bluuebunny/crossref_metadata_2025 huggingface dataset:
Seattle Protocol Is More Effective in Detection of Dysplasia Compared to Technology-Assisted Targeted Biopsies in Patients with Barrett’s Esophagus
Authors: Peleg Noam , Ollech Jacob , Shamah Steven , Sapoznikov Boris
Published: March 2023

Background and aims: With the development of narrow-band imaging (NBI) in the endoscopic evaluation of patients with Barrett’s esophagus (BE), the role of random biopsies according to the Seattle protocol (SP) has been questioned. We aim to compare the utility of advanced imaging to SP in patients with BE. Methods: A prospective cohort of patients with proven BE was retrospectively analyzed. All biopsies were reviewed by an expert GI pathologist. Advanced imaging was tandemly used with SP in each endoscopic procedure. Results: A total of 155 out of 340 patients (45.5%) with BE were diagnosed with dysplasia during a median follow-up of 4.7 years (IQR 3.4–6.1 years) and were part of the statistical analysis. A total of 82 patients had a diagnosis of dysplasia at presentation, whereas 84 patients developed dysplasia during follow up. A total of 67 out of 82 patients with dysplasia at presentation (81.7%), and 65 out of 84 patients that were diagnosed with dysplasia during follow-up (77.4%) were diagnosed using SP. In addition, whereas all the events of EAC were diagnosed using targeted biopsies, 57.1% of the events of HGD and 86.3% of LGD were diagnosed using SP. Conclusion: Our findings demonstrate the significance of SP in the detection of low- and high-grade dysplasia in patients with BE. SP should remain the mainstay of endoscopic surveillance in this population.
Appraisal of Intraoperative Adverse Events to Improve Postoperative Care
Authors: Gawria Larsa , Jaber Ahmed , Ten Broek Richard Peter Gerardus , Bernasconi Gianmaria , Rosenthal Rachel , Van Goor Harry , Dell-Kuster Salome
Published: March 2023

Background: Intraoperative adverse events (iAEs) are associated with adverse postoperative outcomes and cause a significant healthcare burden. However, a critical appraisal of iAEs is lacking. Considering the details of iAEs could benefit postoperative care. We comprehensively analyzed iAEs in a large series including all types of operations and their relation to postoperative complications. Methods: All patients enrolled in the multicenter ClassIntra® validation study (NCT03009929) were included in this analysis. The surgical and anesthesia team prospectively recorded all iAEs. Two researchers, blinded to each other’s ratings, appraised all recorded iAEs according to their origin into four categories: surgery, anesthesia, organization, or other, including subcategories such as organ injury, arrhythmia, or instrument failure. They further descriptively analyzed subcategories of all iAEs. Postoperative complications were assessed using the Comprehensive Complication Index (CCI®), a weighted sum of all postoperative complications according to the Clavien–Dindo classification. The association of iAE origins in addition to the severity grade of ClassIntra® on CCI® was assessed with a multivariable mixed-effects generalized linear regression analysis. Results: Of 2520 included patients, 778 iAEs were recorded in 610 patients. The origin was surgical in 420 (54%), anesthesia in 283 (36%), organizational in 34 (4%), and other in 41 (5%) events. Bleeding (n = 217, 28%), hypotension (n = 118, 15%), and organ injury (n = 98, 13%) were the three most frequent subcategories in surgery and anesthesia, respectively. In the multivariable mixed-effect analysis, no significant association between the origin and CCI® was observed. Conclusion: Analyzing the type and origin of an iAE offers individualized and contextualized information. This detailed descriptive information can be used for targeted surveillance of intra- and postoperative care, even though the overall predictive value for postoperative events was not improved by adding the origin in addition to the severity grade.
Analysis of Clinical Factors Associated with Medical Burden and Functional Status in Pyogenic Spine Infection
Authors: Jeon Seongmin , Yu Dongwoo , Bae Sang Woon , Kim Sang Woo , Jeon Ikchan
Published: March 2023

Background and purpose: Pyogenic spinal infection (PSI) has recently been on the rise due to aging and increasing degenerative spinal disease related procedures. PSI requires long-term antibiotic treatment and is followed by sustained functional disability even after successful treatment. This study aimed to analyze the clinical factors associated with medical burden and functional status of PSI. Methods: This retrospective study involved patients with non-postoperative PSI of thoraco-lumbo-sacral area in a single tertiary hospital. The length/cost of hospitalization with an antibiotic therapy and severity of back pain using the short form 36 (SF-36) were defined as the medical burden and functional status, respectively. We analyzed the clinical factors associated with medical burden and functional status. Results: We enrolled 142 patients (91 males and 51 females). The length and cost of hospitalization were 55.56 ± 27.09 (7–172) days and $14,070.17 ± 9289.39 (1611.87–48,722.35), respectively. A recurrence rate of 7.7% (11/142) and significant improvement of SF-36 at six months after completion of antibiotic treatment were noted (p < 0.05). Procedure-related (OR 2.702), C-reactive protein (CRP; OR 1.062), bacteremia (OR 4.966), additional surgical treatment (OR 6.524), recurrence (OR 12.453), and paraspinal abscess (OR 5.965) for above-average length of hospitalization were observed; female (OR 4.438), CRP (OR 1.071), bacteremia (OR 4.647), additional surgical treatment (OR 6.737), recurrence (OR 22.543), and extent of lesion (OR 1.431) for above-average cost of hospitalization; leg weakness (OR 15.966), white blood cell (WBC; OR 1.116), Charlson’s comorbidity index (CCI, OR 1.485), and identification of causative bacteria (OR 2.913) for below-average initial SF-36 were observed; leg weakness (OR 7.975) and WBC (OR 1.094) for below-average 6-month SF-36 were the statistically significant clinical factors in the multivariable logistic regression analysis (p < 0.05). Conclusion: Recurrence and leg weakness were identified as the most important clinical factors for medical burden and functional status in PSI, respectively. We think that it is necessary to actively suppress recurrence and manage neurological deficits for decreasing medical burden and achieving favorable functional outcome in the treatment of PSI.
Synergetic Effect of Electrical and Topographical Cues in Aniline Trimer-Based Polyurethane Fibrous Scaffolds on Tissue Regeneration
Authors: Zhang Yinglong , Tang Jiajing , Fang Wei , Zhao Qing , Lei Xiaoyu , Zhang Jinzheng , Chen Jieqiong , Li Yubao , Zuo Yi
Published: March 2023

