bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the Berry Quality Traits and Metabolites of ‘Beimei’ Interspecific Hybrid Wine Grapes during Berry Development and Winemaking
Authors: Kuang Yangfu , Ren Chong , Wang Yi , Kirabi Gathunga Elias , Wang Yongjian , Wang Lijun , Fan Peige , Liang Zhenchang
Published: June 2022

The development of grape varieties with cold resistance can be an advantage for the wine industry. ‘Beimei’, an interspecific hybrid wine grape variety with cold resistance and pleasant rose aroma, is now extensively cultivated in China. In the present study, the berry quality traits and metabolites of ‘Beimei’ and other “Bei” varieties were characterized. The sugar (234 g/L–391 g/L) and acid (6.2–8.3 g/L) contents of ‘Beimei’ and four additional “Bei” varieties, i.e., ‘Beihong’, ‘Beixi’, ‘Beixin’, and ‘Xinbeichun’ berries were smilar to that of traditional Vitis vinifera varieties. ‘Beimei’ grapes has the highest volatile compounds composition, especially the content of rose aroma compounds (2-phenyl-ethyl alcohol and neryl alcohol), which was significantly higher than that of the other “Bei” wine grape varieties. After fermentation, ‘Beimei’ wines showed improved quality, with a high resveratrol content (18 mg/L) compared to traditional Eurasian wines. In addition, the high content of main rose aroma compounds (acetic acid 2-phenylethyl acetate, phenylethyl alcohol, neryl alcohol and beta-damascenone) contribute to a pleasant rose aroma in ‘Beimei’ wines. In summary, these results indicate that ‘Beimei’ grapes could be used as a winemaking grape variety considering global climate changes.
Oyster Shell Modified Tobacco Straw Biochar: Efficient Phosphate Adsorption at Wide Range of pH Values
Authors: Feng Menghan , Li Mengmeng , Zhang Lisheng , Luo Yuan , Zhao Di , Yuan Mingyao , Zhang Keqiang , Wang Feng
Published: June 2022

In order to improve the phosphate adsorption capacity of Ca-loaded biochar at a wide range of pH values, Ca (oyster shell) was loaded as Ca(OH)2 on the tobacco stalk biochar (Ca-BC), which was prepared by high-temperature calcination, ultrasonic treatment, and stirring impregnation method. The phosphorus removal performance of Ca-BC adsorption was studied by batch adsorption experiments, and the mechanism of Ca-BC adsorption and phosphorus removal was investigated by SEM-EDS, FTIR, and XRD. The results showed that after high-temperature calcination, oyster shells became CaO, then converted into Ca(OH)2 in the process of stirring impregnation and had activated the pore expansion effect of biochar. According to the Langmuir model, the adsorption capacity of Ca-BC for phosphate was 88.64 mg P/g, and the adsorption process followed pseudo-second-order kinetics. The Ca(OH)2 on the surface of biochar under the initial pH acidic condition preferentially neutralizes with H+ acid-base in solution, so that Ca-BC chemically precipitates with phosphate under alkaline conditions, which increases the adsorption capacity by 3–15 times compared with other Ca-loaded biochar. Ca-BC phosphate removal rate of livestock wastewater (pig and cattle farms) is 91~95%, whereas pond and domestic wastewater can be quantitatively removed. This study provides an experimental basis for efficient phosphorus removal by Ca-modified biochar and suggesting possible applications in real wastewater.
Booster Doses of Anti COVID-19 Vaccines: An Overview of Implementation Policies among OECD and EU Countries
Authors: Bert Fabrizio , Scaioli Giacomo , Vola Lorenzo , Accortanzo Davide , Lo Moro Giuseppina , Siliquini Roberta
Published: June 2022

The need for an anti-COVID-19 booster dose posed an organizational challenge for health policy makers worldwide. Therefore, this study aimed to explore the health policies regarding the booster dose through an overview of recommendations issued in high-income countries. Between 10 November and 16 December 2021, the authors searched for state-level official documents about the offer of the booster dose, considering the 43 countries belonging to the European Union (EU) or the Organisation for Economic Co-operation and Development (OECD). Mainly due to the lack of English translation, 15 countries were excluded. A total of 135 documents were selected. Almost all the countries started administering the booster dose between September and November 2021. The most used products were mRNA vaccines, followed by Vaxzevria-AstraZeneca and Jcovden-Janssen/Johnson & Johnson. All countries established criteria to define categories of individuals to be vaccinated as a priority. A six/five-months interval was the main choice for general population vaccinated with mRNA vaccines, while shorter intervals were chosen for vulnerable individuals or other vaccines. Despite diversities related to the differences in health systems, economical resources, and population numbers, and the need to adapt all these factors to a massive vaccination campaign, a progressive convergence towards the same vaccination policies was highlighted.
Concept for the Evaluation of Carcinogenic Substances in Population-Based Human Biomonitoring
Authors: Wollin Klaus-Michael , Apel Petra , Chovolou Yvonni , Pabel Ulrike , Schettgen Thomas , Kolossa-Gehring Marike , Röhl Claudia ,   Agency
Published: June 2022

