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C-reactive protein (CRP) is a protein made by the liver, which is released into the bloodstream in response to inflammation. Furthermore, CRP is a potential risk factor for heart disease. Hence, it is of great importance to develop a rapid, sensitive, accurate, and cost-effective method for CRP detection. Herein, we report an enzyme-free fluorescent assay for the rapid and ultra-sensitive detection of CRP with a limit of detection (LOD) reaching as low as 3.08 pg/mL (i.e., ~ 27 fM). The high sensitivity of our method was simply achieved via dual-functionalized gold nanoparticles (AuNPs). By regulating the molar ratio of DNA to CRP antibody immobilized on the AuNP surface, hundreds to thousands-fold amplification in the analyte signal could be instantly accomplished. Furthermore, our sensor was selective: non-target proteins such as interleukin-6, interleukin-1β, procalcitonin, bovine serum albumin, and human serum albumin did not interfere with the target CRP detection. Moreover, simulated serum samples were successfully analyzed. Given the excellent sensitivity, selectivity, and high resistance to complicated matrices, the enzyme-free CRP detection strategy developed in this work can be used as a generic platform to construct sensors for a wide variety of protein biomarkers and hence offers potential as a tool for rapid, accurate, and low-cost medical diagnosis. [ABSTRACT FROM AUTHOR]

Background Methods and Results Conclusions Knowledge regarding adenocarcinoma of the rete testis (ACRT) is extremely limited due to its scarcity.This study enrolled 18 patients with ACRT from multiple institutions. Clinicopathological and immunohistochemical features were investigated, together with a comprehensive review of 95 previously reported cases. One case was assessed using next‐generation sequencing (NGS). The median age of the patient cohort was 54 years (range = 20–69 years), with the majority presenting with a testicular mass (13 of 18); predominantly right‐sided (11 of 18). Six patients died within the second year following diagnosis. The morphology of ACRT spans a wide spectrum, including newly identified mucinous carcinoid‐like features, with mucous cells floating in mucus and signet‐ring cells. Notably, transition from a benign to a malignant rete epithelium was noted in 38.9% of cases (seven of 18). Immunohistochemically, tumour cells most frequently showed strong positivity for CK7 (12 of 16) and CK20 (10 of 17), with occasionally positivity for calretinin (three of 16), WT‐1 (two of 17) and PAX‐8 (two of 15). According to NGS in a single case, MET was amplified, leading to the patient benefiting from mesenchymal–epidermal transition factor (MET) inhibitors. Furthermore, MET amplification was assessed in 13 cases using fluorescence in‐situ hybridisation and detected in two cases (15.4%). No significant correlation between MET amplification and mesenchymal–epidermal transition factor (MET) levels was observed in the cases studied.Primary ACRT is a rare malignant tumour which poses a diagnostic challenge, and is associated with poor prognosis. Cases of ACRT with MET amplification might represent promising candidates for the treatment with MET inhibitors. [ABSTRACT FROM AUTHOR]

Bismuth‐doped fibers (BDFs) are renowned in wideband amplification due to their numerous gain bands, such as O, E, S, and U. However, the low amplification coefficient and excessive usage length hinder its further application, how to achieve a high amplification coefficient remains an unresolved challenge. In this study, a high‐efficiency bismuth‐doped germanosilicate fiber (BGDF) for E+S band amplification is developed using modified chemical vapor deposition (MCVD) combined with the solution doping technique. The BGDF achieves a gain of 48.5 dB using a length of only 12 m. The effects of bismuth active centers (BACs) and unsaturable loss (UL) determined by fiber drawing parameters and bismuth concentrations on amplification properties of the BGDFs are discussed. New observations and analysis are conducted on how variations in oxygen vacancies and the bismuth concentration impact BGDFs' luminescence intensity and lifetime. A successful optimization approach is devised to increase BACs levels and decrease UL by modifying drawing parameters and the bismuth concentration to facilitate the formation of low‐valence bismuth and oxygen vacancies. The results suggest that BGDFs are significant for the future expansion of the gain band to the E+S band. [ABSTRACT FROM AUTHOR]

