bluuebunny/crossref_metadata_2025 huggingface dataset:
Can We Identify Patients in Danger of Delayed Treatment? Management of COVID-19 Pandemic Backlog in Urology Care in Poland
Authors: Ratajczak Jakub Marek , Gawrońska Anna , Fischer Margaret , Hladun Taras , Marczak Michał
Published: December 2022

The COVID-19 pandemic had a tremendous impact on healthcare systems around the world. This study aims to research the course of surgical treatment in urology during the pandemic in 2020, evaluate the volume of deferred treatment in urology in Poland, and indicate groups of patients that are especially vulnerable to a delay in the delivery of healthcare services. The National Health Found statistics (NHF) database was searched for information on procedures completed in urology departments from 2015 to 2020. Changes in hospital discharges of adults from 2019 to 2021 were investigated using monthly reports of NHF on patient billing groups. Statistics of PSA, testosterone, and creatinine testing were extracted from NHF reports. Annual changes in the number of surgeries were calculated. Then, the estimation of the expected quantity of procedures without the occurrence of the pandemic was performed using linear regression based on data from 2015 to 2020. The estimation was assumed reliable at R2 > 0.8. The difference between collected and estimated data was analysed. In 2020, the volume of radical prostatectomies, cystectomies, and kidney surgeries noted downturns following lockdowns in March and November. All analysed procedures, except radical cystectomy, noted a reduction in the entire year. The declines reached −34% in shockwave lithotripsy, −13% in ureterorenoscopic lithotripsy, −22% in cystolithotripsy, −28% in percutaneous lithotripsy, −12% in transurethral resection of a bladder tumour (TURBT), −31% in transurethral resection of the prostate, −15% in nephrectomy and kidney tumorectomy, and −10% in radical prostatectomy. Among the analysed procedures, only radical cystectomy rates increased 5%. Prostate-specific antigen and creatinine tests fell −17%, and testosterone testing was down −18%. In conclusion, the patients most vulnerable to delayed treatment due to the post-pandemic backlog are those requiring TURBT, kidney cancer operations, and radical prostatectomies. Solving backlogs in urology should prioritise cancer patients and thus requires improved access to cystoscopy, TURBT, diagnoses and surgery of prostate and kidney tumours. Addressing the needs of patients suffering from benign diseases demands appropriate measures to increase the surgical productivity of urology departments.
Understanding the Psychological Well-Being of International Arrivals in a Purpose-Designed Australian COVID-19 Quarantine Facility
Authors: Mitchell David , Esler Danielle , Straube Kylie Ann , Thomas David P. , Stephens Dianne , Bressington Daniel
Published: December 2022

Equivocal evidence suggests that mandatory supervised quarantine can negatively affect psychological well-being in some settings. It was unclear if COVID-19 supervised quarantine was associated with psychological distress in Australia. The sociodemographic characteristics associated with distress and the lived experiences of quarantine are also poorly understood. Therefore, this study aimed to evaluate the mental well-being of international arrivals undergoing supervised COVID quarantine in a purpose designed facility in the Northern Territory, Australia. We conducted a concurrent triangulation mixed-methods study comprising of an observational cross-sectional survey (n = 117) and individual qualitative interviews (n = 26). The results revealed that several factors were associated with distress, including significantly higher levels of depression for those who smoked, drank alcohol, had pre-existing mental health conditions and had no social networks in quarantine. Levels of psychological distress were also related to waiting time for re-entry (the time between applying to repatriate and returning to Australia) and flight origin. Qualitative data showed that despite quarantine being viewed as necessary, unclear communication and a perception of lack of control were affecting emotional well-being. This information is useful to inform the further development of models to identify those at most risk and support psychological well-being in quarantine settings.
In Search for an Ionic Liquid with the Best Performance during 210Pb/210Bi Cherenkov Counting in Waters on an LS Counter
Authors: Stojković Ivana , Vraneš Milan , Borović Teona Teodora , Todorović Nataša , Nikolov Jovana , Zečević Milka , Gadžurić Slobodan , Mancini Simona
Published: December 2022

The research presented in this paper aims to investigate the performance of several newly synthesized ionic liquids during 210Pb/210Bi detection in water on a liquid scintillation spectrometer Quantulus 1220 via Cherenkov counting. These experiments have been triggered by the recent reports that certain ionic liquids can act as wavelength shifters, thus significantly increasing the detection efficiency of Cherenkov radiation. The benefit of ionic liquid’s addition to the analysed samples is reflected in the detection limit’s decrement during 210Pb quantification, which is pertinent considering naturally low levels of 210Pb in aqueous samples. Firstly, it was discovered that ionic liquid, 1-butyl-3-methylimidazolium salicylate, is more efficient than the previously explored 2-hydroxypropylammonium salicylate. Consequently, the impact of a few other ionic liquids on Cherenkov counting efficiency with the same cation group (1-butyl-3-methylimidazolium benzoate, 1-butyl-3-methylimidazolium 3-hydroxybenzoate and 1-butyl-3-methylimidazolium 4-hydroxybenzoate) was also explored to test their potential influence. Molecular simulations have been carried out to reveal which structures of ionic liquids assure wavelength-shifting behavior. The obtained results confirmed that, among the investigated ones, only ionic liquids with the salicylate anion exhibited a wavelength shifting effect.
Relationship between Stock Returns and Trading Volume at the Bourse Régionale des Valeurs Mobilières, West Africa
Authors: Gueyie Jean-Pierre , Diallo Mouhamadou Saliou , Diallo Mamadou Fadel
Published: December 2022