The Human Biomonitoring (HBM) Commission at the German Environment Agency holds the opinion that for environmental carcinogens for which no exposure levels can be assumed and are harmless to health, health-based guidance values corresponding to the classical definition of the HBM-I or HBM-II value cannot be established. Therefore, only reference values have been derived so far for genotoxic carcinogens from exposure data of the general population or subpopulations. The concept presented here opens up the possibility of performing health risk assessments of carcinogenic substances in human biomonitoring, and thus goes decisively beyond the purely descriptive statistical reference value concept. Using the presented method, quantitative dose descriptors of internal exposure can be derived from those of external exposure, provided that sufficient toxicokinetic information is available. Dose descriptors of internal exposure then allow the simple estimate of additional lifetime cancer risks for measured biomarker concentrations or, conversely, of equivalent concentrations for selected risks, such as those considered as tolerable for the general population. HBM data of chronic exposures to genotoxic carcinogens can thus be used to assess the additional lifetime cancer risk referring to the general population and to justify and prioritize risk management measures.
The Role of Personalization in the User Experience, Preferences and Engagement with Virtual Reality Environments for Relaxation
Authors: Pardini Susanna , Gabrielli Silvia , Dianti Marco , Novara Caterina , Zucco Gesualdo , Mich Ornella , Forti Stefano
Published: June 2022

Virtual Reality Environments (VREs) are widely deployed in mental health treatments, often associated with relaxation techniques. The personalization of natural VR-based scenarios is a key element that can further facilitate users’ sense of presence and relaxation. This study explored the role of VREs’ personalization in the user experience with an environment supporting relaxation, by deploying mixed methods. Methods: A non-clinical sample of 20 individuals participated in exposure to a supportive body-scan-guided relaxation VRE. In the personalized conditions, the participants had the option of choosing the context (e.g., sea, mountain, or countryside) and including in the scenario different types of sounds, visual elements, and changing the time of day and weather. In the standard conditions, individuals were exposed to a relaxing VRE, but they could choose neither the context nor the auditory and visual elements. The order of presentation of the personalized vs non-personalized environments was randomized. Measures regarding relaxation, state-anxiety perceived levels, VRE-related symptoms, the usability of the Virtual Reality (VR) setting, sense of presence, pleasure, activation, engagement, and level of immersion experienced were collected before and after exposure to the VR environments. Results: Findings showed that personalized VREs were preferred by users. Participants generally preferred to experience a greater immersivity, pleasure, engagement, and relaxation in the personalized virtual settings. Conclusion: The study further confirms the role of personalization as a component positively contributing to relaxation and engagement. Future research may further assess this effect in the context of large-scale controlled studies involving clinical and non-clinical populations.
SARS-CoV-2 Risk Quantification Model and Validation Based on Large-Scale Dutch Test Events
Authors: Kolen Bas , Znidarsic Laurens , Voss Andreas , Donders Simon , Kamphorst Iris , van Rijn Maarten , Bonthuis Dimitri , Clocquet Merit , Schram Maarten , Scharloo Rutger , Boersma Tim , Stobernack Tim , van Gelder Pieter
Published: June 2022

In response to the outbreak of SARS-CoV-2, many governments decided in 2020 to impose lockdowns on societies. Although the package of measures that constitute such lockdowns differs between countries, it is a general rule that contact between people, especially in large groups of people, is avoided or prohibited. The main reasoning behind these measures is to prevent healthcare systems from becoming overloaded. As of 2021 vaccines against SARS-CoV-2 are available, but these do not guarantee 100% risk reduction and it will take a while for the world to reach a sufficient immune status. This raises the question of whether and under which conditions events like theater shows, conferences, professional sports events, concerts, and festivals can be organized. The current paper presents a COVID-19 risk quantification method for (large-scale) events. This method can be applied to events to define an alternative package of measures replacing generic social distancing.
Tetracyclines—An Important Therapeutic Tool for Dermatologists
Authors: Orylska-Ratynska Malgorzata , Placek Waldemar , Owczarczyk-Saczonek Agnieszka
Published: June 2022

Tetracyclines are a group of antibiotics whose first representative was discovered over 70 years ago. Since then, they have been of great interest in dermatology. In addition to their antibacterial activity, they are able to inhibit metalloproteinases and exhibit anti-inflammatory, anti-apoptotic and antioxidant effects. The side effects have been thoroughly studied over the years, the most characteristic and important ones in daily dermatological practice being: phototoxicity, hyperpigmentation, onycholysis, photoonycholysis, induced lupus erythematosus, and idiopathic intracranial hypertension. In this article, we summarize the use of tetracyclines in infectious diseases and inflammatory dermatoses, and further discuss the instances where the efficacy and safety of tetracyclines have been highlighted over the past few years.
Diversity of Toxigenic Fungi in Livestock and Poultry Feedstuffs
Authors: Khalifa Eman , Mohesien Marwa T. , Mossa Monga I. , Piekutowska Magdalena , Alsuhaibani Amnah Mohammed , Abdel-Wahab Basel A. , Sotohy Sotohy Ahmed , Ghosh Soumya , Helmy Yosra A. , Hussein Mohamed , Abdel-Azeem Ahmed M.
Published: June 2022

