bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Fingerprints of Effective Fluoxetine Treatment in the Prefrontal Cortex of Chronically Socially Isolated Rats: Marker Candidates and Predictive Metabolites
Authors: Filipović Dragana , Inderhees Julica , Korda Alexandra , Tadić Predrag , Schwaninger Markus , Inta Dragoš , Borgwardt Stefan
Published: June 2023

The increasing prevalence of depression requires more effective therapy and the understanding of antidepressants’ mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography–high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze the metabolomics data, we employed univariate and multivariate analysis and biomarker capacity assessment using the receiver operating characteristic (ROC) curve. We also identified the most predictive biomarkers using a support vector machine with linear kernel (SVM-LK). Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as marker candidates for fluoxetine efficacy. ROC analysis revealed 4 significant marker candidates for CSIS group discrimination, and 10 for fluoxetine efficacy. SVM-LK with accuracies of 61.50% or 93.30% identified a panel of 7 or 25 predictive metabolites for depressive-like behavior or fluoxetine effectiveness, respectively. Overall, metabolic fingerprints combined with the ROC curve and SVM-LK may represent a new approach to identifying marker candidates or predictive metabolites for ongoing disease or disease risk and treatment outcome.
Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as an Important Scaffold for Anticancer Drug Discovery—In Vitro and In Silico Evaluation
Authors: Kciuk Mateusz , Marciniak Beata , Celik Ismail , Zerroug Enfale , Dubey Amit , Sundaraj Rajamanikandan , Mujwar Somdutt , Bukowski Karol , Mojzych Mariusz , Kontek Renata
Published: June 2023

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides (MM-compounds) are a relatively new class of heterocyclic compounds that exhibit a wide variety of biological actions, including anticancer properties. Here, we used caspase enzyme activity assays, flow cytometry analysis of propidium iodide (PI)-stained cells, and a DNA laddering assay to investigate the mechanisms of cell death triggered by the MM-compounds (MM134, -6, -7, and -9). Due to inconsistent results in caspase activity assays, we have performed a bromodeoxyuridine (BrdU) incorporation assay, colony formation assay, and gene expression profiling. The compounds’ cytotoxic and pro-oxidative properties were also assessed. Additionally, computational studies were performed to demonstrate the potential of the scaffold for future drug discovery endeavors. MM-compounds exhibited strong micromolar (0.06–0.35 µM) anti-proliferative and pro-oxidative activity in two cancer cell lines (BxPC-3 and PC-3). Activation of caspase 3/7 was observed following a 24-h treatment of BxPC-3 cells with IC50 concentrations of MM134, -6, and -9 compounds. However, no DNA fragmentation characteristics for apoptosis were observed in the flow cytometry and DNA laddering analysis. Gene expression data indicated up-regulation of BCL10, GADD45A, RIPK2, TNF, TNFRSF10B, and TNFRSF1A (TNF-R1) following treatment of cells with the MM134 compound. Moreover, in silico studies indicated AKT2 kinase as the primary target of compounds. MM-compounds exhibit strong cytotoxic activity with pro-oxidative, pro-apoptotic, and possibly pro-necroptotic properties that could be employed for further drug discovery approaches.
Search for Dispersed Repeats in Bacterial Genomes Using an Iterative Procedure
Authors: Korotkov Eugene , Suvorova Yulia , Kostenko Dimitry , Korotkova Maria
Published: June 2023

We have developed a de novo method for the identification of dispersed repeats based on the use of random position-weight matrices (PWMs) and an iterative procedure (IP). The created algorithm (IP method) allows detection of dispersed repeats for which the average number of substitutions between any two repeats per nucleotide (x) is less than or equal to 1.5. We have shown that all previously developed methods and algorithms (RED, RECON, and some others) can only find dispersed repeats for x ≤ 1.0. We applied the IP method to find dispersed repeats in the genomes of E. coli and nine other bacterial species. We identify three families of approximately 1.09 × 106, 0.64 × 106, and 0.58 × 106 DNA bases, respectively, constituting almost 50% of the complete E. coli genome. The length of the repeats is in the range of 400 to 600 bp. Other analyzed bacterial genomes contain one to three families of dispersed repeats with a total number of 103 to 6 × 103 copies. The existence of such highly divergent repeats could be associated with the presence of a single-type triplet periodicity in various genes or with the packing of bacterial DNA into a nucleoid.
Selective Killing of BRCA2-Deficient Ovarian Cancer Cells via MRE11 Blockade
Authors: Alblihy Adel , Ali Reem , Algethami Mashael , Ritchie Alison A. , Shoqafi Ahmed , Alqahtani Shatha , Mesquita Katia A. , Toss Michael S. , Ordóñez-Morán Paloma , Jeyapalan Jennie N. , Dekker Lodewijk , Salerno Martina , Hartsuiker Edgar , Grabowska Anna M. , Rakha Emad A. , Mongan Nigel P. , Madhusudan Srinivasan
Published: June 2023

