bluuebunny/crossref_metadata_2025 huggingface dataset:
Simplified Procedure for Rapidly Estimating Inelastic Responses of Numerous High-Rise Buildings with Reinforced Concrete Shear Walls
Authors: Suwansaya Phichaya , Warnitchai Pennung
Published: March 2023

Nonlinear response history analysis (NLRHA) is considered the most accurate procedure for evaluating the seismic performance of high-rise buildings. However, it requires considerable expertise and analysis time, making it inappropriate for some applications involving numerous high-rise buildings (e.g., the seismic loss estimation of a city). To overcome this limitation, a simplified procedure developed based on the uncoupled modal response history analysis (UMRHA) and coupled shear-flexural cantilever beam model (CSFCBM) is proposed. The underlying assumption is that the UMRHA procedure can compute the nonlinear seismic responses mode by mode, where each vibration mode is assumed to behave as a single-degree-of-freedom system. The nonlinear seismic responses are approximately represented by the sum of the modal responses of a few vibration modes. However, UMRHA requires knowledge of the modal properties and modal hysteretic behaviors. Therefore, the CSFCBM was introduced here to estimate the required modal properties and modal hysteretic behaviors. The inelastic seismic demands of the building can be determined using the UMRHA procedure with the computed modal properties obtained by CSFCBM. The accuracy of this proposed procedure was verified considering four high-rise buildings of 19, 30, 34, and 45 stories with reinforced concrete shear walls. The inelastic demands computed by the NLRHA procedure were used as a benchmark and compared with those of the proposed procedure. The results indicate that the proposed procedure provides reasonably accurate demand estimations for all case study buildings. Additionally, the total calculation time for modeling one building, performing dynamic analysis on 24 cases of ground motions, and post-processing the results required by the proposed procedure was about 7 to 45 times lower than that of the NLRHA procedure. Therefore, it can be used for estimating the seismic damage and losses of many high-rise buildings in a city for a specific earthquake scenario or a quick assessment of various seismic design options of a high-rise building in the preliminary design phase.
Feasibility of Multi-Zone Simulation for Estimating Contributions of Outdoor Particulate Pollution to Indoor Particulate Matter Concentration
Authors: Lee Byung-Hee , Baek Seung-Hyo
Published: March 2023

As concerns about the health effects of particulate matter (PM) are growing, controlling indoor PM has become vital for ensuring occupants’ health. Active strategies, such as air purification and high-performance filtering, are widely implemented to control indoor PM. However, passive strategies, including air-tightness and compartmentalization, are promising alternatives, as demonstrated by recent studies. To enhance the implementation of passive strategies, an appropriate evaluation method for passive designs must be established. The objective of this study was to investigate whether a multi-zone-based method is suitable for the evaluation of passive strategies. Multi-zone simulations were performed for four seasons, and indoor/outdoor concentration (I/O) ratios were obtained for the exterior, interior, and corridor on every floor of the reference building. The I/O ratios at different locations indicated that the outdoor particle transport in the building was accurately estimated according to the airflow rate and path. Moreover, in addition to the effects of changes in the outdoor temperature on PM transport through the building envelope, the particle size is a significant factor affecting indoor PM concentrations. The results of this study indicated that the multi-zone method can effectively estimate the number of outdoor particles that penetrate the building envelope in different seasons and the indoor particle concentration at different indoor locations.
Translational Potential of Fluorescence Polarization for Breast Cancer Cytopathology
Authors: Jermain Peter R. , Kandil Dina H. , Muzikansky Alona , Khan Ashraf , Yaroslavsky Anna N.
Published: March 2023

Breast cancer is the most common malignancy in women. The standard of care for diagnosis involves invasive core needle biopsy followed by time-consuming histopathological evaluation. A rapid, accurate, and minimally invasive method to diagnose breast cancer would be invaluable. Therefore, this clinical study investigated the fluorescence polarization (Fpol) of the cytological stain methylene blue (MB) for the quantitative detection of breast cancer in fine needle aspiration (FNA) specimens. Cancerous, benign, and normal cells were aspirated from excess breast tissues immediately following surgery. The cells were stained in aqueous MB solution (0.05 mg/mL) and imaged using multimodal confocal microscopy. The system provided MB Fpol and fluorescence emission images of the cells. Results from optical imaging were compared to clinical histopathology. In total, we imaged and analyzed 3808 cells from 44 breast FNAs. Fpol images displayed quantitative contrast between cancerous and noncancerous cells, whereas fluorescence emission images showed the morphological features comparable to cytology. Statistical analysis demonstrated that MB Fpol is significantly higher (p < 0.0001) in malignant vs. benign/normal cells. It also revealed a correlation between MB Fpol values and tumor grade. The results indicate that MB Fpol could provide a reliable, quantitative diagnostic marker for breast cancer at the cellular level.
Exploring Novel Therapeutic Opportunities for Glioblastoma Using Patient-Derived Cell Cultures
Authors: Ciechomska Iwona A. , Wojnicki Kamil , Wojtas Bartosz , Szadkowska Paulina , Poleszak Katarzyna , Kaza Beata , Jaskula Kinga , Dawidczyk Wiktoria , Czepko Ryszard , Banach Mariusz , Czapski Bartosz , Nauman Pawel , Kotulska Katarzyna , Grajkowska Wieslawa , Roszkowski Marcin , Czernicki Tomasz , Marchel Andrzej , Kaminska Bozena
Published: March 2023