The purpose of this study was to discover how abundant toxigenic fungi and mycotoxins are in animal feedstuff samples. A total of ninety samples representing various types of animal feedstuff samples were collected from ninety sites in Egypt. Isolation, identification, and determination of mycotoxins (aflatoxins B1, B2, G1, G2, and ochratoxin A) were performed. The results revealed that 79 (87.77%) of the samples were contaminated with fungi, and 1.1 × 105 CFU/g were recovered, including 41 fungal species belonging to 18 genera, such as Zygomycota, which was represented by three species (7.31% of the total species number), teleomorphic Ascomycota (10 species, 24.39%), and anamorphic Ascomycota (28 species, 69.29%). When taxonomically investigated, these species were categorized into 2 phyla, 4 classes, 6 orders, and 12 families (one of them with an uncertain position). Moreover, the genus Aspergillus exhibited 16 species (39.02%). Notably, site no. 6 showed the highest Margalef species richness index at 10.87 followed by site no. 4, while the Shannon diversity index (H) of the recovered taxa was 2.20. Based on the frequency of occurrence, Aspergillus flavus recorded the highest percentage (65.56%) followed by A. niger (50%) and Penicillium chrysogenum (40%). Genus Aspergillus was recorded in 75 samples (88.33%), while Penicillium appeared only in 43 samples, accounting for 47.77% out of 90 samples. The High-performance liquid chromatography (HPLC) analysis showed that aflatoxin B1 (AFB1) was recorded in two animal feedstuff samples at a ratio of 0.851 and 1.363 µg/kg, While AFB2 was discovered in only one animal feedstuff sample at a ratio of 0.479 g/kg. The aflatoxins levels in the positive samples (AFB1 and AFB2) Beef cattle sample components were below the permissible limit for animal feedstuff which is (20 g/kg). Although aflatoxins were found in certain samples, the amounts were much below the maximum residue limits (MRLs) defined by the international authorities or Egyptian guidelines. toxigenic fungi found in contaminated animal feed samples pose a major threat to animal and poultry health, productivity, and even human health. Therefore, periodic monitoring is an excellent way to keep track of their existence and mitigate their hazards.
Prior to Implementation of Digital Pathology—Assessment of Expectations among Staff by Means of Normalization Process Theory
Authors: Mikkelsen Minne L. N. , Frederiksen Marianne H. , Marcussen Niels , Williams Bethany , Kidholm Kristian
Published: June 2022

The Region of Southern Denmark is the first in Denmark to implement digital pathology (DIPA), starting at the end of 2020. The DIPA process involves changes in workflow, and the pathologist will have to diagnose based on digital whole slide imaging instead of through the traditional use of the conventional light microscope and glass slides. In addition, in the laboratory, the employees will have to implement one more step to their workflow—scanning of tissue. The aim of our study was to assess the expectations and readiness among employees and management towards the implementation of DIPA, including their thoughts and motivations for starting to use DIPA. We used a mixed-method approach. Based on the findings derived from 18 semi-structured interviews with employees from the region’s departments of pathology, we designed a questionnaire, including questions from the normalization measure development tool. The questionnaires were e-mailed to 181 employees. Of these employees, 131 responded to the survey. Overall, they reported feeling sufficiently tech-savvy to be able to use DIPA, and they had high expectations as well as motivation and readiness for the upcoming changes. However, the employees were skeptical regarding the allocation of resources, and few were aware of reports about the effects of DIPA. Based on the findings, it seems to be important to provide not only a thorough introduction to the new intervention and the changes it will entail, but also to continue to ensure that the staff know how it works and why it is necessary to implement.
The Removal of Erythromycin and Its Effects on Anaerobic Fermentation
Authors: Zhang Huayong , Yin Meixiao , Li Shusen , Zhang Shijia , Han Guixuan
Published: June 2022