Targeted treatment of advanced or metastatic urothelial carcinomas (UCs) requires the identification of druggable mutations. This study describes the development of a 3′ Rapid Amplification of cDNA Ends (3′ RACE)-based targeted RNA sequencing panel which accounts for the status of all genes relevant to UC treatment, namely, FGFR1-4, KRAS, NRAS, BRAF, ERBB2 (HER2), CD274 (PD-L1) and PIK3CA. FGFR2/3-activating point mutations or fusions were found in 54/233 (23.2%) tumors. FGFR3 rearrangements were identified in 11 patients, with eight of them being undetectable by commonly used PCR kits. In addition, one tumor contained a high-copy FGFR2 gene amplification accompanied by strong overexpression of the gene. Mutations in RAS/RAF genes were present in 30/233 (12.9%) UCs and were mutually exclusive with alterations affecting FGFR2/3 genes. On the contrary, activating events in the HER2 oncogene (point mutations and overexpression), as well as PIK3CA mutations, which were relatively common, occurred with similar frequencies in RAS/RAF- or FGFR2/3-positive vs. negative samples. High PD-L1 mRNA expression was associated with advanced disease stage and was not observed in tumors with increased HER2 mRNA expression or in UCs with evidence for FGFR2/3 activation. Three of the studied carcinomas had high-level microsatellite instability (MSI). Overall, more than half of the UCs had potentially druggable genetic alterations. The proposed NGS panel permits comprehensive and cost-efficient analysis of UC-specific molecular targets and may be considered in clinical routine. [ABSTRACT FROM AUTHOR]

Miniature inverted-repeat transposable elements (MITEs) constitute a class of class II transposable elements (TEs) that are abundant in plant genomes, playing a crucial role in their evolution and diversity. Barley (Hordeum vulgare), the fourth-most important cereal crop globally, is widely used for brewing, animal feed, and human consumption. However, despite their significance, the mechanisms underlying the insertion or amplification of MITEs and their contributions to barley genome evolution and diversity remain poorly understood. Through our comprehensive analysis, we identified 32,258 full-length MITEs belonging to 2,992 distinct families, accounting for approximately 0.17% of the barley genome. These MITE families can be grouped into four well-known superfamilies (Tc1/Mariner-like , PIF/Harbinger-like , hAT-like , and Mutator-like) and one unidentified superfamily. Notably, we observed two major expansion events in the barley MITE population, occurring approximately 12-13 million years ago (Mya) and 2-3 Mya. Our investigation revealed a strong preference of MITEs for gene-related regions, particularly in promoters, suggesting their potential involvement in regulating host gene expression. Additionally, we discovered that 7.73% miRNAs are derived from MITEs, thereby influencing the origin of certain miRNAs and potentially exerting a significant impact on post-transcriptional gene expression control. Evolutionary analysis demonstrated that MITEs exhibit lower conservation compared to genes, consistent with their dynamic mobility. We also identified a series of MITE insertions or deletions associated with domestication, highlighting these regions as promising targets for crop improvement strategies. These findings significantly advance our understanding of the fundamental characteristics and evolutionary patterns of MITEs in the barley genome. Moreover, they contribute to our knowledge of gene regulatory networks and provide valuable insights for crop improvement endeavors. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinomas (CCA) are a group of aggressive malignancies with poor prognosis. The distinct subtypes are related to different etiologies and genetic aberrations that are subject to targeted therapies. Mouse double minute 2 homolog (MDM2) is a potent inhibitor of tumor suppressor p53 and is proven to be altered in certain carcinomas. Novel targeted drugs, such as the MDM2-p53 antagonist Brigimadlin, have shown promising results for therapeutic efficacy in patients with MDM2 amplification and wild-type TP53. Objectives: This study therefore aimed to characterize CCAs regarding their MDM2 status, compare the concordance between fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) methods, and elucidate the role of MDM2 amplification in prognosis and other clinicopathological characteristics. Design: Retrospective cohort study. Methods: All patients (n = 52) were diagnosed with CCA and received surgical resection with curative intention at the University Hospital of Cologne. Samples were analyzed retrospectively for MDM2 amplification with FISH and IHC. We correlated results with pre-existing molecular as well as clinical data. Results: We included 52 patients with primary CCA, three of which showed positive MDM2 amplification (5.8%). MDM2 amplification was present only in the intrahepatic CCA type and all patients with positive MDM2 amplification exhibited normal p53 status. Among the large-duct subtypes of intrahepatic CCAs, patients with positive MDM2 amplification demonstrated better survival than patients with negative MDM2 amplification (p = 0.041). Of the patients with MDM2 amplification, two underwent adjuvant therapy post-surgery (66.7%). There was a strong correlation between MDM2 amplification and positive protein expression in IHC. There were no identifiable molecular co-alterations of MDM2 with FGFR2 or SWI/SNF complex alterations. Conclusion: Real-world evidence in our Caucasian patient population confirmed that a significant number of intrahepatic CCAs showcase MDM2 amplification, qualifying for a personalized therapy option with Brigimadlin. MDM2 amplification must therefore be considered in the context of personalized molecular testing in CCA. [ABSTRACT FROM AUTHOR]

Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial and ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the American Association for Cancer Research (AACR) Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; P  < .001, FDR adjusted q < 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic Whites in adjusted models (OR = 2.52, 95%CI = 1.20 to 5.33, P  = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2 -overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes. [ABSTRACT FROM AUTHOR]

A method of expanding the operating range of the amplifier is presented, which allows reducing the coefficient of nonlinear distortions of the calibration signal to 0.003%. The structural diagram of the analog-digital amplifier of the input signal to the output, which provides minimal nonlinear distortion of the output signal, is given. The principle of operation of the amplifier is described. The input scaling amplifier and output highvolt digital-to-analog converter transmission coefficients dependens diagrams on the input signal amplitude are given. The results of experimental studies of the metrological characteristics of the experimental sample of the amplifier are given. References 10, figures 2. [ABSTRACT FROM AUTHOR]

Background Temocillin is increasingly considered as an alternative to carbapenems. However, there is no consensus on optimal dosing strategies and limited data on temocillin efficacy in systemic infections. Objectives We compared temocillin dosing strategies using pharmacokinetic/pharmacodynamic (PK/PD) modelling and simulation based on plasma exposure and in vitro time–kill data. Methods Temocillin effects on four Escherichia coli strains were evaluated using static time–kill experiments and the hollow-fibre infection model, in which unbound plasma concentrations following intermittent and continuous infusion regimens of 4 and 6 g daily were replicated over 72 h. A PK/PD model was developed to describe the time–kill data. The PK/PD model was coupled to a population PK model of temocillin in critically ill patients to predict bacterial killing and resistance development following various dosing regimens. Results Amplification of resistant subpopulations was observed within 24 h for all strains. The PK/PD model described the observed bacterial kill kinetics and resistance development from both experimental systems well. Simulations indicated dose-dependent bacterial killing within and beyond the currently used daily dose range, and a superiority of continuous compared with intermittent infusions. However, regrowth of resistant subpopulations was frequently observed. For two strains, bacteriostasis over 72 h was predicted only with doses that are higher than those currently licensed. Conclusions Continuous infusions and 6 g daily doses of temocillin kill E. coli more effectively than 4 g daily doses and intermittent infusions, and may increase efficacy in the treatment of systemic infections. However, higher daily doses may be required to suppress resistance development. [ABSTRACT FROM AUTHOR]

Biodiversity loss and anthropogenic modifications to species communities are impacting the frequency and magnitude of disease emergence events. These changes may be related through mechanisms in which biodiversity either increases (amplifies) or decreases (dilutes) disease prevalence. Biodiversity effects can be direct, when contacts among competent hosts are replaced by contacts with sink hosts, or indirect through the regulation of host abundances.Here, we introduce a multihost compartmental disease model, weighting host competences by their evolutionary relatedness. Our model simulates host communities with substitutive and additive assembly patterns and frequency‐ and density‐dependent pathogen transmission modes, from which we estimate the community disease outbreak potential R0.Simulations show how differences in phylogenetic structure can switch host communities from diluting to amplifying a disease, even when species richness is unchanged. We additionally show that phylogenetic dilution can occur simultaneously with (classic) amplification through species richness.We illustrate our model using empirical data describing the relationship between phylogenetic distances separating hosts and their likelihood of disease sharing. Our study demonstrates how host evolutionary histories can drive disease dynamics through a phylogenetic dilution effect. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