Glioblastomas (GBM) are the most common, primary brain tumors in adults. Despite advances in neurosurgery and radio- and chemotherapy, the median survival of GBM patients is 15 months. Recent large-scale genomic, transcriptomic and epigenetic analyses have shown the cellular and molecular heterogeneity of GBMs, which hampers the outcomes of standard therapies. We have established 13 GBM-derived cell cultures from fresh tumor specimens and characterized them molecularly using RNA-seq, immunoblotting and immunocytochemistry. Evaluation of proneural (OLIG2, IDH1R132H, TP53 and PDGFRα), classical (EGFR) and mesenchymal markers (CHI3L1/YKL40, CD44 and phospho-STAT3), and the expression of pluripotency (SOX2, OLIG2, NESTIN) and differentiation (GFAP, MAP2, β-Tubulin III) markers revealed the striking intertumor heterogeneity of primary GBM cell cultures. Upregulated expression of VIMENTIN, N-CADHERIN and CD44 at the mRNA/protein levels suggested increased epithelial-to-mesenchymal transition (EMT) in most studied cell cultures. The effects of temozolomide (TMZ) or doxorubicin (DOX) were tested in three GBM-derived cell cultures with different methylation status of the MGMT promoter. Amongst TMZ- or DOX-treated cultures, the strongest accumulation of the apoptotic markers caspase 7 and PARP were found in WG4 cells with methylated MGMT, suggesting that its methylation status predicts vulnerability to both drugs. As many GBM-derived cells showed high EGFR levels, we tested the effects of AG1478, an EGFR inhibitor, on downstream signaling pathways. AG1478 caused decreased levels of phospho-STAT3, and thus inhibition of active STAT3 augmented antitumor effects of DOX and TMZ in cells with methylated and intermediate status of MGMT. Altogether, our findings show that GBM-derived cell cultures mimic the considerable tumor heterogeneity, and that identifying patient-specific signaling vulnerabilities can assist in overcoming therapy resistance, by providing personalized combinatorial treatment recommendations.
Soluble Guanylate Cyclase β1 Subunit Represses Human Glioblastoma Growth
Authors: Xiao Haijie , Zhu Haifeng , Bögler Oliver , Mónica Fabiola Zakia , Kots Alexander Y. , Murad Ferid , Bian Ka
Published: March 2023

Malignant glioma is the most common and deadly brain tumor. A marked reduction in the levels of sGC (soluble guanylyl cyclase) transcript in the human glioma specimens has been revealed in our previous studies. In the present study, restoring the expression of sGCβ1 alone repressed the aggressive course of glioma. The antitumor effect of sGCβ1 was not associated with enzymatic activity of sGC since overexpression of sGCβ1 alone did not influence the level of cyclic GMP. Additionally, sGCβ1-induced inhibition of the growth of glioma cells was not influenced by treatment with sGC stimulators or inhibitors. The present study is the first to reveal that sGCβ1 migrated into the nucleus and interacted with the promoter of the TP53 gene. Transcriptional responses induced by sGCβ1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGCβ1 overexpression impacted signaling in glioblastoma multiforme, including the promotion of nuclear accumulation of p53, a marked reduction in CDK6, and a significant decrease in integrin α6. These anticancer targets of sGCβ1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment.
Characteristics of PTEN Mutation in Thyroid Tumours: A Retrospective Chart Review
Authors: Bandargal Saruchi , Rajab Mohannad , Forest Véronique-Isabelle , Pusztaszeri Marc Philippe , Hier Michael P. , da Silva Sabrina Daniela , Payne Richard J.
Published: March 2023

While some studies suggest that PTEN mutations correlate with a low-risk phenotype in pediatric thyroid nodules, the relationship between the mutation and malignancy in the adult populations is abstruse. This study investigated whether PTEN mutations result in thyroid malignancy, and whether these malignancies are aggressive. This multicenter study involved 316 patients who underwent preoperative molecular testing, and subsequent lobectomy or total thyroidectomy at two quaternary care hospitals. A four-year retrospective review was performed on the 16 charts of patients that opted for surgery following a positive PTEN mutation on molecular testing results from January 2018 to December 2021. Of the total 16 patients, 37.5% (n = 6) had malignant tumours, 18.75% (n = 3) had non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs), and 43.75% (n = 7) had benign disease. Aggressive features were detected in 33.33% of the malignant tumours. Malignant tumours were found to have a statistically significant higher allele frequency (AF). The aggressive nodules were all poorly differentiated thyroid carcinomas (PDTCs) with copy number alterations (CNAs) and the highest AFs.
Liquid Biopsies, Novel Approaches and Future Directions
Authors: Armakolas Athanasios , Kotsari Maria , Koskinas John
Published: March 2023