The objective of this paper is to study the contemporaneous relationship and the dynamic relationship between the stock index return and the trading volume on the Bourse Régionale des Valeurs Mobilières using daily data from 5 January 2015 to 31 October 2022. Estimations are made using the generalized method of moments (GMM) and generalized autoregressive conditional heteroscedasticity or GARCH (1,1) specifications for the contemporaneous regressions and the vector autoregressive specification for the dynamic (causal) relationship. The contemporaneous specifications show that there is no significant relationship between stock returns and trading volume. Neither of the two variables significantly influences the other. Furthermore, the dynamic specification shows a causality running from stock returns to trading volume but the reverse is not true. For the period covered by the study, the results invalidate both the mixture of distribution hypothesis and the sequential information arrival hypothesis and open the way for other considerations such as behavioral models.
Spatial Distribution of Urban Parks’ Effect on Air Pollution-Related Health and the Associated Factors in Beijing City
Authors: Ji Huimin , Wang Juan , Zhu Yanrong , Shi Changsheng , Wang Shaohua , Zhi Guoqing , Meng Bin
Published: December 2022

Urban parks play an essential role in mitigating the effects of air pollution on human health in a healthy city construction process. However, due to the data limitations, little is known about the spatial distribution of real-time expressed air pollution-related health (APRH) across different urban parks and the contribution of the associated factors. To fill this research gap, this research was conducted based on social media Weibo data (Chinese Twitter) and other geographical data using semantic analyses and the Geo-Detector method by taking 169 urban parks in Beijing as the study area. The results showed that there were more Weibo items relating to APRH clustered within the third ring road and decreasing outward along the ring road. A total of 16 factors in three categories were introduced to analyze the driving forces of this spatial distribution. Accessibility was outstanding with a q-value of the number of subway stations (X14) as high as 0.79, followed by built environment and finally park attributes. Distinguished from those reports based on the traditional statistical data, this research demonstrated that although the urban parks improved the APRH, the exposure to air pollution also increased the health risks when visiting the urban park. It also provides a geographical understanding of the urban parks’ effect on APRH and theoretical guidance for urban park planning and construction.
Improved NMDA Receptor Activation by the Secreted Amyloid-Protein Precursor-α in Healthy Aging: A Role for D-Serine?
Authors: Billard Jean-Marie , Freret Thomas
Published: December 2022

Impaired activation of the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) by D-serine is linked to cognitive aging. Whether this deregulation may be used to initiate pharmacological strategies has yet to be considered. To this end, we performed electrophysiological extracellular recordings at CA3/CA1 synapses in hippocampal slices from young and aged mice. We show that 0.1 nM of the soluble N-terminal recombinant fragment of the secreted amyloid-protein precursor-α (sAPPα) added in the bath significantly increased NMDAR activation in aged but not adult mice without impacting basal synaptic transmission. In addition, sAPPα rescued the age-related deficit of theta-burst-induced long-term potentiation. Significant NMDAR improvement occurred in adult mice when sAPPα was raised to 1 nM, and this effect was drastically reduced in transgenic mice deprived of D-serine through genetic deletion of the synthesizing enzyme serine racemase. Altogether, these results emphasize the interest to consider sAPPα treatment targeting D-serine-dependent NMDAR deregulation to alleviate cognitive aging.
Host Cell Binding Mediated by Leptospira interrogans Adhesins
Authors: Takahashi Maria Beatriz , Teixeira Aline Florencio , Nascimento Ana Lucia Tabet Oller
Published: December 2022

Leptospirosis is a neglected infectious disease with global impact on both humans and animals. The increase in urban development without sanitation planning is one of the main reasons for the disease spreading. The symptoms are similar to those of flu-like diseases, such as dengue, yellow fever, and malaria, which can result in a misleading clinical diagnosis. The characterization of host–pathogen interactions is important in the development of new vaccines, treatments, and diagnostics. However, the pathogenesis of leptospirosis is not well understood, and many gaps remain to be addressed. Here, we aimed to determine if Leptospira strains, virulent, culture-attenuated, and saprophytic, and the major outer membrane proteins OmpL37, OmpL1, LipL21, LipL41, and LipL46 are able to adhere to different endothelial, epithelial and fibroblast cell lines in vitro. We showed that virulent leptospires robustly bind to all cells compared to the culture-attenuated and saprophytic lines. The recombinant proteins exhibited certain adhesion, but only OmpL1 and LipL41 were able to bind to several cell lines, either in monolayer or in cell suspension. Blocking OmpL1 with polyclonal antibodies caused a decrease in bacterial binding to cells, contrasting with an increase observed when anti-LipL41 antibodies were used. The adhesion of OmpL1 to HMEC-1 and EA.hy926 was inhibited when cells were pre-incubated with collagen IV, suggesting that both compete for the same cell receptor. We present here for the first time the interaction of five leptospiral outer membrane proteins with several cell lines, and we conclude that LipL41 and OmpL1 may have an impact on leptospiral adhesion to mammalian cells and may mediate the colonization process in leptospiral pathogenesis.
Impact of Volatile Organic Compounds on the Growth of Aspergillus flavus and Related Aflatoxin B1 Production: A Review
Authors: Josselin Laurie , De Clerck Caroline , De Boevre Marthe , Moretti Antonio , Fauconnier Marie-Laure
Published: December 2022

