bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Epigenetics of Age-Related Kidney Diseases
Authors: Liu Feng , Chen Jiefang , Li Zhenqiong , Meng Xianfang
Published: April 2022

Renal aging has attracted increasing attention in today’s aging society, as elderly people with advanced age are more susceptible to various kidney disorders such as acute kidney injury (AKI) and chronic kidney disease (CKD). There is no clear-cut universal mechanism for identifying age-related kidney diseases, and therefore, they pose a considerable medical and public health challenge. Epigenetics refers to the study of heritable modifications in the regulation of gene expression that do not require changes in the underlying genomic DNA sequence. A variety of epigenetic modifiers such as histone deacetylases (HDAC) inhibitors and DNA methyltransferase (DNMT) inhibitors have been proposed as potential biomarkers and therapeutic targets in numerous fields including cardiovascular diseases, immune system disease, nervous system diseases, and neoplasms. Accumulating evidence in recent years indicates that epigenetic modifications have been implicated in renal aging. However, no previous systematic review has been performed to systematically generalize the relationship between epigenetics and age-related kidney diseases. In this review, we aim to summarize the recent advances in epigenetic mechanisms of age-related kidney diseases as well as discuss the application of epigenetic modifiers as potential biomarkers and therapeutic targets in the field of age-related kidney diseases. In summary, the main types of epigenetic processes including DNA methylation, histone modifications, non-coding RNA (ncRNA) modulation have all been implicated in the progression of age-related kidney diseases, and therapeutic targeting of these processes will yield novel therapeutic strategies for the prevention and/or treatment of age-related kidney diseases.
Independent COL5A1 Variants in Cats with Ehlers-Danlos Syndrome
Authors: Kiener Sarah , Apostolopoulos Neoklis , Schissler Jennifer , Hass Pascal-Kolja , Leuthard Fabienne , Jagannathan Vidhya , Schuppisser Carole , Soto Sara , Welle Monika , Mayer Ursula , Leeb Tosso , Fischer Nina M. , Kaessmeyer Sabine
Published: April 2022

We investigated four cats with similar clinical skin-related signs strongly suggestive of Ehlers-Danlos syndrome (EDS). Cases no. 1 and 4 were unrelated and the remaining two cases, no. 2 and 3, were reportedly siblings. Histopathological changes were characterized by severely altered dermal collagen fibers. Transmission electron microscopy in one case demonstrated abnormalities in the collagen fibril organization and structure. The genomes of the two unrelated affected cats and one of the affected siblings were sequenced and individually compared to 54 feline control genomes. We searched for private protein changing variants in known human EDS candidate genes and identified three independent heterozygous COL5A1 variants. COL5A1 is a well-characterized candidate gene for classical EDS. It encodes the proα1 chain of type V collagen, which is needed for correct collagen fibril formation and the integrity of the skin. The identified variants in COL5A1 are c.112_118+15del or r.spl?, c.3514A>T or p.(Lys1172*), and c.3066del or p.(Gly1023Valfs*50) for cases no. 1, 2&3, and 4, respectively. They presumably all lead to nonsense-mediated mRNA decay, which results in haploinsufficiency of COL5A1 and causes the alterations of the connective tissue. The whole genome sequencing approach used in this study enables a refinement of the diagnosis for the affected cats as classical EDS. It further illustrates the potential of such experiments as a precision medicine approach in animals with inherited diseases.
The Prevalence and Predictors of Restless Legs Syndrome in Patients with Liver Cirrhosis
Authors: Plotogea Oana-Mihaela , Diaconu Camelia Cristina , Gheorghe Gina , Stan-Ilie Madalina , Oprita Ruxandra , Sandru Vasile , Bacalbasa Nicolae , Constantinescu Gabriel
Published: April 2022

Introduction and aim. Sleep disorders are highly prevalent in patients with liver cirrhosis. The aim of this study was to investigate the prevalence of restless legs syndrome (RLS), as well as its risk factors and possible predictors, in a cohort of patients with liver cirrhosis. Material and methods. We performed a cross-sectional prospective study over a period of 14 months and enrolled 69 patients with liver cirrhosis, after applying the inclusion and exclusion criteria. The cases of RLS were assessed according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria and severity scale. Results. Out of the total number of patients, 55% fulfilled the criteria for RLS. Age, diabetes, severity of cirrhosis, serum creatinine, glomerular filtration rate (GFR), and mean hemoglobin were associated with the presence of RLS. Moreover, there was a significantly higher prevalence of RLS among patients with decompensated cirrhosis. From all the risk factors introduced into the multivariate analysis, only the GFR could predict the presence of RLS. Conclusions. This research shows that patients with liver cirrhosis have a high risk of RLS. Even though there are multiple risk factors associated with RLS, only the GFR could predict its occurrence in our cohort.
The Reproducibility and Usefulness of Estimated Average Glucose for Hyperglycemia Management during Health Checkups: A Retrospective Cross-Sectional Study
Authors: Nah Eun-Hee , Cho Seon , Park Hyeran , Noh Dongwon , Kwon Eunjoo , Cho Han-Ik
Published: April 2022