The main goal of this research is to evaluate the strain energy in a brittle material during the interaction of the semi-infinite crack with a neighboring micro-crack. The problem is formulated by considering a cracked thin plate having a micro-crack that rotates around itself and around the semi-infinite crack whose the cracked plate is subjected to a uniform load under mode I. During the interaction between the semi-infinite crack and micro-crack, the strain energy and stress field can be generated at the crack tip of semi-infinite crack. The theoretical analysis of this interaction is treated mathematically by the complex potentials functions. It is shown that the positioning of the micro-crack relative to the semi-infinite crack leads to amplification, reduction and absorption of the strain energy at the crack-tip. The theoretical results agree with those found numerically. [ABSTRACT FROM AUTHOR]

The present study compares effects of expressive suppression to a less researched form of expression-focused emotion regulation (namely, amplification) in terms of impact on authenticity and socioemotional outcomes. We expected amplification to result in more positive outcomes than suppression because of its role in facilitating communication. Participants (N = 306) formed 153 previously unacquainted dyads and were randomly assigned to a suppression of expression, amplification of expression, or control condition. After discussing recent personal negative events, participants reported their subjective authenticity, emotional experience, and impressions of their partner. Results revealed that suppressors felt less authentic compared to amplifiers and participants in the control condition. Partners' perceptions of authenticity, however, did not differ across conditions, and only suppressors were rated as less likeable than those in the control condition. Consistent with prior work, amplification was unrelated to change in emotional experience, while suppression predicted decreased positive emotions from before to after the interaction. Building on prior work, these findings support the notion that expressive suppression can lead to interpersonal costs that hinder relationship formation, even though the inauthenticity suppression creates may largely go undetected by others. In contrast, amplification may serve as a relatively more adaptive expression-based strategy, at least in the context of non-close interactions. [ABSTRACT FROM AUTHOR]

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Surface topographic irregularities can alter ground motion. In this study, we investigated the influence of various topographic factors such as relative elevation, slope angle, and curvature on ground-motion amplification. A finite element analysis with absorbing boundary layer was performed using actual topographic data and ground motion data from earthquakes of magnitude 3.8–9 recorded in Japan. To identify the effect of wave velocity on ground motion amplification, we considered the variability in topography and three sets of shear and longitudinal wave velocities by considering five cross-sectional profiles for the topographic models in the numerical analyses. We demonstrate that the topographic amplification factor, which is the ratio of the estimated spectral acceleration on the surface to the median spectral acceleration within the entire surface domain, is significantly influenced by curvature and relative elevation. Furthermore, we have proposed models that estimate ground-motion amplification using the two topographic factors—curvature and relative elevation—as variables. [ABSTRACT FROM AUTHOR]

The aim of the present study was to confirm the presence of the polled intersex syndrome (PIS) deletion in hermaphroditic individuals and polled bucks, transmitting at least one of its copies to PIS individuals. Two sex-reversed animals (Czech White Improved and Polish White Improved), two polled and two horned bucks were examined. Three primer pairs were designed for the identification of the PIS deletion in the sex-reversed individuals and polled bucks. Additional 24 primer pairs were used for the identification of the deletion region in sex-reversed individuals. Selected PCR products were sequenced. The identification of the PIS deletion in hermaphroditic individuals and polled bucks based on the primers designed on the reference template was impossible. Therefore, an attempt was made to determine the reasons for the failure of deletion identification in these individuals. For the polled bucks, the deletion region was amplified similarly to the horned ones, except for an initial sequence. In the two sex-reversed individuals, four inserts were identified in the deletion region. Despite the fact that PIS in goats has been known to breeders and scientists for several decades, many of its aspects, including the molecular reason, are still controversial and require further detailed research. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of non-Hodgkin lymphoma (NHL). Significant efforts have been focused on utilizing advanced genomic technologies to further subclassify DLBCL, NOS into clinically relevant subtypes. These efforts have led to the implementation of novel algorithms to support optimal risk-oriented therapy and improvement in the overall survival of DLBCL patients. The pathogenesis of DLBCL at the molecular level indicates copy number variation (CNV) as one of the major forms of genetic alterations in the somatic mutational landscape. Random deregulation that results in complex breaks of chromosomes and restructuring of shattered chromosomal segments is called chromothripsis. Gene expression changes influenced by chromothripsis have been reported in cancer and congenital diseases. This chaotic phenomenon results in complex CNV, gene fusions, and amplification and loss of tumor suppressor genes. We present herein a summary of the most clinically relevant genomic aberrations, with particular focus on copy number aberrations in a case that highlights DLBCL, NOS arising from relapsed Hodgkin lymphoma. The focus of our study was to understand the relationship between the clinical, morphological, and genomic abnormalities in DLBCL, NOS through multiple techniques for therapeutic considerations.