Processibility and biodegradability of conductive polymers are major concerns when they are applied to tissue regeneration. This study synthesizes dissolvable and conductive aniline trimer-based polyurethane copolymers (DCPU) and processes them into scaffolds by using electrospinning with different patterns (random, oriented, and latticed). The effects of topographic cue changes on electrical signal transmission and further regulation of cell behaviors concerning bone tissue are researched. Results show that DCPU fibrous scaffolds possessed good hydrophilicity, swelling capacity, elasticity, and fast biodegradability in enzymatic liquid. In addition, the conductivity and efficiency of electrical signal transmission can be tuned by changing the surface’s topological structure. Among them, oriented DCPU scaffolds (DCPU-O) showed the best conductivity with the lowest ionic resistance value. Furthermore, the viability and proliferation results of bone mesenchymal stem cells (BMSCs) demonstrate a significant increase on three DCPU scaffolds compared to AT-free scaffolds (DPU-R). Especially, DCPU-O scaffolds exhibit superior abilities to promote cell proliferation because of their unique surface topography and excellent electroactivity. Concurrently, the DCPU-O scaffolds can synergistically promote osteogenic differentiation in terms of osteogenic differentiation and gene expression levels when combined with electrical stimulation. Together, these results suggest a promising use of DCPU-O fibrous scaffolds in the application of tissue regeneration.
Effect of Quadratus Lumborum Block on Pain and Stress Response after Video Laparoscopic Surgeries: A Randomized Clinical Trial
Authors: Brandão Virna Guedes Alves , Silva Gustavo Nascimento , Perez Marcelo Vaz , Lewandrowski Kai-Uwe , Fiorelli Rossano Kepler Alvim
Published: March 2023

Background: There are many surgical and anesthetic factors that affect pain and the endocrine–metabolic response to trauma. The ability of anesthetic agents and neuronal blockade to modify the response to surgical trauma has been widely studied in the last few years. Objective: To evaluate if the anterior quadratus lumborum block contributes to improved surgical recovery, using as parameters analgesia, pulmonary function and neuroendocrine response to trauma. Methods: We carried out a prospective, randomized, controlled, and blinded study, in which 51 patients scheduled for laparoscopic cholecystectomy. Patients were randomly selected and assigned to 2 groups. The control group received balanced general anesthesia and venous analgesia, and the intervention group was treated under general, venous analgesia and anterior quadratus lumborum block. The parameters evaluated were: demographic data, postoperative pain, respiratory muscle pressure and inflammatory response to surgical stress with the plasma dosage of IL-6 (Interleukin 6), CRP (C-Reactive protein) and cortisol. Results: Anterior quadratus lumborum block induced the slowing of IL-6 cytokine production and a decrease in cortisol release. This effect was accompanied by the significant reduction of postoperative pain scores. Conclusion: Anterior quadratus lumborum block is an important strategy for analgesia in abdominal laparoscopic surgery and contributes to reducing the inflammatory response to surgical trauma with an early return of preoperative baseline physiological functions.
Strategies of Endoscopic Management of Upper Tract Urothelial Carcinoma among Endourologists: A Global Survey
Authors: Shvero Asaf , Carmona Orel , Zilberman Dorit E. , Dotan Zohar A. , Haifler Miki , Kleinmann Nir
Published: March 2023

Up-to-date guidelines on the management of upper tract urothelial carcinoma (UTUC) are continuously published. We aim to assess the variability of diagnosis and treatment strategies in the endoscopic management of UTUC and adherence to European Association of Urology and National Comprehensive Cancer Network guidelines. A 15-question survey was designed to query practitioners on approaches to clinical practice and knowledge about endoscopic treatment indications and techniques. It was emailed to all members of the Endourologic Society through the society’s office, and to all Israeli non-member endourologists. Eighty-eight urologists participated in the survey. Adherence to guidelines on indications for endoscopic management was only 51%. Most of the survey respondents (87.5%) use holmium laser for tumor ablation, and ~50% use forceps for biopsy while the other half use baskets. Only 50% stated that they would use Jelmyto® for specific indications. Most (80%) indicated that they repeat the ureteroscopy 3 months after the first one, and 52.3% continue with follow-up ureteroscopy every 3 months during the first year after diagnosis. There is vast variability among endourologists in the technical aspects of UTUC, the indications for endoscopic management, and adherence to the available guidelines for managing UTUC.
Comprehensive Evaluation of Ecological-Economic Value of Guangxi Based on Land Consolidation
Authors: Zhang Lili , Hu Baoqing , Zhang Ze , Liang Gaodou , Huang Simin
Published: March 2023