HbA1c reflects average glucose levels over 3 months, but it does not measure glycemic variability. This study aimed to determine the reproducibility and usefulness of HbA1c-derived estimated average glucose (eAG) and to analyze the factors associated with eAG during health checkups. This cross-sectional retrospective study consecutively selected subjects who had undergone health checkups at 16 health-promotion centers in 13 Korean cities in 2020. The subjects comprised 182,848 healthy subjects with normoglycemia, 109,555 with impaired fasting glucose (IFG), and 35,632 with diabetes. eAG was calculated using Nathan’s regression equation. In all subjects, fasting plasma glucose (FPG) was found to be fairly strongly correlated with eAG (r = 0.811). When the subjects were divided into FPG subgroups, the strength of the correlation decreased among those with normoglycemia and IFG (p < 0.001). Higher eAG levels were associated with older age, females, higher FPG, and lower HDL-C and triglycerides (p < 0.05). The proportion of subjects with a higher value of FPG than eAG was 46.3% in poorly controlled diabetic patients, compared with only 1.5% in normoglycemic subjects. This suggests eAG could help patients to understand their glycemic variability intuitively and healthcare providers to identify patients who might worsen in hyperglycemia control through measuring the difference between eAG and FPG.
General Health and Resilience of Breast Cancer Patients: The Mediator Role of Affective Well-Being
Authors: Cerezo M. Victoria , Álvarez-Olmo Ana , Rueda Pilar
Published: April 2022

A considerable percentage of breast cancer patients present adequate psychological adjustment and do not become distressed after a breast cancer diagnosis, or, if they do, they manage to recover quickly, which is reflected in their general health. This study aims to determine the role of some psychological mechanisms that affect psycho-oncological adjustment, specifically, resilience and well-being, in a sample of 109 breast cancer patients. For this purpose, participants completed questionnaires on general health, resilience, and well-being (life satisfaction and affect). Correlation analyses and a multiple mediation model were carried out. The results revealed that Pearson correlations between all variables showed strong associations between general health scores and positive and negative affect scores, and moderate associations with life satisfaction and resilience scores. Furthermore; in the mediation model, the total percentage of variance explained by the overall model was 55% (R2 = 0.55), where resilience was associated with positive and negative affect, and that influenced general health. These results show that affective well-being is especially relevant in breast cancer patients in terms of its mediating role in resilience, making it clear that an appropriate intervention focused on managing patients’ affective status can have a favorable impact on their overall health.
Incidence of Congenital Clubfoot: Preliminary Data from Italian CeDAP Registry
Authors: Dibello Daniela , Torelli Lucio , Di Carlo Valentina , d’Adamo Adamo Pio , Faletra Flavio , Mangogna Alessandro , Colin Giulia
Published: April 2022

(1) Background: We find the incidence of clubfoot in Italy from “Certificate of Delivery Care Registry (CeDAP)”, a database of the Italian Ministry of Health, the most comprehensive public data available for this purpose. (2) Methods: The CeDAP registry is a web system that provides epidemiological and sociodemographic information about newborns. It started on 1 January 2002, following the ministerial Decree no. 349 of 16 July 2001. The certificate is structured into six sections; each collects specific information referring to the birthplace, parents, pregnancy, childbirth, newborn, and the possible presence of congenital malformations or the causes of neonatal mortality. The midwife or the doctor draws up the certificate no later than ten days after birth. Each region transmits the data every six months to the Ministry of Health. The period between 2013 and 2017 has been selected for the study, with every Italian region’s data. We conducted a retrospective descriptive study. (3) Results: The overall rate in northern Italy is 1.09 (with some exceptions described), but we think it is essential to reevaluate this number again, given more accurate data collections by every Italian hospital. (4) Conclusions: This study intends to build a framework for future epidemiologic studies about clubfoot in Italy.
Mini Trampoline, a New and Promising Way of SCUBA Diving Preconditioning to Reduce Vascular Gas Emboli?
Authors: Lambrechts Kate , Germonpré Peter , Vandenheede Joaquim , Delorme Manon , Lafère Pierre , Balestra Costantino
Published: April 2022

Background: Despite evolution in decompression algorithms, decompression illness is still an issue nowadays. Reducing vascular gas emboli (VGE) production or preserving endothelial function by other means such as diving preconditioning is of great interest. Several methods have been tried, either mechanical, cardiovascular, desaturation aimed or biochemical, with encouraging results. In this study, we tested mini trampoline (MT) as a preconditioning strategy. Methods: In total, eight (five females, three males; mean age 36 ± 16 years; body mass index 27.5 ± 7.1 kg/m2) healthy, non-smoking, divers participated. Each diver performed two standardized air dives 1 week apart with and without preconditioning, which consisted of ±2 min of MT jumping. All dives were carried out in a pool (NEMO 33, Brussels, Belgium) at a depth of 25 m for 25 min. VGE counting 30 and 60 min post-dive was recorded by echocardiography together with an assessment of endothelial function by flow-mediated dilation (FMD). Results: VGE were significantly reduced after MT (control: 3.1 ± 4.9 VGE per heartbeat vs. MT: 0.6 ± 1.1 VGE per heartbeat, p = 0.031). Post-dive FMD exhibited a significant decrease in the absence of preconditioning (92.9% ± 7.4 of pre-dive values, p = 0.03), as already described. MT preconditioning prevented this FMD decrease (103.3% ± 7.1 of pre-dive values, p = 0.30). FMD difference is significant (p = 0.03). Conclusions: In our experience, MT seems to be a very good preconditioning method to reduce VGE and endothelial changes. It may become the easiest, cheapest and more efficient preconditioning for SCUBA diving.
Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery in Dragon Boat Athletes: Evidence from a Pilot Study
Authors: Dong Gengxin , Fu Jiahui , Bao Dapeng , Zhou Junhong
Published: April 2022