In view of the problems of antibiotic pollution, anaerobic fermentation technology was adopted to remove erythromycin in this study. The removal of erythromycin and its effects mechanism on anaerobic fermentation were studied, including biogas performance, process stability, substrate degradability, enzyme activity, and microbial communities. The results showed that the removal rates of erythromycin for all tested concentrations were higher than 90% after fermentation. Erythromycin addition inhibited biogas production. The more erythromycin added, the lower the CH4 content obtained. The high concentration of erythromycin (20 and 40 mg/L) resulted in more remarkable variations of pH values than the control group and 1 mg/L erythromycin added during the fermentation process. Erythromycin inhibited the hydrolysis process in the early stage of anaerobic fermentation. The contents of chemical oxygen demand (COD), NH4+–N, and volatile fatty acids (VFA) of erythromycin added groups were lower than those of the control group. Erythromycin inhibited the degradation of lignocellulose in the late stage of fermentation. Cellulase activity increased first and then decreased during the fermentation and addition of erythromycin delayed the peak of cellulase activity. The inhibitory effect of erythromycin on the activity of coenzyme F420 increased with elevated erythromycin concentrations. The relative abundance of archaea in erythromycin added groups was lower than the control group. The decrease in archaea resulted in the delay of the daily biogas peak. Additionally, the degradation rate of erythromycin was significantly correlated with the cumulative biogas yield, COD, pH, and ORP. This study supports the reutilization of antibiotic-contaminated biowaste and provides references for further research.
Determinants of Time for Publication Annual Reports: Empirical Evidence from Non-Financial Listed Companies in Vietnam
Authors: Nguyen Anh Huu , Nguyen Hieu Thanh , Tran Chung Quang , Le Lien Quynh
Published: June 2022

This article studied the factors affecting the time taken for annual report submission through an analysis of 654 non-financial listed companies on the Vietnamese stock market from 2016 to 2020. Data collected were processed by using fixed-effect models (FEM), random effect models (REM), adjusted REM, and general least square (GLS) to ensure the validity of research results. The main objective of this paper was to explore the effects of independent variables including retained earnings (RETA), earnings before interest and tax (EBITTA), liquidity (WCTA), capital structure (BVETD), bankruptcy risk (ZSCORE), size (SIZE), number of years in business (AGE), characteristics of financial reports (CONSO), and type of audit firm (AUDIT) on the number of days for publication annual reports (TIME). The results obtained from the adjusted-REM and GLS regression showed that retained earnings, firm age, and firm size have positive effects on time for disclosure annual reports, whereas earnings before interest and tax and audit firm type have negative effects. In addition, the results showed that working capital, capital structure, feature of consolidated reports, and bankruptcy risk have no significant effects on time to publish annual reports.
An Integrated Environment for Monitoring and Documenting Quality in Map Composition Utilizing Cadastral Data
Authors: Kavadas Ioannis , Tsoulos Lysandros
Published: June 2022

Topographic maps show both physical and artificial entities of the surface of the Earth which represent distinct features forming the building blocks in map composition. Their portrayal on the map is subject to constraints dependent on the method of data collection, the map scale, the data processing procedures and the requirements of map users. In addition to constraints, geospatial data contain uncertainties and errors that are either inherent in the data or a result of the map composition process. The type and significance of these errors determine the quality of maps. This paper elaborates on the development of an integrated environment for monitoring and documenting quality in the map composition process. In this environment, quality plays a vital role in all phases of map production whereby it is continuously assessed and documented. The methodology described involves the design and implementation of a “quality model” based on international Standards. An integrated software application for the utilization of cadastral information to produce and update topographic maps at a scale of 1:25,000 was also developed. The aim is to implement the proposed methodology in a real production environment and to use it as a proof of concept.
Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model
Authors: Lee Min Ji , Bae Jinkun , Lee Jung Ho , Park Ye Jin , Lee Han A Reum , Mun Sehwan , Kim Yun-seok , Yune Chang June , Chung Tae Nyoung , Kim Kyuseok
Published: June 2022

Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2′,7′-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.
Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury
Authors: Hosohata Keiko , Harnsirikarn Tanisorn , Chokesuwattanaskul Susama
Published: June 2022

Ferroptosis is a recently recognized form of nonapoptotic cell death that is triggered by reactive oxidative species (ROS) due to iron overload, lipid peroxidation accumulation, or the inhibition of phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Recent studies have reported that ferroptosis plays a vital role in the pathophysiological process of multiple systems such as the nervous, renal, and pulmonary systems. In particular, the kidney has higher rates of O2 consumption in its mitochondria than other organs; therefore, it is susceptible to imbalances between ROS and antioxidants. In ischemia/reperfusion (I/R) injury, which is damage caused by the restoring blood flow to ischemic tissues, the release of ROS and reactive nitrogen species is accelerated and contributes to subsequent inflammation and cell death, such as ferroptosis, as well as apoptosis and necrosis being induced. At the same time, I/R injury is one of the major causes of acute kidney injury (AKI), causing significant morbidity and mortality. This review highlights the current knowledge on the involvement of ferroptosis in AKI via oxidative stress.
Lanthanide (Eu3+/Tb3+)-Loaded γ-Cyclodextrin Nano-Aggregates for Smart Sensing of the Anticancer Drug Irinotecan
Authors: Guo Yaowei , Liu Jin , Tang Qinglin , Li Cuicui , Zhang Yanying , Wang Yao , Wang Yanxin , Bi Yupeng , Snow Christopher D. , Kipper Matt J. , Belfiore Laurence A. , Tang Jianguo
Published: June 2022