Simple Summary: Canine lung adenocarcinomas are malignant tumors generally treated by surgical excision. When inoperable, chemotherapy can be performed with limited benefit. For this reason, the use of targeted drugs can be attempted, as has already happened in human medicine. In this retrospective study, 19 canine lung adenocarcinomas were investigated with three different methods to evaluate the expression of HER2. This transmembrane receptor for the human epidermal growth factor is often altered in human epithelial tumors, for which many targeted drugs have recently been produced. Using immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing, we found 3 cases out of 19 with protein overexpression, 2 cases with amplification, and only 1 case with a specific type of mutation (V659E), probably sensitive to tyrosine kinase inhibitory drugs. Due to the similar HER2 molecular changes in dogs and humans, this study provides preliminary information regarding the possible future use of targeted therapies in canine pulmonary adenocarcinomas. Recently, human epidermal growth factor receptor 2 (HER2) has emerged as a therapeutic target of interest for non-small-cell lung cancer in humans. The role of HER2 in canine pulmonary adenocarcinomas is poorly documented. To address this gap, this study employed three methodologies: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) to investigate the protein expression, gene amplification, and mutation of HER2 in 19 canine primary pulmonary adenocarcinomas. By IHC, 3 out of 19 cases were overexpressed 3+, 6 were 2+, and 10 were negative. With FISH, 2 cases were amplified (12.5%), 3 were inadequate for the analyses, and the others were non-amplified. With NGS, seven cases were inadequate. All other cases were wild-type, except for one IHC 3+ case, which was amplified with FISH and with a specific mutation already described in human pulmonary adenocarcinoma, V659E. This mutation is probably sensitive to tyrosine kinase inhibitory drugs. These results are similar to those in human medicine and to the few data in the literature on canine lung carcinomas; the presence of 12.5% of amplified cases in dogs lays the foundation for future targeted drugs against HER2 alterations. [ABSTRACT FROM AUTHOR]

Background: Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high‐risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively. Methods: In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β‐value of the corresponding regression coefficient. A predictive risk‐scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21‐involved risk with the established R‐ISS and R2‐ISS models. Results: Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21‐involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no‐ASCT, and TP53 deletion. This model, termed the ultra‐high‐risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R‐ISS stage 3 and R2‐ISS stage 4. Conclusion: The UHR model, which integrates the presence of +1q21 with no‐ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM. [ABSTRACT FROM AUTHOR]

Food falsification is a pressing issue in today's food industry, with fraudulent substitution of costly ingredients with cheaper alternatives occurring globally. Consequently, developing straightforward and efficient diagnostic systems to detect such fraud is a top priority in scientific research. The aim of the work was to develop a test system and protocol for polymerase chain reaction (PCR) to detect in food products of animal origin the substitution of expensive meat raw materials for by-products of poultry processing. For this, real-time polymerase chain reaction (RT-PCR) was used, which allows determining the qualitative and quantitative substitution in raw and technologically prepared products. Other methods for detecting falsification – enzyme immunoassay (ELISA/ELISA) or express methods in the form of a lateral flow immunoassay are less informative. The extraction of nucleic acids for real-time polymerase chain reaction depends on the source matrix, with higher concentrations obtained from germ cells and parenchymal organs. Extraction from muscle and plant tissues is more challenging, but thorough grinding of these samples improves nucleic acid concentration by 1.5 times using DNA extraction kits. The selection of primers and fluorescent probes through GenBank and PCR Primer Design/DNASTAR software enables efficient amplification and identification of target chicken DNA fragments in various matrices. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive overview of Gallium nitride (GaN)-based power amplifier (PA) design for various frequency bands. GaN-based technology has emerged as a promising alternative to traditional silicon-based amplifiers due to its superior performance characteristics, which are discussed in this paper. This paper also discusses the key design parameters and challenges associated with PA design. Various design techniques and topologies for GaN power amplifiers are explored besides addressing theoretical considerations of PA design along with a complete systematic design procedure for L-Band amplifier using the wolfspeed large signal GaN HEMT model. To further demonstrate the useful methodology, the designs of S-band and C-band PAs are also presented. GaN-based devices are very promising candidates for high-power applications. It is widely used in various high-power applications including communication and radar. [ABSTRACT FROM AUTHOR]