(1) Background: Exercise that exceeds the body’s accustomed load can lead to oxidative stress and increased fatigue during intense training or competition, resulting in decreased athletic performance and an increased risk of injury, and the new medicinal H2 may be beneficial as an antioxidant. Therefore, we explored the effect of short-term supplementation of hydrogen-rich water (HRW) on the work performance and fatigue recovery of dragon boat athletes after training. (2) Methods: Eighteen dragon boat athletes who trained for 4 h a day (2 h in the morning and 2 h in the afternoon) were divided into an HRW group (n = 9) and a placebo water (PW) group (n = 9), drinking HRW or PW for 7 days. Each participant completed 30 s rowing dynamometer tests, monitoring the heart rate at baseline (i.e., Day 1) and after the intervention (on Day 8). (3) Result: Drinking HRW increased the maximum power and average power of the 30 s rowing test and decreased the maximum heart rate during the period. After the rowing test, the HRW group’s heart rate dropped significantly after 2 min of recovery, while the PW group’s heart rate did not drop. There was no significant difference between the 30 s rowing distance and the predicted duration of rowing 500 m. (4) Conclusions: Drinking HRW in the short term can effectively improve the power performance of dragon boat athletes and is conducive to the recovery of the heart rate after exercise, indicating that HRW may be a suitable means of hydration for athletes.
Variation and Predictors of Gross Motor Coordination Development in Azorean Children: A Quantile Regression Approach
Authors: Pereira Sara , Bastos Flávio , Santos Carla , Maia José , Tani Go , Robinson Leah , Katzmarzyk Peter
Published: April 2022

We investigated the development of gross motor coordination (GMC) as well as its predictors in school-aged Azorean children. The sample included 181 children (90 girls), followed consecutively for 4 years from 6 to 9 years of age. GMC was assessed with the Körperkoordinationstest für Kinder, and predictors included body mass index, standing long jump, 50-yard dash, and shuttle run. The changes in GMC and the effects of predictors were analyzed with mean-modeling as well as quantile regression. In the latter, we considered the following three quantiles (Q): Q20, Q50, and Q80 as markers of low, median, and high GMC levels, respectively. All analyses were conducted using R software and alpha was set at 5%. The GMC changes were curvilinear in both models, but the quantile approach showed a more encompassing picture of the changes across the three quantiles in both boys and girls with different rates of change. Further, the predictors had different effect sizes across the quantiles in both sexes, but in the mean-model their effects were constant. In conclusion, quantile regression provides more detailed information and permits a more thorough understanding of changes in GMC over time and the influence of putative predictors.
The Big Five Personality Traits and Positive Orientation in Polish Adults with Multiple Sclerosis: The Role of Meaning in Life
Authors: Szcześniak Małgorzata , Potemkowski Andrzej , Brola Waldemar , Kroplewski Zdzisław , Szałachowski Roman Ryszard , Zak Marek , Wilski Maciej , Sobolewski Piotr , Bartosik-Psujek Halina , Kapica-Topczewska Katarzyna , Tarasiuk Joanna , Czarnowska Agata , Kułakowska Alina , Zakrzewska-Pniewska Beata , Kubicka-Bączyk Katarzyna , Morawiec Natalia , Adamczyk-Sowa Monika , Stępień Adam , Zaborski Jacek , Ratajczak Anna , Ratajczak Marcin
Published: April 2022

Scientific achievements concerning the direct relation between personality traits and positive orientation among patients with multiple sclerosis do not explain the role of potential mediators. In fact, some researchers argue that the traits–positivity association is much more complex than it seems to be. For this reason, we made an attempt to analyze the indirect relationship between the above-mentioned variables, including meaning in life as a mediator. In total, 618 patients with MS took part in the study. The NEO Five-Factor Inventory, the Positive Orientation Scale, and the Meaning in Life Questionnaire were used. The results showed that positive orientation/the presence of meaning/searching for meaning correlated positively with extraversion, openness to experience, agreeableness, and conscientiousness, and were negatively associated with neuroticism. Moreover, meaning in life in both its dimensions acted as a mediator in 9 of 10 models. It can be assumed that a propensity to establish interpersonal relationships (extraversion), use active imagination (openness), inspire confidence among others (agreeableness), and take responsibility (conscientiousness) can have an impact on someone’s positive attitude toward oneself and the surrounding world (positive orientation) when people have meaning in life and when they are seeking it.
Deficiency of Daily Calcium and Vitamin D in Primary School Children in Lviv, Ukraine
Authors: Tytusa Andrii , Wyszyńska Jutyna , Yatsula Marta , Nyankovskyy Serhiy , Mazur Artur , Dereń Katarzyna
Published: April 2022

This study was conducted to determine the prevalence of calcium and vitamin D deficiency in school children aged 6 to 11 years in Lviv (Ukraine). The aim of this study was also to assess the effect of nutritional intervention and supplementation on serum calcium and vitamin D levels in children diagnosed with calcium deficiency. A 3 day diet was analyzed in 172 children. In 56 children with a deficiency of calcium and/or vitamin D, the level of total calcium, ionized calcium, and 25-hydroxyvitamin D in blood, as well as the calcium content in hair samples, was determined. Thirty children with confirmed calcium and/or vitamin D deficiency underwent a dietary intervention to increase calcium and vitamin D intake for 3 months. The study group (n = 15) was provided with a nutritional correction by modifying their diet with supplementation of calcium and vitamin D. The control group (n = 15) received only a diet modification. Decreased daily calcium intake was observed in 50.68% of boys and 70.71% of girls. A decreased level of daily vitamin D consumption was found in 84.93% of boys and 96.97% of girls. Among 56 children with insufficient daily consumption of calcium and/or vitamin D, 26.8% had reduced levels of total calcium in the blood, 16.1% had reduced levels of ionized calcium in the blood, and 48.2% had reduced levels of vitamin D. After 3 months of correction, normal calcium level was found in the hair of 10 students (66.7%) from the study group and in three subjects (20.0%) from the control group. Modification of the diet along with supplementation of calcium and vitamin D seems to be a more effective method for increasing the level of calcium among children aged 6 to 11 years.
Malaria and Helminthic Co-Infection during Pregnancy in Sub-Saharan Africa: A Systematic Review and Meta-Analysis
Authors: Tadesse Boltena Minyahil , El-Khatib Ziad , Kebede Abraham Sahilemichael , Asamoah Benedict Oppong , Yaw Appiah Seth Christopher , Kamara Kassim , Constant Assogba Phénix , Tadesse Boltena Andualem , Adane Hawult Taye , Hailemeskel Elifaged , Biru Mulatu
Published: April 2022