The clinical use of anticancer drugs necessitates new technologies for their safe, sensitive, and selective detection. In this article, lanthanide (Eu3+ and Tb3+)-loaded γ-cyclodextrin nano-aggregates (ECA and TCA) are reported, which sensitively detects the anticancer drug irinotecan by fluorescence intensity changes. Fluorescent lanthanide (Eu3+ and Tb3+) complexes exhibit high fluorescence intensity, narrow and distinct emission bands, long fluorescence lifetime, and insensitivity to photobleaching. However, these lanthanide (Eu3+ and Tb3+) complexes are essentially hydrophobic, toxic, and non-biocompatible. Lanthanide (Eu3+ and Tb3+) complexes were loaded into naturally hydrophilic γ-cyclodextrin to form fluorescent nano-aggregates. The biological nontoxicity and cytocompatibility of ECA and TCA fluorescent nanoparticles were demonstrated by cytotoxicity experiments. The ECA and TCA fluorescence nanosensors can detect irinotecan selectively and sensitively through the change of fluorescence intensity, with detection limits of 6.80 μM and 2.89 μM, respectively. ECA can safely detect irinotecan in the cellular environment, while TCA can detect irinotecan intracellularly and is suitable for cell labeling.
A Maize CBM Domain Containing the Protein ZmCBM48-1 Positively Regulates Starch Synthesis in the Rice Endosperm
Authors: Peng Xiaojian , Yu Wei , Chen Yirong , Jiang Yingli , Ji Yaru , Chen Long , Cheng Beijiu , Wu Jiandong
Published: June 2022

Starch directly determines the grain yield and quality. The key enzymes participating in the process of starch synthesis have been cloned and characterized. Nevertheless, the regulatory mechanisms of starch synthesis remain unclear. In this study, we identified a novel starch regulatory gene, ZmCBM48-1, which contained a carbohydrate-binding module 48 (CBM48) domain. ZmCBM48-1 was highly expressed in the maize endosperm and was localized in the plastids. Compared with the wild type lines, the overexpression of ZmCBM48-1 in rice altered the grain size and 1000-grain weight, increased the starch content, and decreased the soluble sugar content. Additionally, the transgenic rice seeds exhibited an alterant endosperm cell shape and starch structure. Meanwhile, the physicochemical characteristics (gelatinization properties) of starch were influenced in the transgenic lines of the endosperm compared with the wild type seeds. Furthermore, ZmCBM48-1 played a positive regulatory role in the starch synthesis pathway by up-regulating several starch synthesis-related genes. Collectively, the results presented here suggest that ZmCBM48-1 acts as a key regulatory factor in starch synthesis, and could be helpful for devising strategies for modulating starch production for a high yield and good quality in maize endosperm.
Modafinil Administration to Preadolescent Rat Impairs Non-Selective Attention, Frontal Cortex D2 Expression and Mesolimbic GABA Levels
Authors: Cid-Jofré Valeska , Moreno Macarena , Sotomayor-Zárate Ramón , Cruz Gonzalo , Renard Georgina M.
Published: June 2022

The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D2) expression and behavior (non-selective attention “NSA”) in the mesocorticolimbic system of young healthy Sprague–Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D2 protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D2 expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.
Application of Sensitivity Analysis to Discover Potential Molecular Drug Targets
Authors: Kardynska Malgorzata , Smieja Jaroslaw , Paszek Pawel , Puszynski Krzysztof
Published: June 2022

Mathematical modeling of signaling pathways and regulatory networks has been supporting experimental research for some time now. Sensitivity analysis, aimed at finding model parameters whose changes yield significantly altered cellular responses, is an important part of modeling work. However, sensitivity methods are often directly transplanted from analysis of technical systems, and thus, they may not serve the purposes of analysis of biological systems. This paper presents a novel sensitivity analysis method that is particularly suited to the task of searching for potential molecular drug targets in signaling pathways. Using two sample models of pathways, p53/Mdm2 regulatory module and IFN-β-induced JAK/STAT signaling pathway, we show that the method leads to biologically relevant conclusions, identifying processes suitable for targeted pharmacological inhibition, represented by the reduction of kinetic parameter values. That, in turn, facilitates subsequent search for active drug components.
RETRACTED: Kannan et al. AEG-1/miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN/PI3K/AKT Signaling Pathway. Int. J. Mol. Sci. 2019, 20, 5526
Authors:   International Journal of Molecular Sciences Editorial Office
Published: June 2022

The journal retracts the article, “AEG-1/miR-221 Axis Cooperatively Regulates the Progression of Hepatocellular Carcinoma by Targeting PTEN/PI3K/AKT Signaling Pathway” [...]
Depression and Complicated Grief, and Associated Factors, of Bereaved Family Members of Patients Who Died of Malignant Pleural Mesothelioma in Japan
Authors: Nagamatsu Yasuko , Sakyo Yumi , Barroga Edward , Koni Riwa , Natori Yuji , Miyashita Mitsunori
Published: June 2022