Between September 17 and 18, 2022, a series of earthquakes struck the southern Longitudinal Valley of Taiwan, causing severe damage to infrastructure, particularly bridges, railroads, buildings, and highways in Taitung and Hualien. The primary event in this sequence was the Chihshang earthquake, measuring magnitude of M L 6.9, preceded by a significant foreshock of M L 6.4 the day before. Notably, the highest intensity reported in the epicentral region during this earthquake sequence reached 6 + , marking the highest intensity ever recorded since the Central Weather Bureau (CWB) revised its seismic intensity scale. In this study, we examined the strong ground motion data recorded by the low-cost P-alert network to investigate the cause of structural damage to buildings, railway stations, schools, and other structures in the affected area. Our analysis encompassed data from a total of 17 monitoring stations. The observed peak ground acceleration (PGA) ranges from 0.06 g and 0.78 g, the peak spectral acceleration or response spectrum (PSA) spanned from 0.20 g at 0.50 s to 3.87 g at 0.41 s, and site amplification varied from 4 at 0.6 Hz to 12.6 at 5.2 Hz. The reported damage of single storey house at Taitung City is correlated with the higher amplification 4.5 at 0.14 s; Bridge and factory at Chihshang Township is correlated with the higher amplification 5 at 0.17 s; Railway station at Zhuoxi Township with the higher amplification 7.5 at 0.3 s; of three storey building at Yuli Township with amplification 8 at 0.26 s and, also higher PSA 2.83 g at 0.29 s, and several schools at Kaoshiung City with amplification 7.2 at 0.37 s and with high PSA 3.87 g at 0.41 s. Additionally, we studied the static Coulomb stress changes resulting from the coseismic slip of the main shock, which contributed to an increase in aftershock occurrences. The occurrence of a high-intensity earthquake ( M L 6.9) on September 18, 2022, within a region of positive Coulomb stress changes, provides support for the hypothesis of aftershock triggering. Through analysis, we found that stronger foreshock ( M L 6.4) occurred in the rupture area of mainshock foreshock, positioned adjacent to the main fault. [ABSTRACT FROM AUTHOR]