Volatile organic compounds (VOCs) are secondary metabolites of varied chemical nature that are emitted by living beings and participate in their interactions. In addition, some VOCs called bioactive VOCs cause changes in the metabolism of other living species that share the same environment. In recent years, knowledge on VOCs emitted by Aspergillus flavus, the main species producing aflatoxin B1 (AFB1), a highly harmful mycotoxin, has increased. This review presents an overview of all VOCs identified as a result of A. flavus toxigenic (AFB1-producing) and non-toxigenic (non AFB1-producing) strains growth on different substrates, and the factors influencing their emissions. We also included all bioactive VOCs, mixes of VOCs or volatolomes of microbial species that impact A. flavus growth and/or related AFB1 production. The modes of action of VOCs impacting the fungus development are presented. Finally, the potential applications of VOCs as biocontrol agents in the context of mycotoxin control are discussed.
Targeted Methylation Profiling of Single Laser-Capture Microdissected Post-Mortem Brain Cells by Adapted Limiting Dilution Bisulfite Pyrosequencing (LDBSP)
Authors: Riemens Renzo J. M. , Kenis Gunter , Nolz Jennifer , Susano Chaves Sonia C. , Duroux Diane , Pishva Ehsan , Mastroeni Diego , Van Steen Kristel , Haaf Thomas , van den Hove Daniël L. A.
Published: December 2022

A reoccurring issue in neuroepigenomic studies, especially in the context of neurodegenerative disease, is the use of (heterogeneous) bulk tissue, which generates noise during epigenetic profiling. A workable solution to this issue is to quantify epigenetic patterns in individually isolated neuronal cells using laser capture microdissection (LCM). For this purpose, we established a novel approach for targeted DNA methylation profiling of individual genes that relies on a combination of LCM and limiting dilution bisulfite pyrosequencing (LDBSP). Using this approach, we determined cytosine-phosphate-guanine (CpG) methylation rates of single alleles derived from 50 neurons that were isolated from unfixed post-mortem brain tissue. In the present manuscript, we describe the general workflow and, as a showcase, demonstrate how targeted methylation analysis of various genes, in this case, RHBDF2, OXT, TNXB, DNAJB13, PGLYRP1, C3, and LMX1B, can be performed simultaneously. By doing so, we describe an adapted data analysis pipeline for LDBSP, allowing one to include and correct CpG methylation rates derived from multi-allele reactions. In addition, we show that the efficiency of LDBSP on DNA derived from LCM neurons is similar to the efficiency obtained in previously published studies using this technique on other cell types. Overall, the method described here provides the user with a more accurate estimation of the DNA methylation status of each target gene in the analyzed cell pools, thereby adding further validity to this approach.
Dual Role of Fibroblasts Educated by Tumour in Cancer Behavior and Therapeutic Perspectives
Authors: Toledo Belén , Picon-Ruiz Manuel , Marchal Juan Antonio , Perán Macarena
Published: December 2022

Tumours are complex systems with dynamic interactions between tumour cells, non-tumour cells, and extracellular components that comprise the tumour microenvironment (TME). The majority of TME’s cells are cancer-associated fibroblasts (CAFs), which are crucial in extracellular matrix (ECM) construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour cell motility. CAF subtypes have been identified based on the expression of protein markers. CAFs may act as promoters or suppressors in tumour cells depending on a variety of factors, including cancer stage. Indeed, CAFs have been shown to promote tumour growth, survival and spread, and secretome changes, but they can also slow tumourigenesis at an early stage through mechanisms that are still poorly understood. Stromal–cancer interactions are governed by a variety of soluble factors that determine the outcome of the tumourigenic process. Cancer cells release factors that enhance the ability of fibroblasts to secrete multiple tumour-promoting chemokines, acting on malignant cells to promote proliferation, migration, and invasion. This crosstalk between CAFs and tumour cells has given new prominence to the stromal cells, from being considered as mere physical support to becoming key players in the tumour process. Here, we focus on the concept of cancer as a non-healing wound and the relevance of chronic inflammation to tumour initiation. In addition, we review CAFs heterogeneous origins and markers together with the potential therapeutic implications of CAFs “re-education” and/or targeting tumour progression inhibition.
Human Dental Pulp Stem Cells Differentiate into Cementoid-Like-Secreting Cells on Decellularized Teeth Scaffolds
Authors: Mata Manuel , Peydró Santiago , de Llano José Javier Martín , Sancho-Tello María , Carda Carmen
Published: December 2022

Periodontitis is a common inflammatory disease that in some cases can cause tooth loss. Cementum is a mineralized tissue that forms part of the insertion periodontium and serves to fix the teeth to the alveolar bone. In addition, it acts as a reservoir of different growth and differentiation factors, which regulate the biology of the teeth. Cementogenesis is a complex process that is still under investigation and involves different factors, including dentin sialophosphoprotein (DSPP). In this work we studied the role of surface microtopography in the differentiation of human dental pulp stem cells (hDPSCs) into cementoid-like secreting cells. We cultured hDPSCs on decellularized dental scaffolds on either dentin or cementum surfaces. Cell morphology was evaluated by light and electron microscopy. We also evaluated the DSPP expression by immunohistochemistry. The hDPSCs that was cultured on surfaces with accessible dentinal tubules acquired an odontoblastic phenotype and emitted characteristic processes within the dentinal tubules. These cells synthesized the matrix components of a characteristic reticular connective tissue, with fine collagen fibers and DSPP deposits. The hDPSCs that was cultured on cementum surfaces generated a well-organized tissue consisting of layers of secretory cells and dense fibrous connective tissue with thick bundles of collagen fibers perpendicular to the scaffold surface. Intra- and intercellular deposits of DSPP were also observed. The results presented here reinforce the potential for hDPSCs to differentiate in vitro into cells that secrete a cementoid-like matrix in response to the physical stimuli related to the microtopography of contact surfaces. We also highlight the role of DSPP as a component of the newly formed matrix.
Hydroxychloroquine Mitigates Dilated Cardiomyopathy Phenotype in Transgenic D94A Mice
Authors: Kanashiro-Takeuchi Rosemeire M. , Kazmierczak Katarzyna , Liang Jingsheng , Takeuchi Lauro M. , Sitbon Yoel H. , Szczesna-Cordary Danuta
Published: December 2022