Malaria and helminthic co-infection during pregnancy causes fetomaternal haemorrhage and foetal growth retardation. This study determined the pooled burden of pregnancy malaria and helminthic co-infection in sub-Saharan Africa. CINAHL, EMBASE, Google Scholar, Scopus, PubMed, and Web of Science databases were used to retrieve data from the literature, without restricting language and publication year. The Joanna Briggs Institute’s critical appraisal tool for prevalence studies was used for quality assessment. STATA Version 14.0 was used to conduct the meta-analysis. The I2 statistics and Egger’s test were used to test heterogeneity and publication bias. The random-effects model was used to estimate the pooled prevalence at a 95% confidence interval (CI). The review protocol has been registered in PROSPERO, with the number CRD42019144812. In total, 24 studies (n = 14,087 participants) were identified in this study. The pooled analysis revealed that 20% of pregnant women were co-infected by malaria and helminths in sub-Saharan Africa. The pooled prevalence of malaria and helminths were 33% and 35%, respectively. The most prevalent helminths were Hookworm (48%), Ascaris lumbricoides (37%), and Trichuris trichiura (15%). Significantly higher malaria and helminthic co-infection during pregnancy were observed. Health systems in sub-Saharan Africa must implement home-grown innovative solutions to underpin context-specific policies for the early initiation of effective intermittent preventive therapy.
Placental Cyclophilin A Expression in Pregnancies Complicated with Hypertension
Authors: Shaaya Elia Shazniza , Yahaya Azyani , Mustangin Muaatamarulain , Alfian Nurwardah , Aizuddin Azimatun Noor , Wong Yin Ping , Tan Geok Chin
Published: April 2022

Introduction: Cyclophilin A was reported to be increased in the serum of mothers with preeclampsia, and is implicated in its pathogenesis. This study aimed to determine the expression of cyclophilin A in the placenta of mothers with and without hypertension, and to correlate its expression with maternal complications and adverse perinatal outcomes. Materials and Methods: This study consisted of a total of 70 cases (35 cases of mothers with hypertension, and 35 normotensive mothers as a control). Cyclophilin A immunohistochemistry was performed on a paraffin-embedded tissue section of placenta submitted at full thickness in order to evaluate the expression in fetal endothelial cells, cytotrophoblasts, syncytiotrophoblasts, maternal endothelial cells and decidual cells. The cyclophilin A expression was scored as weak, moderate or strong intensity. Results: The hypertensive group was more likely to have preterm deliveries (p < 0.0001), caesarean sections (p < 0.0001), and infants admitted to the intensive care unit (p < 0.001). Fifty-one percent of the fetal endothelial cells and cytotrophoblasts expressed cyclophilin A in the hypertensive group, compared to only 28.6% in the normotensive group. However, the difference was not statistically significant (p = 0.086). Conclusion: We found no significant difference in placental cyclophilin A expression between hypertensive and normotensive mothers. There was also no difference in expression in mothers with and without maternal complications and adverse perinatal outcomes.
Sedentary Behaviour and Its Relationship with Early Vascular Ageing in the General Spanish Population: A Cross-Sectional Study
Authors: Llamas-Ramos Inés , Llamas-Ramos Rocío , Alonso-Domínguez Rosario , Gómez-Sánchez Leticia , Tamayo-Morales Olaya , Lugones-Sánchez Cristina , Rodríguez-Sánchez Emiliano , García-Ortiz Luis , Gómez-Marcos Manuel A.
Published: April 2022

Sedentary behaviour is associated with a greater predisposition to developing cardiovascular diseases. The aim of the study was to analyse the relationship between sedentary time and early vascular ageing. A total of 501 participants (49.70% men) were recruited through random sampling stratified by age group and sex. Vascular ageing was evaluated considering three criteria: (1) the vascular ageing index (VAI); (2) the carotid–femoral pulse wave velocity (cfPWV) 10th and 90th percentiles of the reference values in the European population by age; and (3) the Framingham’s heart age. The carotid intima–media thickness was measured using a Sonosite Micromaxx ultrasound, the presence of peripheral artery disease was assessed by calculating the ankle–brachial index using a VaSera VS-1500, and the cfPWV was measured with a SphygmoCor® device. Weekly sedentary hours were evaluated through a sitting time questionnaire. The average age of the population was 55.90 ± 14.24 years. The men spent more hours sitting per week (47.6 ± 16.6 vs. 36.8 ± 17.3 h/W), at work (16.7 ± 16.2 vs. 9.73 ± 14.9 h/W), and watching TV (21.6 ± 12.5 vs. 18.7 ± 11.9 h/W). In the logistic regression analysis, the individuals with early vascular aging (EVA), with respect to those with healthy vascular aging (HVA), spent more hours sitting per week (OR = 1.03 vs. OR = 1.02; p < 0.05) and watching TV (OR = 1.03 vs. OR = 1.03; p < 0.05), using the criteria of the European guideline and VAI, and more hours sitting when commuting (OR = 1.04; p < 0.05), using Framingham’s heart age to define EVA. The results of this study indicate that sedentary time is associated with early vascular ageing. Therefore, reducing sedentary time would improve vascular health.
Effects of the Mobility-Fit Physical Activity Program on Strength and Mobility in Older Adults in Assisted Living: A Feasibility Study
Authors: Yang Yijian , van Schooten Kimberley S. , Komisar Vicki , McKay Heather A. , Sims-Gould Joanie , Cheong Debbie , Robinovitch Stephen N.
Published: April 2022