Biosensing for diagnostics has risen rapidly in popularity over the past decades. With the discovery of new nanomaterials and morphologies, sensitivity is being constantly improved enough for reliable detection of trace biomarkers in human samples, like serum or sweat. This precision has enabled detailed research on the efficacy of biosensors. However, current biosensors suffer from reduced speed of operation. To make better use of this sensitivity, the development of a conductometric biosensor with in-situ use of an Laser Emitting Device (LED) display can provide rapid determination of sample results, steadily pushing biosensors toward more clinical, point-of-care (POC) applications. In this research, a simple LED was used for facile optical determination and visual output of an ultrasensitive bio-signal amplification circuit was made to interface with a B-type Natriuretic Peptide (BNP) biosensor. Tuning circuit gain enables an elegant method for adjustable separation of concentrations into 3 discrete categories: sub-threshold, analog, and saturation regions. These regions corresponded to 0 < [C] < 500 pg/mL (25, 100, 250 pg/mL, LED off), 500 < [C] < 1000 pg/mL (LED varying intensity), and 1000 pg/mL < [C] (LED full intensity). System efficacy was tested using human blood serum samples from University of Pittsburgh Medical Center patients, which were able to be accurately detected and sorted for rapid low cost and power. determination without need for complex digital elements. Additional specificity testing suggests insignificant impact of non-target biomarkers. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of non-Hodgkin lymphoma (NHL). Significant efforts have been focused on utilizing advanced genomic technologies to further subclassify DLBCL, NOS into clinically relevant subtypes. These efforts have led to the implementation of novel algorithms to support optimal risk-oriented therapy and improvement in the overall survival of DLBCL patients. The pathogenesis of DLBCL at the molecular level indicates copy number variation (CNV) as one of the major forms of genetic alterations in the somatic mutational landscape. Random deregulation that results in complex breaks of chromosomes and restructuring of shattered chromosomal segments is called chromothripsis. Gene expression changes influenced by chromothripsis have been reported in cancer and congenital diseases. This chaotic phenomenon results in complex CNV, gene fusions, and amplification and loss of tumor suppressor genes. We present herein a summary of the most clinically relevant genomic aberrations, with particular focus on copy number aberrations in a case that highlights DLBCL, NOS arising from relapsed Hodgkin lymphoma. The focus of our study was to understand the relationship between the clinical, morphological, and genomic abnormalities in DLBCL, NOS through multiple techniques for therapeutic considerations. [ABSTRACT FROM AUTHOR]

Simple Summary: The current investigation identifies differentially expressed genes that specifically influence the serous subtype of ovarian cancer. This subtype accounts for around three-quarters of ovarian cancer cases. To identify these genes, transcriptomic profiles of serous ovarian cancer and non-cancerous tissue samples were extracted from the Gene Expression Omnibus. Differentially expressed genes were derived using GEO2R tool analyses; genes consistently found among upregulated genes in these profiles were considered to be a serous gene set. Next, the serous gene set was examined for its ontological function using the Molecular Signatures Database and its mutational impact on the gene expression profile of high-grade serous ovarian (HGSO) adenocarcinoma. Results showed that 26 genes are amplified in over 5% of HGSO cancer patients, and many of these amplified genes are related to the cell cycle. These cell cycle-related genes were also identified as being involved in the recurrence of serous ovarian cancer. Overall, this study identifies genes that are potential prognostic markers for serous ovarian cancer. The objective of this study was to identify differentially expressed genes and their potential influence on the carcinogenesis of serous-type ovarian cancer tumors. Serous cancer is an epithelial ovarian cancer subtype and is the most common type of ovarian cancer. Transcriptomic profiles of serous cancer and non-cancerous datasets were obtained from the Gene Expression Omnibus (GEO-NCBI). Differentially expressed genes were then derived from those profiles; the identified genes were consistently upregulated in three or more transcriptomic profiles. These genes were considered as the serous ovarian cancer gene set for further study. The serous gene set derived from the transcriptomic profiles was then evaluated for ontological functional analysis using the Molecular Signatures Database. Next, we examined the mutational impact of this serous gene set on the transcriptomic profile of high-grade serous ovarian (HGSO) adenocarcinoma using the cBioPortal database. Results from OncoPrint revealed that 26 genes were amplified in more than 5% of HGSO cancer patients. Interestingly, several of these genes are involved in cell cycle processes, including genes ATPase family AAA domain containing 2 (ATAD2), recQ-like helicase 4 (RECQL4), cyclin E1 (CCNE1), anti-silencing function 1B histone chaperone (ASF1B), ribonuclease H2 subunit A (RNASEH2A), structural maintenance of chromosome 4 (SMC4), cell division cycle associated 20 (CDC20), and cell division cycle associated 8 (CDCA8). The receiver operating characteristic (ROC) curve results also revealed higher specificity and sensitivity for this subtype of tumors. Furthermore, these genes may affect the recurrence of serous ovarian carcinogenesis. Overall, our analytical study identifies cell cycle-related genes that can potentially be targeted as diagnostic and prognostic markers for serous ovarian cancer. [ABSTRACT FROM AUTHOR]

