bluuebunny/crossref_metadata_2025 huggingface dataset:
Cold Climate Impact on Air-Pollution-Related Health Outcomes: A Scoping Review
Authors: Wine Osnat , Osornio Vargas Alvaro , Campbell Sandra , Hosseini Vahid , Koch Charles , Shahbakhti Mahdi
Published: January 2022

In cold temperatures, vehicles idle more, have high cold-start emissions including greenhouse gases, and have less effective exhaust filtration systems, which can cause up to ten-fold more harmful vehicular emissions. Only a few vehicle technologies have been tested for emissions below −7 °C (20 °F). Four-hundred-million people living in cities with sub-zero temperatures may be impacted. We conducted a scoping review to identify the existing knowledge about air-pollution-related health outcomes in a cold climate, and pinpoint any research gaps. Of 1019 papers identified, 76 were selected for review. The papers described short-term health impacts associated with air pollutants. However, most papers removed the possible direct effect of temperature on pollution and health by adjusting for temperature. Only eight papers formally explored the modifying effect of temperatures. Five studies identified how extreme cold and warm temperatures aggravated mortality/morbidity associated with ozone, particles, and carbon-monoxide. The other three found no health associations with tested pollutants and temperature. Additionally, in most papers, emissions could not be attributed solely to traffic. In conclusion, evidence on the relationship between cold temperatures, traffic-related pollution, and related health outcomes is lacking. Therefore, targeted research is required to guide vehicle regulations, assess extreme weather-related risks in the context of climate change, and inform public health interventions.
Birthing under the Condition of the COVID-19 Pandemic in Germany: Interviews with Mothers, Partners, and Obstetric Health Care Workers
Authors: Schmiedhofer Martina , Derksen Christina , Dietl Johanna Elisa , Häussler Freya , Louwen Frank , Hüner Beate , Reister Frank , Strametz Reinhard , Lippke Sonia
Published: January 2022

Background: The COVID-19 pandemic and the necessary containment measures challenge obstetric care. Support persons were excluded while protection measures burdened and disrupted the professionals’ ability to care and communicate. The objective of this study was to explore the first-hand experience of the impact of the COVID-19 pandemic on mothers, their partners, and obstetric professionals regarding birth and obstetric care in a university hospital. Methods: To answer the descriptive research questions, we conducted a qualitative content analysis using a data triangulation approach. We carried out 35 semi-structured interviews with two stratified purposive samples. Sample one consisted of 25 mothers who had given birth during the pandemic and five partners. Sample two included 10 obstetric professionals whose insights complemented the research findings and contributed to data validation. Participants were recruited from the study sample of a larger project on patient safety from two German university hospitals from February to August 2021. The study was approved by two ethics committees and informed consent was obtained. Results: Mothers complied with the rules, but felt socially isolated and insecure, especially before transfer to the delivery room. The staff equally reported burdens from their professional perspective: They tried to make up for the lack of partner and social contacts but could not live up to their usual professional standards. The exclusion of partners was seen critically, but necessary to contain the pandemic. The undisturbed time for bonding in the maternity ward was considered positive by both mothers and professionals. Conclusion: The negative effects of risk mitigation measures on childbirth are to be considered carefully when containment measures are applied.
Online Information on Painful Sexual Dysfunction in Women: Quality Analysis of Websites in SPANISH about Dyspareunia, Vaginismus and Vulvodynia
Authors: Vicente-Neira Andrea , Prieto-Gómez Virginia , Navarro-Brazález Beatriz , Lirio-Romero Cristina , Bailón-Cerezo Javier , Torres-Lacomba María
Published: January 2022

The objective of this study was to evaluate the content, quality, and readability of websites containing information on dyspareunia, vaginismus, and vulvodynia in Spanish. Web pages were retrieved entering the terms “dyspareunia”, “vaginismus”, and “vulvodynia” in Google, Yahoo!, and Bing search engines. Two researchers employed the DISCERN and Bermúdez-Tamayo questionnaires to analyze the content and quality of the websites, and the INFLESZ scale to evaluate their readability. IBM SPSS® version 25 statistical software was employed for data analysis. The internet search yielded 262 websites, 91 of which were included after applying the selection criteria. Websites with information on dyspareunia obtained median scores of 24 (30–21) in the DISCERN, 38 (41.0–35.5) in the Bermúdez-Tamayo, and 55.3 (57.2–50.9) in the INFLESZ tools. The results for websites on vaginismus revealed median scores of 23.5 (30–20) in the DISCERN, 37 (42–35) in the Bermúdez-Tamayo, and 52.9 (55.6–46.4) in the INFLESZ. Finally, the median scores for vulvodynia sites was 25.5 (30–20) in the DISCERN, 38 (43–33.7) in the Bermúdez-Tamayo, and 54.2 (57.3–47.2) in the INFLESZ. These outcomes indicate that the quality of information in these websites is very low, while the overall quality of the web pages is moderate. Sites on vaginismus and vulvodynia were “somewhat difficult” to read, while readability was “normal” for websites on dyspareunia. Healthcare professionals should be aware of the shortcomings of these websites and address them through therapeutic education with resources containing updated, quality information. This raises the need for health professionals to generate these resources themselves or for experts and/or scientific societies in the field to check the quality and timeliness of the contents, regardless of whether or not the websites are endorsed with quality seals.
Searching for the Optimal Method of Financing Hospital Emergency Departments—Comparison of Polish and Selected European Solutions
Authors: Tyrańska-Fobke Anna , Robakowska Marlena , Ślęzak Daniel , Pogorzelczyk Katarzyna , Basiński Andrzej
Published: January 2022

