a nihilistic rejection of these values – focus Gothic spotlights on each country’s anxieties.
Mammalian derived lipocalin and secretoglobin respiratory allergens strongly bind ligands with potentially immune modulating properties
Authors: Janssen-Weets Bente , Kerff Frédéric , Swiontek Kyra , Kler Stéphanie , Czolk Rebecca , Revets Dominique , Kuehn Annette , Bindslev-Jensen Carsten , Ollert Markus , Hilger Christiane
Published: August 2022

Allergens from furry animals frequently cause sensitization and respiratory allergic diseases. Most relevant mammalian respiratory allergens belong either to the protein family of lipocalins or secretoglobins. Their mechanism of sensitization remains largely unresolved. Mammalian lipocalin and secretoglobin allergens are associated with a function in chemical communication that involves abundant secretion into the environment, high stability and the ability to transport small volatile compounds. These properties are likely to contribute concomitantly to their allergenic potential. In this study, we aim to further elucidate the physiological function of lipocalin and secretoglobin allergens and link it to their sensitizing capacity, by analyzing their ligand-binding characteristics. We produced eight major mammalian respiratory allergens from four pet species in E.coli and compared their ligand-binding affinities to forty-nine ligands of different chemical classes by using a fluorescence-quenching assay. Furthermore, we solved the crystal-structure of the major guinea pig allergen Cav p 1, a typical lipocalin. Recombinant lipocalin and secretoglobin allergens are of high thermal stability with melting temperatures ranging from 65 to 90°C and strongly bind ligands with dissociation constants in the low micromolar range, particularly fatty acids, fatty alcohols and the terpene alcohol farnesol, that are associated with potential semiochemical and/or immune-modulating functions. Through the systematic screening of respiratory mammalian lipocalin and secretoglobin allergens with a large panel of potential ligands, we observed that total amino acid composition, as well as cavity shape and volume direct affinities to ligands of different chemical classes. Therefore, we were able to categorize lipocalin allergens over their ligand-binding profile into three sub-groups of a lipocalin clade that is associated with functions in chemical communication, thus strengthening the function of major mammalian respiratory allergens as semiochemical carriers. The promiscuous binding capability of hydrophobic ligands from environmental sources warrants further investigation regarding their impact on a molecule's allergenicity.
16S-ITGDB: An Integrated Database for Improving Species Classification of Prokaryotic 16S Ribosomal RNA Sequences
Authors: Hsieh Yu-Peng , Hung Yuan-Mao , Tsai Mong-Hsun , Lai Liang-Chuan , Chuang Eric Y.
Published: August 2022

Analyzing 16S ribosomal RNA (rRNA) sequences allows researchers to elucidate the prokaryotic composition of an environment. In recent years, third-generation sequencing technology has provided opportunities for researchers to perform full-length sequence analysis of bacterial 16S rRNA. RDP, SILVA, and Greengenes are the most widely used 16S rRNA databases. Many 16S rRNA classifiers have used these databases as a reference for taxonomic assignment tasks. However, some of the prokaryotic taxonomies only exist in one of the three databases. Furthermore, Greengenes and SILVA include a considerable number of taxonomies that do not have the resolution to the species level, which has limited the classifiers’ performance. In order to improve the accuracy of taxonomic assignment at the species level for full-length 16S rRNA sequences, we manually curated the three databases and removed the sequences that did not have a species name. We then established a taxonomy-based integrated database by considering both taxonomies and sequences from all three 16S rRNA databases and validated it by a mock community. Results showed that our taxonomy-based integrated database had improved taxonomic resolution to the species level. The integrated database and the related datasets are available at https://github.com/yphsieh/ItgDB.
Novel Designed Proteolytically Resistant VEGF-B186R127S Promotes Angiogenesis in Mouse Heart by Recruiting Endothelial Progenitor Cells
Authors: Mallick Rahul , Gurzeler Erika , Toivanen Pyry I. , Nieminen Tiina , Ylä-Herttuala Seppo
Published: August 2022

Background: Previous studies have indicated that vascular endothelial growth factor B186 (VEGF-B186) supports coronary vascular growth in normal and ischemic myocardium. However, previous studies also indicated that induction of ventricular arrhythmias is a severe side effect preventing the use of VEGF-B186 in cardiac gene therapy, possibly mediated by binding to neuropilin 1 (NRP1). We have designed a novel VEGF-B186 variant, VEGF-B186R127S, which is resistant to proteolytic processing and unable to bind to NRP1. Here, we studied its effects on mouse heart to explore the mechanism of VEGF-B186-induced vascular growth along with its effects on cardiac performance.