The MRE11 nuclease is essential during DNA damage recognition, homologous recombination, and replication. BRCA2 plays important roles during homologous recombination and replication. Here, we show that effecting an MRE11 blockade using a prototypical inhibitor (Mirin) induces synthetic lethality (SL) in BRCA2-deficient ovarian cancer cells, HeLa cells, and 3D spheroids compared to BRCA2-proficient controls. Increased cytotoxicity was associated with double-strand break accumulation, S-phase cell cycle arrest, and increased apoptosis. An in silico analysis revealed Mirin docking onto the active site of MRE11. While Mirin sensitises DT40 MRE11+/− cells to the Top1 poison SN-38, it does not sensitise nuclease-dead MRE11 cells to this compound confirming that Mirin specifically inhibits Mre11 nuclease activity. MRE11 knockdown reduced cell viability in BRCA2-deficient PEO1 cells but not in BRCA2-proficient PEO4 cells. In a Mirin-resistant model, we show the downregulation of 53BP1 and DNA repair upregulation, leading to resistance, including in in vivo xenograft models. In a clinical cohort of human ovarian tumours, low levels of BRCA2 expression with high levels of MRE11 co-expression were linked with worse progression-free survival (PFS) (p = 0.005) and overall survival (OS) (p = 0.001). We conclude that MRE11 is an attractive SL target, and the pharmaceutical development of MRE11 inhibitors for precision oncology therapeutics may be of clinical benefit.
Zeolite Nanoparticles Loaded with 2-Methoxystradiol as a Novel Drug Delivery System for the Prostate Cancer Therapy
Authors: Mena-Silva Denisse , Alfaro Aline , León Andrea , Guajardo-Correa Emanuel , Elgueta Estefania , Diaz Patricia , Vilos Cristian , Cardenas Hugo , Denardin Juliano C. , Orihuela Pedro A.
Published: June 2023

The estrogen metabolite 2-methoxyestradiol (2ME) is a promissory anticancer drug mainly because of its pro-apoptotic properties in cancer cells. However, the therapeutic use of 2ME has been hampered due to its low solubility and bioavailability. Thus, it is necessary to find new ways of administration for 2ME. Zeolites are inorganic aluminosilicates with a porous structure and are considered good adsorbents and sieves in the pharmaceutical field. Here, mordenite-type zeolite nanoparticles were loaded with 2ME to assess its efficiency as a delivery system for prostate cancer treatment. The 2ME-loaded zeolite nanoparticles showed an irregular morphology with a mean hydrodynamic diameter of 250.9 ± 11.4 nm, polydispersity index of 0.36 ± 0.04, and a net negative surface charge of −34 ± 1.73 meV. Spectroscopy with UV-vis and Attenuated Total Reflectance Infrared Fourier-Transform was used to elucidate the interaction between the 2ME molecules and the zeolite framework showing the formation of a 2ME-zeolite conjugate in the nanocomposite. The studies of adsorption and liberation determined that zeolite nanoparticles incorporated 40% of 2ME while the liberation of 2ME reached 90% at pH 7.4 after 7 days. The 2ME-loaded zeolite nanoparticles also decreased the viability and increased the mRNA of the 2ME-target gene F-spondin, encoded by SPON1, in the human prostate cancer cell line LNCaP. Finally, the 2ME-loaded nanoparticles also decreased the viability of primary cultures from mouse prostate cancer. These results show the development of 2ME-loaded zeolite nanoparticles with physicochemical and biological properties compatible with anticancer activity on the human prostate and highlight that zeolite nanoparticles can be a good carrier system for 2ME.
The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer
Authors: Gonzalez-Martin Roberto , Palomar Andrea , Quiñonero Alicia , Pellicer Nuria , Fernandez-Saavedra Rocio , Conde-Vilda Estefania , Quejido Alberto J. , Whitehead Christine , Scott Richard T. , Dominguez Francisco
Published: June 2023

Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the follicular fluid and plasma, in addition to plasma manganese. Alternatively, elevated follicular fluid lithium concentrations were significantly associated with poor preimplantation outcomes while the urinary molybdenum concentration was significantly associated with a lower probability of implantation, clinical pregnancy, and live birth. Urinary lithium and chromium concentrations were significantly associated with a lower probability of achieving a live birth. Our results suggest that the essential trace elements present in follicular fluid, plasma, and urine of women are directly associated with their reproductive outcomes, with copper and manganese exerting positive effects and lithium and molybdenum exerting negative effects.
Association of Differentially Altered Liver Fibrosis with Deposition of TGFBi in Stabilin-Deficient Mice
Authors: Krzistetzko Jessica , Géraud Cyrill , Dormann Christof , Riedel Anna , Leibing Thomas
Published: June 2023