The “Two Mountains” concept of “green water and green mountains are gold and silver mountains” plays an important value-oriented role in the ecological transformation of land consolidation. In this study, Guangxi was divided into five consolidation zones in combination with relevant policies, and the evolution characteristics and change intensity of ecological-economic values before and after the three phases of land consolidation in Guangxi and each consolidation zone in 2010, 2015 and 2020 were explored by bivariate spatial autocorrelation, standard deviation ellipse, and linear regression equation. Finally, the ecological-economic values of each consolidation area, which were obtained separately, were standardized by z-score, and the standardized results were matched by dividing quadrants for analysis. The ecological-economic value matching states of each consolidation area are ecological-economic value coordinated development type (central karst basin area of Guangxi), ecological value imbalance type (southeast plain area and coastal hilly plain area of Guangxi), economic value imbalance type (northwest mountain area of Guangxi) and ecological-economic value low imbalance type (northeast hilly mountain area of Guangxi). The study aims to provide a theoretical basis for the planning and differentiated management of land consolidation in Guangxi and promote the ecological-economic value transformation of the region.
Assessing Livestock Grazing Distribution in Communal Rangelands of the Eastern Cape, South Africa: Towards Monitoring Livestock Movements in Rangelands
Authors: Gusha Bukho , Palmer Anthony R. , Zondani Thantaswa C.
Published: March 2023

In the past, rangelands were managed in a semi-nomadic manner, where pastoralists would distribute livestock to different parts of the rangeland depending on the availability of forage. However, understanding how livestock use rangelands has not been a subject of many studies as the devices to monitor livestock were not available. The objective of this study was to assess livestock grazing distribution in communal rangeland of the Eastern Cape in South Africa in order to improve livestock grazing. The study used Global Positioning Systems (GPS) that were placed on six animals including three sheep and three cattle, selected randomly from participating households. The GPS collars recorded the geographic position of the areas where animals were grazing, at five-minute intervals during the wet and dry season. Grass species composition was surveyed using line transects on areas where livestock grazing occurred. The study further identified three production domains, which were separated by bound polygons on Google Earth Pro to extract MODIS EVI where livestock grazing occurred. Livestock grazing distribution was analysed using T-LoCoH installed in R. The results revealed that both sheep and cattle spent most of their time grazing in areas associated with human features. The dominant grass species were Hyperrenia hirta and Eragrostis plana, suggesting a negative impact of the current livestock grazing distribution. Possible explanations of the current grazing distribution might be that these areas are close to homesteads and provide grazing lawns that contain a high nitrogen content. This study will help in providing an informed basis for the development of South African communal rangeland policies for effective livestock management.
Association between Inflammatory Bowel Disease and Subsequent Development of Restless Legs Syndrome and Parkinson’s Disease: A Retrospective Cohort Study of 35,988 Primary Care Patients in Germany
Authors: Loosen Sven H. , Yaqubi Kaneschka , May Petra , Konrad Marcel , Gollop Celina , Luedde Tom , Kostev Karel , Roderburg Christoph
Published: March 2023

Background: In addition to the gastrointestinal symptoms, inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is associated with extraintestinal manifestations, including neurological disorders, which are gaining increasing attention due to a recently increased focus on the gut–brain axis. Here we aim to evaluate the association between IBD and restless legs syndrome (RLS) as well as Parkinson’s disease (PD) in a cohort of primary care patients in Germany. Methods: The study included 17,994 individuals with a diagnosis of IBD (7544 with CD and 10,450 with UC) and 17,994 propensity-score-matched individuals without IBD from the Disease Analyzer database (IQVIA). An initial diagnosis of RLS or PD was assessed as a function of IBD. Associations between CD and UC with RLS and PD were analyzed using Cox regression models. Results: During the 10-year observation period, 3.6% of CD patients vs. 1.9% of matched non-IBD pairs (p < 0.001) and 3.2% of UC patients vs. 2.7% of matched pairs (p < 0.001) were diagnosed with RLS. The results were confirmed by Cox regression analysis, which showed a significant association between UC (HR: 1.26; 95% CI: 1.02–1.55) and CD (HR: 1.60; 95% CI: 1.23–2.09) and subsequent RLS. The incidence of PD in IBD patients was not significantly increased. However, we observed a non-significant trend towards a higher incidence of PD in male patients with CD but not UC (HR: 1.55; 95%CI: 0.98–2.45, p = 0.064). Conclusions: The present analysis suggests a significant association between IBD and the subsequent development of RLS. These findings should stimulate further pathophysiological research and may eventually lead to specific screening measures in patients with IBD.
Microstructure and Tensile Property of Hybrid Fabricated Ti-6Al-4V Alloy by Investment Casting and Laser Additive Manufacturing
Authors: Zong Xiao , Ji Zhijun , Zhao Zijun , Feng Xin , Ding Xianfei , Nan Hai
Published: March 2023