Cancer is among the leading causes of death worldwide. Early diagnosis and prognosis are vital to improve patients’ outcomes. The gold standard of tumor characterization leading to tumor diagnosis and prognosis is tissue biopsy. Amongst the constraints of tissue biopsy collection is the sampling frequency and the incomplete representation of the entire tumor bulk. Liquid biopsy approaches, including the analysis of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating miRNAs, and tumor-derived extracellular vesicles (EVs), as well as certain protein signatures that are released in the circulation from primary tumors and their metastatic sites, present a promising and more potent candidate for patient diagnosis and follow up monitoring. The minimally invasive nature of liquid biopsies, allowing frequent collection, can be used in the monitoring of therapy response in real time, allowing the development of novel approaches in the therapeutic management of cancer patients. In this review we will describe recent advances in the field of liquid biopsy markers focusing on their advantages and disadvantages.
Myeloid-Derived Suppressor Cells (MDSC) in Melanoma Patients Treated with Anti-PD-1 Immunotherapy
Authors: Tomela Katarzyna , Pietrzak Bernadeta , Galus Łukasz , Mackiewicz Jacek , Schmidt Marcin , Mackiewicz Andrzej Adam , Kaczmarek Mariusz
Published: March 2023

Myeloid-derived suppressor cells (MDSC) are a subset of immature myeloid cells with suppressive activity well described in the context of cancer. They inhibit anti-tumour immunity, promote metastasis formation and can lead to immune therapy resistance. In a retrospective study, blood probes of 46 advanced melanoma patients were analysed before the first administration of anti-PD-1 immunotherapy and in the third month of treatment for MDSC, immature monocytic (ImMC), monocytic MDSC (MoMDSC) and granulocytic MDSC (GrMDSC) by multi-channel flow cytometry. Cell frequencies were correlated with response to immunotherapy, progression-free survival (PFS) and lactate dehydrogenase (LDH) serum level. Responders to anti-PD-1 therapy had higher MoMDSC levels (4.1 ± 1.2%) compared to non-responders (3.0 ± 1.2%) (p = 0.0333) before the first administration of anti-PD-1. No significant changes in MDSCs frequencies were observed in the groups of patients before and in the third month of therapy. The cut-off values of MDSCs, MoMDSCs, GrMDSCs and ImMCs for favourable 2- and 3-year PFS were established. Elevated LDH level is a negative prognostic factor of response to the treatment and is related to an elevated ratio of GrMDSCs and ImMCs level compared to patients’ LDH level below the cut-off. Our data may provide a new perspective for more careful consideration of MDSCs, and specially MoMDSCs, as a tool for monitoring the immune status of melanoma patients. Changes in MDSC levels may have a potential prognostic value, however a correlation with other parameters must be established.
Performance of Dental Cements Used for Bonding Zirconia Crowns with Titanium Implants Embedded in an Innovative Bi-Layered Artificial Bone
Authors: Satpathy Megha , Pham Hai , Shah Shreya
Published: March 2023

This study aimed to investigate four dental adhesive cements and develop a new method for constructing a bi-layered bone holder for implant testing. HahnTM Tapered Titanium Implants (Glidewell Laboratories) were embedded in mono- and bi-layered holders, and the implant components were assembled. First molar zirconia crowns and crowns for the tensile bond strength test were milled and sintered. Three self-adhesive resin cements (SARC) and one resin-modified glass ionomer (RMGI, Glidewell Laboratories) cement were used to cement the crowns on the abutment. Tensile bond strength, compressive load, and oblique load tests were performed on the implants. The Glidewell Experimental SARC (GES, Glidewell Laboratories) and RMGI cements had the highest tensile bond strength after thermocycling. The implant assemblies with these two cements had the highest mean compressive strength after thermocycling. Under oblique load, the implants with Denali (Glidewell Laboratories) and GES had the highest strength before thermocycling. However, after thermocycling, Dencem (Dentex) and RMGI had the highest strength under an oblique load. The GES cement and RMGI cement had a better overall performance with zirconia crowns and titanium abutments. In addition, a novel technique for constructing an artificial, bi-layered bone holder was successfully developed to mimic the natural structure of the jawbone.
Nanoscratch Testing of 3Al2O3·2SiO2 EBCs: Assessment of Induced Damage and Estimation of Adhesion Strength
Authors: Botero Carlos Alberto , Cabezas Laura , Sarin Vinod Kumar , Llanes Luis , Jiménez-Piqué Emilio
Published: March 2023

In this study, the structural integrity of mullite (3Al2O3·2SiO2) films, deposited on silicon carbide (SiC) substrates using chemical vapor deposition (CVD), was investigated via increasing load nanoscratch tests. The films were configured by mullite columns of stoichiometric composition growing from a silica-rich layer in contact with the SiC substrate. Controlled damage was induced in the 3Al2O3·2SiO2 films at relatively low scratch loads. Radial and lateral cracking were applied until final delamination and repeated chipping were achieved as the load increased. The intrinsic integrity of the 3Al2O3∙2SiO2 film and the performance of the coated 3Al2O3·2SiO2/SiC system, regarded as a structural unit, were analyzed. With the aid of advanced characterization techniques at the surface and subsurface levels, the configuration and morphology of the damage induced in the coated system by the nanoscratch tests were characterized, and the scratch damage micromechanisms were identified. Finally, the adhesion of the film, in terms of energy of adhesion and interfacial fracture toughness, was determined using different models proposed in the literature. The results from this investigation contribute to the understanding of the mechanical performance and structural integrity of EBC/SiC-based systems, which over the past few years have increasingly been implemented in novel applications for gas turbines and aircraft engines.
Team Mindfulness in Online Academic Meetings to Reduce Burnout
Authors: Nash Carol
Published: March 2023