In this study, we aimed to investigate whether short-term and low-dose treatment with hydroxychloroquine (HCQ), an antimalarial drug, can modulate heart function in a preclinical model of dilated cardiomyopathy (DCM) expressing the D94A mutation in cardiac myosin regulatory light chain (RLC) compared with healthy non-transgenic (NTg) littermates. Increased interest in HCQ came with the COVID-19 pandemic, but the risk of cardiotoxic side effects of HCQ raised concerns, especially in patients with an underlying heart condition, e.g., cardiomyopathy. Effects of HCQ treatment vs. placebo (H2O), administered in Tg-D94A vs. NTg mice over one month, were studied by echocardiography and muscle contractile mechanics. Global longitudinal strain analysis showed the HCQ-mediated improvement in heart performance in DCM mice. At the molecular level, HCQ promoted the switch from myosin’s super-relaxed (SRX) to disordered relaxed (DRX) state in DCM-D94A hearts. This result indicated more myosin cross-bridges exiting a hypocontractile SRX-OFF state and assuming the DRX-ON state, thus potentially enhancing myosin motor function in DCM mice. This bottom-up investigation of the pharmacological use of HCQ at the level of myosin molecules, muscle fibers, and whole hearts provides novel insights into mechanisms by which HCQ therapy mitigates some abnormal phenotypes in DCM-D94A mice and causes no harm in healthy NTg hearts.
Melanins from the Lichens Lobaria pulmonaria and Lobaria retigera as Eco-Friendly Adsorbents of Synthetic Dyes
Authors: Rassabina Anna , Khabibrakhmanova Venera , Babaev Vasily , Daminova Amina , Minibayeva Farida
Published: December 2022

Synthetic dyes are widely used in the industry; they are chemically stable, difficult to neutralize, and therefore they are a threat to the environment when released into wastewaters. The dyes have a significant impact on plant performance by impairing photosynthesis, inhibiting growth, and entering the food chain and may finally result in the toxicity, mutagenicity and carcinogenicity of food products. Implementation of the dark piment melanin for the adsorption of the synthetic dyes is a new ecologically friendly approach for bioremediation. The aim of the present work was to study the physico-chemical characteristics of melanins from the lichens Lobaria pulmonaria and Lobaria retigera, analyze their adsorption/desorption capacities towards synthetic dyes, and assess the capacity of melanins to mitigate toxicity of the dyes for a common soil bacterium Bacillus subtilis. Unique chelating properties of melanins determine the perspectives of the use of these high molecular weight polymers for detoxification of xenobiotics.
Rat Hepatocytes Mitigate Cadmium Toxicity by Forming Annular Gap Junctions and Degrading Them via Endosome–Lysosome Pathway
Authors: Yuan Junzhao , Huang Xiaoqian , Zhao Yumeng , Gu Jianhong , Yuan Yan , Liu Zongping , Zou Hui , Bian Jianchun
Published: December 2022

Gap junction protein connexin 43 (Cx43) plays a critical role in gap junction communication in rat hepatocytes. However, those located between hepatocytes are easily internalized following exposure to poisons. Herein, we investigated the potential of buffalo rat liver 3A (BRL 3A) cells to generate annular gap junctions (AGJs) proficient at alleviating cadmium (Cd) cytotoxic injury through degradation via an endosome–lysosome pathway. Our results showed that Cd-induced damage of liver microtubules promoted Cx43 internalization and increased Cx43 phosphorylation at Ser373 site. Furthermore, we established that Cd induced AGJs generation in BRL 3A cells, and AGJs were subsequently degraded through the endosome–lysosome pathway. Overall, our results suggested that Cx43 internalization and the generation of AGJs were cellular protective mechanisms to alleviate Cd toxicity in rat hepatocytes.
Zingerone Attenuates Carfilzomib-Induced Cardiotoxicity in Rats through Oxidative Stress and Inflammatory Cytokine Network
Authors: Alam Mohammad Firoz , Hijri Sami I. , Alshahrani Saeed , Alqahtani Saad S. , Jali Abdulmajeed M. , Ahmed Rayan A. , Adawi Mansour M. , Algassmi Sameeh M. , Shaheen Emad Sayed , Moni Sivakumar S. , Anwer Tarique
Published: December 2022

Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1β, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies.
Effects of Salinity and Temperature on the Flexibility and Function of a Polyextremophilic Enzyme
Authors: Laye Victoria J. , Solieva Shahlo , Voelz Vincent A. , DasSarma Shiladitya
Published: December 2022