Physical activity programs focusing on fall prevention often overlook upper-limb strength, which is important for transferring, balance recovery, and arresting a fall. We developed and evaluated a physical activity program, Mobility-Fit for older adults in Assisted Living (AL) that includes upper-limb strengthening, agility, coordination, and balance exercises. Thirty participants (85 ± 6 years) were recruited from two AL facilities; 15 were assigned to Mobility-Fit (three times/week, 45 min/session for 12 weeks) and 15 maintained usual care. Twenty-two participants (11 in each group) completed the study. We compared outcome changes between groups and interviewed participants and staff to explore the effectiveness and feasibility of the program. Among participants who attended Mobility-Fit, knee extension strength increased by 6%, reaction time decreased by 16%, and five-time sit-to-stand duration decreased by 15%. Conversely, participants in the usual care group had a 6% decrease in handgrip strength. Changes of these outcomes were significantly different between two groups (p < 0.05). Participants enjoyed the program and staff suggested some changes to improve attendance. Our results indicate that Mobility-Fit is feasible to deliver and beneficial for older adults in AL and may guide future clinical trials to evaluate the effectiveness of upper limb strengthening on safe mobility of older adults in care facilities.
Populus euphratica Phospholipase Dδ Increases Salt Tolerance by Regulating K+/Na+ and ROS Homeostasis in Arabidopsis
Authors: Zhang Ying , Yao Jun , Yin Kexin , Liu Zhe , Zhang Yanli , Deng Chen , Liu Jian , Zhang Yinan , Hou Siyuan , Zhang Huilong , Yu Dade , Zhao Nan , Zhao Rui , Chen Shaoliang
Published: April 2022

Phospholipase Dα (PLDα), which produces signaling molecules phosphatidic acid (PA), has been shown to play a critical role in plants adapting to salt environments. However, it is unclear whether phospholipase Dδ (PLDδ) can mediate the salt response in higher plants. PePLDδ was isolated from salt-resistant Populus euphratica and transferred to Arabidopsis thaliana to testify the salt tolerance of transgenic plants. The NaCl treatment (130 mM) reduced the root growth and whole-plant fresh weight of wild-type (WT) A. thaliana, vector controls (VC) and PePLDδ-overexpressed lines, although a less pronounced effect was observed in transgenic plants. Under salt treatment, PePLDδ-transgenic Arabidopsis exhibited lower electrolyte leakage, malondialdehyde content and H2O2 levels than WT and VC, resulting from the activated antioxidant enzymes and upregulated transcripts of genes encoding superoxide dismutase, ascorbic acid peroxidase and peroxidase. In addition, PePLDδ-overexpressed plants increased the transcription of genes encoding the plasma membrane Na+/H+ antiporter (AtSOS1) and H+-ATPase (AtAHA2), which enabled transgenic plants to proceed with Na+ extrusion and reduce K+ loss under salinity. The capacity to regulate reactive oxygen species (ROS) and K+/Na+ homeostasis was associated with the abundance of specific PA species in plants overexpressing PePLDδ. PePLDδ-transgenic plants retained a typically higher abundance of PA species, 34:2 (16:0–18:2), 34:3 (16:0–18:3), 36:4 (18:2–18:2), 36:5 (18:2–18:3) and 36:6 (18:3–18:3), under control and saline conditions. It is noteworthy that PA species 34:2 (16:0–18:2), 34:3 (16:0–18:3), 36:4 (18:2–18:2) and 36:5 (18:2–18:3) markedly increased in response to NaCl in transgenic plants. In conclusion, we suppose that PePLDδ-derived PA enhanced the salinity tolerance by regulating ROS and K+/Na+ homeostasis in Arabidopsis.
Long-Term Heat Selection of the Coral Endosymbiont Cladocopium C1acro (Symbiodiniaceae) Stabilizes Associated Bacterial Communities
Authors: Buerger Patrick , Vanstone Ruby T. , Maire Justin , van Oppen Madeleine J. H.
Published: April 2022

Heat-tolerant strains of the coral endosymbiont, Cladocopium C1acro (Symbiodiniaceae), have previously been developed via experimental evolution. Here, we examine physiological responses and bacterial community composition (using 16S rRNA gene metabarcoding) in cultures of 10 heat-evolved (SS) and 9 wild-type (WT) strains, which had been exposed for 6 years to 31 °C and 27 °C, respectively. We also examine whether the associated bacterial communities were affected by a three-week reciprocal transplantation to both temperatures. The SS strains had bacterial communities with lower diversities that showed more stability and lower variability when exposed to elevated temperatures compared with the WT strains. Amplicon sequence variants (ASVs) of the bacterial genera Labrenzia, Algiphilus, Hyphobacterium and Roseitalea were significantly more associated with the SS strains compared with the WT strains. WT strains showed higher abundance of ASVs assigned to the genera Fabibacter and Tropicimonas. We hypothesize that these compositional differences in associated bacterial communities between SS and WT strains also contribute to the thermal tolerance of the microalgae. Future research should explore functional potential between bacterial communities using metagenomics to unravel specific genomic adaptations.
An Approach to Churn Prediction for Cloud Services Recommendation and User Retention
Authors: Saias José , Rato Luís , Gonçalves Teresa
Published: April 2022