Burnout, a negative job-related psychological state common with health professionals, results in valuable healthcare research loss. Team mindfulness, promoting work engagement, represents an aspect effective in reducing burnout. In a series of diverse-membership academic meetings intended to reduce research burnout—employing writing prompts, doodling, and continuous developmental feedback—team mindfulness was demonstrated when conducted in person. Therefore, whether team mindfulness is evident when meetings are held online is relevant. During the first eighteen months of COVID-19 limitations requiring these meetings to be online, it was previously reported that team mindfulness was diminished. Question-asking, submitted doodles, and feedback responses were analyzed for the following year of the same group, both quantitively and qualitatively, and with respect to COR theory, to determine if the result persisted. Team mindfulness was also compromised in the second year with respect to the entire group but not regarding the individual relationship with the facilitator. For a diverse-membership group to demonstrate team mindfulness, it is suggested that creating and using avatars similar to those used in online games might be effective. To continue the successful aspect of team mindfulness found online for this group or similarly designed groups, a one-on-one meeting between participant and facilitator is recommended.
Evaluation of Intravenous Immunoglobulin Administration for Hyperbilirubinemia in Newborn Infants with Hemolytic Disease
Authors: Mohan Daniel R. , Lu Hannah , McClary Jacquelyn , Marasch Jaime , Nock Mary L. , Ryan Rita M.
Published: March 2023

The primary objective of this research was to evaluate the use of intravenous immunoglobulin (IVIG) in infants with hemolytic disease, to assess compliance with the American Academy of Pediatrics (AAP) guideline recommendations, and to review the data on which the guidelines were based. This retrospective study evaluated all infants in the NICU (neonatal intensive care unit) who received IVIG between January 2018 and December 2020 (n = 71). Total serum bilirubin (TSB) levels surrounding the time of IVIG administration, rate of rise of bilirubin, and direct antiglobulin test (DAT) status were evaluated to determine the appropriateness of IVIG use based on the 2004 AAP recommendations that was current at the time of the study. Fifty-nine infants received IVIG for hyperbilirubinemia. Of them, 80% had an ABO mismatch, 19% had Rh mismatch, and 71% were DAT-positive. Phototherapy was started at an average of 7 h of age, and the first IVIG dose was administered at an average of 13 h of life; nearly 25% received a second IVIG dose. One infant (1.6%) met all three AAP guideline criteria of being DAT-positive, bilirubin within 3 of exchange level, and rising bilirubin despite intensive phototherapy. Twenty-five (42%) babies were DAT positive and met one of the other two criteria. Only 12% (n = 7) had a bilirubin within 3 of exchange level. Most infants who received IVIG for hyperbilirubinemia did not meet the AAP criteria, prompting us to develop an institution-specific IVIG clinical practice guideline. The 2022 AAP guideline was published after our study was completed, but it confirmed our belief that IVIG usage should be more restricted and the criteria more explicit.
Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities—A Narrative Review
Authors: Ko Mary Hsin-Ju , Chen Hui-Ju
Published: March 2023

Unexplained global developmental delay (GDD) and intellectual disabilities (ID) together affect nearly 2% of the pediatric population. Establishing an etiologic diagnosis is crucial for disease management, prognostic evaluation, and provision of physical and psychological support for both the patient and the family. Advancements in genome sequencing have allowed rapid accumulation of gene–disorder associations and have accelerated the search for an etiologic diagnosis for unexplained GDD/ID. We reviewed recent studies that utilized genome-wide analysis technologies, and we discussed their diagnostic yield, strengths, and limitations. Overall, exome sequencing (ES) and genome sequencing (GS) outperformed chromosomal microarrays and targeted panel sequencing. GS provides coverage for both ES and chromosomal microarray regions, providing the maximal diagnostic potential, and the cost of ES and reanalysis of ES-negative results is currently still lower than that of GS alone. Therefore, singleton or trio ES is the more cost-effective option for the initial investigation of individuals with GDD/ID in clinical practice compared to a staged approach or GS alone. Based on these updated evidence, we proposed an evaluation algorithm with ES as the first-tier evaluation for unexplained GDD/ID.
Treatment of Refractory Congenital Pseudoarthrosis of Tibia with Contralateral Vascularized Fibular Bone Graft and Anatomic Distal Tibial Locking Plate: A Case Series and Literature Review
Authors: Chou Te-Feng Arthur , Liu Ting-Yu , Wang Matthew N. , Yang Chen-Yuan
Published: March 2023

Background: Congenital pseudoarthrosis of the tibia (CPT) remains a challenge for physicians. Several treatment options have been proposed, but the standard of care remains inconclusive. In this study, we present three patients for whom the failure of prior treatments was managed with a contralateral vascularized fibular bone graft (VFG) and an anatomic distal tibial locking plate. Methods: Between 2017 and 2021, three patients were referred for failed treatment of CPT. All patients had undergone multiple prior surgeries, including tumor excision and fixation with ring external fixators, plates, and screws. We performed radical tumor resection and reconstruction of bone defects with a VFG. The construct was fixed with an anatomic locking plate, and the patients were followed up for a mean of 45.7 months. Results: All three patients were able to obtain graft union at 19.3 weeks. At the final follow-up, all grafts achieved bony hypertrophy without evidence of bone resorption or local tumor recurrence. There was a mean leg length difference of 8.5 cm preoperatively, compared with 6.3 cm postoperatively. The average lower leg angulation was 7.4 degrees and the average ankle range of motion was 58.3 degrees. The mean VAS score was 0 and the mean AOFAS score was 88.3. No significant complications were noted. Conclusions: Implantation of a VFG and an anatomic distal tibia locking plate can be considered an option for treatment-refractory CPT. Patients can expect to achieve bone consolidation, ambulate as tolerated, and have a low complication rate.
Metallizing the Surface of Halloysite Nanotubes—A Review
Authors: Masoud Abdul-Razak , Alakija Femi , Perves Bappy Mohammad , Mills Patrick , Mills David
Published: March 2023