The polyextremophilic β-galactosidase enzyme of the haloarchaeon Halorubrum lacusprofundi functions in extremely cold and hypersaline conditions. To better understand the basis of polyextremophilic activity, the enzyme was studied using steady-state kinetics and molecular dynamics at temperatures ranging from 10 °C to 50 °C and salt concentrations from 1 M to 4 M KCl. Kinetic analysis showed that while catalytic efficiency (kcat/Km) improves with increasing temperature and salinity, Km is reduced with decreasing temperatures and increasing salinity, consistent with improved substrate binding at low temperatures. In contrast, kcat was similar from 2–4 M KCl across the temperature range, with the calculated enthalpic and entropic components indicating a threshold of 2 M KCl to lower the activation barrier for catalysis. With molecular dynamics simulations, the increase in per-residue root-mean-square fluctuation (RMSF) was observed with higher temperature and salinity, with trends like those seen with the catalytic efficiency, consistent with the enzyme’s function being related to its flexibility. Domain A had the smallest change in flexibility across the conditions tested, suggesting the adaptation to extreme conditions occurs via regions distant to the active site and surface accessible residues. Increased flexibility was most apparent in the distal active sites, indicating their importance in conferring salinity and temperature-dependent effects.
Increased Oxidative Stress Markers in Acute Ischemic Stroke Patients Treated with Thrombolytics
Authors: Pawluk Hanna , Kołodziejska Renata , Grześk Grzegorz , Woźniak Alina , Kozakiewicz Mariusz , Kosinska Agnieszka , Pawluk Mateusz , Grzechowiak Elżbieta , Wojtasik Jakub , Kozera Grzegorz
Published: December 2022

One of the most common neurological disorders involving oxidative stress is stroke. During a stroke, the balance of redox potential in the cell is disturbed, and, consequently, protein oxidation or other intracellular damage occurs, ultimately leading to apoptosis. The pineal gland hormone, melatonin, is one of the non-enzymatic antioxidants. It not only modulates the perianal rhythm but also has anti-inflammatory properties and protects against stress-induced changes. The focus of this research was to evaluate the concentration of the carbonyl groups and melatonin metabolite in time in patients with acute ischemic stroke that were treated with intravenous thrombolysis. This included a comparison of the functional status of patients assessed according to neurological scales with the control sample comprising healthy people. The studies showed that the serum concentrations of carbonyl groups, which were elevated in patients with ischemic stroke (AIS) in comparison to the control samples, had an impact on the patients’ outcome. A urine concentration of the melatonin metabolite, which was lower in patients than controls, was related to functional status after 24 h from cerebral thrombolysis. It shows that determination of carbonyl groups at different time intervals may be an important potential marker of protein damage in patients with AIS treated with cerebral thrombolysis, and that impaired melatonin metabolism induces a low antioxidant protection. Thus, due to the neuroprotective effects of melatonin, attention should also be paid to the design and conduct of clinical trials and hormone supplementation in AIS patients to understand the interactions between exogenous melatonin and its endogenous rhythm, as well as how these relationships may affect patient outcomes.
Does Potassium (K+) Contribute to High-Nitrate (NO3−) Weakening of a Plant’s Defense System against Necrotrophic Fungi?
Authors: Limami Anis , Hirel Bertrand , Lothier Jérémy
Published: December 2022

In this opinion article, we have analyzed the relevancy of a hypothesis which is based on the idea that in Arabidopsis thaliana jasmonic acid, a (JA)-mediated defense system against necrotrophic fungi is weakened when NO3− supply is high. Such a hypothesis is based on the fact that when NO3− supply is high, it induces an increase in the amount of bioactive ABA which induces the sequestration of the phosphatase ABI2 (PP2C) into the PYR/PYL/RCAR receptor. Consequently, the Ca sensors CBL1/9-CIPK23 are not dephosphorylated by ABI2, thus remaining able to phosphorylate targets such as AtNPF6.3 and AtKAT1, which are NO3− and K+ transporters, respectively. Therefore, the impact of phosphorylation on the regulation of these two transporters, could (1) reduce NO3− influx as in its phosphorylated state AtNPF6.3 shifts to low capacity state and (2) increase K+ influx, as in its phosphorylated state KAT1 becomes more active. It is also well known that in roots, K+ loading in the xylem and its transport to the shoot is activated in the presence of NO3−. As such, the enrichment of plant tissues in K+ can impair a jasmonic acid (JA) regulatory pathway and the induction of the corresponding biomarkers. The latter are known to be up-regulated under K+ deficiency and inhibited when K+ is resupplied. We therefore suggest that increased K+ uptake and tissue content induced by high NO3− supply modifies the JA regulatory pathway, resulting in a weakened JA-mediated plant’s defense system against necrotrophic fungi.
Rhizophagus irregularis and Azotobacter chroococcum Uphold Eggplant Production and Quality under Low Fertilization
Authors: Sharma Meenakshi , Delta Anil , Brar Navjot , Yadav Alpa , Dhanda Parmdeep , Baslam Marouane , Kaushik Prashant
Published: December 2022

Microorganisms are essential parts of soil and play an important role in mediating many processes and influencing plant health. Arbuscular mycorrhizal fungi (AMF) and nitrogen-fixing bacteria (NFB), the most common of such microorganisms, can benefit plants by enhancing the nutrient-absorbing ability of roots through bio-inoculation, also called biofertilization. Different methods have been tested and proven to be effective in the enhancement of soil nutrient availability. However, the effects of increased application of biological methods with minimal chemical fertilizers are still inconsistent. In this 2-year of fixed-point greenhouse test, we aimed to evaluate the impact of AMF (Rhizophagus irregularis) and/or NFB (Azotobacter) on growth, quality, and yield of eggplants under different N levels. Data showed that biofertilizer application with reduced chemical fertilizer had the highest impact on eggplant performance and yield. Indeed, low chemical fertilizers combined with adequate amounts of biofertilizers produced a higher plant height, length and width of leaves, dry matter, number of fruits per plant with better morphology, total yield per plant, and total soluble solids (TSS), suggesting that the use of Azotobacter and R. irregularis as biofertilizers could substantially reduce the use of chemical fertilizers without impairing the quality and yield of eggplant.
A PPARG Splice Variant in Granulosa Cells Is Associated with Polycystic Ovary Syndrome
Authors: Shi Chao-Yi , Xu Jing-Jing , Li Cheng , Yu Jia-Le , Wu Yan-Ting , Huang He-Feng
Published: December 2022