Hybrid manufacturing of titanium alloys by investment casting and laser additive manufacturing (LAM) combines the advantages of both techniques and can further reduce the cost. In this study, microstructure evolution in the bonding zone and tensile property of the hybrid manufacturing Ti-6Al-4V alloy are carefully investigated. Results show that the hybrid sample consists of the LAM zone, the heat-affected zone (HAZ) and the base casting zone. A transition zone (TZ) forms within the HAZ close to the fusion line. Grains in the bottom of the LAM zone are much finer with a mixture of equiaxed grain and small columnar grain, and gradually coarsening to fully large columnar grains. Typical ultra-fine basket-wave microstructure forms in the LAM zone. In the TZ, the microstructure gradually changes from a fine basket-wave microstructure to a coarsened bimodal microstructure. The highest microhardness of the bonding zone is 491 HV. The fracture of the hybrid sample occurs in the casting half, and the tensile strength of the hybrid sample reaches (821 ± 31) MPa, which is higher than that of the pure casting sample ((778 ± 22) MPa). However, the elongation of the hybrid sample ((8.0 ± 0.5)%) is lower than that of the pure casting sample ((10.0 ± 1.7)%).
Discovery of Novel EGFR Inhibitor Targeting Wild-Type and Mutant Forms of EGFR: In Silico and In Vitro Study
Authors: Todsaporn Duangjai , Zubenko Alexander , Kartsev Victor , Aiebchun Thitinan , Mahalapbutr Panupong , Petrou Anthi , Geronikaki Athina , Divaeva Liudmila , Chekrisheva Victoria , Yildiz Ilkay , Choowongkomon Kiattawee , Rungrotmongkol Thanyada
Published: March 2023

Targeting L858R/T790M and L858R/T790M/C797S mutant EGFR is a critical challenge in developing EGFR tyrosine kinase inhibitors to overcome drug resistance in non-small cell lung cancer (NSCLC). The discovery of next-generation EGFR tyrosine kinase inhibitors (TKIs) is therefore necessary. To this end, a series of furopyridine derivatives were evaluated for their EGFR-based inhibition and antiproliferative activities using computational and biological approaches. We found that several compounds derived from virtual screening based on a molecular docking and solvated interaction energy (SIE) method showed the potential to suppress wild-type and mutant EGFR. The most promising PD13 displayed strong inhibitory activity against wild-type (IC50 of 11.64 ± 1.30 nM), L858R/T790M (IC50 of 10.51 ± 0.71 nM), which are more significant than known drugs. In addition, PD13 revealed a potent cytotoxic effect on A549 and H1975 cell lines with IC50 values of 18.09 ± 1.57 and 33.87 ± 0.86 µM, respectively. The 500-ns MD simulations indicated that PD13 formed a hydrogen bond with Met793 at the hinge region, thus creating excellent EGFR inhibitory activity. Moreover, the binding of PD13 in the hinge region of EGFR was the major determining factor in stabilizing the interactions via hydrogen bonds and van der Waals (vdW). Altogether, PD13 is a promising novel EGFR inhibitor that could be further clinically developed as fourth-generation EGFR-TKIs.
Alkali-Etched NiCoAl-LDH with Improved Electrochemical Performance for Asymmetric Supercapacitors
Authors: Hou Liyin , Zhou Xufeng , Kong Lina , Ma Zhipeng , Su Li , Liu Zhaoping , Shao Guangjie
Published: March 2023

Hydrotalcite, first found in natural ores, has important applications in supercapacitors. NiCoAl-LDH, as a hydrotalcite-like compound with good crystallinity, is commonly synthesized by a hydrothermal method. Al3+ plays an important role in the crystallization of hydrotalcite and can provide stable trivalent cations, which is conducive to the formation of hydrotalcite. However, aluminum and its hydroxides are unstable in a strong alkaline electrolyte; therefore, a secondary alkali treatment is proposed in this work to produce cation vacancies. The hydrophilicity of the NiCoAl-OH surface with cation vacancy has been greatly improved, which is conducive to the wetting and infiltration of electrolyte in water-based supercapacitors. At the same time, cation vacancies generate a large number of defects as active sites for energy storage. As a result, the specific capacity of the NiCoAl-OH electrode after 10,000 cycles can be maintained at 94.1%, which is much better than the NiCoAl-LDH material of 74%.
Preparation of Molybdenum Disulfide with Different Nanostructures and Its Adsorption Performance for Copper (Ⅱ) Ion in Water
Authors: Yao You-Zhi , Shi Yong-Jie , Hu Kun-Hong
Published: March 2023

The environmental problems in the world are attracting increasing amounts of attention, and heavy metal pollution in the water has become one of the focuses of the ecological environment. Molybdenum disulfide (MoS2) has excellent adsorption performance because of its extremely high specific surface area and unique active site structure, which has attracted an increasing amount of attention in the field of heavy metal disposal in various types of water. In this paper, two sorts of MoS2 nanoparticles, spherical and lamellar, were synthesized by different chemical methods. Their morphology and structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and a Raman spectrometer. The adsorption properties of two sorts of MoS2 nanoparticles for copper (Ⅱ) ions in water were investigated by changing the pH value, adsorption time, initial concentration of solution, adsorption temperature, etc. Finally, the adsorption mechanism was analyzed by kinetic, isothermal, and thermodynamic models. The results show that two microstructures of MoS2 nanoparticles can be used as efficient adsorption materials for removing heavy metal ions from water, although there are differences in adsorption capacity between them, which expands the theoretical basis of heavy metal adsorption in a water environment.
Development of Carbon-Nanodot-Loaded PLA Nanofibers and Study of Their Barrier Performance for Medical Applications
Authors: Munir Muhammad Usman , Mayer-Gall Thomas , Gutmann Jochen S. , Ali Wael , Etemad-Parishanzadeh Omid , Khanzada Haleema , Mikučioniene Daiva
Published: March 2023