Halloysite nanotubes (HNTs) have been shown to be ideal nanoparticles for polymer reinforcement, sustained drug release, nano-reactor synthesis, toxic material removal, regenerative medicine, and as a substrate material for nanostructured coatings. Metal and metal oxide nanoparticles have been used for centuries in various medical applications, primarily for their antimicrobial, antifungal, and antiviral properties. The focus of this review is the metallization of HNT surfaces. Different technologies use specific metal compounds and multi-step chemical reactions to metalize the HNT surface. This review begins with a brief overview of the current methods for metallizing the HNT surface. Our focus then provides a detailed study on specific applications of metal-coated HNTs (mHNTs) in the field of nanomedicine. The focus is on using mHNTs and Mhnt polymer composites in anti-infective therapy, immunotherapy, dentistry, regenerative medicine, and wound healing. The importance of HNTs in aerospace, defense, and industry has emerged, and the application potential and enormous market value for metal oxide nanoparticles is apparent. The commercialization potential of metal-coated HNTs is also discussed.
Study on Residual Stress Evolution Mechanism and Influencing Factors of 316L/Q235B Composite Plate during Solution Heat Treatment
Authors: Ji Xiangyun , Zhao Zhimin , Sun Changshuai , Liu Xin , Wang Rui , Su Chunjian
Published: March 2023

In this study, the formation and evolution mechanism of residual stress in the process of solution heat treatment of a 316L/Q235B composite plate and the influence law of different factors on residual stress were analyzed by combining experiments and simulation. The results showed that the bending stress caused by interlayer thermal stress was the main factor that formed residual stress in the process of solution heat treatment of a 316L/Q235B composite plate. Tensile load was helpful to reduce the bending deformation of the composite plate during heat treatment, and ultimately improve the uniformity of residual stress distribution in the composite plate. With the increase in the total thickness, the interlayer thermal stress and bending stress between layers increased, and the primary and secondary relationship between them and residual stress was related to the specific thickness. The composite ratio had a great influence on the distribution of residual stress. When the composite ratio increased, the interlayer thermal stress between layers of the base layer increased, while that of the cladding layer decreased. At the same time, the bending stress increased with the increase in the composite ratio, and then affected the residual stress distribution.
The European Ground Squirrel’s Genetic Diversity in Its Ancestral Land: Landscape Insights and Conservation Implications
Authors: Koshev Yordan , Říčanová Štěpánka , Kachamakova Maria , Říčan Oldřich
Published: March 2023

The European ground squirrel is an endangered rodent whose populations are declining throughout its range. Only in Bulgaria, the genetic hotspot of the species, are some abundant populations still present. We employed 12 microsatellite loci in ten Bulgarian populations to look at population structure, gene flow and recent bottlenecks. We found that the populations are in good condition in terms of heterozygosity, where values ranged from 0.55 to 0.78. However, the inbreeding index (FIS) was significant for most populations. A recent bottleneck was detected in only one population. Based on Bayesian clustering methods, the populations in Bulgaria were attributed to two groups, northern and southern, with admixture in the northern one. The AMOVA test between these groups showed no differentiation in genetic diversity. The mean value of FST was 0.184, which shows strong diversification among all populations. Hence, gene flow is probably limited. All these results indicate that Bulgaria is the main area to focus the efforts for conservation of the species by ensuring that the complex and rich genetic structure of Bulgarian populations is preserved.
An Investigation on the Relationships between Mass Spectrometric Collisional Data and Biological Activity/Stability of Some N-Acylethanolamine Acid Amidase (NAAA) β-Lactone Inhibitors
Authors: Isak Ilena , Duranti Andrea , Traldi Pietro
Published: March 2023

The rationale of the present study is that relationships between in vitro biological activity and mass spectrometric (MS) collisional data of molecular species have been already reported in the literature. Herein, the same approach has been employed to investigate possible correlations between MS stability and biological activity/stability data of a series of β-lactone amides and carbamates N-acylethanolamine acid amidase (NAAA) inhibitors. Electrospray ionization MS experiments were performed using an LCQ Deca ion trap and samples were introduced by direct infusion. Mass spectra of positive and negative ions have been obtained, and collisional experiments were performed on selected ionic species. Collisional-induced fragmentation pathways of molecular species related to β-lactone amide inhibitors are different in comparison to those of carbamates, being the former species more stable than the latter, due to β-lactone reactivity. Correlations were found between the characteristic collision energy (CE50) obtained by the breakdown curves and in vitro NAAA inhibitory potency of the β-lactone amides and carbamates analyzed. In the case of carbamates, a relationship between CE50 values and bovine serum albumin (BSA) stability data was also found, while any correlation was not found for amides due to their instability to BSA. β-Lactone NAAA inhibitors’ activity can be qualitatively associated with their lability, as measured by CE50 values. The results obtained could suggest that MS may be used as a preliminary experimental tool to identify carbamate NAAA inhibitors endowed with good biological stability.
Update on the Effect of the Urinary Microbiome on Urolithiasis
Authors: Jung Hae Do , Cho Seok , Lee Joo Yong
Published: March 2023