Liver sinusoidal endothelial cells (LSECs) control clearance of Transforming growth factor, beta-induced, 68kDa (TGFBi) and Periostin (POSTN) through scavenger receptors Stabilin-1 (Stab1) and Stabilin-2 (Stab2). Stabilin inhibition can ameliorate atherosclerosis in mouse models, while Stabilin-double-knockout leads to glomerulofibrosis. Fibrotic organ damage may pose a limiting factor in future anti-Stabilin therapies. While Stab1-deficient (Stab1−/−) mice were shown to exhibit higher liver fibrosis levels upon challenges, fibrosis susceptibility has not been studied in Stab2-deficient (Stab2−/−) mice. Wildtype (WT), Stab1−/− and Stab2−/− mice were fed experimental diets, and local ligand abundance, hepatic fibrosis, and ligand plasma levels were measured. Hepatic fibrosis was increased in both Stab1−/− and Stab2−/− at baseline. A pro-fibrotic short Methionine-Choline-deficient (MCD) diet induced slightly increased liver fibrosis in Stab1−/− and Stab2−/− mice. A Choline-deficient L-amino acid-defined (CDAA) diet induced liver fibrosis of similar distribution and extent in all genotypes (WT, Stab1−/− and Stab2−/−). A hepatic abundance of Stabilin ligand TGFBi correlated very highly with liver fibrosis levels. In contrast, plasma levels of TGFBi were increased only in Stab2−/− mice after the CDAA diet but not the MCD diet, indicating the differential effects of these diets. Here we show that a single Stabilin deficiency of either Stab1 or Stab2 induces mildly increased collagen depositions under homeostatic conditions. Upon experimental dietary challenge, the local abundance of Stabilin ligand TGFBi was differentially altered in Stabilin-deficient mice, indicating differentially affected LSEC scavenger functions. Since anti-Stabilin-directed therapies are in clinical evaluation for the treatment of diseases, these findings bear relevance to treatment with novel anti-Stabilin agents.
Whole-Genome Resequencing Reveals the Diversity of Patchouli Germplasm
Authors: Li Zhipeng , Chen Yiqiong , Li Yangyan , Zeng Ying , Li Wanying , Ma Xiaona , Huang Lili , Shen Yanting
Published: June 2023

As an important medicinal and aromatic plant, patchouli is distributed throughout most of Asia. However, current research on patchouli’s genetic diversity is limited and lacks genome-wide studies. Here, we have collected seven representative patchouli accessions from different localities and performed whole-genome resequencing on them. In total, 402,650 single nucleotide polymorphisms (SNPs) and 153,233 insertions/deletions (INDELs) were detected. Based on these abundant genetic variants, patchouli accessions were primarily classified into the Chinese group and the Southeast Asian group. However, the accession SP (Shipai) collected from China formed a distinct subgroup within the Southeast Asian group. As SP has been used as a genuine herb in traditional Chinese medicine, its unique molecular markers have been subsequently screened and verified. For 26,144 specific SNPs and 16,289 specific INDELs in SP, 10 of them were validated using Polymerase Chain Reaction (PCR) following three different approaches. Further, we analyzed the effects of total genetic variants on genes involved in the sesquiterpene synthesis pathway, which produce the primary phytochemical compounds found in patchouli. Eight genes were ultimately investigated and a gene encoding nerolidol synthetase (PatNES) was chosen and confirmed through biochemical assay. In accession YN, genetic variants in PatNES led to a loss of synthetase activity. Our results provide valuable information for understanding the diversity of patchouli germplasm resources.
Co-Administration of Resolvin D1 and Peripheral Nerve-Derived Stem Cell Spheroids as a Therapeutic Strategy in a Rat Model of Spinal Cord Injury
Authors: Jeong Seung-Young , Lee Hye-Lan , Wee SungWon , Lee HyeYeong , Hwang GwangYong , Hwang SaeYeon , Yoon SolLip , Yang Young-Il , Han Inbo , Kim Keung-Nyun
Published: June 2023

Spinal cord injury (SCI), primarily caused by trauma, leads to permanent and lasting loss of motor, sensory, and autonomic functions. Current therapeutic strategies are focused on mitigating secondary injury, a crucial aspect of SCI pathophysiology. Among these strategies, stem cell therapy has shown considerable therapeutic potential. This study builds on our previous work, which demonstrated the functional recovery and neuronal regeneration capabilities of peripheral nerve-derived stem cell (PNSC) spheroids, which are akin to neural crest stem cells, in SCI models. However, the limited anti-inflammatory capacity of PNSC spheroids necessitates a combined therapeutic approach. As a result, we investigated the potential of co-administering resolvin D1 (RvD1), known for its anti-inflammatory and neuroprotective properties, with PNSC spheroids. In vitro analysis confirmed RvD1’s anti-inflammatory activity and its inhibitory effect on pro-inflammatory cytokines. In vivo studies involving a rat SCI model demonstrated that combined therapy of RvD1 and PNSC spheroids outperformed monotherapies, exhibiting enhanced neuronal regeneration and anti-inflammatory effects as validated through behavior tests, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry. Thus, our findings suggest that the combined application of RvD1 and PNSC spheroids may represent a novel therapeutic approach for SCI management.
FTO Gene Polymorphisms and Their Roles in Acromegaly
Authors: Jawiarczyk-Przybyłowska Aleksandra , Kuliczkowska-Płaksej Justyna , Kolačkov Katarzyna , Zembska Agnieszka , Halupczok-Żyła Jowita , Rolla Małgorzata , Miner Michał , Kałużny Marcin , Bolanowski Marek
Published: June 2023

The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs). The polymorphisms of the fat mass and obesity-associated gene (FTO) are associated with obesity, as well as with an increased risk of CVDs. The aim of the study was to determine the relationship of risk alleles of four FTO gene polymorphisms with selected parameters of lipid and glucose metabolism as well as with IGF-1 and GH levels in the group of patients with acromegaly compared to the control group. The study group consisted of 104 patients with acromegaly and 64 healthy subjects constituting the control group. In the whole acromegaly group, the data reveal that the homozygous for risk allele carriers (rs1421085, rs9930506, rs9939609) as well as carriers of only one risk allele have lower IGF-1 concentrations. In the well-controlled acromegaly group, the homozygous for three risk allele carriers of FTO gene polymorphisms have lower HDL cholesterol concentration (rs1121980, rs1421085, rs993609). In the cured acromegaly group, homozygous risk allele carriers rs9930506 tend to have higher levels of total cholesterol and LDL cholesterol. These associations are not observed in the control group. Conclusion: there is an association between FTO gene polymorphisms and the metabolism of lipids, suggesting that the FTO gene may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1, implying that FTO gene may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.
Data Mining Using Association Rules for Intuitionistic Fuzzy Data
Authors: Petry Frederick , Yager Ronald
Published: June 2023