The COVID-19 pandemic has increased the usage of personal protective equipment (PPE) all round the world and, in turn, it has also increased the waste caused by disposable PPE. This has exerted a severe environmental impact, so in our work, we propose the utilization of a sustainable electrospun nanofiber based on poly lactic acid (PLA), as it is biobased and conditionally degradable. We optimized the weight percentage of the PLA-precursor solution and found that 19% PLA produces fine nanofibers with good morphology. We also introduced carbon nanodots (CNDs) in the nanofibers and evaluated their antibacterial efficiency. We used 1, 2, 3, and 4% CNDs with 19% PLA and found increased antibacterial activity with increased concentrations of CNDs. Additionally, we also applied a spunbond-nanofiber layered assembly for the medical face masks and found that with the addition of only 0.45 mg/cm2 on the nonwoven sheet, excellent particle filtration efficiency of 96.5% and a differential pressure of 39 Pa/cm2 were achieved, meeting the basic requirements for Type I medical face masks (ASTM-F2100).
Sesamin Metabolites Suppress the Induction of Cellular Senescence
Authors: Araki Chie , Takemoto Daisuke , Kitagawa Yoshinori , Tateishi Norifumi , Rogi Tomohiro , Izumo Takayuki , Kawamoto Shimpei , Shibata Hiroshi , Hara Eiji , Nakai Masaaki
Published: March 2023

Cellular senescence induces inflammation and is now considered one of the causes of organismal aging. Accumulating evidence indicates that age-related deterioration of mitochondrial function leads to an increase in reactive oxygen species (ROS) and DNA damage, which in turn causes cellular senescence. Thus, it is important to maintain mitochondrial function and suppress oxidative stress in order to inhibit the accumulation of senescent cells. Sesamin and its isomer episesamin are types of lignans found in sesame oil, and after being metabolized in the liver, their metabolites have been reported to exhibit antioxidant properties. However, their effects on cellular senescence remain unknown. In this study, the effects of sesamin, episesamin, and their metabolites SC1 and EC1-2 on replicative senescence were evaluated using human diploid lung fibroblasts, and TIG-3 cells. The results showed that sesamin and episesamin treatment had no effect on proliferative capacity compared to the untreated late passage group, whereas SC1 and EC1-2 treatment improved proliferative capacity and mitigated DNA damage of TIG-3 cells. Furthermore, other cellular senescence markers, such as senescence-associated secretory phenotype (SASP), mitochondria-derived ROS, and mitochondrial function (ROS/ATP ratio) were also reduced by SC1 and EC1-2 treatment. These results suggest that SC1 and EC1-2 can maintain proper mitochondrial function and suppress the induction of cellular senescence.
Prevalence of Front-of-Pack Warning Signs among Commercial Complementary Foods in Seven High and Upper Middle-Income Countries
Authors: Bassetti Eleonora , Khosravi Asha , Pries Alissa M.
Published: March 2023

Front-of-pack nutrition labelling (FOPNL) can provide a mechanism for communicating the nutritional quality of commercially produced complementary foods (CPCF) to caregivers. To better understand the role FOPNL may provide for CPCF, this study aimed to evaluate CPCFs against national and global FOPNL systems to determine the proportion that would warrant warning or traffic light signs for high levels of concerning nutrients. A cross-sectional assessment was conducted to evaluate the levels of selected nutrients in CPCF available in Australia (n = 266), Brazil (n = 41), Chile (n = 73), Mexico (n = 164), the United States (n = 562), the United Arab Emirates (n = 135), and the United Kingdom (n = 643). The analysis was based on national FOPNL systems and the WHO Regional Office for Europe CPCF nutrient profiling model’s ‘high sugar’ FOPNL warning. A substantial proportion of CPCFs contained excessive levels of total sugar, total fat or saturated fat that would warrant a red/amber traffic light or warning sign on product labels. Additionally, the high prevalence of added sugars and sweeteners identified in CPCFs was concerning. Based on these findings, the use of FOPNL among CPCFs could be beneficial to communicate the nutritional quality of these products to caregivers and trigger the reformulation of CPCFs with inappropriate nutrient profiles.
Effects of Probiotics on Glycemic Control and Metabolic Parameters in Gestational Diabetes Mellitus: Systematic Review and Meta-Analysis
Authors: Yefet Enav , Bar Liron , Izhaki Ido , Iskander Rula , Massalha Manal , Younis Johnny S. , Nachum Zohar
Published: March 2023

Objectives: To assess the effects of probiotic supplements on glycemic control and metabolic parameters in women with gestational diabetes mellitus (GDM) by performing a systematic review and meta-analysis of randomized controlled trials. The primary outcome was glycemic control, i.e., serum glucose and insulin levels. Secondary outcomes were maternal weight gain, neonatal birth weight, and lipid parameters. Weighted mean difference (WMD) was used. Cochrane’s Q test of heterogeneity and I2 were used to assess heterogeneity. Results: Of the 843 papers retrieved, 14 (n = 854 women) met the inclusion criteria and were analyzed. When compared with placebo, women receiving probiotic supplements had significantly lower mean fasting serum glucose, fasting serum insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, total cholesterol, and VLDL levels. Decreased neonatal birth weight was witnessed in supplements containing Lactobacillus acidophilus. Conclusion: Probiotic supplements may improve glycemic control and lipid profile and reduce neonatal birth weight in women with GDM.
The ADORA2A TT Genotype Is Associated with Anti-Inflammatory Effects of Caffeine in Response to Resistance Exercise and Habitual Coffee Intake
Authors: Rahimi Mohammad Rahman , Semenova Ekaterina A. , Larin Andrey K. , Kulemin Nikolay A. , Generozov Edward V. , Łubkowska Beata , Ahmetov Ildus I. , Golpasandi Hadi
Published: March 2023