Microbiota are ecological communities of commensal, symbiotic, and pathogenic microorganisms. The microbiome could be involved in kidney stone formation through hyperoxaluria and calcium oxalate supersaturation, biofilm formation and aggregation, and urothelial injury. Bacteria bind to calcium oxalate crystals, which causes pyelonephritis and leads to changes in nephrons to form Randall’s plaque. The urinary tract microbiome, but not the gut microbiome, can be distinguished between cohorts with urinary stone disease (USD) and those without a history of the disease. In the urine microbiome, the role is known of urease-producing bacteria (Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Providencia stuartii, Serratia marcescens, and Morganella morganii) in stone formation. Calcium oxalate crystals were generated in the presence of two uropathogenic bacteria (Escherichia coli and K. pneumoniae). Non-uropathogenic bacteria (S. aureus and Streptococcus pneumoniae) exhibit calcium oxalate lithogenic effects. The taxa Lactobacilli and Enterobacteriaceae best distinguished the healthy cohort from the USD cohort, respectively. Standardization is needed in urine microbiome research for urolithiasis. Inadequate standardization and design of urinary microbiome research on urolithiasis have hampered the generalizability of results and diminished their impact on clinical practice.
Novel Host Response-Based Diagnostics to Differentiate the Etiology of Fever in Patients Presenting to the Emergency Department
Authors: Atallah Johnny , Ghebremichael Musie , Timmer Kyle D. , Warren Hailey M. , Mallinger Ella , Wallace Ellen , Strouts Fiona R. , Persing David H. , Mansour Michael K.
Published: March 2023

Fever is a common presentation to urgent-care services and is linked to multiple disease processes. To rapidly determine the etiology of fever, improved diagnostic modalities are necessary. This prospective study of 100 hospitalized febrile patients included both positive (FP) and negative (FN) subjects in terms of infection status and 22 healthy controls (HC). We evaluated the performance of a novel PCR-based assay measuring five host mRNA transcripts directly from whole blood to differentiate infectious versus non-infectious febrile syndromes as compared to traditional pathogen-based microbiology results. The FP and FN groups observed a robust network structure with a significant correlation between the five genes. There were statistically significant associations between positive infection status and four of the five genes: IRF-9 (OR = 1.750, 95% CI = 1.16–2.638), ITGAM (OR = 1.533, 95% CI = 1.047–2.244), PSTPIP2 (OR = 2.191, 95% CI = 1.293–3.711), and RUNX1 (OR = 1.974, 95% CI = 1.069–3.646). We developed a classifier model to classify study participants based on these five genes and other variables of interest to assess the discriminatory power of the genes. The classifier model correctly classified more than 80% of the participants into their respective groups, i.e., FP or FN. The GeneXpert prototype holds promise for guiding rapid clinical decision-making, reducing healthcare costs, and improving outcomes in undifferentiated febrile patients presenting for urgent evaluation.
A Familial Case of Multiple Endocrine Neoplasia 2A: From Morphology to Genetic Alterations Penetration in Three Generations of a Family
Authors: Chen Lan , Zhang Jing-Xin , Liu Dong-Ge , Liu Hong-Gang
Published: March 2023

This paper illustrates a rare syndrome of multiple endocrine neoplasia type 2A (MEN2A) in a family of three generations. In our case, the father, son and one daughter developed phaeochromocytoma (PHEO) and medullary thyroid carcinoma (MTC) over a period of 35 years. Because of the metachronous onset of the disease and lack of digital medical records in the past, the syndrome was not found until a recent fine needle aspiration of an MTC-metastasized lymph node from the son. All resected tumors from the family members were then reviewed and supplemented with immunohistochemical studies, previously wrong diagnoses were then corrected. Further molecular study of targeted sequencing also revealed a RET germline mutation (C634G) in the family tree including the three members with onset of the disease and one granddaughter who had no disease at the time of testing. Despite the syndrome being well-known, it may still be misdiagnosed because of its rarity and long disease onset. A few lessons can be learned from this unique case. Successful diagnosis requires high suspicion and surveillance and a tri-level methodology including a careful review of family history, pathology and genetic counselling.
Left Atrioventricular Transvalvular Pressure Gradients Derived from Intraoperative and Postoperative Echocardiograms following Atrioventricular Septal Defect Repair
Authors: Bamberg Maximilian , Simon Mark , Bandini Andrea , Hahn Julia Kelley , Schlensak Christian , Icheva Vanya , Hofbeck Michael , Rosenberger Peter , Magunia Harry , Keller Marius
Published: March 2023