Objectives: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan. Methods: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG. Results: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient’s MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient’s MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG. Conclusions: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.
Correction: Liu et al. Less Fluctuation in Hemodynamics of the Wide-Awake Local Anesthesia No Tourniquet Technique Than General Anesthesia in Distal Radius Plating Surgery: A Prospective Case-Control Study. J. Clin. Med. 2022, 11, 1123
Authors: Liu Wen-Chih , Lu I-Cheng , Chang Chung-Chia , Chen Chih-Ting , Chen Chung-Hwan , Shih Chia-Lung , Fu Yin-Chih , Jupiter Jesse Bernard
Published: June 2022

In the original publication [...]
The Role of Antihyperglycemic Drugs and Diet on Erectile Function: Results from a Perspective Study on a Population with Prediabetes and Diabetes
Authors: Defeudis Giuseppe , Di Tommaso Alfonso Maria , Di Rosa Claudia , Cimadomo Danilo , Khazrai Yeganeh Manon , Faggiano Antongiulio , Cincione Raffaele Ivan , Napoli Nicola , Mazzilli Rossella
Published: June 2022

Background. The purpose of this study was to evaluate the effect of diet and antihyperglycemic drugs on erectile dysfunction (ED) in a setting of subjects affected by diabetes mellitus (DM) or preDM. Methods. This is a prospective observational study on 163 consecutive subjects with preDM or DM. All patients have undergone a medical evaluation (age, Body Mass Index (BMI), family history of DM, duration of DM, smoking, physical activity, dyslipidemia, cardiovascular comorbidities, and testosterone and HbA1c levels) and the International Index of Erectile Function (IIEF)-5 questionnaire. Results. Overall, the mean age was 62.8 ± 9.3 years, and the mean BMI was 28.4 ± 4.6 kg/m2. The IIEF-5 score mean value was 14.4 ± 6.2 (range 4–25). Among all confounders investigated for their association with the IIEF-5 score, only age and the duration of DM among diabetic patients showed a significant trend. The IIEF-5 score was higher in patients using GLP-1a compared to insulin (16.7 ± 4.7 vs. 12.9 ± 6.2; p = 0.02). This association was confirmed after adjustment for age and duration of DM (p = 0.01). All other treatments were similar (14.9 ± 6.2, 14.8 ± 9.2, 15.3 ± 5.4, and 13.6 ± 6.8 for metformin, sulfonylureas (SU), dipeptidyl-peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) treatment, respectively). Conclusions. This prospective observational study increases attention and focus on the effect of antihyperglycemic drugs and diet on ED, above all about the role of new classes, showing a significant higher IIEF-5 mean value in patients using GLP-1a compared to patients on insulin treatment.
First 24-Hour Potassium Concentration and Variability and Association with Mortality in Patients Requiring Continuous Renal Replacement Therapy in Intensive Care Units: A Hospital-Based Retrospective Cohort Study
Authors: Mao I-Chieh , Lin Pei-Ru , Wu Shin-Hwar , Hsu Hsin-Hui , Hung Pei-Shan , Kor Chew-Teng
Published: June 2022

Serum potassium (K+) levels between 3.5 and 5.0 mmol/L are considered safe for patients. The optimal serum K+ level for critically ill patients with acute kidney injury undergoing continuous renal replacement therapy (CRRT) remains unclear. This retrospective study investigated the association between ICU mortality and K+ levels and their variability. Patients aged >20 years with a minimum of two serum K+ levels recorded during CRRT who were admitted to the ICU in a tertiary hospital in central Taiwan between January 01, 2010, and April 30, 2021 were eligible for inclusion. Patients were categorized into different groups based on their mean K+ levels: <3.0, 3.0 to <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mmol/L; K+ variability was divided by the quartiles of the average real variation. We analyzed the association between the particular groups and in-hospital mortality by using Cox proportional hazard models. We studied 1991 CRRT patients with 9891 serum K+ values recorded within 24 h after the initiation of CRRT. A J-shaped association was observed between serum K+ levels and mortality, and the lowest mortality was observed in the patients with mean K+ levels between 3.0 and 4.0 mmol/L. The risk of in-hospital death was significantly increased in those with the highest variability (HR and 95% CI = 1.61 [1.13–2.29] for 72 h mortality; 1.39 [1.06–1.82] for 28-day mortality; 1.43 [1.11–1.83] for 90-day mortality, and 1.31 [1.03–1.65] for in-hospital mortality, respectively). Patients receiving CRRT may benefit from a lower serum K+ level and its tighter control. During CRRT, progressively increased mortality was noted in the patients with increasing K+ variability. Thus, the careful and timely correction of dyskalemia among these patients is crucial.
Differences in Ectopic Pregnancy Rates between Fresh and Frozen Embryo Transfer after In Vitro Fertilization: A Large Retrospective Study
Authors: Hu Zhijie , Li Danjun , Chen Qiuju , Chai Weiran , Lyu Qifeng , Cai Renfei , Kuang Yanping , Lu Xuefeng
Published: June 2022