Background: We explored whether there are splice variants (SVs) of peroxisome proliferator-activated receptor-gamma (PPARG) in polycystic ovary syndrome (PCOS) patients and its relationship with clinical features and KGN cell functions. Methods: We performed a study involving 153 women with PCOS and 153 age-matched controls. One type of PPARG SV was detected by SMARTer RACE. The correlations between PPARG SV expression levels, clinical features, and KGN cell functions were analyzed. The effect of the PPARG SV on the expression of important genes in metabolism-related pathways was explored by PCR array. Results: The expression of the PPARG SV in PCOS patients was significantly higher than that in the controls. Clinical features were more significant in the PCOS group with the SV. Compared with overexpression of PPARG, the overexpression of the PPARG SV inhibited the proliferation, migration, and apoptosis of KGN cells in vitro. The genes related to the PPARG SV were mainly involved in lipid metabolism. Conclusion: While granulosa cells contribute greatly to the development of follicles, our results suggest that the identified PPARG SV may regulate cell proliferation, migration, and apoptosis in granulosa cells, which could partially explain the mechanisms of ovulation dysfunction in PCOS. Further investigation of the utility of this PPARG SV as a biomarker for PCOS is warranted.
Leukocyte Count Predicts Carotid Artery Stenosis in Men with Ischemic Stroke: Sub Study of the Preventive Antibiotics in Stroke Study (PASS)
Authors: van Velzen Twan J. , Stolp Jeffrey , Westendorp Willeke F. , Roos Yvo B. W. E. M. , van de Beek Diederik , Nederkoorn Paul J.
Published: December 2022

Background: Inflammation is important in the development of atherosclerosis. Research suggested sex-dependent differences for the value of inflammatory markers for risk stratification of stroke patients with internal carotid artery stenosis (ICAS). We investigated whether leukocytes and thrombocytes were associated with ≥50% ICAS in acute stroke and whether this was sex-dependent. Patients included in the Preventive Antibiotics in Stroke Study (PASS) were used. PASS is a randomized controlled trial that randomized between four days of preventive ceftriaxone intravenously or standard stroke care alone. It investigated whether ceftriaxone could improve functional outcome at three months after stroke. Methods: Patients included in PASS were evaluated for the predictive value of leukocytes and thrombocytes for ICAS. Ischemic stroke and TIA patients were selected out of PASS patients. Logistic regression analysis was performed adjusting for NIHSS and other covariates. Results: 2550 patients were included in PASS. 1413 of 2550 patients (55%) were evaluated in this sub study. Female patients showed a mean of 8.55 × 109/L for leukocytes and 259 × 109/L for thrombocytes. Men showed a mean of 8.29 × 109/L for leukocytes and 224 × 109/L for thrombocytes. Multivariate logistic regression analysis showed that leukocytes were independently associated with ICAS ≥ 50% in male patients (OR 1.094, p = 0.008), but not in female patients (OR 1.041, p = 0.360). Thrombocytes were not associated with ICAS. Conclusions: We conclude that blood leukocyte count independently predicts ICAS in men after acute stroke, but not in women. Clinical Trial unique identifier: ISRCTN66140176.
Cardiac Troponins for the Clinical Management of Patients with Claudication and without Cardiac Symptoms
Authors: Mouselimis Dimitrios , Hagstotz Saskia , Lichtenberg Michael , Donas Konstantinos P. , Heinrich Ulrike , Avranas Konstantinos , Dimitriadis Zisis , Blessing Erwin , Langhoff Ralf , Frey Norbert , Katus Hugo A. , Korosoglou Grigorios
Published: December 2022

Many patients with peripheral arterial disease (PAD) exhibit undiagnosed obstructive coronary artery disease. We aim to identify the patients with lifestyle limiting claudication due to PAD and without cardiac symptoms, requiring coronary revascularization based on high-sensitive troponin T (hsTnT) values. We assessed hsTnT in consecutive patients referred for elective endovascular treatment due to claudication [Rutherford categories (RC) 2 & 3] between January 2018 and December 2021. Diagnostic work-up by non-invasive imaging and, if required, cardiac catheterization was performed according to clinical data, ECG findings and baseline hsTnT. The occurrence of cardiac death, myocardial infarction or urgent revascularization during follow-up was the primary endpoint. Of 346 patients, 14 (4.0%) exhibited elevated hsTnT ≥ 14 ng/L, including 7 (2.0%) with acute myocardial injury by serial hsTnT sampling. Coronary revascularization by percutaneous coronary intervention was necessary in 6 of 332 (1.5%) patients with normal versus nine of 14 (64.3%) patients with elevated hsTnT (p < 0.001). During 2.4 ± 1.4 years of follow-up, 20 of 286 (7.0%) patients with normal versus four of 13 (30.8%) with elevated hsTnT at baseline reached the composite primary endpoint (p = 0.03 by log-rank test). In conclusion, elevated troponins in cardiac asymptomatic patients with claudication modify subsequent cardiac management and may increase the need for closer surveillance and more aggressive conservative management in polyvascular disease.
Risk Factors, Radiological and Clinical Outcomes in Subclinical and Clinical Pituitary Apoplexy
Authors: Biagetti Betina , Sarria-Estrada Silvana , Cordero Asanza Esteban , Chaachou-Charradi Anas , Ng-Wong Yiken , Cicuendez Marta , Hernandez Irene , Rojano-Toimil Alba , Costa Pilar , Martinez-Saez Elena , Casteràs Anna , Simò Rafael
Published: December 2022