Background: Left atrioventricular valve (LAVV) stenosis following an atrioventricular septal defect (AVSD) repair is a rare but potentially life-threatening complication. While echocardiographic quantification of diastolic transvalvular pressure gradients is paramount in the evaluation of a newly corrected valve function, it is hypothesized that these measured gradients are overestimated immediately following a cardiopulmonary bypass (CPB) due to the altered hemodynamics when compared to postoperative valve assessments using awake transthoracic echocardiography (TTE) upon recovery after surgery. Methods: Out of the 72 patients screened for inclusion at a tertiary center, 39 patients undergoing an AVSD repair with both intraoperative transesophageal echocardiograms (TEE, performed immediately after a CPB) and an awake TTE (performed prior to hospital discharge) were retrospectively selected. The mean (MPGs) and peak pressure gradients (PPGs) were quantified using a Doppler echocardiography and other measures of interest were recorded (e.g., a non-invasive surrogate of the cardiac output and index (CI), left ventricular ejection fraction, blood pressures and airway pressures). The variables were analyzed using the paired Student’s t-tests and Spearman’s correlation coefficients. Results: The MPGs were significantly higher in the intraoperative measurements when compared to the awake TTE (3.0 ± 1.2 vs. 2.3 ± 1.1 mmHg; p < 0.01); however, the PPGs did not significantly differ (6.6 ± 2.7 vs. 5.7 ± 2.8 mmHg; p = 0.06). Although the assessed intraoperative heart rates (HRs) were also higher (132 ± 17 vs. 114 ± 21 bpm; p < 0.001), there was no correlation found between the MPG and the HR, or any other parameter of interest, at either time-point. In a further analysis, a moderate to strong correlation was observed in the linear relationship between the CI and the MPG (r = 0.60; p < 0.001). During the in-hospital follow-up period, no patients died or required an intervention due to LAVV stenosis. Conclusions: The Doppler-based quantification of diastolic transvalvular LAVV mean pressure gradients using intraoperative transesophageal echocardiography seems to be prone to overestimation due to altered hemodynamics immediately after an AVSD repair. Thus, the current hemodynamic state should be taken into consideration during the intraoperative interpretation of these gradients.
Dynamic Ultrasound Examination for Extensor Pollicis Longus Tendon Rupture after Palpation-Guided Corticosteroid Injection
Authors: Chen Ying-Chun , Wu Wei-Ting , Mezian Kamal , Ricci Vincenzo , Özçakar Levent , Chang Ke-Vin
Published: March 2023

This report aimed to present a case of wrist-tendon rupture and to discuss a rare complication after corticosteroid injection. A 67-year-old woman had difficulty extending her left-thumb interphalangeal joint several weeks after a palpation-guided local corticosteroid injection. Passive motions remained intact without sensory abnormalities. Ultrasound examination showed hyperechoic tissues at the site of the extensor pollicis longus (EPL) tendon at the wrist level and an atrophic EPL muscle stump at the forearm level. Dynamic imaging demonstrated no motion in the EPL muscle during passive thumb flexion/extension. The diagnosis of complete EPL rupture, possibly due to inadvertent intratendinous corticosteroid injection, was therefore confirmed.
Perspectives on the Application of Cytogenomic Approaches in Chronic Lymphocytic Leukaemia
Authors: Wan Mohamad Zamri Wan Norizzati , Mohd Yunus Nazihah , Abdul Aziz Ahmad Aizat , Zulkipli Ninie Nadia , Sulong Sarina
Published: March 2023

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy characterised by the accumulation of monoclonal mature B lymphocytes (positive for CD5+ and CD23+) in peripheral blood, bone marrow, and lymph nodes. Although CLL is reported to be rare in Asian countries compared to Western countries, the disease course is more aggressive in Asian countries than in their Western counterparts. It has been postulated that this is due to genetic variants between populations. Various cytogenomic methods, either of the traditional type (conventional cytogenetics or fluorescence in situ hybridisation (FISH)) or using more advanced technology such as DNA microarrays, next generation sequencing (NGS), or genome wide association studies (GWAS), were used to detect chromosomal aberrations in CLL. Up until now, conventional cytogenetic analysis remained the gold standard in diagnosing chromosomal abnormality in haematological malignancy including CLL, even though it is tedious and time-consuming. In concordance with technological advancement, DNA microarrays are gaining popularity among clinicians as they are faster and better able to accurately diagnose the presence of chromosomal abnormalities. However, every technology has challenges to overcome. In this review, CLL and its genetic abnormalities will be discussed, as well as the application of microarray technology as a diagnostic platform.
Cross-Departmental Collaboration Approach for Earthquake Emergency Response Based on Synchronous Intersection between Traditional and Logical Petri Nets
Authors: Tian Yinhua , Pang Xiaowen , Su Yan , Han Dong , Du Yuyue
Published: March 2023

In order to reduce the harm of earthquakes to human society, all governments actively promote the construction and development of earthquake emergency rescue work. The earthquake emergency response involves many departments, multiple personnel and large rescue forces, which presents a great challenge to the ability to carry out cross-departmental rescue work in a collaborative and joint manner. A novel collaboration approach based on traditional and logical Petri nets is proposed to improve the cross-departmental collaboration in earthquake emergency response. The approach extends the synchronization of transitions in traditional Petri nets to that of traditional and logical transitions in traditional and logical Petri nets, and defines the intersection of related logical functions. The approach builds a model for the earthquake emergency response plans of various departments with the help of traditional and logical Petri net models, and then performs synchronous intersection operations on the two kinds of Petri nets and merges the two kinds of Petri nets into new logical Petri nets. Meanwhile, through realizing the collaboration ability of cross-departmental work, the approach improves the rescue efficiency and reduces the damage of the earthquake emergency.
Super-Resolution of Compressed Images Using Residual Information Distillation Network
Authors: Zhang Yanqing , Li Jie , Lin Nan , Cao Yangjie , Yang Cong
Published: March 2023