Caffeine is an adenosine A2A receptor (ADORA2A) antagonist with ergogenic and anti-inflammatory effects. Previous studies have reported that the ADORA2A gene regulates glutamate metabolism and immune responses, with the ADORA2A rs5751876 TT genotype (with high sensitivity to caffeine) showing larger ergogenic effect following caffeine ingestion. We therefore hypothesized that the TT genotype would be associated with greater anti-inflammatory effects of caffeine in response to exercise, and with higher coffee intake in physically active individuals. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A variant with the anti-inflammatory effects of caffeine in response to intense resistance exercise (RE), and (2) to analyze the association of the rs5751876 with coffee intake in physically active individuals (n = 134). Fifteen resistance-trained athletes participated in a randomized, double-blind, placebo-controlled cross-over study, where they consumed 6 mg/kg of caffeine or placebo one hour prior to performing an RE protocol. Blood samples were taken immediately from the arterial vein before, immediately after, and 15 min after RE for the analysis of inflammatory markers myeloperoxidase (MPO) and acetylcholinesterase (AChE). We found that the ADORA2A TT genotype carriers experienced lower exercise-induced inflammatory responses (p < 0.05 for AchE) when compared to the C allele carriers (i.e., CC/CT) one hour following the ingestion of caffeine. Furthermore, the ADORA2A TT genotype was positively associated with coffee intake (p = 0.0143; irrespective of CYP1A2 rs762551 polymorphism). In conclusion, we found that the ADORA2A gene polymorphism is associated with anti-inflammatory effects of caffeine in response to resistance exercise, as well as with habitual coffee intake in physically active individuals.
Artepillin C Time−Dependently Alleviates Metabolic Syndrome in Obese Mice by Regulating CREB/CRTC2−BMAL1 Signaling
Authors: Wang Lei , Zhou Lingqin , Liu Shuai , Liu Yaxin , Zhao Jia , Chen Yaqiong , Liu Yi
Published: March 2023

Artepillin C (APC), a cAMP-response element−binding (CREB)/CREB regulated transcription coactivator 2 (CRTC2) inhibitor isolated from Brazilian green propolis, can ameliorate metabolic syndrome in obese mice. Because the sensitivity and responsiveness of the body to the drug depend on the time of day and the circadian clock alignment, the optimal administration time of APC for desired efficacy in treating metabolic syndrome remains unclear. In this study, APC (20 mg/kg) or the vehicle was intraperitoneally injected into obese mice once daily for one or three weeks. The results of the insulin tolerance test, pyruvate tolerance test, and histological and biochemical assays showed that APC could improve whole−body glucose homeostasis and decrease hepatic lipid synthesis following a circadian rhythm. Further exploration of the underlying mechanism revealed that APC may disturb the diurnal oscillations of the expression of brain and muscle ARNT−like protein (BMAL1) in primary hepatocytes and the livers of the study subjects. Moreover, APC could inhibit hepatic BMAL1 expression by blocking the CREB/CRTC2 transcription complex. BMAL1 overexpression in primary hepatocytes or the livers of db/db mice antagonized the inhibitory effect of APC on hepatic lipid metabolism. In conclusion, the chronotherapy of APC may relieve metabolic syndrome in obese mice, and the mechanism behind APC−mediated time−of−day effects on metabolic syndrome were unveiled, thereby providing a foundation for optimized APC treatment from a mechanistic perspective.
Trimethylamine N-Oxide (TMAO) Mediates Increased Inflammation and Colonization of Bladder Epithelial Cells during a Uropathogenic E. coli Infection In Vitro
Authors: Wu Rongrong , Kumawat Ashok Kumar , Demirel Isak
Published: March 2023

Urinary tract infections (UTIs) are among the most common infections in humans and are often caused by uropathogenic E. coli (UPEC). Trimethylamine N-oxide (TMAO) is a proinflammatory metabolite that has been linked to vascular inflammation, atherosclerosis, and chronic kidney disease. As of today, no studies have investigated the effects of TMAO on infectious diseases like UTIs. The aim of this study was to investigate whether TMAO can aggravate bacterial colonization and the release of inflammatory mediators from bladder epithelial cells during a UPEC infection. We found that TMAO aggravated the release of several key cytokines (IL-1β and IL-6) and chemokines (IL-8, CXCL1 and CXCL6) from bladder epithelial cells during a CFT073 infection. We also found that CFT073 and TMAO mediate increased release of IL-8 from bladder epithelial cells via ERK 1/2 signaling and not bacterial growth. Furthermore, we showed that TMAO enhances UPEC colonization of bladder epithelial cells. The data suggest that TMAO may also play a role in infectious diseases. Our results can be the basis of further research to investigate the link between diet, gut microbiota, and urinary tract infection.
Clearing and Masking Agents in Pretargeting Strategies
Authors: Staudt Markus , Herth Matthias M.
Published: March 2023

‘Pretargeting’ led to increased target-to-background ratios of nanomedicines in short timeframes. However, clearing or masking agents are needed to reach the full potential of pretargeted approaches. This review gives an overview of clearing and masking agents employed in pretargeting strategies in both preclinical and clinical settings and discusses how these agents work.
Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca2+ Pathway
Authors: Ahmed Mohamed I. , Abdelrazek Heba M. A. , Moustafa Yasser M. , Alshawwa Samar Z. , Mobasher Maysa A. , Abdel-Wahab Basel A. , Abdelgawad Fathy Elsayed , Khodeer Dina M.
Published: March 2023