Methods: Following the characterization of VEGF-B186R127S, we performed ultrasound-guided adenoviral VEGF-B186R127S gene transfers into the murine heart. Vascular growth and heart functions were analyzed using immunohistochemistry, RT-PCR, electrocardiogram and ultrasound examinations. Endothelial progenitor cells (EPCs) were isolated from the circulating blood and characterized. Also, in vitro experiments were carried out in cardiac endothelial cells with adenoviral vectors.

Results: The proteolytically resistant VEGF-B186R127S significantly induced vascular growth in mouse heart. Interestingly, VEGF-B186R127S gene transfer increased the number of circulating EPCs that secreted VEGF-A. Other proangiogenic factors were also present in plasma and heart tissue after the VEGF-B186R127S gene transfer. Importantly, VEGF-B186R127S gene transfer did not cause any side effects, such as arrhythmias.

Conclusion: VEGF-B186R127S induces vascular growth in mouse heart by recruiting EPCs. VEGF-B186R127S is a novel therapeutic agent for cardiac therapeutic angiogenesis to rescue myocardial tissue after an ischemic insult.
Intra-articular MMP-1 in the spinal facet joint induces sustained pain and neuronal dysregulation in the DRG and spinal cord, and alters ligament kinematics under tensile loading
Authors: Ita Meagan E. , Singh Sagar , Troche Harrison R. , Welch Rachel L. , Winkelstein Beth A.
Published: August 2022

Chronic joint pain is a major healthcare challenge with a staggering socioeconomic burden. Pain from synovial joints is mediated by the innervated collagenous capsular ligament that surrounds the joint and encodes nociceptive signals. The interstitial collagenase MMP-1 is elevated in painful joint pathologies and has many roles in collagen regulation and signal transduction. Yet, the role of MMP-1 in mediating nociception in painful joints remains poorly understood. The goal of this study was to determine whether exogenous intra-articular MMP-1 induces pain in the spinal facet joint and to investigate effects of MMP-1 on mediating the capsular ligament’s collagen network, biomechanical response, and neuronal regulation. Intra-articular MMP-1 was administered into the cervical C6/C7 facet joints of rats. Mechanical hyperalgesia quantified behavioral sensitivity before, and for 28 days after, injection. On day 28, joint tissue structure was assessed using histology. Multiscale ligament kinematics were defined under tensile loading along with microstructural changes in the collagen network. The amount of degraded collagen in ligaments was quantified and substance P expression assayed in neural tissue since it is a regulatory of nociceptive signaling. Intra-articular MMP-1 induces behavioral sensitivity that is sustained for 28 days (p < 0.01), absent any significant effects on the structure of joint tissues. Yet, there are changes in the ligament’s biomechanical and microstructural behavior under load. Ligaments from joints injected with MMP-1 exhibit greater displacement at yield (p = 0.04) and a step-like increase in the number of anomalous reorganization events of the collagen fibers during loading (p ≤ 0.02). Collagen hybridizing peptide, a metric of damaged collagen, is positively correlated with the spread of collagen fibers in the unloaded state after MMP-1 (p = 0.01) and that correlation is maintained throughout the sub-failure regime (p ≤ 0.03). MMP-1 injection increases substance P expression in dorsal root ganglia (p < 0.01) and spinal cord (p < 0.01) neurons. These findings suggest that MMP-1 is a likely mediator of neuronal signaling in joint pain and that MMP-1 presence in the joint space may predispose the capsular ligament to altered responses to loading. MMP-1-mediated pathways may be relevant targets for treating degenerative joint pain in cases with subtle or no evidence of structural degeneration.
Perinatal derivatives: How to best characterize their multimodal functions in vitro. Part C: Inflammation, angiogenesis, and wound healing
Authors: Flores Ana I. , Pipino Caterina , Jerman Urška Dragin , Liarte Sergio , Gindraux Florelle , Kreft Mateja Erdani , Nicolas Francisco J. , Pandolfi Assunta , Tratnjek Larisa , Giebel Bernd , Pozzobon Michela , Silini Antonietta R. , Parolini Ornella , Eissner Günther , Lang-Olip Ingrid
Published: August 2022