The digital world is very dynamic. The ability to timely identify possible vendor migration trends or customer loss risks is very important in cloud-based services. This work describes a churn risk prediction system and how it can be applied to guide cloud service providers for recommending adjustments in the service subscription level, both to promote rational resource consumption and to avoid CSP customer loss. A training dataset was built from real data about the customer, the subscribed service and its usage history, and it was used in a supervised machine-learning approach for prediction. Classification models were built and evaluated based on multilayer neural networks, AdaBoost and random forest algorithms. From the experiments with our dataset, the best results for a churn prediction were obtained with a random forest-based model, with 64 estimators, having 0.988 accuracy and 0.997 AUC value.
The Prognostic Value of Natriuretic Peptides in Stable Patients with Suspected Acute Myocarditis: A Retrospective Study
Authors: Moady Gassan , Perlmutter Shahar , Atar Shaul
Published: April 2022

Risk stratification in acute myocarditis is based on the clinical signs of heart failure, the degree of cardiac dysfunction, and the findings in cardiac magnetic resonance (CMR). The aim of the current study is to examine the prognostic yield of the natriuretic peptide N-terminal-pro hormone Brain Natriuretic Peptide (NT-proBNP) and C-reactive protein (CRP) in acute myocarditis among patients with preserved/mildly reduced left ventricular ejection fraction (LVEF). We retrospectively analyzed 59 patients (median age 28 years, 76% males) with ICD-9 discharge diagnosis of acute myocarditis. Basic characteristics, echocardiographic, and laboratory parameters were obtained from computerized files. The median length of stay was 3, (IQR 2–5) days, and the median LVEF was 48% (IQR, 54–62%). High levels of NT-proBNP and CRP were associated with increased length of stay (r = 0.57, p < 0.001; r = 0.4 p = 0.001, respectively), while troponin level was not (r = 0.068, p = 0.61). During the index hospitalization, complications occurred in 14 (23.7%) patients. High NT-proBNP and CRP levels were associated with complications (p < 0.001, and p = 0.001, respectively), while troponin level was not (p = 0.452). In conclusion, routine measurement of NT-proBNP and CRP are preferred over troponin for risk stratification in hemodynamically stable myocarditis.
FGFR Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC)
Authors: Raphael Ari , Dudnik Elizabeth , Hershkovitz Dov , Jain Suyog , Olsen Steve , Soussan-Gutman Lior , Ben-Shitrit Taly , Dvir Addie , Nechushtan Hovav , Peled Nir , Onn Amir , Agbarya Abed ,   on behalf of the Israel Lung Cancer Group
Published: April 2022

Background. FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited. Methods. The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and FGFR2/3 fusions; FGFR2/3 fusion prevalence with and without a co-existing EGFR mutation was assessed. The ED of Tel-Aviv Sourasky Medical Center (TASMC, June 2020–June 2021) was evaluated for cases of aNSCLC and de novo FGFR1/2/3 fusions. Patients with EGFR mutant aNSCLC progressing on EGFR TKIs and developing an FGFR1/2/3 fusion were selected from the ED of Davidoff Cancer Center (DCC) and Oncology Department, Bnei-Zion hospital (BZ) (April 2014–April 2021). Clinicopathological characteristics, systemic therapies, and outcomes were assessed. Results. In the GH ED (n = 57,445), the prevalence of FGFR2 and FGFR3 fusions were 0.02% and 0.26%, respectively. FGFR3-TACC3 fusion predominated (91.5%). In 23.8% of cases, FGFR2/3 fusions co-existed with EGFR sensitizing mutations (exon 19 del, 64.1%; L858R, 33.3%, L861Q, 2.6%). Among samples with concurrent FGFR fusions and EGFR sensitizing mutations, 41.0% also included EGFR resistant mutations. In TASMC (n = 161), 1 case of de novo FGFR3-TACC3 fusion was detected (prevalence, 0.62%). Of three patients from DCC and BZ with FGFR3-TACC3 fusions following progression on EGFR TKIs, two received EGFR TKI plus erdafitinib, an FGFR TKI, with clinical benefit duration of 13.0 and 6.0 months, respectively. Conclusions. Over 23% of FGFR2/3 fusions in aNSCLC may be associated with acquired resistance following treatment with EGFR TKIs. In this clinical scenario, a combination of EGFR TKIs and FGFR TKIs represents a promising treatment strategy.
Impact of Preterm Birth on Neurodevelopmental Disorders in South Korea: A Nationwide Population-Based Study
Authors: Cha Jong Ho , Ahn Ja-Hye , Kim Yun Jin , Lee Bong Gun , Kim Johanna Inhyang , Park Hyun-Kyung , Kim Bung-Nyun , Lee Hyun Ju
Published: April 2022