Background: Pituitary apoplexy (PA) can be symptomatic, namely acute apoplexy (APA), or asymptomatic or subclinical (SPA). Objective: To describe the clinical characteristics and evolution of the patients with APA compared to SPA Patients and methods: Retrospective, longitudinal database analysis. Results: We identified 58 patients with PA, and 37 accomplished the inclusion criteria (17 men, median age 47.7 years). A total of 29 (78.4%) had APA (17 underwent surgery, and 12 were conservatively managed), and 8 (21.6%) had SPA. The presence of non-functioning pituitary adenoma (NFPA) odds ratio (OR): 29.36 (95% confidence interval (CI): 1.86–462.36) and the largest size OR 1.10 (95% CI: 1.01–1.2) elevated the risk of having surgery. Hypopituitarism developed in 35.1% without significant differences between APA and SPA. In non-surgical patients, adenoma volume shrunk spontaneously at one year magnetic resonance imaging (MRI), without statistical differences between the conservatively treated and SPA group. Conclusions: APA is more frequent in larger NFPAs, and this subset of patients has a higher risk of surgery. Hypopituitarism is quite frequent even in patients with SPA, and, therefore, long-term follow-up is mandatory. In the non-surgical group, the pituitary tumour shrinkage is clinically relevant after one year of PA. Consequently, surgery indication in NFPA should be delayed and reassessed if patients remain asymptomatic.
The Peripandemic Impact of the First Wave of the COVID-19 Pandemic on Management and Prognosis of ST-Segment Elevation Myocardial Infarction in China
Authors: Yang Hongbo , Luo Lingfeng , Cao Jiatian , Song Yanan , Weng Xueyi , Zhang Feng , Zhou Xiaofeng , Huo Yong , Qian Juying , Zheng Yan , Huang Zheyong , Ge Junbo
Published: December 2022

Background: Rapid reperfusion of ST-segment elevation myocardial infarction (STEMI) has been challenging during the coronavirus disease 2019 (COVID-19) outbreak. Whether and to what degree there will be a residual impact when the COVID-19 pandemic has passed is unclear. Methods: This nationwide retrospective study was based on electronic records of STEMI patients registered in the Chinese Cardiovascular Association Database. Results: We analyzed 141,375 STEMI patients (including 4871 patients in Hubei province, where 80% of COVID-19 cases in China occurred in 2019–2020) during the pre-outbreak (23 October 2019–22 January 2020), outbreak (23 January 2020–22 April 2020), and post-outbreak (23 April 2020–22 July 2020) periods. In the post-outbreak period in Hubei province, the increased in-hospital mortality dropped to become insignificant (adjusted odds ratio compared to the pre-outbreak level (aOR) 1.40, [95% confidential interval (CI): 0.97–2.03]) and was lower than that in the outbreak period (1.62 [1.09–2.41]). The decreased odds of primary percutaneous coronary intervention (PCI) (0.73 [0.55–0.96]) and timely reperfusion (0.74 [0.62–0.88]) persisted, although they were substantially improved compared to the outbreak period (aOR of primary PCI: 0.23 [0.18–0.30] and timely reperfusion: 0.43 [0.35–0.53]). The residual impact of COVID-19 on STEMI in the post-outbreak period in non-Hubei provinces was insignificant. Conclusions: Residual pandemic impacts on STEMI management persisted after the first wave of the COVID-19 outbreak in Hubei province, the earliest and hardest hit area in China.
Hypersensitivity to Biological Treatments in Juvenile Idiopathic Arthritis: How Should It Be Managed?
Authors: Kasap Cuceoglu Muserref , Basaran Ozge , Soyer Ozge , Ozen Seza
Published: December 2022

Juvenile idiopathic arthritis (JIA) is one of the most frequent diseases in the practice of pediatric rheumatology. JIA treatments have been modified and improved with the use of biological drugs along with technological innovations. However, different types of hypersensitivity reactions to biological drugs have also been reported. Anaphylaxis and infusion reactions occurring during the intravenous infusion require a critical approach in the acute period. On the other hand, the detection of drug-related late-type reactions and the development of antibodies to the agent highlight the need for an understanding of the drug-induced etiology to prevent the patient from continuing the treatment with the culprit drug. The chronic disease process, concomitant immune dysregulation, and multiple drug use may result in these hypersensitivity reactions. In this review, the hypersensitivity reactions to the biological treatments used in patients with juvenile idiopathic arthritis and the management of these conditions are discussed.
Conversion to mTOR-Inhibitors Plus IV Immunoglobulins in Kidney-Transplant Recipients with BKV Infection: A Retrospective Comparative Study
Authors: Vela Carla , Jouve Thomas , Chevallier Eloi , Imerzoukene Farida , Germi Raphaële , Le Marechal Marion , Truffot Aurélie , Fiard Gaëlle , Janbon Bénédicte , Giovannini Diane , Malvezzi Paolo , Rostaing Lionel , Noble Johan
Published: December 2022