This paper considers approaches to the computation of association rules for intuitionistic fuzzy data. Association rules can provide guidance for assessing the significant relationships that can be determined while analyzing data. The approach uses the cardinality of intuitionistic fuzzy sets that provide a minimum and maximum range for the support and confidence metrics. A new notation is used to enable the representation of the fuzzy metrics. A running example of queries about the desirable features of vacation locations is used to illustrate.
Design and Evaluation of the Internal Space Layout of High-Speed Health Trains Based on Improved Systematic Layout Planning
Authors: Zhao Yi , Wu Yongmeng , Zhao Mingjing , Xiang Zerui , Zhi Jinyi , Xu Bochu
Published: June 2023

High-speed health trains have the advantages of large rescue volume, strong continuous operation capability, and medical treatment on the way. It is the best transport platform for large-scale medical transfer tasks. To solve the problem of space limitations and the vehicle formation of high-speed health trains, a new method of space layout design and evaluation of high-speed health trains based on improved systematic layout planning (SLP) was proposed. First, SLP was improved, and the relationship between functional carriages was reasonably marshaled using the improved SLP. Then, according to the space constraints of high-speed trains and the requirements of the man–machine environment, the space layout of the vehicles was designed, and 3ds MAX software was used to visualize the designed layout structure. Finally, the static and dynamic simulation effects and adaptability of the design scheme were evaluated using the digital virtual simulation software JACK. The design scheme can meet the requirements of human–computer interaction efficiency. Compared with previous studies, the results of this study reflect the superiority and rationality of the design in functional configuration, space utilization, medical treatment, and injury-carrying capacity. The results of this study can provide theoretical support for the formation of high-speed health trains, and provide a reference for the research and development of such trains. It has certain practical application value.
Cardiac Magnetic Resonance Relaxometry Parameters, Late Gadolinium Enhancement, and Feature-Tracking Myocardial Longitudinal Strain in Patients Recovered from COVID-19
Authors: Fijalkowska Jadwiga , Glinska Anna , Fijalkowski Marcin , Sienkiewicz Katarzyna , Kulawiak-Galaska Dorota , Szurowska Edyta , Pienkowska Joanna , Dorniak Karolina
Published: June 2023

COVID-19 infection is associated with myocarditis, and cardiovascular magnetic resonance (CMR) is the reference non-invasive imaging modality for myocardial tissue characterization. Quantitative CMR techniques, such as feature tracking (FT) and left ventricular global longitudinal strain (GLS) analysis, have been introduced as promising diagnostic tools to improve the diagnostic accuracy of suspected myocarditis. The aim of this study was to analyze the left ventricular global longitudinal strain (GLS) and the influence of T1 and T2 relaxation times, ECV, and LGE appearance on GLS parameters in a multiparametric imaging protocol in patients who recovered from COVID-19. The 86 consecutive patients enrolled in the study had all recovered from mild or moderate COVID-19 infections; none required hospitalization. Their persistent symptoms and suspected myocarditis led to cardiac magnetic resonance imaging within 3 months of the diagnosis of the SARS-CoV-2 infection. Results: Patients with GLS less negative than −15% had significantly lower LVEF (53.6% ± 8.9 vs. 61.6% ± 4.8; <0.001) and were significantly more likely to have prolonged T1 (28.6% vs. 7.5%; p = 0.019). Left ventricular GLS correlated significantly with T1 (r = 0.303; p = 0.006) and LVEF (r = −0.732; p < 0.001). Left ventricular GLS less negative than −15% was 7.5 times more likely in patients with prolonged T1 (HR 7.62; 95% CI 1.25–46.64). The reduced basal inferolateral longitudinal strain had a significant impact on the global left ventricular longitudinal strain. ROC results suggested that a GLS of 14.5% predicted prolonged T1 relaxation time with the best sensitivity and specificity. Conclusions: CMR abnormalities, including a myocarditis pattern, are common in patients who have recovered from COVID-19. The CMR feature-tracking left ventricular GLS is related to T1 relaxation time and may serve as a novel parameter to detect global and regional myocardial injury and dysfunction in patients with suspected myocardial involvement after recovery from COVID-19.
Adipokines as Predictive Biomarkers for Training Adaptation in Subjects with Multimorbidity—A Hypothesis-Generating Study
Authors: Maturana Felipe Mattioni , Rolf Rebecca , Schweda Simone , Reimer Max , Widmann Manuel , Burgstahler Christof , Nieß Andreas M. , Krauss Inga , Munz Barbara
Published: June 2023