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Serotonin (5-HT) release during myocardial ischemia plays an important role in the progression of myocardial cellular injury. This study was conducted to investigate the possible cardioprotective effect of flibanserin (FLP) against isoproterenol (ISO)-induced MI in rats. Rats were randomly divided into five groups and were treated orally (p.o.) with FLP (15, 30, and 45 mg/kg) for 28 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 27th and 28th days to induce MI. ISO-induced myocardial infarcted rats exhibited a significant increase in cardiac markers, oxidative stress markers, cardiac and serum 5-HT levels, and total cardiac calcium (Ca2+) concentration. ISO-induced myocardial infarcted rats also revealed a remarkable alteration of electrocardiogram (ECG) pattern and significantly upregulated expression of the 5-Hydroxytryptamine 2A (5-HT2A) receptors gene. Moreover, ISO-induced myocardial infarcted rats showed significant histopathological findings of MI and hypertrophic signs. However, pretreatment with FLP significantly attenuated the ISO-induced MI in a dose-dependent manner, as the effect of FLP (45 mg/kg) was more pronounced than that of the other two doses, FLP (15 and 30 mg/kg). The present study provides evidence for the cardioprotective efficacy of FLP against ISO-induced MI in rats.
Formulation and Evaluation of Amikacin Sulfate Loaded Dextran Nanoparticles against Human Pathogenic Bacteria
Authors: Syed Rahamat Unissa , Moni Sivakumar S. , Nawaz Muhammad , Bin Break Mohammed Khaled , Khalifa Nasrin E. , Abdelwahab Siddig Ibrahim , Alharbi Reham Meshal , Alfaisal Raghad Huraid , Al Basher Bayan Naif , Alhaidan Entsar Mohammed
Published: March 2023

Amikacin sulfate-loaded dextran sulfate sodium nanoparticles were formulated, lyophilized (LADNP), and then analyzed. The LADNP had a −20.9 ± 8.35 mV zeta potential, PDI of 0.256, and % PDI of 67.7. The zeta average nano size of LADNP was 317.9 z. d.nm, while the dimension of an individual particle was 259.3 ± 73.52 nm, and nanoparticle conductivity in colloidal solution was 2.36 mS/cm. LADNP has distinct endothermic peaks at temperatures at 165.77 °C, according to differential scanning calorimetry (DSC). The thermogravimetric analysis (TGA) showed the weight loss of LADNP, which was observed as 95% at 210.78 °C. XRD investigation on LADNP exhibited distinct peaks at 2θ as 9.6°, 10.4°, 11.4°, 18.9°, 20.3°, 24.4°, 28.2°, 33.2°, 38.9°, and 40.4° confirming crystalline structure. The amikacin release kinetics from LADNP revealed zero order kinetics with a linear release showed zero order kinetics with 37% of drug release in 7 h and had an R2 value of 0.99. The antibacterial effect of LADNP showed broad-spectrum activity against tested human pathogenic bacteria. The preset study demonstrated that LADNP is a promising antibacterial agent.
Development of Transdermal Oleogel Containing Olmesartan Medoxomil: Statistical Optimization and Pharmacological Evaluation
Authors: El-Dahmy Rania Moataz , Elsayed Ibrahim , Hussein Jihan , Althubiti Mohammad , Almaimani Riyad A. , El-Readi Mahmoud Zaki , Elbaset Marawan A. , Ibrahim Bassant M. M.
Published: March 2023

Olmesartan medoxomil (OLM) is a first-line antihypertensive drug with low oral bioavailability (28.6%). This study aimed to develop oleogel formulations to decrease OLM side effects and boost its therapeutic efficacy and bioavailability. OLM oleogel formulations were composed of Tween 20, Aerosil 200, and lavender oil. A central composite response surface design chose the optimized formulation, containing Oil/Surfactant (SAA) ratio of 1:1 and Aerosil % of 10.55%, after showing the lowest firmness and compressibility, and the highest viscosity, adhesiveness, and bioadhesive properties (Fmax and Wad). The optimized oleogel increased OLM release by 4.21 and 4.97 folds than the drug suspension and gel, respectively. The optimized oleogel formulation increased OLM permeation by 5.62 and 7.23 folds than the drug suspension and gel, respectively. The pharmacodynamic study revealed the superiority of the optimized formulation in maintaining normal blood pressure and heart rate for 24 h. The biochemical analysis revealed that the optimized oleogel achieved the best serum electrolyte balance profile, preventing OLM-induced tachycardia. The pharmacokinetic study showed that the optimized oleogel increased OLM’s bioavailability by more than 4.5- and 2.5-folds compared to the standard gel and the oral market tablet, respectively. These results confirmed the success of oleogel formulations in the transdermal delivery of OLM.
Seed Size, Not Dispersal Syndrome, Determines Potential for Spread of Ricefield Weeds by Gulls
Authors: Peralta-Sánchez Juan Manuel , Ansotegui Albán , Hortas Francisco , Redón Stella , Martín-Vélez Víctor , Green Andy J. , Navarro-Ramos María J. , Lovas-Kiss Adam , Sánchez Marta I.
Published: March 2023