Hospital emergency departments are units of the State Medical Rescue system in Poland, which was established to help people in a state of a health emergency. The aim of this study is to develop an optimal method of financing emergency departments in Poland. The study used Polish data from 2016–2019 on the financing of services at the Clinical Emergency Department of the University Clinical Center in Gdańsk. For benchmarking and mathematical modeling, data for the Czech Republic, Germany and Latvia was used. The results of the analysis shows significant differences, to the disadvantage of Clinical Emergency Department, between the potential contract values in the tested models and the actual amounts of funds transferred by the National Health Fund Pomeranian Voivodeship Branch for the activities of Clinical Emergency Department under the concluded contracts. The introduction of co-payment on the part of patients reporting to the emergency departments with minor ailments that do not require hospitalization generates financial revenues, but does not significantly improve the financial results of the analyzed ward. However, it may be educational for patients in terms of raising their awareness of the correct place to seek assistance in the event of a sudden illness.
Gender Differences in Smoking Initiation and Cessation Associated with the Intergenerational Transfer of Smoking across Three Generations: The Nagahama Study
Authors: Nakagawa Sachiko , Takahashi Yoshimitsu , Nakayama Takeo , Muro Shigeo , Mishima Michiaki , Sekine Akihiro , Tabara Yasuharu , Matsuda Fumihiko , Kosugi Shinji
Published: January 2022

Global tobacco policies lowered overall and male smoking rates, but female smoking rates have remained unchanged. Parent–child studies revealed the effects of parental smoking, but gender differences had mixed results. We investigated the effects of long-term smoking behavior in families over three generations in order to clarify gender differences. A cross-sectional study in a community-based genome cohort was conducted using a self-reported questionnaire. A total of 8652 respondents were stratified by gender regarding smoking initiation. A logistic regression analysis was performed to analyze the family smoking history. A total of 2987 current smokers and ever-smokers were compared regarding smoking cessation. With respect to smoking initiation, women were affected by their smoking mothers (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.8–3.2) and grandmothers (OR, 1.7; CI, 1.1–2.4). Women who continued smoking were affected only by their smoking mothers (OR, 1.6; CI, 1.05–2.49). In conclusion, gender differences in smoking initiation and cessation are possibly associated with family smoking history. Mothers and grandmothers were shown to have a strong influence on women with respect to both smoking initiation and cessation. Future research should focus on providing evidence for effective gender-specific intervention programs to curb long-term smoking in women.
Pain-Related Worrying and Goal Preferences Determine Walking Persistence in Women with Fibromyalgia
Authors: Pastor-Mira María Ángeles , López-Roig Sofía , Toribio Eva , Martínez-Zaragoza Fermín , Nardi-Rodríguez Ainara , Peñacoba Cecilia
Published: January 2022

Physical activity and exercise are relevant behaviors for fibromyalgia health outcomes; however, patients have difficulties undertaking and maintaining an active lifestyle. With a cross-sectional design, this study explored the role of pain-related worrying and goal preferences in the walking persistence of women with fibromyalgia. The sample included 111 women who attended a tertiary health setting. We adapted the Six-Minute Walk Test where participants decided either to stop or continue walking in five voluntary 6 min bouts. Women who were categorized higher in pain-related worrying reported higher preference for pain avoidance goals (t = −2.44, p = 0.02) and performed worse in the walking task (LongRank = 4.21; p = 0.04). Pain avoidance goal preference increased the likelihood of stopping after the first (OR = 1.443), second (OR = 1.493), and third (OR = 1.540) 6 min walking bout, and the risk of ending the walking activity during the 30 min task (HR = 1.02, [1.0–1.03]). Influence of pain-related worrying on total walking distance was mediated by goal preferences (ab = −3.25). In interventions targeting adherence in physical activity and exercise, special attention is needed for women who are particularly worried about pain to help decrease their preference for short-term pain avoidance goals relative to long-term goals such as being active through walking.
Is Anyone Else Feeling Completely Nonessential? Meaningful Work, Identification, Job Insecurity, and Online Organizational Behavior during a Lockdown in The Netherlands
Authors: Ouwerkerk Jaap W. , Bartels Jos
Published: January 2022