Ectopic pregnancy (EP) is increasingly found in women treated with in vitro fertilization and embryo transfer (IVF–ET). With the development of the freeze-all policy in reproductive medicine, it is controversial whether frozen embryo transfer (FET) could reduce the rate of EP. In this single-center, large-sample retrospective study, we analyzed 16,048 human chorionic gonadotrophin (hCG)-positive patients who underwent fresh embryo transfer (ET) or FET cycles between January 2013 and March 2022. Throughout the study, the total EP rate was 2.09% (336/16,048), 2.16% (82/3803) in the ET group, and 2.07% (254/12,245) in the FET group. After adjustment for age, infertility causes, and other confounding factors, logistic regression results showed no statistical difference in EP rates between FET and ET groups (odds ratio (OR) 0.93 (0.71–1.22), p > 0.05). However, among the 3808 patients who underwent fresh ET cycles, the OR for EP was significantly lower in the long agonist protocol group than in the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol group (OR 0.45 (0.22–0.93), p < 0.05). Through a large retrospective study, we demonstrated a slightly lower EP rate in FET cycles than in fresh ET cycles, but there was no significant difference. The long agonist protocol in ET cycles had a significantly lower risk of EP than the GnRH-ant protocol.
Magnesium Sulfate and Cerebral Oxygen Saturation in Mild Traumatic Brain Injury: A Randomized, Double-Blind, Controlled Trial
Authors: Sohn Hye-Min , Ahn Hyoeun , Seo Won-Seok , Yi In Kyong , Park Jun
Published: June 2022

Perioperative cerebral hypoperfusion/ischemia is considered to play a pivotal role in the development of secondary traumatic brain injury (TBI). This prospective randomized, double-blind, controlled study investigated whether magnesium sulfate (MgSO4) infusion was associated with neuroprotection in maintaining regional cerebral oxygen saturation (rSO2) values in patients with mild TBI undergoing general anesthesia. Immediately after intubation, we randomly assigned patients with TBI to receive either intravenous MgSO4 (30 mg/kg for 10 min, followed by a continuous infusion of 15 mg/kg/h) or a placebo (saline) during surgery. We also implemented an intervention protocol for a sudden desaturation exceeding 20% of the initial baseline rSO2. The intraoperative rSO2 values were similar with respect to the median (left. 67% vs. 66%, respectively; p = 0.654), lowest, and highest rSO2 in both groups. The incidence (left 31.2% vs. 24.3%; p = 0.521) and duration (left 2.6% vs. 3.5%; p = 0.638) of cerebral desaturations (the relative decline in rSO2 < 80% of the baseline value) were also similar for both groups. Although the patients suffered serious traumatic injuries, all critical desaturation events were restored (100%) following stringent adherence to the intervention protocol. Intraoperative remifentanil consumption, postoperative pain intensity, and fentanyl consumption at 6 h were lower in the MgSO4 group (p = 0.024, 0.017, and 0.041, respectively) compared to the control group, whereas the satisfaction score was higher in the MgSO4 group (p = 0.007). The rSO2 did not respond to intraoperative MgSO4 in mild TBI. Nevertheless, MgSO4 helped the postoperative pain intensity, reduce the amount of intraoperative and postoperative analgesics administered, and heighten the satisfaction score.
Norethisterone Reduces Vaginal Bleeding Caused by Progesterone-Only Birth Control Pills
Authors: Vilk Ayalon Naama , Segev Lior , Samson Abraham O. , Yagel Simcha , Cohen Sarah M. , Green Tamar , Hochler Hila
Published: June 2022

(1) Background: Progesterone-only pills (POP) are widely used contraceptives. About 40% of women taking these pills report vaginal bleeding/spotting; 25% find this a reason for cessation. To date, no effective remedy has been described. We aimed to examine the therapeutic approaches offered by health providers. (2) Methods: A prospective questionnaire-based study of women experiencing vaginal bleeding due to POP, comparing the effectiveness of prescribed therapies. Women were recruited through social networks, and subsequently divided into groups according to the treatment offered: (1) POP with norethisterone (n = 36); (2) double dose POP (n = 19); (3) single dose POP (continuing initial treatment, n = 57); and (4) different POP formula (n = 8). Women rated bleeding quantity and frequency at four intervals, at weeks 0, 2, 4, and 6. (3) Results: Women who added 5 mg norethisterone acetate reported a significant decrease in bleeding frequency compared to the other groups, observed after 2, 4, and 6 weeks (p-values 0.019, 0.002, and 0.002, respectively). Women also reported an overall decrease in combined bleeding quantity and frequency (p-values 0.028, 0.003, and 0.005, respectively). There was no difference in the rate of side effects among groups. (4) Conclusions: Adding 5 mg norethisterone acetate (Primolut-nor) to progesterone-only pills significantly reduces bleeding and spotting associated with POP contraception.
Exercise throughout Pregnancy Prevents Excessive Maternal Weight Gain during the COVID-19 Pandemic: A Randomized Clinical Trial
Authors: Silva-Jose Cristina , Sánchez-Polán Miguel , Barakat Rubén , Díaz-Blanco Ángeles , Carrero Martínez Vanessa , García Benasach Fátima , Alzola Irune , Mottola Michelle F. , Refoyo Ignacio
Published: June 2022