Recent field data suggest that migratory gulls disperse many rice field weeds by gut passage (endozoochory), most of which are dry fruited and widely assumed to have no long-distance dispersal mechanisms, except via human activity. We investigated this mechanism with a feeding experiment, in which seeds of five common rice field weeds (in order of increasing seed size: Juncus bufonius, Cyperus difformis, Polypogon monspeliensis, Amaranthus retroflexus, and the fleshy-fruited Solanum nigrum) were fed to seven individuals of lesser black-backed gulls Larus fuscus held in captivity. We quantified seed survival after collecting faeces at intervals for 33 h after ingestion, then extracting intact seeds and running germination tests, which were also conducted for control seeds. All five species showed high seed survival after gut passage, of >70%. Gut retention times averaged 2–4 h, but maxima exceeded 23 h for all species. Germinability after gut passage was 16–54%, and gut passage accelerated germination in J. bufonius and S. nigrum, but slowed it down in the other species. All species had lower germinability after gut passage compared to control seeds (likely due to stratification prior to the experiment), but the loss of germinability was higher in smaller seeds. There was no evidence that the different dispersal syndromes assigned to the five species (endozoochory, epizoochory or barochory) had any influence on our results. In contrast, mean gut retention time was strongly and positively related to seed size, likely because small seeds pass more quickly from the gizzard into the intestines. Non-classical endozoochory of dry-fruited seeds by waterbirds is a major but overlooked mechanism for potential long-distance dispersal, and more research into this process is likely essential for effective weed management.
Functional Groups Response to Water Deficit in Mediterranean Ecosystems
Authors: Castro Helena , Dias Maria Celeste , Sousa José Paulo , Freitas Helena
Published: March 2023

Enhanced drought, more frequent rainfall events and increased inter-annual variability of precipitation are the main trends of climate expected for the Mediterranean. Drought is one of the most important stressors for plants and significantly impacts plant communities causing changes in plant composition and species dominance. Through an experiment under controlled conditions, we assessed the response of Mediterranean species from different functional groups (annual grass, annual forb, annual legume, and perennial shrub) to moderate and severe water deficit. Changes in plant traits (leaf dry matter), biomass and physiology (water status, photosynthesis, pigments, and carbohydrate) were evaluated. The studied species differed in their response to water deficit. Ornithopus compressus, the legume, showed the strongest response, particularly under severe conditions, decreasing leaf relative water content (RWC), pigments and carbohydrates. The grass, Agrostis pourreti and the forb, Tolpis barbata, maintained RWC, indicating a higher ability to cope with water deficit. Finally, the shrub, Cistus salviifolius, had the lowest response to stress, showing a higher ability to cope with water deficit. Despite different responses, plant biomass was negatively affected by severe water deficit in all species. These data provide background for predicting plant diversity and species composition of Mediterranean grasslands and Montado under climate change conditions.
Genome-Wide Identification of the Rose SWEET Gene Family and Their Different Expression Profiles in Cold Response between Two Rose Species
Authors: Song Xiangshang , Kou Yaping , Duan Mingao , Feng Bo , Yu Xiaoyun , Jia Ruidong , Zhao Xin , Ge Hong , Yang Shuhua
Published: March 2023

Sugars Will Eventually be Exported Transporter (SWEET) gene family plays indispensable roles in plant physiological activities, development processes, and responses to biotic and abiotic stresses, but no information is known for roses. In this study, a total of 25 RcSWEET genes were identified in Rosa chinensis ‘Old Blush’ by genome-wide analysis and clustered into four subgroups based on their phylogenetic relationships. The genomic features, including gene structures, conserved motifs, and gene duplication among the chromosomes of RcSWEET genes, were characterized. Seventeen types of cis-acting elements among the RcSWEET genes were predicted to exhibit their potential regulatory roles during biotic and abiotic stress and hormone responses. Tissue-specific and cold-response expression profiles based on transcriptome data showed that SWEETs play widely varying roles in development and stress tolerance in two rose species. Moreover, the different expression patterns of cold-response SWEET genes were verified by qRT-PCR between the moderately cold-resistant species R. chinensis ‘Old Blush’ and the extremely cold-resistant species R. beggeriana. Especially, SWEET2a and SWEET10c exhibited species differences after cold treatment and were sharply upregulated in the leaves of R. beggeriana but not R. chinensis ‘Old Blush’, indicating that these two genes may be the crucial candidates that participate in cold tolerance in R. beggeriana. Our results provide the foundation for function analysis of the SWEET gene family in roses, and will contribute to the breeding of cold-tolerant varieties of roses.
Goss’s Wilt Resistance in Corn Is Mediated via Salicylic Acid and Programmed Cell Death but Not Jasmonic Acid Pathways
Authors: Shumilak Alexander , El-Shetehy Mohamed , Soliman Atta , Tambong James T. , Daayf Fouad
Published: March 2023

A highly aggressive strain (CMN14-5-1) of Clavibacter nebraskensis bacteria, which causes Goss’s wilt in corn, induced severe symptoms in a susceptible corn line (CO447), resulting in water-soaked lesions followed by necrosis within a few days. A tolerant line (CO450) inoculated with the same strain exhibited only mild symptoms such as chlorosis, freckling, and necrosis that did not progress after the first six days following infection. Both lesion length and disease severity were measured using the area under the disease progression curve (AUDPC), and significant differences were found between treatments. We analyzed the expression of key genes related to plant defense in both corn lines challenged with the CMN14-5-1 strain. Allene oxide synthase (ZmAOS), a gene responsible for the production of jasmonic acid (JA), was induced in the CO447 line in response to CMN14-5-1. Following inoculation with CMN14-5-1, the CO450 line demonstrated a higher expression of salicylic acid (SA)-related genes, ZmPAL and ZmPR-1, compared to the CO447 line. In the CO450 line, four genes related to programmed cell death (PCD) were upregulated: respiratory burst oxidase homolog protein D (ZmrbohD), polyphenol oxidase (ZmPPO1), ras-related protein 7 (ZmRab7), and peptidyl-prolyl cis-trans isomerase (ZmPPI). The differential gene expression in response to CMN14-5-1 between the two corn lines provided an indication that SA and PCD are involved in the regulation of corn defense responses against Goss’s wilt disease, whereas JA may be contributing to disease susceptibility.