COVID-19 has affected employees worldwide, and in many countries, governments have used lockdowns to control the pandemic. In some countries, employees were divided into essential and nonessential workers. A survey among Dutch employees (N = 408) investigated how a lockdown in response to the pandemic affected work perceptions. The study found that employees who were not working during lockdown, or whose work hours were reduced sharply, perceived their job as contributing less to the greater good, identified less strongly with their organization, and experienced more job insecurity compared with those who retained a large percentage of their work activities. The longer employees were in lockdown, the weaker their greater-good motivations and the more job insecurity. Furthermore, identification with colleagues and perception of positive meaning in one’s job were significant predictors of online organizational citizenship behavior directed at other individuals (OCB-I), whereas organizational identification predicted such behavior directed at the organization (OCB-O). Moreover, indicative of a job preservation motive, increased job insecurity was related to more online OCB-O, and more deviant online behaviors directed at others in the form of cyberostracism and cyberincivility. We further discuss practical lessons for future lockdowns to minimize negative consequences for organizations and employees.
Research Priorities of Applying Low-Cost PM2.5 Sensors in Southeast Asian Countries
Authors: Lung Shih-Chun Candice , Thi Hien To , Cambaliza Maria Obiminda L. , Hlaing Ohnmar May Tin , Oanh Nguyen Thi Kim , Latif Mohd Talib , Lestari Puji , Salam Abdus , Lee Shih-Yu , Wang Wen-Cheng Vincent , Tsou Ming-Chien Mark , Cong-Thanh Tran , Cruz Melliza Templonuevo , Tantrakarnapa Kraichat , Othman Murnira , Roy Shatabdi , Dang Tran Ngoc , Agustian Dwi
Published: January 2022

The low-cost and easy-to-use nature of rapidly developed PM2.5 sensors provide an opportunity to bring breakthroughs in PM2.5 research to resource-limited countries in Southeast Asia (SEA). This review provides an evaluation of the currently available literature and identifies research priorities in applying low-cost sensors (LCS) in PM2.5 environmental and health research in SEA. The research priority is an outcome of a series of participatory workshops under the umbrella of the International Global Atmospheric Chemistry Project–Monsoon Asia and Oceania Networking Group (IGAC–MANGO). A literature review and research prioritization are conducted with a transdisciplinary perspective of providing useful scientific evidence in assisting authorities in formulating targeted strategies to reduce severe PM2.5 pollution and health risks in this region. The PM2.5 research gaps that could be filled by LCS application are identified in five categories: source evaluation, especially for the distinctive sources in the SEA countries; hot spot investigation; peak exposure assessment; exposure–health evaluation on acute health impacts; and short-term standards. The affordability of LCS, methodology transferability, international collaboration, and stakeholder engagement are keys to success in such transdisciplinary PM2.5 research. Unique contributions to the international science community and challenges with LCS application in PM2.5 research in SEA are also discussed.
Dental Emergency Admissions in Emergency Oral Health Care Centers during COVID-19 Pandemic in Buenos Aires, Argentina
Authors: Rodriguez Pablo Alejandro , Gatti Patricio , Cabirta María Lorena , Baquerizo Nicolas Roman , Prada Silvio , Gualtieri Ariel , Puia Sebastian , Squassi Aldo
Published: January 2022

This study aimed to describe patients’ demographic characteristics and treatment delivered in private and public dental emergency clinics and to compare them with a pre-pandemic period. A retrospective cross-sectional study was carried out on patients attending the University Dental Hospital of the University of Buenos Aires and on one private dental clinic, situated in Buenos Aires, between March and June of 2019 and 2020. The sample considered all the patients’ medical records of those requiring emergency dental treatment at these centers during that period. We systematize the treatments required and delivered by the emergency providers into categories. In 2019, 36,071 patients were treated at the university dental hospital and the private clinic. In 2020, 7485 patients received emergency treatment, showing a fivefold reduction. During a pre-pandemic period, in 2019, both oral care centers provided 44,894 treatments, around three times the treatments provided in 2020 during the same period. We have found significant differences in the age groups of people who required emergency treatment in the pandemic period compared to the pre-pandemic period. During the pandemic period, the most represented types of treatment were radiographic exams (3061) and tooth extractions (2583). Conversely, during the pre-pandemic period, the most frequent treatments were radiographic examinations (16,649) and general consultations (10,591). The percentages of all types of treatments differ significantly between the two years except for pediatric consultations and prosthetics emergencies. As the pandemic is still an ongoing sanitary problem, urgent dental care patterns should be considered.
Acknowledgment to Reviewers of International Journal of Financial Studies in 2021
Authors:   International Journal of Financial Studies Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases
Authors: Oton-Gonzalez Lucia , Mazziotta Chiara , Iaquinta Maria Rosa , Mazzoni Elisa , Nocini Riccardo , Trevisiol Lorenzo , D’Agostino Antonio , Tognon Mauro , Rotondo John Charles , Martini Fernanda
Published: January 2022