Super-Resolution (SR) is a fundamental computer vision task, which reconstructs high-resolution images from low-resolution ones. Existing SR methods mainly recover images from clear low-resolution images, leading to unsatisfactory results when processing compressed low-resolution images. In the paper, we propose a two-stage SR method for compressed images, which consists of the Compression Artifact Removal Module (CARM) and Super-Resolution Module (SRM). The compressed low-resolution image is used to reconstruct the clear low-resolution image by CARM, and the high-resolution image is obtained by SRM. In addition, we propose a residual information distillation block to learn the texture details which are lost during the compression process. The proposed method has been validated and compared with the state of the art, and experimental results show that the proposed method outperforms other super-resolution methods in terms of visual effects and objective evaluation metrics.
A Study of Weather-Image Classification Combining VIT and a Dual Enhanced-Attention Module
Authors: Li Jing , Luo Xueping
Published: March 2023

A weather-image-classification model combining a VIT (vision transformer) and dual augmented attention module is proposed to address the problems of the insufficient feature-extraction capability of traditional deep-learning methods with the recognition accuracy still to be improved and the limited types of weather phenomena existing in the dataset. A pre-trained model vision transformer is used to acquire the basic semantic feature representation of weather images. Dual augmented attention combined with convolutional self-attention and Atrous self-attention modules are used to acquire the low-level and high-level deep-image semantic representations, respectively, and the feature vectors are spliced and fed into the linear layer to obtain the weather types. Experimental validation is performed on the publicly available standard weather-image datasets MWD (Multi-class Weather Database) and WEAPD (Weather Phenomenon Database), and the two datasets are combined to enhance the comprehensiveness of the model for weather-phenomena recognition. The results show that the model achieves the highest F1 scores of 97.47%, 87.69% and 92.73% on the MWD, WEAPD and merged datasets, respectively. These scores are higher than the scores of recent deep-learning models with excellent performance in the experimental comparison, thereby, proving the effectiveness of the model.
Single-Event Transient Study of 28 nm UTBB-FDSOI Technology Using Pulsed Laser Mapping
Authors: Chen Rui , Chen Li , Li Sai , Liu Rui , Li Xuantian , Shi Shuting , Gu Cheng , Han Jianwei
Published: March 2023

Single-event transient (SET)-induced soft errors are becoming a more significant threat to the reliability of electronic systems in space, especially for advanced technologies. The SET pulse width, which is vulnerable to SET propagation, is a critical parameter for developing SET mitigation techniques. This paper investigates the pulse-broadening effect in the process of SET propagation in logic circuits and the SET-sensitive region distribution in the layout using the pulsed-laser mapping technique in logic circuits implemented with 28 nm Ultra-Thin Body and BOX (UTBB) FDSOI technology. The experiments were carried out at the Naval Research Laboratory (NRL) to measure the SET-induced errors and map the SET-sensitive region distribution at various clock frequencies and laser energy levels. The results illustrate that the number of errors increases with the clock frequency and energy for combinational logic circuits and that the flip-flop SEU rate is less sensitive to clock frequency. The SET pulse-broadening effect was also observed using SET mapping for an OR gate chain at different laser energy levels. In addition, the simulation results revealed the mechanism of the SET pulse-broadening effect in an OR gate chain.
Deleting Cellular Retinoic-Acid-Binding Protein-1 (Crabp1) Gene Causes Adult-Onset Primary Hypothyroidism in Mice
Authors: Najjar Fatimah , Nhieu Jennifer , Wei Chin-Wen , Milbauer Liming , Burmeister Lynn , Seelig Davis , Wei Li-Na
Published: March 2023

Adult-onset primary hypothyroidism is commonly caused by iatrogenic or autoimmune mechanisms; whether other factors might also contribute to adult hypothyroidism is unclear. Cellular Retinoic-Acid-Binding Protein 1 (CRABP1) is a mediator for Non-canonical signalling of all-trans retinoic acid (atRA). CRABP1 Knockout (CKO) mice develop and reproduce normally but begin to exhibit primary hypothyroidism in adults (~3 months old) including increased body weight, decreased body temperature, reduced plasma levels of triiodothyronine and thyroxine, and elevated levels of thyroid-stimulating hormone. Histopathological and gene expression studies reveal significant thyroid gland morphological abnormalities and altered expression of genes involved in thyroid hormone synthesis, transport, and metabolism in the CKO thyroid gland at ~6 months old. These significantly affected genes in CKO mice are also found to be genetically altered in human patients with hypothyroidism which could result in a loss of function, supporting the clinical relevance of CKO mice in humans with hypothyroidism. This study identifies, for the first time, an important role for CRABP1 in maintaining the health of the thyroid gland in adults and reports that CKO mice may provide an experimental animal model for studying the mechanisms underlying the development of adult hypothyroidism in humans.