Perinatal derivatives (PnD) are birth-associated tissues, such as placenta, umbilical cord, amniotic and chorionic membrane, and thereof-derived cells as well as secretomes. PnD play an increasing therapeutic role with beneficial effects on the treatment of various diseases. The aim of this review is to elucidate the modes of action of non-hematopoietic PnD on inflammation, angiogenesis and wound healing. We describe the source and type of PnD with a special focus on their effects on inflammation and immune response, on vascular function as well as on cutaneous and oral wound healing, which is a complex process that comprises hemostasis, inflammation, proliferation (including epithelialization, angiogenesis), and remodeling. We further evaluate the different in vitro assays currently used for assessing selected functional and therapeutic PnD properties. This review is a joint effort from the COST SPRINT Action (CA17116) with the intention to promote PnD into the clinics. It is part of a quadrinomial series on functional assays for validation of PnD, spanning biological functions, such as immunomodulation, anti-microbial/anti-cancer activities, anti-inflammation, wound healing, angiogenesis, and regeneration.
NOTCH signaling in COVID-19: a central hub controlling genes, proteins, and cells that mediate SARS-CoV-2 entry, the inflammatory response, and lung regeneration
Authors: Baindara Piyush , Sarker Md Bodruzzaman , Earhart Alexander P. , Mandal Santi M. , Schrum Adam G.
Published: August 2022

In the lungs of infected individuals, the downstream molecular signaling pathways induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are incompletely understood. Here, we describe and examine predictions of a model in which NOTCH may represent a central signaling axis in lung infection in Coronavirus Disease 2019 (COVID-19). A pathway involving NOTCH signaling, furin, ADAM17, and ACE2 may be capable of increasing SARS-CoV-2 viral entry and infection. NOTCH signaling can also upregulate IL-6 and pro-inflammatory mediators induced to hyperactivation in COVID-19. Furthermore, if NOTCH signaling fails to turn down properly and stays elevated, airway regeneration during lung healing can be inhibited—a process that may be at play in COVID-19. With specific NOTCH inhibitor drugs in development and clinical trials for other diseases being conducted, the roles of NOTCH in all of these processes central to both infection and healing merit contemplation if such drugs might be applied to COVID-19 patients.
Early immune surveillance to predict cytomegalovirus outcomes after allogeneic hematopoietic stem cell transplantation
Authors: Xia Jintao , Li Xuejie , Gui Genyong , Wu Jian , Gong Shengnan , Shang Yuxin , Fan Jun
Published: August 2022

Background

There is no method of predicting human cytomegalovirus (HCMV) outcomes in allogeneic hematopoietic stem cell transplant recipients clinically, leading in some cases to excessive or insufficient antiviral therapy. We evaluated the early immune response of recipients with disparate HCMV outcomes.

Methods

The HCMV outcomes of recipients were determined by long-term monitoring of HCMV DNA levels posttransplant. HCMV IgG and IgM concentrations at 1 week before and 1 week after transplantation, absolute lymphocyte counts, and HCMV-specific IFN-γ secreting cells at 1 month posttransplant were evaluated based on HCMV outcome.

Results

All recipients were negative for HCMV IgM. Significant differences between recipients with and without HCMV reactivation were observed in pre- and post-transplant HCMV IgG antibody levels, absolute lymphocyte counts, and HCMV-specific IFN-γ secreting cells (P < 0.05). HCMV IgG antibody levels significantly increased after transplantation in recipients with HCMV reactivation (P = 0.032), but not in those without reactivation. Multivariate analysis revealed that except for the absolute lymphocyte count these biomarkers were related to HCMV reactivation, independent of other clinical factors. In time-to-event analyses, lower levels of these biomarkers were associated with an increased 150-day cumulative incidence of HCMV reactivation (log-rank P < 0.05). In recipients with HCMV reactivation, the duration of HCMV DNAemia had negative correlation with HCMV-specific IFN-γ-secreting cells (P = 0.015, r = -0.372). The relationships between the peak HCMV DNA load and absolute lymphocyte count and HCMV-specific IFN-γ-secreting cells followed the same trends (P = 0.026, r = -0.181 and P = 0.010, r = -0.317).