Bone metabolism consists of a balance between bone formation and bone resorption, which is mediated by osteoblast and osteoclast activity, respectively. In order to ensure bone plasticity, the bone remodeling process needs to function properly. Mesenchymal stem cells differentiate into the osteoblast lineage by activating different signaling pathways, including transforming growth factor β (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1 (Wnt)/β-catenin pathways. Recent data indicate that bone remodeling processes are also epigenetically regulated by DNA methylation, histone post-translational modifications, and non-coding RNA expressions, such as micro-RNAs, long non-coding RNAs, and circular RNAs. Mutations and dysfunctions in pathways regulating the osteoblast differentiation might influence the bone remodeling process, ultimately leading to a large variety of metabolic bone diseases. In this review, we aim to summarize and describe the genetics and epigenetics of the bone remodeling process. Moreover, the current findings behind the genetics of metabolic bone diseases are also reported.
Insertion Sequence (IS) Element-Mediated Activating Mutations of the Cryptic Aromatic β-Glucoside Utilization (BglGFB) Operon Are Promoted by the Anti-Terminator Protein (BglG) in Escherichia coli
Authors: Zhang Zhongge , Zhou Kingswell , Tran Dennis , Saier Milton
Published: January 2022

The cryptic β-glucoside GFB (bglGFB) operon in Escherichia coli (E. coli) can be activated by mutations arising under starvation conditions in the presence of an aromatic β-glucoside. This may involve the insertion of an insertion sequence (IS) element into a “stress-induced DNA duplex destabilization” (SIDD) region upstream of the operon promoter, although other types of mutations can also activate the bgl operon. Here, we show that increased expression of the bglG gene, encoding a well-characterized transcriptional antiterminator, dramatically increases the frequency of both IS-mediated and IS-independent Bgl+ mutations occurring on salicin- and arbutin-containing agar plates. Both mutation rates increased with increasing levels of bglG expression but IS-mediated mutations were more prevalent at lower BglG levels. Mutations depended on the presence of both BglG and an aromatic β-glucoside, and bglG expression did not influence IS insertion in other IS-activated operons tested. The N-terminal mRNA-binding domain of BglG was essential for mutational activation, and alteration of BglG’s binding site in the mRNA nearly abolished Bgl+ mutant appearances. Increased bglG expression promoted residual bgl operon expression in parallel with the increases in mutation rates. Possible mechanisms are proposed explaining how BglG enhances the frequencies of bgl operon activating mutations.
Computational Analysis of Molnupiravir
Authors: Sharov Artem , Burkhanova Tatyana , Taskın Tok Tugba , Babashkina Maria , Safin Damir
Published: January 2022

In this work, we report in-depth computational studies of three plausible tautomeric forms, generated through the migration of two acidic protons of the N4-hydroxylcytosine fragment, of molnupiravir, which is emerging as an efficient drug to treat COVID-19. The DFT calculations were performed to verify the structure of these tautomers, as well as their electronic and optical properties. Molecular docking was applied to examine the influence of the structures of the keto-oxime, keto-hydroxylamine and hydroxyl-oxime tautomers on a series of the SARS-CoV-2 proteins. These tautomers exhibited the best affinity behavior (−9.90, −7.90, and −9.30 kcal/mol, respectively) towards RdRp-RTR and Nonstructural protein 3 (nsp3_range 207–379-MES).
Testing the Role of Glutamate NMDA Receptors in Peripheral Trigeminal Nociception Implicated in Migraine Pain
Authors: Guerrero-Toro Cindy , Koroleva Kseniia , Ermakova Elizaveta , Gafurov Oleg , Abushik Polina , Tavi Pasi , Sitdikova Guzel , Giniatullin Rashid
Published: January 2022

The pro-nociceptive role of glutamate in the CNS in migraine pathophysiology is well established. Glutamate, released from trigeminal afferents, activates second order nociceptive neurons in the brainstem. However, the function of peripheral glutamate receptors in the trigeminovascular system suggested as the origin site for migraine pain, is less known. In the current project, we used calcium imaging and patch clamp recordings from trigeminal ganglion (TG) neurons, immunolabelling, CGRP assay and direct electrophysiological recordings from rat meningeal afferents to investigate the role of glutamate in trigeminal nociception. Glutamate, aspartate, and, to a lesser extent, NMDA under free-magnesium conditions, evoked calcium transients in a fraction of isolated TG neurons, indicating functional expression of NMDA receptors. The fraction of NMDA sensitive neurons was increased by the migraine mediator CGRP. NMDA also activated slowly desensitizing currents in 37% of TG neurons. However, neither glutamate nor NMDA changed the level of extracellular CGRP. TG neurons expressed both GluN2A and GluN2B subunits of NMDA receptors. In addition, after removal of magnesium, NMDA activated persistent spiking activity in a fraction of trigeminal nerve fibers in meninges. Thus, glutamate activates NMDA receptors in somas of TG neurons and their meningeal nerve terminals in magnesium-dependent manner. These findings suggest that peripherally released glutamate can promote excitation of meningeal afferents implicated in generation of migraine pain in conditions of inherited or acquired reduced magnesium blockage of NMDA channels and support the usage of magnesium supplements in migraine.
Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production
Authors: Bolognesi Federico , Fazio Nicola , Boriani Filippo , Fabbri Viscardo Paolo , Gravina Davide , Pedrini Francesca Alice , Zini Nicoletta , Greco Michelina , Paolucci Michela , Re Maria Carla , Asioli Sofia , Foschini Maria Pia , D’Errico Antonietta , Baldini Nicola , Marchetti Claudio
Published: January 2022