The purpose of this study was to examine the effects of a virtual exercise program throughout pregnancy during the COVID-19 pandemic on maternal weight gain. A randomized clinical trial (NCT NCT04563065) was performed. In total, 300 pregnant individuals were assessed for eligibility, and a total of 157 were randomized, of which 79 were in the control group (CG), and 78 were in the intervention group (IG). Those in the intervention group participated in a virtual supervised exercise program throughout pregnancy, 3 days per week. Fewer pregnant participants exceeded the weight gain recommendations in the IG group than in the CG (n = 4/5.9% vs. n = 31/43.1%, p = 0.001). Weight gain during pregnancy was lower in the IG than in the CG (9.96 ± 3.27 kg vs. 12.48 ± 4.87 kg, p = 0.001). Analysis of subgroups based on pre-pregnancy body mass index, showed significant differences in excessive maternal weight gain between study groups in normal-weight (IG, n = 0/0% vs. CG, n = 10/25%, p = 0.001) and those with overweight (IG, n = 2/18% vs. CG, n = 12/60%, p = 0.025). A virtual supervised exercise program throughout pregnancy could be a clinical tool to manage maternal weight gain during the COVID-19 pandemic by controlling excessive gain.
JAK2 Unmutated Polycythaemia—Real-World Data of 10 Years from a Tertiary Reference Hospital
Authors: Jalowiec Katarzyna Aleksandra , Vrotniakaite-Bajerciene Kristina , Jalowiec Jakub , Frey Noel , Capraru Annina , Wojtovicova Tatiana , Joncourt Raphael , Angelillo-Scherrer Anne , Tichelli Andre , Porret Naomi Azur , Rovó Alicia
Published: June 2022

(1) Background: Polycythaemia is defined by an increase in haemoglobin (Hb) concentration, haematocrit (Hct) or red blood cell (RBC) count above the reference range adjusted to age, sex and living altitude. JAK2 unmutated polycythaemia is frequent but under-investigated in original publications. In this retrospective cohort study, we investigated the clinical and laboratory data, underlying causes, management and outcomes of JAK2 unmutated polycythaemia patients. (2) Methods: The hospital database was searched to identify JAK2 unmutated patients fulfilling WHO 2016 Hb/Hct criteria for PV (Hb >16.5 g/dL in men and >16 g/dL in women, or Hct > 49% in men and >48% in women, or RBC mass > 25% above mean normal predicted value) between 2008 and 2019. Clinical and laboratory data were collected and analysed. (3) Results: From 727,731 screened patients, 294 (0.04%) were included, the median follow-up time was 47 months. Epo and P50 showed no clear pattern in differentiating causes of polycythaemia. In 30%, the cause remained idiopathic, despite extensive work-up. Sleep apnoea was the primary cause, also in patients under 30. Around 20% had received treatment at any time, half of whom had ongoing treatment at the end of follow-up. During follow-up, 17.2% developed a thromboembolic event, of which 8.5% were venous and 8.8% arterial. The mortality was around 3%. (4) Conclusions: Testing for Epo and P50 did not significantly facilitate identification of underlying causes. The frequency of sleep apnoea stresses the need to investigate this condition. Idiopathic forms are common. A diagnostic flowchart based on our data is proposed here. NGS testing should be considered in young patients with persisting polycythaemia, irrespective of Epo and P50 levels.
Modified Mini-Keystone Flaps for Coverage of Tiny Volar Pulp Defects of the Fingertips in Cases with Missing Amputation Skin Stumps: A Retrospective Study
Authors: Yoo Byung Woo , Oh Seungyoon , Kim Junekyu , Oh Kap Sung , Shin Hyun Woo , Kim Kyu Nam
Published: June 2022

This study aimed to demonstrate the expanding versatility of keystone flap reconstruction in fingertips. Fifteen patients who underwent the modified mini-keystone flap reconstruction for tiny volar pulp defects of the fingertip between September 2020 and February 2021 were included in this study (average age: 43.4 ± 13.52 years, range: 19–61 years). Patient data were retrospectively collected from their medical records. The two-point discrimination test was used to evaluate the degree of sensory recovery. All defects were successfully covered with the modified mini-keystone flap. The defect sizes ranged from 0.5 cm × 1 cm to 1.2 cm × 2.0 cm, and the flap sizes ranged from 0.7 cm × 1.5 cm to 1.5 cm × 3.0 cm. Although one patient showed a small distal margin maceration, all flaps survived fully. The overall outcomes were favorable at the mean follow-up period of 5.73 ± 0.79 months. We suggest that the modified mini-keystone flap technique is a promising alternative modality for covering tiny volar pulp defects of the fingertip, with few complications and favorable outcomes.