BK virus-associated nephropathy (PvAN) increases the risk of graft failure justifying treatment. Conversion to mammalian target of rapamycin inhibitors (mTORi) and Human polyclonal immunoglobulins (IVIg) could prevent the risk of PvAN. Our retrospective study assessed the efficacy of mTORi associated with IVIg therapy (mTORi±IVIg group) versus standard immunosuppression reduction to clear BKV DNAemia. Among forty-three kidney-transplanted patients with positive BKV DNAemia, we included twenty-six patients in the mTORi±IVIg group and reduced immunosuppression therapy for seventeen patients. We focused on BKV DNAemia clearance on the first-year. Renal function, rejection rate, evolution to PvAN, and complications of immunosuppression were assessed. BKV DNAemia decreased faster and significantly in the control group as compared to the mTORi±IVIg group (p < 0.001). Viral clearance was significantly higher in the control group compared to the mTORi±IVIg group (88% vs. 58%; p = 0.033). Death-censored graft loss, rejection rates and kidney-graft function at 12 months did not significantly differ. Multivariate analyses significantly associated BKV DNAemia clearance with reducing immunosuppression (OR = 0.11 (0.06–0.9), p = 0.045), female kidney donor (OR = 0.10 (0.01–0.59/)], p = 0.018) and time to first DNAemia, (OR = 0.88 (0.76–0.96), p = 0.019). In our study, the standard treatment for BKV DNAemia had better outcomes than an mTORi±IVIg conversion.
Glaucoma Incidence and Progression in Diabetics: The Canary Islands Study Using the Laguna ONhE Application
Authors: Gonzalez-Hernandez Marta , Gonzalez-Hernandez Daniel , Betancor-Caro Nisamar , Guedes-Guedes Isabel , Guldager Morten Kirk , Gonzalez de la Rosa Manuel
Published: December 2022

Background: Laguna ONhE provides a globin distribution function (GDF), in which a glaucoma discriminator based on deep learning plays an important role, and there is also an optimized globin individual pointer (GIP) for progression analysis. Methods: Signs of optic nerve glaucoma were identified in 1,124,885 fundus images from 203,115 diabetics obtained over 15 years and 117,813 control images. Results: A total of 743,696 images from 313,040 eyes of 173,661 diabetics were analysed. Some exclusions occurred due to excessive illumination, poor quality, or the absence of optic discs. Suspicion of glaucoma was reported in 6.70%, for an intended specificity of 99% (GDF < −15). More signs of glaucoma occur in diabetics as their years of disease increase, and after age 60, compared to controls. The GIP detected progression (p < 0.01) in 2.59% of cases with 4 controls and in 42.6% with 14 controls was higher in cases with lower GDF values. The GDF was corrected for the disc area and proved to be independent of it (r = 0.001925; p = 0.2814). Conclusions: The GDF index suggests a higher and increasing glaucoma probability in diabetics over time. Doubling the number of check-ups from four to eight increases the ability to detect GIP index progression by a factor of 5.
Stepwise Reduction of Mycophenolate Mofetil with Conversion to Everolimus for the Treatment of Active BKV in Kidney Transplant Recipients: A Single-Center Experience in Vietnam
Authors: Kien Truong Quy , Kien Nguyen Xuan , Thang Le Viet , Nghia Phan Ba , Van Diem Thi , Duc Nguyen Van , Ha Do Manh , Dung Nguyen Thi Thuy , Ha Nguyen Thi Thu , Loan Vu Thi , Vinh Hoang Trung , Manh Bui Van , Su Hoang Xuan , Tien Tran Viet , Rostaing Lionel , Toan Pham Quoc
Published: December 2022

Background: No specific antiviral drug can effectively treat BKV reactivation after kidney transplantation. Thus, we evaluated stepwise-reduced immunosuppression to treat BKV reactivation. Methods: 341 kidney-transplant recipients were monitored for BKV infection (BKV-viremia, BKV-viruria). Positive samples with a significant virus load were nested PCR-genotyped in the VP1 region. In 97/211 patients presenting BKV viremia ≥104 copies/mL and/or BKV viruria ≥107 copies/mL, or BKV-nephropathy immunosuppression (i.e., mycophenolate mofetil [MMF]) was reduced by 50%. If viral load did not decrease within 28 days, MMF dose was further reduced by 25%, although calcineurin-inhibitor (CNI) therapy remained unchanged. If BKV viral load did not decrease within another 28 days, MMF was withdrawn and replaced by everolimus combined with reduced CNIs. Results: Only 41/97 BKV (+) cases completed the 6-month follow-up. Among these, 29 (71%) were in the BKV-I group and 12 (29%) were in BKV-IV. BKV viruria and BKV viremia were significantly decreased from 9.32 to 6.09 log10 copies/mL, and from 3.59 to 2.45 log10 copies/mL (p < 0.001 and p = 0.024, respectively). 11/32 (34.4%) patients were cleared of BKV viremia; 2/32 (6.3%) patients were cleared of BKV in both serum and urine, and 9/9 (100%) only had BKV viruria but did not develop BKV viremia. eGFR remained stable. No patient with BKV-related nephropathy had graft loss. There was a significant inverse relationship between changes in eGFR and serum BKV load (r = −0.314, p = 0.04). Conclusions: This stepwise immunosuppressive strategy proved effective at reducing BKV viral load in kidney transplant recipients that had high BKV loads in serum and/or urine. Renal function remained stable without rejection.