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze–thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.
The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism
Authors: Ruiz-Serrano Amalia , Boyle Christina , Monné Rodríguez Josep , Günter Julia , Jucht Agnieszka , Pfundstein Svende , Bapst Andreas , Lutz Thomas , Wenger Roland , Scholz Carsten
Published: January 2022

Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.
Grape ASR-Silencing Sways Nuclear Proteome, Histone Marks and Interplay of Intrinsically Disordered Proteins
Authors: Atanassov Hristo , Parrilla Jonathan , Artault Caroline , Verbeke Jérémy , Schneider Thomas , Grossmann Jonas , Roschitzki Bernd , Atanassova Rossitza
Published: January 2022

In order to unravel the functions of ASR (Abscisic acid, Stress, Ripening-induced) proteins in the nucleus, we created a new model of genetically transformed grape embryogenic cells by RNAi-knockdown of grape ASR (VvMSA). Nuclear proteomes of wild-type and VvMSA-RNAi grape cell lines were analyzed by quantitative isobaric tagging (iTRAQ 8-plex). The most significantly up- or down-regulated nuclear proteins were involved in epigenetic regulation, DNA replication/repair, transcription, mRNA splicing/stability/editing, rRNA processing/biogenesis, metabolism, cell division/differentiation and stress responses. The spectacular up-regulation in VvMSA-silenced cells was that of the stress response protein VvLEA D-29 (Late Embryogenesis Abundant). Both VvMSA and VvLEA D-29 genes displayed strong and contrasted responsiveness to auxin depletion, repression of VvMSA and induction of VvLEA D-29. In silico analysis of VvMSA and VvLEA D-29 proteins highlighted their intrinsically disordered nature and possible compensatory relationship. Semi-quantitative evaluation by medium-throughput immunoblotting of eighteen post-translational modifications of histones H3 and H4 in VvMSA-knockdown cells showed significant enrichment/depletion of the histone marks H3K4me1, H3K4me3, H3K9me1, H3K9me2, H3K36me2, H3K36me3 and H4K16ac. We demonstrate that grape ASR repression differentially affects members of complex nucleoprotein structures and may not only act as molecular chaperone/transcription factor, but also participates in plant responses to developmental and environmental cues through epigenetic mechanisms.
Bio-Efficacy of Chrysoeriol7, a Natural Chemical and Repellent, against Brown Planthopper in Rice
Authors: Kim Eun-Gyeong , Yun Sopheap , Park Jae-Ryoung , Jang Yoon-Hee , Farooq Muhammad , Yun Byoung-Ju , Kim Kyung-Min
Published: January 2022

Brown planthopper (BPH, Nilaparvata lugens Stal.) is the most damaging rice pest affecting stable rice yields worldwide. Currently, methods for controlling BPH include breeding a BPH-resistant cultivar and using synthetic pesticides. Nevertheless, the continuous cultivation of resistant cultivars allows for the emergence of various resistant races, and the use of synthetic pesticides can induce environmental pollution as well as the emergence of unpredictable new pest species. As plants cannot migrate to other locations on their own to combat various stresses, the production of secondary metabolites allows plants to protect themselves from stress and tolerate their reproduction. Pesticides using natural products are currently being developed to prevent environmental pollution and ecosystem disturbance caused by synthetic pesticides. In this study, after BPH infection in rice, chrysoeriol7 (C7), a secondary metabolite that induces resistance against BPH, was assessed. After C7 treatment and BPH infection, relative expression levels of the flavonoid-related genes were elevated, suggesting that in plants subjected to BPH, compounds related to flavonoids, among the secondary metabolites, play an important role in inducing resistance. The plant-derived natural compound chrysoeriol7 can potentially thus be used to develop environmentally friendly pesticides. The suggested control of BPH can be effectively used to alleviate concerns regarding environmental pollution and to construct a relatively safe rice breeding environment.
Adipose Stromal/Stem Cell-Derived Extracellular Vesicles: Potential Next-Generation Anti-Obesity Agents
Authors: Zuccarini Mariachiara , Giuliani Patricia , Di Liberto Valentina , Frinchi Monica , Caciagli Francesco , Caruso Vanni , Ciccarelli Renata , Mudò Giuseppa , Di Iorio Patrizia
Published: January 2022

Over the last decade, several compounds have been identified for the treatment of obesity. However, due to the complexity of the disease, many pharmacological interventions have raised concerns about their efficacy and safety. Therefore, it is important to discover new factors involved in the induction/progression of obesity. Adipose stromal/stem cells (ASCs), which are mostly isolated from subcutaneous adipose tissue, are the primary cells contributing to the expansion of fat mass. Like other cells, ASCs release nanoparticles known as extracellular vesicles (EVs), which are being actively studied for their potential applications in a variety of diseases. Here, we focused on the importance of the con-tribution of ASC-derived EVs in the regulation of metabolic processes. In addition, we outlined the advantages/disadvantages of the use of EVs as potential next-generation anti-obesity agents.
Up-Regulation of Cyclooxygenase-2 (COX-2) Expression by Temozolomide (TMZ) in Human Glioblastoma (GBM) Cell Lines
Authors: Lombardi Francesca , Augello Francesca Rosaria , Artone Serena , Gugu Mitilda Karoli , Cifone Maria Grazia , Cinque Benedetta , Palumbo Paola
Published: January 2022