Neurodevelopmental disorder (NDD) in preterm infants has become of great interest. We aimed to investigate the impact of preterm birth on the proportion of NDD using nationwide data provided by the Korean National Health Insurance Service. We included 4894 extremely preterm or extremely low-birth-weight (EP/ELBW; <28 weeks of gestation or birth weight < 1000 g) infants, 70,583 other preterm or low-birth-weight (OP/LBW; 28–36 weeks of gestation or birth weight < 2500 g) infants, and 264,057 full-term infants born between 2008 and 2015. We observed their neurodevelopment until 6 years of age or until the year 2019, whichever occurred first. Diagnoses of NDDs were based on the World Health Organization’s International Classification of Diseases 10th revision. An association between preterm birth and NDD was assessed using a multivariable logistic regression model. There was a stepwise increase in the risk of overall NDD with increasing degree of prematurity, from OP/LBW (adjusted odds ratio 4.46; 95% confidence interval 4.34–4.58), to EP/ELBW (16.15; 15.21–17.15). The EP/ELBW group was strongly associated with developmental delay (21.47; 20.05–22.99), cerebral palsy (88.11; 79.89–97.19), and autism spectrum disorder (11.64; 10.37–13.06). Preterm birth considerably increased the risk of NDD by the degree of prematurity.
Differences in Optimal Platelet Reactivity after Potent P2Y12 Inhibitor Treatment in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention
Authors: Song Kai , Jin Xuan , Kim Moo-Hyun , Li Jia-Xin , Jin Cai-De , Yuan Song-Lin , Song Zhao-Yan , Jin En-Ze , Lee Kwang-Min , Lim Kyung-Hee , Cho Young-Rak
Published: April 2022

Background: East Asian patients receiving treatment with the potent P2Y12 inhibitors prasugrel or ticagrelor experience more potent platelet inhibition than with clopidogrel. Methods: This study investigated differences in OPR rates with reduced doses of prasugrel (n = 38) or ticagrelor (n = 40) for maintenance therapy in 118 Korean ACS patients who had undergone PCI, in comparison to conventional-dose clopidogrel (n = 40). We assessed drug responses at one- and three-months post-PCI with VerifyNow and multiple electrode aggregometry assays. Results: At the one-month period, patients receiving standard-dose prasugrel or ticagrelor had lower platelet reactivity as determined by the three assays than those receiving the conventional dose of clopidogrel (VN: p = 0.000; MEA: p = 0.000; LTA: p = 0.000). At the 3-month point, platelet reactivity was lower in those receiving reduced-dose prasugrel or ticagrelor than the clopidogrel-treated patients (VN: p = 0.000; MEA: p = 0.012; LTA: p = 0.002). Prasugrel resulted in significantly lower platelet inhibition than ticagrelor as determined by VN and LTA (VN: p = 0.000; LTA: p = 0.003). At three months, there was a significant overall difference in OPR among the three groups when measured by VN (p < 0.001), but not when measured by MEA (p = 0.596). OPR in the reduced-dose prasugrel group was not significantly different to the clopidogrel group at three months (VN: p = 0.180; MEA: p = 0.711). OPR in the reduced-dose ticagrelor group was similar to clopidogrel as determined by MEA at three months, but was different when assessed by VN (VN: p = 0.000; MEA: p = 0.540). Compared to standard-dose, the reduced-dose prasugrel OPR rate was significantly increased (VN: p = 0.008; MEA: p = 0.020). Conclusions: OPR values for reduced-dose prasugrel and conventional-dose clopidogrel at three months were similar but higher than for reduced-dose ticagrelor as determined by VN, but no differences were noted by MEA. The MEA assay might have less sensitivity and consistency than the VN assay. Further studies are needed to explore this discrepancy.
Effectiveness of an Active and Continuous Surveillance Program for Intensive Care Units Infections Based on the EPIC III (Extended Prevalence of Infection in Intensive Care) Approach
Authors: Montrucchio Giorgia , Sales Gabriele , Catozzi Giulia , Bosso Stefano , Scanu Martina , Vignola Titty Vita , Costamagna Andrea , Corcione Silvia , Urbino Rosario , Filippini Claudia , De Rosa Francesco Giuseppe , Brazzi Luca
Published: April 2022

We evaluated the effectiveness of the Extended Prevalence of Infection in Intensive Care (EPIC) III data collection protocol as an active surveillance tool in the eight Intensive Care Units (ICUs) of the Intensive and Critical Care Department of the University Hospital of Turin. A total of 435 patients were included in a six-day study over 72 ICU beds. 42% had at least one infection: 69% at one site, 26% at two sites and 5% at three or more sites. ICU-acquired infections were the most common (64%), followed by hospital-associated infections (22%) and community-acquired (20%), considering that each patient may have developed more than one infection type. 72% of patients were receiving at least one antibiotic: 48% for prophylaxis and 52% for treatment. Mortality, the length of ICU and hospital stays were 13%, 14 and 29 days, respectively, being all estimated to be significantly different in patients without and with infection (8% vs. 20%; 4 vs. 20 and 11 vs. 50 (p < 0.001). Our data confirm a high prevalence of infections, sepsis and the use of antimicrobials. The repeated punctual prevalence survey seems an effective method to carry out the surveillance of infections and the use of antimicrobials in the ICU. The use of the European Centre for Disease Prevention and Control (ECDC) definitions and the EPIC III protocol seems strategic to allow comparisons with national and international contexts.
Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?
Authors: Belamkar Aditya , Harris Alon , Oddone Francesco , Verticchio Vercellin Alice , Fabczak-Kubicka Anna , Siesky Brent
Published: April 2022

Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by irreversible retinal ganglion cell damage and visual field loss. The global POAG prevalence is estimated to be 3.05%, and near term is expected to significantly rise, especially within aging Asian populations. Primary angle-closure glaucoma disproportionately affects Asians, with up to four times greater prevalence of normal-tension glaucoma reported compared with high-tension glaucoma. Estimates for overall POAG prevalence in Asian populations vary, with Chinese and Indian populations representing the majority of future cases. Structural characteristics associated with glaucoma progression including the optic nerve head, retina, and cornea are distinct in Asians, serving as intermediates between African and European descent populations. Patterns in IOP suggest some similarities between races, with a significant inverse relationship between age and IOP only in Asian populations. Genetic differences have been suggested to play a role in these differences, however, a clear genetic pattern is yet to be established. POAG pathogenesis differs between Asians and other ethnicities, and it may differ within the broad classification of the Asian race. Greater awareness and further research are needed to improve treatment plans and outcomes for the increasingly high prevalence of normal tension glaucoma within aging Asian populations.
Osteonecrosis in Korean Paediatric and Young Adults with Acute Lymphoblastic Leukaemia or Lymphoblastic Lymphoma: A Nationwide Epidemiological Study
Authors: Hahn Seung Min , Lee Myeongjee , Huser Aaron , Gim Yeonji , Kim Eun Hwa , Kim Minsoo , Aldosari Amaal M. , Jung Inkyung , Kwak Yoon Hae
Published: April 2022

Osteonecrosis (ON) is a serious complication of acute lymphocytic leukaemia (ALL) or lymphoblastic lymphoma (LBL) treatment, and there is little information regarding ON in Korean paediatric and young adult patients. This retrospective cohort study assessed the cumulative incidence of and risk factors for ON using national health insurance claims data from 2008 to 2019 in 4861 ALL/LBL patients. The Kaplan–Meier method was used to estimate the cumulative incidence of ON according to age groups; the Cox proportional hazard regression model was used to identify risk factors related to ON development after diagnosing ALL/LBL. A cause-specific hazard model with time-varying covariates was used to assess the effects of risk factors. Overall, 158 (3.25%) patients were diagnosed with ON, among whom 23 underwent orthopaedic surgeries. Older age, radiotherapy (HR = 2.62, 95% confidence interval (CI) 1.87–3.66), HSCT (HR = 2.40, 95% CI 1.74–3.31), steroid use and anthracycline use (HR = 2.76, CI 1.85–4.14) were related to ON in the univariate analysis. In the multivariate analysis, age and steroid and asparaginase use (HR = 1.99, CI 1.30–3.06) were factors associated with ON. These results suggest that Korean patients with ALL/LBL who used steroids and asparaginase should be closely monitored during follow-up, even among young adult patients.
Raynaud’s Phenomenon with Focus on Systemic Sclerosis
Authors: Maciejewska Magdalena , Sikora Mariusz , Maciejewski Cezary , Alda-Malicka Rosanna , Czuwara Joanna , Rudnicka Lidia
Published: April 2022

Raynaud’s phenomenon is a painful vascular condition in which abnormal vasoconstriction of the digital arteries causes blanching of the skin. The treatment approach can vary depending on the underlying cause of disease. Raynaud’s phenomenon can present as a primary symptom, in which there is no evidence of underlying disease, or secondary to a range of medical conditions or therapies. Systemic sclerosis is one of the most frequent causes of secondary Raynaud’s phenomenon; its appearance may occur long before other signs and symptoms. Timely, accurate identification of secondary Raynaud’s phenomenon may accelerate a final diagnosis and positively alter prognosis. Capillaroscopy is fundamental in the diagnosis and differentiation of primary and secondary Raynaud’s phenomenon. It is helpful in the very early stages of systemic sclerosis, along with its role in disease monitoring. An extensive range of pharmacotherapies with various routes of administration are available for Raynaud’s phenomenon but a standardized therapeutic plan is still lacking. This review provides insight into recent advances in the understanding of Raynaud’s phenomenon pathophysiology, diagnostic methods, and treatment approaches.
Sediment and Radioactivity Transport in the Bohai, Yellow, and East China Seas: A Modeling Study
Authors: Brovchenko Igor , Kim Kyeong Ok , Maderich Vladimir , Jung Kyung Tae , Bezhenar Roman , Ryu Joo Hyung , Min Jee Eun
Published: April 2022

This paper is concerned with the development of a radionuclide dispersion model for the nuclear power plants in the Bohai, Yellow, and East China seas (BYECS) characterized by high turbidity and multi-scale circulations, focusing on the comparison of dispersion processes of 137Cs depending upon, in particular, the suspended sediment concentration and erosion/sedimentation processes. The simulations were carried out using a multi-fraction sediment transport model embedded in the semi-implicit Eulerian–Lagrangian finite-element coupled wave-circulation model linked with the model of radionuclide transport, which describes the key radionuclide transfer processes in the system of water–multi-fraction sediments. In contrast to the Eulerian models used for hydrodynamics and sediment transport processes, the Lagrangian technique was applied to simulate the transport of radionuclides. The simulation results for total suspended concentration agreed with in situ measurements and the Geostationary Ocean Color Imager data. The results of the simulation of hypothetical releases of 137Cs from four nuclear power plants (NPPs) placed in BYECS essentially differ from the real release of activity in the Pacific Ocean shelf due to the Fukushima Daiichi accident, which took place at the same time and released activity that was similar. The total amount of bottom contamination of 137Cs in releases from the Sanmen, Hanbit, and Hongyanhe NPPs was about 40% of dissolved component, and the total amount of suspended component was about 20% of dissolved component, in contrast with the Fukushima Daiichi accident, where the particulate component was only 2%. The results demonstrate the importance of erosion processes in the budget of 137Cs in shallow areas around the Sanmen and Hanbit NPPs, where strong wind and tidal currents took place.