Background. Physical exercise exerts a positive effect on many chronic conditions, specifically lifestyle-related diseases such as overweight and obesity, type 2 diabetes mellitus (T2DM), cardiovascular conditions and osteoarthritis (OA). As a result of common risk factors, most of these patients present with multiple conditions. Exercise- and disease-related biomarkers, such as adipokines, are emerging tools in training supervision and regulation; however, their significance in subjects with multimorbidities is unknown. Subjects and Methods. To address this issue, adipokines leptin, adiponectin and resistin were assessed in a cohort of subjects with multimorbidities (n = 39) presenting with at least two of the abovementioned conditions or relevant risk factors before and after a six-month exercise and lifestyle intervention program (‘MultiPill-Exercise’), and correlated with training adaptation, namely changes in relative maximum oxygen uptake (V·O2max). Results. There was a significant negative correlation between baseline leptin concentrations and training effect for relative V·O2max (after three months: rho = −0.54, p = 0.020 *; after six months: rho = −0.45, p = 0.013 *), with baseline leptin explaining 35% of the variance in delta relative V·O2max after three months and 23% after six months. Conclusions. Leptin might be a suitable surrogate biomarker in the context of exercise-based lifestyle intervention programs in subjects with multimorbidity.
“Multiple Mode Procedures” of Ultra-Pulse Fractional CO2 Laser: A Novel Treatment Modality of Facial Atrophic Acne Scars
Authors: Pan Zhonglan , Tang Yanqiu , Hua Hui , Hou Zuoqiong , Zhou Bingrong
Published: June 2023

Background and aim: Fractional CO2 laser is therapeutic for acne atrophic scar, but its effect usually is limited after multiple sessions, with occasional adverse reactions. This study aimed to evaluate the efficacy and safety of a new modality combining ultra-pulse CO2 laser and fractional CO2 laser (multiple mode procedures [MMP]) in the treatment of acne atrophic scars. Method: From December 2017 to January 2023, a total of 103 patients with facial acne atrophic scars treated with MMP technique were retrospectively analyzed. MMP was performed for 1–4 sessions with an interval of approximately three months. Based on photographs taken before and after treatment, overall atrophic scar improvement was assessed according to the ECCA grading scale, the modified Manchester Scar Scale and the 4-point Global Assessment Scale (GAS). The safety was evaluated by the degree of pain during treatment and postoperative adverse reactions. Results: All the 103 patients received treatment and completed follow-up, with an average of two sessions. The mean ECCA score decreased from 162.7 to 93.1 with statistically significant difference (p < 0.001). The mean GAS score increased by an average of 2.3 ± 0.9. The GAS improvement more evident for “boxcar” atrophic scars (2.7 ± 0.8) than for “rolling” (2.3 ± 0.8) and “icepick” scars (1.7 ± 0.8) (p < 0.001). The average improvement scores for color, distortion and texture were 2.0 ± 0.9, 2.2 ± 0.9 and 2.3 ± 0.8, respectively. The mean pain score during treatment was 3.9 ± 0.8, and the mean duration of erythema was 30.7 ± 3.5 days. Only three patients developed hyperpigmentation at the treated site within a few months. Discussion: Ultra-pulse CO2 fractional laser MMP technique can effectively improve the condition of facial atrophic acne scars with limited adverse reactions.
Post-Severe-COVID-19 Cardiopulmonary Rehabilitation: A Comprehensive Study on Patient Features and Recovery Dynamics in Correlation with Workout Intensity
Authors: Dumitrescu Andreea , Doros Gabriela , Lazureanu Voichita Elena , Septimiu-Radu Susa , Bratosin Felix , Rosca Ovidiu , Patel Harshkumar , Porosnicu Tamara Mirela , Vitcu Gabriela Mut , Mirea Andrei , Oancea Cristian , Mihaicuta Stefan , Stoicescu Emil Robert , Barata Paula Irina
Published: June 2023

The aftermath of severe COVID-19 frequently involves considerable cardiopulmonary damage, necessitating rehabilitation. This study aimed to evaluate the impact of COVID-19 on cardiopulmonary health and assess the effectiveness of various rehabilitative interventions. Conducted between September 2021 and September 2022, this prospective study included patients who had been diagnosed with severe COVID-19 and admitted at the “Victor Babes” Infectious Diseases and Pulmonology Hospital, Timisoara, Romania. The patients were stratified into low- and high-intensity rehabilitation groups. The rehabilitation protocols were individually tailored, and the patient recovery was closely monitored over a 3-month period. Our cohort comprised 84 patients, with a mean age of 56.3 years for the low-intensity group (n = 42) and 53.1 years for the high-intensity group (n = 42). Both groups showed significant improvements in the lung injury area, need for oxygen supplementation, ejection fraction, systolic pulmonary artery pressure, and forced vital capacity. Additionally, considerable enhancements were observed in maximal voluntary ventilation, FEV1, FEV1/FVC ratio, peak expiratory flow, and forced expiratory flow at 25–75%. The work intensity also demonstrated substantial improvements from the initial testing to the 3-month mark in both groups. This study provides evidence that personalized, targeted rehabilitation strategies can improve long-term cardiopulmonary health in patients recovering from severe COVID-19, proving both low-intensity and high-intensity training as sufficient to improve heart and lung function if performed correctly and over a relatively short duration of 3 months. The study findings underscore the importance of implementing comprehensive cardiopulmonary rehabilitation protocols in the care of post-COVID-19 patients and highlight the value of stratified rehabilitation intensity based on individual patient dynamics and recovery features.
Difficulties in Interpreting IGF-1 Levels in Short Stature Children Born Small for Gestational Age (SGA) Treated with Recombinant Human Growth Hormone (rhGH) Based on Data from Six Clinical Centers in Poland
Authors: Glińska Marta , Walczak Mieczysław , Wikiera Beata , Pyrżak Beata , Majcher Anna , Paluchowska Monika , Gawlik Aneta , Antosz Aleksandra , Kusz Marcin , Bossowski Artur , Stożek Karolina , Wędrychowicz Anna , Starzyk Jerzy , Petriczko Elżbieta
Published: June 2023