TMZ-resistance remains a main limitation in glioblastoma (GBM) treatment. TMZ is an alkylating agent whose cytotoxicity is modulated by O6-methylguanine-DNA methyltransferase (MGMT), whose expression is determined by MGMT gene promoter methylation status. The inflammatory marker COX-2 has been implicated in GBM tumorigenesis, progression, and stemness. COX-2 inhibitors are considered a GBM add-on treatment due to their ability to increase TMZ-sensitivity. We investigated the effect of TMZ on COX-2 expression in GBM cell lines showing different COX-2 levels and TMZ sensitivity (T98G and U251MG). β-catenin, MGMT, and SOX-2 expression was analyzed. The effects of NS398, COX-2 inhibitor, alone or TMZ-combined, were studied evaluating cell proliferation by the IncuCyte® system, cell cycle/apoptosis, and clonogenic potential. COX-2, β-catenin, MGMT, and SOX-2 expression was evaluated by RT-PCR, Western blotting, and immunofluorescence and PGE2 by ELISA. Our findings, sustaining the role of COX-2/PGE2 system in TMZ-resistance of GBM, show, for the first time, a relevant, dose-dependent up-regulation of COX-2 expression and activity in TMZ-treated T98G that, in turn, correlated with chemoresistance. Similarly, all the COX-2-dependent signaling pathways involved in TMZ-resistance also resulted in being up-modulated after treatment with TMZ. NS398+TMZ was able to reduce cell proliferation and induce cell cycle arrest and apoptosis. Moreover, NS398+TMZ counteracted the resistance in T98G preventing the TMZ-induced COX-2, β-catenin, MGMT, and SOX-2 up-regulation.
Human Endothelial Progenitor Cells Protect the Kidney against Ischemia-Reperfusion Injury via the NLRP3 Inflammasome in Mice
Authors: Jang Ha Nee , Kim Jin Hyun , Jung Myeong Hee , Tak Taekil , Jung Jung Hwa , Lee Seunghye , Jung Sehyun , Chang Se-Ho , Kim Hyun-Jung
Published: January 2022

Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and progression to chronic kidney disease (CKD). However, no effective therapeutic intervention has been established for ischemic AKI. Endothelial progenitor cells (EPCs) have major roles in the maintenance of vascular integrity and the repair of endothelial damage; they also serve as therapeutic agents in various kidney diseases. Thus, we examined whether EPCs have a renoprotective effect in an IRI mouse model. Mice were assigned to sham, EPC, IRI-only, and EPC-treated IRI groups. EPCs originating from human peripheral blood were cultured. The EPCs were administered 5 min before reperfusion, and all mice were killed 72 h after IRI. Blood urea nitrogen, serum creatinine, and tissue injury were significantly increased in IRI mice; EPCs significantly improved the manifestations of IRI. Apoptotic cell death and oxidative stress were significantly reduced in EPC-treated IRI mice. Administration of EPCs decreased the expression levels of NLRP3, cleaved caspase-1, p-NF-κB, and p-p38. Furthermore, the expression levels of F4/80, ICAM-1, RORγt, and IL-17RA were significantly reduced in EPC-treated IRI mice. Finally, the levels of EMT-associated factors (TGF-β, α-SMA, Snail, and Twist) were significantly reduced in EPC-treated IRI mice. This study shows that inflammasome-mediated inflammation accompanied by immune modulation and fibrosis is a potential target of EPCs as a treatment for IRI-induced AKI and the prevention of progression to CKD.
Oncogenic Mutation BRAF V600E Changes Phenotypic Behavior of THLE-2 Liver Cells through Alteration of Gene Expression
Authors: Śmiech Magdalena , Leszczyński Paweł , Wardell Christopher , Poznański Piotr , Pierzchała Mariusz , Taniguchi Hiroaki
Published: January 2022

The accumulation of mutations in cancer driver genes, such as tumor suppressors or proto-oncogenes, affects cellular homeostasis. Disturbances in the mechanism controlling proliferation cause significant augmentation of cell growth and division due to the loss of sensitivity to the regulatory signals. Nowadays, an increasing number of cases of liver cancer are observed worldwide. Data provided by the International Cancer Genome Consortium (ICGC) have indicated many alterations within gene sequences, whose roles in tumor development are not well understood. A comprehensive analysis of liver cancer (virus-associated hepatocellular carcinoma) samples has identified new and rare mutations in B-Raf proto-oncogene (BRAF) in Japanese HCC patients, as well as BRAF V600E mutations in French HCC patients. However, their function in liver cancer has never been investigated. Here, using functional analysis and next generation sequencing, we demonstrate the tumorigenic effect of BRAF V600E on hepatocytes (THLE-2 cell line). Moreover, we identified genes such as BMP6, CXCL11, IL1B, TBX21, RSAD2, MMP10, and SERPIND1, which are possibly regulated by the BRAF V600E-mediated, mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. Through several functional assays, we demonstrate that BRAF L537M, D594A, and E648G mutations alone are not pathogenic in liver cancer. The investigation of genome mutations and the determination of their impact on cellular processes and functions is crucial to unraveling the molecular mechanisms of liver cancer development.
Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector via nSMase2/Smpd3, Satellite, and Immune Cells in Duchenne Muscular Dystrophy
Authors: Matsuzaka Yasunari , Hirai Yukihiko , Hashido Kazuo , Okada Takashi
Published: January 2022