Conclusions

HCMV IgG, absolute lymphocyte count, and HCMV-specific IFN-γ secreting cells represent the humoral and cellular immune response. Early monitoring of these immune markers could enable prediction of HCMV outcomes posttransplant and assessment of the severity of HCMV DNAemia.
Cervicovaginal microbiota significantly changed for HPV-positive women with high-grade squamous intraepithelial lesion
Authors: Guo Chunlei , Dai Wenkui , Zhou Qian , Gui Liming , Cai Han , Wu Di , Hou Jun , Li Changzhong , Li Shuaicheng , Du Hui , Wu Ruifang
Published: August 2022

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SIL-positive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection.
Cardiovascular Imaging in Pregnancy: Valvulopathy, Hypertrophic Cardiomyopathy, and Aortopathy
Authors: Ismail Haneen , Bradley Andrew J. , Lewis Jannet F.
Published: August 2022

Pregnancy is associated with profound hemodynamic changes that are particularly impactful in patients with underlying cardiovascular disease. Management of pregnant women with cardiovascular disease requires careful evaluation that considers the well-being of both the woman and the developing fetus. Clinical assessment begins before pregnancy and continues throughout gestation into the post-partum period and is supplemented by cardiac imaging. This review discusses the role of imaging, specifically echocardiography, cardiac MRI, and cardiac CT, in pregnant women with valvular diseases, hypertrophic cardiomyopathy, and aortic pathology.
Risk of cardiovascular disease among different fluoropyrimidine-based chemotherapy regimens as adjuvant treatment for resected colorectal cancer
Authors: Huang Wen-Kuan , Ho Wei-Pang , Hsu Hung-Chih , Chang Shu-Hao , Chen Dong-Yi , Chou Wen-Chi , Chang Pei-Hung , Chen Jen-Shi , Yang Tsai-Sheng , See Lai-Chu
Published: August 2022

Background

Patients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives.

Methods

We assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups.

Results

From 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age <70 years, stage II and age ≥70 years, stage III and age <70 years, stage III and age ≥70 years) as the overall population was observed.

Conclusion

Higher heart failure and ischemic stroke rates were found in the UFT group than in the other two chemotherapy groups, especially those with stage III CRC and ≥70 years of age. Careful monitoring of this subset of patients when prescribing UFT is warranted.
Prognostic value of blood pressure and resting heart rate in patients with tricuspid regurgitation
Authors: Guo Shuai , Zhang Bin , Ye Yunqing , Li Zhe , Liu Qingrong , Zhao Zhenyan , Wang Weiwei , Yu Zikai , Zhang Haitong , Zhao Qinghao , Duan Zhenya , Lv Junxing , Zhang Erli , Wang Bincheng , Zhao Yanyan , Gao Runlin , Xu Haiyan , Wu Yongjian
Published: August 2022

Background

The prognostic value of blood pressure (BP) and resting heart rate (RHR) in tricuspid regurgitation (TR) patients is unknown.

Aims

This study aimed to investigate the associations of BP and RHR with all-cause mortality in patients with TR.

Methods

A total of 2,013 patients with moderate or severe TR underwent echocardiography and BP measurement. The associations of routinely measured BP and RHR with 2-year all-cause mortality were analyzed.

Results

The cohort had 45.9% male patients and a mean age of 62.5 ± 15.9 years. At the 2-year follow-up, 165 patient deaths had occurred. The risk of death decreased rapidly, negatively correlating with systolic blood pressure (SBP) up to 120 mmHg and diastolic blood pressure (DBP) up to 70 mmHg. For RHR, the risk increased in direct proportion, starting at 80 beats per min. After adjusting for age, sex, body mass index (BMI), diabetes, coronary heart disease, pulmonary hypertension, estimated glomerular filtration rate (eGFR), and NYHA class, SBP [hazard ratio (HR):0.89; 95% CI:0.823–0.957 per 10 mmHg increase; P =0.002], DBP (HR:0.8; 95% CI:0.714–0.908 per 10 mmHg increase; P < 0.001), and RHR (HR: 1.1; 95% CI: 1.022–1.175 per 10 beats per min increase; P = 0.011) were independently associated with all-cause mortality. These associations persisted after further adjustments for echocardiographic indices, medications, serological tests, and etiologies.

Conclusion

In this cohort of patients with TR, routinely measured BP and RHR were associated with all-cause mortality independently. However, further large-scale, high-quality studies are required to validate our findings.
Ablation index-guided ablation with milder targets for atrial fibrillation: Comparison between high power and low power ablation
Authors: Liu Zheng , Liu Li-feng , Liu Xiao-qin , Liu Jiapeng , Wang Yu-xin , Liu Ye , Liu Xing-peng , Yang Xin-chun , Chen Mu-lei
Published: August 2022

Background

High power-ablation index (HP-AI)-guided ablation for atrial fibrillation (AF) targeting high AIs has been implemented in European countries. However, milder AI targets are widely used in Asia. The safety and efficacy of HP-AI-guided ablation compared with those of low-power AI-guided ablation in a milder AI-targeting setting are unknown. The goal of this study was to explore the efficacy and safety of HP-AI-guided ablation in a milder AI-targeting setting.