The assessment of IGF-1 concentrations is one of the parameters used for evaluating response to rhGH treatment. An increase in IGF-1 concentration positively correlates with growth improvement, whereas IGF-1 concentrations significantly above the reference range may increase the risk of possible side effects. The aim of this study was to evaluate the IGF-1 local reference ranges for the rhGH treatment centers concerned and to compare these values with the population reference ranges. A retrospective analysis was conducted on auxological data from 229 SGA patients who received rhGH treatment between 2016 and 2020 at six university clinical centers in Poland. The IGF-1 levels were assessed at baseline, after 12 and 24 months, and compared to the reference ranges provided by the local laboratory and to the population reference ranges. After 12 months, 56 patients (24%) presented IGF-1 values > 97th percentile for the local reference range, whereas only 8 (3.5%) did so using the population reference ranges; p < 0.001. After 24 months of treatment, the values were: 47 (33%) > 97th percentile by local vs. 6 (4.2%) by population standards; p < 0.001. Thirty-nine patients had rhGH dose reduced after 12 months, of whom twelve (25%) had IGF-1 > 97th percentile according to the local reference ranges and five (13%) > 97th percentile for the population. Our data suggest that different methods used to determine IGF-1 concentration and the different IGF-1 reference ranges result in a significant proportion of rhGH-treated children with elevated IGF-1 concentration and experiencing dose reductions, which may negatively affect growth rate.
Initial Experience of Vericiguat Treatment in Patients with Heart Failure and Reduced Ejection Fraction
Authors: Nakamura Makiko , Imamura Teruhiko , Kinugawa Koichiro
Published: June 2023

Background: Vericiguat, a novel oral soluble guanylate cyclase stimulator, decreased the incidence of cardiovascular death and heart failure hospitalization in the cohort receiving triple therapy for heart failure with reduced ejection fraction. However, efficacy and optimal patient selection in real-world practice in the era of “quadruple therapy” remains unknown. Methods: Consecutive patients who received vericiguat between September 2021 and December 2022 were retrospectively evaluated. Results: A total of 28 patients (median age 66 years, median left ventricular ejection fraction 33%) were included. Of them, 21 patients (75%) received quadruple therapy, and the dose of sacubitril/valsartan was 100 mg in the median. Three patients receiving dobutamine infusion discontinued vericiguat due to symptomatic hypotension. One patient with a high N-terminal pro-B-type natriuretic peptide of 4848 pg/mL at the baseline underwent unexpected heart failure hospitalization. Efficacy was evaluated in 21 patients who continued vericiguat for more than 4 months. The plasma B-type natriuretic peptide concentration tended to increase during the six-month pre-treatment period from 104 pg/mL to 179 pg/mL on median (p = 0.665) but remained unchanged after six-month vericiguat treatment to 170 pg/mL on median (p = 0.188). Conclusions: Vericiguat therapy might be feasible and effective upon quadruple therapy for those with heart failure, although further investigation is warranted to validate our findings.
Effect of Obesity on the Expression of Genes Associated with Severe Asthma—A Pilot Study
Authors: Bantulà Marina , Arismendi Ebymar , Tubita Valeria , Roca-Ferrer Jordi , Mullol Joaquim , de Hollanda Ana , Sastre Joaquín , Valero Antonio , Baos Selene , Cremades-Jimeno Lucía , Cárdaba Blanca , Picado César
Published: June 2023

Asthma is a complex condition resulting from the interaction of genes and environment. Obesity is a risk factor to develop asthma and contributes to poor response to asthma therapy and severity. The aim of the study was to evaluate the effect of obesity on the expression levels of genes previously associated with severe asthma. Three groups of subjects were studied: non-obese asthmatics (NOA), obese asthma patients (OA), and non-asthmatic obese subjects (O). Previously reported overexpressed (IL-10, MSR1, PHLDA1, SERPINB2, and CD86) and underexpressed genes (CHI3L1, CPA3, IL-8, and PI3) in severe asthma were analyzed by RT-qPCR in peripheral blood mononuclear cells (PBMCs). In the overexpressed genes, obesity significantly decreased the expression of MSR1 and PHLDA1 and had no effects on CD86, IL-10, and SERPINB2. In underexpressed genes, obesity did not affect PI3, CHI3L1, and IL-8 and significantly reduced CPA3 expression. The results of this study show that obesity should be included among the known factors that can contribute toward modifying the expression of genes associated with asthma and, in particular, severe asthma.
Tranexamic Acid Use in Pediatric Craniotomies at a Large Tertiary Care Pediatric Hospital: A Five Year Retrospective Study
Authors: Wang Jue T. , Seshadri Samir C. , Butler Carolyn G. , Staffa Steven J. , Kordun Anna S. , Lukovits Karina E. , Goobie Susan M.
Published: June 2023

Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has proven efficacy and is recommended for major pediatric surgery to decrease perioperative blood loss. Accumulating evidence suggests that TXA reduces bleeding and transfusion in a variety of adult neurosurgical settings. However, there is a paucity of research regarding TXA indications for pediatric neurosurgery and thus, there are currently no recommendations for its use with this specific population. The objective of this study is to evaluate the existing practice of TXA administration for pediatric neurosurgery at a U.S. tertiary care pediatric hospital over a five-year period. The authors conclude that TXA administration is feasible and should be considered for pediatric neurosurgical cases where potential blood loss is a concern.
Assessing the Security and Privacy of Baby Monitor Apps
Authors: Schmidt Lukas , Hosseini Henry , Hupperich Thomas
Published: June 2023

Emerging technologies in video monitoring solutions seriously threaten personal privacy, as current technologies hold the potential for total surveillance. These concerns apply in particular to baby monitor solutions incorporating mobile applications due to the potential privacy impact of combining sensitive video recordings with access to the vast amount of private data on a cell phone. Therefore, this study extends the state of privacy research by assessing the security and privacy of popular baby monitor apps. We analyze network security measures that aim to protect baby monitoring streams, evaluate the corresponding privacy policies, and identify privacy leaks by performing network traffic analysis. Our results point to several problems that may compromise user privacy. We conclude that our methods can support the evaluation of the security and privacy of video surveillance solutions and discuss how to improve the protection of user data.
The Tumor Suppressor Adenomatous Polyposis Coli (apc) Is Required for Neural Crest-Dependent Craniofacial Development in Zebrafish
Authors: Liu Xiaolei , Jones William D. , Quesnel-Vallières Mathieu , Devadiga Sudhish A. , Lorent Kristin , Valvezan Alexander J. , Myers Rebecca L. , Li Ning , Lengner Christopher J. , Barash Yoseph , Pack Michael , Klein Peter S.
Published: June 2023

Neural crest (NC) is a unique vertebrate cell type arising from the border of the neural plate and epidermis that gives rise to diverse tissues along the entire body axis. Roberto Mayor and colleagues have made major contributions to our understanding of NC induction, delamination, and migration. We report that a truncating mutation of the classical tumor suppressor Adenomatous Polyposis Coli (apc) disrupts craniofacial development in zebrafish larvae, with a marked reduction in the cranial neural crest (CNC) cells that contribute to mandibular and hyoid pharyngeal arches. While the mechanism is not yet clear, the altered expression of signaling molecules that guide CNC migration could underlie this phenotype. For example, apcmcr/mcr larvae express substantially higher levels of complement c3, which Mayor and colleagues showed impairs CNC cell migration when overexpressed. However, we also observe reduction in stroma-derived factor 1 (sdf1/cxcl12), which is required for CNC migration into the head. Consistent with our previous work showing that APC directly enhances the activity of glycogen synthase kinase 3 (GSK-3) and, independently, that GSK-3 phosphorylates multiple core mRNA splicing factors, we identify 340 mRNA splicing variations in apc mutant zebrafish, including a splice variant that deletes a conserved domain in semaphorin 3f (sema3f), an axonal guidance molecule and a known regulator of CNC migration. Here, we discuss potential roles for apc in CNC development in the context of some of the seminal findings of Mayor and colleagues.
A Systematic Review and Meta-Analysis of Exercise Beneficial for Locomotion in Community-Dwelling Elderly Peoplewith Sarcopenia
Authors: Song Seunghyeok , Kim Gushik , Kim Hyunjoong
Published: June 2023

Sarcopenia, in addition to aging and reduced physical activity, is a progressive skeletal muscle disorder that causes the loss of muscle mass and strength. The most prominent functional change is mobility, which contributes to a decrease in the quality of life. Therefore, we aimed to perform qualitative and quantitative analyses by synthesizing randomized controlled trials (RCTs) that evaluated exercises that affected locomotion in patients with sarcopenia. The RCTs were retrieved in April 2023 from three international electronic databases (Embase, MEDLINE, and PubMed). RCTs published after 2013 were compared with a control group that did not include exercise. Qualitative and quantitative analyses were performed on the identified studies using RevMan 5.4 and risk of bias assessment provided by Cochrane. RCTs involving 594 patients with sarcopenia were included in this study. The analysis model was synthesized as a random effects model, and the standard mean difference (SMD) was used as the effect measure. Exercise interventions were found to not change muscle mass in individuals with sarcopenia (SMD = 0.04; 95% CI: −0.15 to 0.22). However, they had positive effects on lower extremity muscle strength (SMD = 0.34; 95% CI: 0.02 to 0.66) and walking speed (SMD = 0.42; 95% CI: 0.11 to 0.72). For community-dwelling elderly people with sarcopenia, exercise intervention did not lead to an increase in reduced muscle mass, but it brought positive improvements in lower extremity strength and gait speed to improve locomotion.
Production Behavior of Hydrate-Bearing Sediments with Mixed Fracture- and Pore-Filling Hydrates
Authors: Li Yaobin , Xin Xin , Xu Tianfu , Zang Yingqi , Yu Zimeng , Zhu Huixing , Yuan Yilong
Published: June 2023