Duchenne muscular dystrophy (DMD) is caused by loss-of-function mutations in the dystrophin gene on chromosome Xp21. Disruption of the dystrophin–glycoprotein complex (DGC) on the cell membrane causes cytosolic Ca2+ influx, resulting in protease activation, mitochondrial dysfunction, and progressive myofiber degeneration, leading to muscle wasting and fragility. In addition to the function of dystrophin in the structural integrity of myofibers, a novel function of asymmetric cell division in muscular stem cells (satellite cells) has been reported. Therefore, it has been suggested that myofiber instability may not be the only cause of dystrophic degeneration, but rather that the phenotype might be caused by multiple factors, including stem cell and myofiber functions. Furthermore, it has been focused functional regulation of satellite cells by intracellular communication of extracellular vesicles (EVs) in DMD pathology. Recently, a novel molecular mechanism of DMD pathogenesis—circulating RNA molecules—has been revealed through the study of target pathways modulated by the Neutral sphingomyelinase2/Neutral sphingomyelinase3 (nSMase2/Smpd3) protein. In addition, adeno-associated virus (AAV) has been clinically applied for DMD therapy owing to the safety and long-term expression of transduction genes. Furthermore, the EV-capsulated AAV vector (EV-AAV) has been shown to be a useful tool for the intervention of DMD, because of the high efficacy of the transgene and avoidance of neutralizing antibodies. Thus, we review application of AAV and EV-AAV vectors for DMD as novel therapeutic strategy.
Hepatitis B Flare in Hepatitis B e Antigen-Negative Patients: A Complicated Cascade of Innate and Adaptive Immune Responses
Authors: Chang Ming-Ling , Liaw Yun-Fan
Published: January 2022

Chronic hepatitis B virus (HBV) infection is a dynamic process involving interactions among HBV, hepatocytes, and the host immune system. The natural course of chronic hepatitis B (CHB) is divided into four chronological phases, including the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases. During HBV flare, alanine aminotransferase (ALT) levels abruptly rise to >5× the upper limit of normal; this is thought to occur due to the immune response against an upsurge in serum HBV DNA and antigen levels. Hepatitis flares may occur spontaneously, during or after antiviral therapy, or upon immunosuppression or chemotherapy in both HBeAg-positive and HBeAg-negative patients. The clinical spectrum of HBV flares varies from asymptomatic to hepatic decompensation or failure. HBeAg seroconversion with ≥ 1 year of consolidation therapy is accepted as an endpoint of oral antiviral therapy in HBeAg-positive patients, but recommendations for treating HBeAg-negative patients differ. Thus, the management of HBeAg-negative patients has attracted increasing interest. In the current review, we summarize various types of HBV flares and the associated complex cascade of innate and adaptive immune responses, with a focus on HBeAg-negative CHB patients. Hopefully, this review will provide insight into immunopathogenesis to improve the management of HBV flares in HBeAg-negative CHB patients.
Different Expression Levels of DLK2 Inhibit NOTCH Signaling and Inversely Modulate MDA-MB-231 Breast Cancer Tumor Growth In Vivo
Authors: Naranjo Ana-Isabel , González-Gómez María-Julia , Baladrón Victoriano , Laborda Jorge , Nueda María-Luisa
Published: January 2022

NOTCH signaling is implicated in the development of breast cancer tumors. DLK2, a non-canonical inhibitor of NOTCH signaling, was previously shown to be involved in skin and breast cancer. In this work, we studied whether different levels of DLK2 expression influenced the breast cancer characteristics of MDA-MB-231 cells. We found that DLK2 overexpression inhibited NOTCH activation in a dose-dependent manner. Moreover, depending on the level of inhibition of NOTCH1 activation generated by different levels of DLK2 expression, cell proliferation, cell cycle dynamics, cell apoptosis, cell migration, and tumor growth in vivo were affected in opposite directions. Low levels of DLK2 expression produced a slight inhibition of NOTCH1 activation, and enhanced MDA-MB-231 cell invasion in vitro and cell proliferation both in vitro and in vivo. In contrast, MDA-MB-231 cells expressing elevated levels of DLK2 showed a strong inhibition of NOTCH1 activation, decreased cell proliferation, increased cell apoptosis, and were unable to generate tumors in vivo. In addition, DLK2 expression levels also affected some members of other cell signaling pathways implicated in cancer, such as ERK1/2 MAPK, AKT, and rpS6 kinases. Our data support an important role of DLK2 as a protein that can finely regulate NOTCH signaling and affect the tumor properties and growth dynamics of MDA-MB-231 breast cancer cells.
Genomics and Newborn Screening: Perspectives of Public Health Programs
Authors: Goldenberg Aaron J. , Ponsaran Roselle , Gaviglio Amy , Simancek Dalton , Tarini Beth A.
Published: January 2022