Methods

Patients who underwent pulmonary vein isolation (PVI) for AI-guided atrial fibrillation ablation in our center were enrolled and divided into 2 groups according to the ablation power used. In the HP-AI group, the ablation power was over 45 W, while the low power-AI group was ablated with <35 W power. The targeted AIs were 450–500 in the anterior wall and 350–400 in the posterior wall. The efficacy outcome was expressed as the single-procedure atrial arrhythmia-free survival between 91 days and 1 year. Safety outcomes included severe adverse events (SAEs), including symptomatic pulmonary vein (PV) stenosis, atrioesophagal fistula, cardiac tamponade, stroke, thromboembolism events, myocardial infarction, and major bleeding.

Results

A total of 134 patients were enrolled, of whom 74 underwent PVI using HP-AI, while 60 received low power-AI ablation. After a mean follow-up time of 7.4 months, 22 (16.4%) patients showed arrhythmia recurrence: 5 (6.8%) patients in the HP-AI group and 17 (28.3%) patients in the low power-AI group. The HP-AI group showed a significantly higher arrhythmia-free survival than the low power-AI group (p = 0.011). Two patients in the low power-AI group and 1 patient in the HP-AI group developed an SAE (p = NS). Compared with the low power-AI group, the HP-AI group demonstrated a higher PV first-pass isolation rate, shorter ablation time, and fewer patients with anatomical leakages and sites of unreached AI.

Conclusion

In a milder AI setting, HP-AI ablation might result in significantly higher arrhythmia-free survival than low power-AI ablation and a similar safety profile.
Distinctive Sedimentary Evolution at the East Edge of the Central Yellow Sea Mud Over the Past 45 kyr: Evidence From Detrital Mineralogy
Authors: Zhang Yao , Meng Xianwei , Han Zongzhu , Jin Bingfu , Lai Zhiqing , Liu Jinqing
Published: August 2022

The central Yellow Sea Mud (CYSM) is a vital part of the coastal sand and distal mud depositional system in the South Yellow Sea (SYS). Previous studies concerning the sedimentary evolution of this area have almost exclusively concentrated on its interior during the Holocene instead of its periphery. In this study, we used a sediment core (H10), with a significantly slow sedimentary rate, to reconstruct the sedimentary evolution at the east edge of the CYSM since MIS3a (∼45 kyr). This mainly involved using detrital minerals, the chemical compositions of garnet, and grain size. The provenance of coarser sediments has remarkable Yellow River-derived characteristics, especially during MIS2 and MIS1. The sedimentary evolution was primarily controlled by hydrodynamic regimes accompanied by changes in relative sea levels (RSLs) and climates. During MIS3a, frequent RSL fluctuations and powerful tidal current erosion were responsible for two facie shifts from the neritic sea to the shore and the lower sedimentary rate in the study area. A paleo-cold water mass and muddy deposition occurred during the high RSL stages with authigenic pyrite enrichment. During MIS2, the paleo-Yellow River was distributed on the SYS and flowed through the study area. Fluvial deposition on the shelf may be eroded by the strong winter monsoon, with an extremely dry and cold climate. Since ∼9.6 kyr, intense hydrodynamic regimes, which were induced by tidal current and upwelling, were responsible for the very much thin deposition, and coarser sediments remained in the study area. Notably, combined with previously studied cores, a much more detailed and intuitional cognition for CYSM formation can be obtainedviaour special perspective: mud periphery. This study elucidates the sedimentary system evolution and mud area formation of continental shelf seas.
Security Region of Integrated Heat and Electricity System Considering Thermal Dynamics
Authors: Wang Zhuhua , Huang Wencheng , Cai Xiaowei
Published: August 2022

The broad development of integrated heat and electricity systems (IHES) improved the energy utilization efficiency, but it also increased the risk of cascaded accidents and the difficulty of operation. The security region that defines the permitted operation range is efficient for the planning and control of IHESs, while the accurate formulation of security region boundary renders its applications. To address this problem, this article first proposes a novel equivalent thermal model (ETM) to build the direct connection between the operations states and the control variables in the heating system. The ETM directly characterizes the network response to the inputs and accurately describes the dynamic process in the heat system. On this basis, the method to construct the security region for IHES is presented considering the thermal dynamics, where the critical boundary is formulated with a set of accurate hyperplanes. To describe the thermal dynamics, numerical simulations from different aspects verify the effectiveness of the ETM. The results of security region indicate that the thermal dynamics influence the operation security and renewable penetration in the power system significantly.