Most hydrate-bearing sediments worldwide exhibit mixed pore- and fracture-filling hydrates. Due to the high exploitation value, pore-filling hydrate production is the focus of current hydrate production research, and there is a lack of systematic research on the decomposition of fracture-filling hydrates and their effects on the evolution of temperature and pressure in hydrate-bearing sediments. If only the decomposition characteristics of pore-filling hydrates are studied while the fracture-filling hydrates decomposition and its effects on the hydrate-bearing sediments production process are ignored, the obtained research results would be inconsistent with the actual situation. Therefore, in this study, the effects of fracture-filling hydrates with different dipping angles on the hydrate production process were studied, and the necessity of considering the phenomenon of mixed pore- and fracture-filling hydrates in hydrate-bearing sediments was illustrated. On this basis, the simulation of a typical site (GMGS2-16) with mixed pore- and fracture-filling hydrates was constructed, and the production process was researched and optimized. The results indicated that: (a) fracture-filling hydrates formed in shallow fine-grained sediments and gradually approached the area of pore-filling hydrates, before a stable mixed zone was formed; (b) the occurrence of fracture-filling hydrates was conducive to the hydrate-bearing sediment depressurization production, and the promoting effect of the fracture-filling hydrate with smaller dipping angles was stronger; and (c) depressurization combined with heat injection could effectively compensate for the local low temperature and secondary hydrate caused by the mass decomposition of fracture-filled hydrates.
Prediction of Wave Forces on the Box-Girder Superstructure of the Offshore Bridge with the Influence of Floating Breakwater
Authors: Wang Shaorui , Liu Song , Xiang Chenqing , Li Maosheng , Yang Zhiying , Huang Bo
Published: June 2023

In recent years, with global warming and frequent natural disasters, existing offshore bridges are facing the risk of extreme wave action. The research on disaster prevention and mitigation measures of the box-girder superstructure of offshore bridges under extreme wave action is still scarce. In this paper, a numerical model based on the RANS equation and k-ε turbulence model is established to study the wave forces on the box-girder superstructures of offshore bridges with the influence of a floating breakwater. A numerical method for studying the interaction of waves and structures is proposed and verified through experimental data. The effects of many parameters of the floating breakwater on wave attenuation are investigated and a prediction model of the wave reduction rate based on neural network algorithm is proposed. The results show that the reduction rate of wave forces for fixed breakwaters can reach more than 30%, which indicates that a floating breakwater has a significant effect in reducing the wave forces on the box-girder superstructure. The wave reduction performances of the displacement-restricted breakwater and the fixed breakwater are better than that of an elastic restricted breakwater. The prediction model proposed based on the BP neural network is accurate in estimating the maximum wave forces on the box-girder superstructure with the influence of the floating breakwater.
Investigation on Bearing Characteristics of Gravity Wharf Rubble-Mound Foundation in Different Influencing Factors
Authors: Zhang Cong , Zhu Zhende , Dai Lun , Wang Shanyong , Shi Chong , Zhu Duan
Published: June 2023

The use of the heavy hammer compaction method can enhance the bearing characteristics of underwater rubble-mound foundations. This is crucial to ensure the safety and stability of port and coastal engineering projects. In the present work, a combination of image-recognition technology, 3D laser scanning technology, a discrete element numerical simulation, and a field test was first utilized to establish riprap particles and reconstruct a discrete element numerical model of a rubble-mound foundation, and then the effects of various influencing factors on the bearing characteristics of the rubble-mound foundation were studied. The main conclusions are as follows. (1) The load–settlement curve of the rubble-mound foundation can be divided into three stages: rapid growth stage, slow growth stage, and failure stage. (2) The ultimate bearing capacity of the rubble-mound foundation is positively correlated with the vibration time and vibration amplitude. The riprap particle size and the foundation thickness have negligible effects on the ultimate bearing capacity of the rubble-mound foundation. (3) When adjusting the vibration time, vibration amplitude, and foundation thickness, the settlement value of the rubble-mound foundation tends to increase as the compactness increases. On the other hand, the effects of factors such as the riprap particle size, riprap particle gradation, and vibration frequency on the compactness and settlement value of the rubble-mound foundation are less significant.
Seasonal Dynamics of Marine Bacterial Communities in Aquaculture Farms: The case of the Northern Ionian Coastal Ecosystem (Mediterranean Sea)
Authors: Kyritsi Maria , Tsoureki Antiopi , Koukaras Konstantinos , Kamidis Nikolaos , Krey Grigorios , Michailidou Sofia , Argiriou Anagnostis
Published: June 2023

Coastal aquaculture systems are complex environments with multiple microbial interactions that affect fish health and productivity. High-throughput amplicon sequencing is a valuable tool for identifying such bacterial communities and investigating the relationship between bacterial diversity and sustainability in these systems. In the present study, the seasonal dynamics of marine bacterial communities were assessed, in terms of diversity and composition, in three marine aquaculture farms in the northern Ionian Sea (western Greece) and a distant control site unaffected by aquaculture activities, using 16S rRNA amplicon metabarcoding. Results revealed that Proteobacteria, Bacteroidota, Cyanobacteria, and Verrucomicrobiota were the dominant phyla in the bacterial communities. Alpha diversity was significantly lower in the aquaculture farms compared to the control site. Season was the major factor driving bacterial community fluctuations. Comparative analysis between seasons revealed the presence of differentially abundant amplicon sequence variants (ASVs) in all pairwise comparisons, with the majority of them belonging to the phyla Bacteroidota (families Flavobacteriaceae, Cryomorphaceae) and Proteobacteria (family Rhodobacteraceae). Our study provides the first detailed description of bacterial communities present in Greek coastal aquaculture farms using amplicon metabarcoding analysis and expands our understanding of the impact of seasonality and environmental variables on marine bacterial community diversity and composition.