This study assesses the benefits and challenges of using genomics in Newborn Screening Programs (NBS) from the perspectives of State program officials. This project aims to help programs develop policies that will aid in the integration of genomic technology. Discussion groups were conducted with the NBS Program and Laboratory Directors in the seven HRSA Regional Genomics Collaboratives (August 2014–March 2016). The discussion groups addressed expected uses of genomics, potential benefits, and challenges of integrating genomic technology, and educational needs for parents and other NBS stakeholders: Twelve focus groups were conducted, which included participants from over 40 state programs. Benefits of incorporating genomics included improving screening modalities, supporting diagnostic procedures, and screening for a wider spectrum of disorders. Challenges included the costs of genomics, the ability to educate parents and health care providers about results, and the potential negative psychosocial impact of genomic information. Attempts to address the challenges of integrating genomics must focus on preserving the child welfare goals of NBS programs. Health departments will need to explore how genomics could be used to enhance programs while maintaining universal access to screening.
Acknowledgment to Reviewers of IJTM in 2021
Authors:   IJTM Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Influence of Sunlight Incidence and Fruit Chemical Features on Oviposition Site Selection in Mango by Anastrepha obliqua: Implications for Management
Authors: Guillén Larissa , Monribot-Villanueva Juan L. , Guerrero-Analco José A. , Ortega Rafael , Altúzar-Molina Alma , Mena Victoria , Ruiz-May Eliel , Aluja Martín
Published: January 2022

With the aim of identifying key factors that determine oviposition decisions by Anastrepha obliqua for management purposes, we conducted a behavioral study under natural/semi-natural field conditions to identify where exactly in the fruit (upper, middle, or lower sections) females preferred to lay eggs in a highly susceptible mango cultivar (“Criollo”), and whether sunlight incidence and fruit chemical compounds influenced oviposition site selection by this pestiferous fly. Females oviposited in shaded, upper fruit sections where pulp had higher total carbohydrate concentrations but similar total protein, lipid, and polyphenol concentrations than non-oviposited sections. Peel had higher overall nutrient and mangiferin/quercetin-3-D-galactoside (polyphenols) concentrations. An untargeted metabolomic analysis of oviposited and non-oviposited fruit sections identified abscisic acid (ABA) and dihydrophaseic acid glucoside, a by-product of ABA catabolism, as potential chemical markers that could play a role in fruit acceptance behaviors by female flies. We conclude that females preferentially oviposit in fruit sections with optimal chemical and environmental conditions for larval development: more carbohydrates and antioxidants such as mangiferin and ferulic acid and lesser sunlight exposure to avoid lethal egg/larval desiccation/overheating. We make specific recommendations for A. obliqua management based on female host selection behavior, a tree pruning scheme exposing fruit to direct sunlight, application of a host marking pheromone, and the use of egg sinks in the orchard.
Acknowledgment to Reviewers of IoT in 2021
Authors:   IoT Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Acknowledgment to Reviewers of J in 2021
Authors:   J Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Acknowledgment to Reviewers of Journal of Cardiovascular Development and Disease in 2021
Authors:   Journal of Cardiovascular Development and Disease Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Clinical Significance of Multiparameter Intracranial Pressure Monitoring in the Prognosis Prediction of Hypertensive Intracerebral Hemorrhage
Authors: Yang Yongbo , Pan Yuchun , Chen Chunlei , Zhao Penglai , Hang Chunhua
Published: January 2022

Objective: The present study aimed to investigate the clinical significance of multiparameter intracranial pressure (ICP) monitoring in the prediction of the prognosis of hypertensive intracerebral hemorrhage (HICH). Methods: A retrospective analysis was performed on the clinical data of 53 HICH patients. The patients underwent removal of intracranial hemorrhage and decompressive craniectomy after admission. A ventricular ICP monitoring probe was used to continuously and invasively monitor mean arterial pressure (MAP) and ICP after surgery. The NEUMATIC system was used to collect ICP data, including pressure reactivity index (PRx), ICP dose (DICP), amplitude and pressure regression (RAP), and cerebral perfusion pressure (CPP). The mean PRx, CPP, RAP, ICP, and DICP20 mmHg × h were calculated with 1 h as the time segment. According to the Glasgow outcome scale (GOS) scores after discharge, the patients were grouped into the poor prognosis group (GOS I–III) and the good prognosis group (GOS IV and V). The two groups were compared in terms of GOS scores in the treatment and prediction of prognosis of patients. Results: The good prognosis group showed significantly lower values of mean ICP, DICP20 mmHg × h, RAP, and PRx than the poor prognosis group, while CPP was significantly higher (p < 0.001). Conclusions: PRx, DICP, RAP, and CPP could reflect intracranial changes in patients and were significantly correlated with the prognosis of the patients. Mean ICP, PRx, DICP20 mmHg × h, and RAP were negatively correlated with prognosis, while CPP was positively correlated with prognosis.