While targeted rehabilitation can enhance hearing aid self-efficacy (HASE), little research has been done to determine the factors contributing to its predictive value. By investigating the experiences of individuals who successfully use HAs and have high levels of HASE, we hoped to illuminate specific strategies and/or sources of support these individuals share that might explain why high HASE is often linked to successful outcomes. This qualitative study explored the experiences of five older adults who were successful HA users and reported having high HASE. Semi-structured interview guides were developed using the transtheoretical model of behavioral change as a framework. Interviews were analyzed thematically and holistically. Participants attributed their HA success to: intrinsic motivation to improve their hearing, confident self-reliance when making health decisions, willingness to act on advice from trusted others, pro-social personal attributes, positive expectations about HA outcomes, and actively pursuing an optimal HA outcome. For these participants, internal factors related to emotional state and source of motivation, and, to a lesser extent, verbal persuasion played a crucial role in their long-term success. This suggests that external influencers might be less impactful in facilitating success for those with high HASE. [ABSTRACT FROM AUTHOR]

Winter extreme cold events (ECEs) have profound impacts on human health, transportation, energy consumption and the economy, particularly associated with high‐humidity conditions. Recent research has indicated a growing interest in extreme temperature events that account for the presence of water vapour. However, the characteristics of humidity‐related ECEs (HECEs) remain unclear. Given the rise in atmospheric moisture due to global warming, understanding the influence of water vapour on HECEs becomes crucial. This study examined variations in HECEs identified using the wet‐bulb globe temperature (WBGT) in China during 1959–2020 and quantified the impacts of water vapour. The results revealed a decrease in the intensity and frequency of HECEs in China during this period, except for in northern China, where the intensity increased, which contrasts with the trends in traditional ECEs. Furthermore, strong HECEs were found to exhibit greater frequency, duration and intensity in northern China than weak HECEs. Additionally, the specific humidity for all categories of HECEs in China exhibited an upward trend, with a more rapid increase for strong HECEs. The findings indicated that the intensity of HECEs is positively correlated with the increase in water vapour. Defining a water vapour amplification factor revealed amplified intensity and duration at most grid points, particularly across northern China. Therefore, while winter warming reduces traditional ECEs, HECEs persist and even intensify as humidity increases, confirming significant amplification by water vapour. Our results emphasized the importance of increasing water vapour, driven by global warming, which may increase the risk of HECEs in the future. [ABSTRACT FROM AUTHOR]

• A multifunctional mechanical model with both amplified illusion and cloaking properties is proposed. • The amplified function can make a small object to produce the same displacement distribution as a large object. • Intelligent control system with the detective and control functions is introduced. • Effectively broaden the effective frequency range of structure in 3300Hz×4400 Hz and 1200Hz×3100 Hz. • The cloaking characteristics of the structure are verified through theoretical, numerical and experimental analysis. Illusion device can make an object to produce a field distribution different from its own, offering potential applications in diverse fields. In this work, we propose a multifunctional metamaterial with intelligent control systems, which exhibits amplified illusion and cloaking characteristics for detecting or hiding objects over different frequency ranges. The amplification function allows a small object to generate the same displacement distribution as a larger object, while the cloaking function renders an object invisible and undetectable. Simulation and experimental results demonstrate the exceptional amplification and cloaking properties of the multifunctional configuration. In contrast to single-function structures like cloaking and focusing, which can only fulfill a specific function, designing a multifunctional structure capable of achieving two or more properties within a single configuration presents a significant challenge. [ABSTRACT FROM AUTHOR]

In this paper we consider flexural-gravity waves propagating in a layer of water of constant depth limited by a vertical wall simulating a straight coastline. The water surface is covered with an elastic ice sheet of constant thickness. The ice sheet is split by one or two straight cracks parallel to the coastline, simulating the structure of land-fast ice with a refrozen lead. Analytical solutions of hydrodynamic equations describing the interaction of flexural-gravity waves with the ice sheet and cracks have been constructed and studied. In this paper, the amplification of the amplitude of incident waves between the shoreline and cracks was described depending on the incident angle of the wave coming from offshore. The constructed solutions allow the existence of edge waves propagating along the coastline and attenuated offshore. The energy of edge waves is trapped between the coastline and ice cracks. The application of the constructed solutions to describe wave phenomena observed in the land-fast ice of the Arctic shelf of Alaska is discussed. [ABSTRACT FROM AUTHOR]

To estimate changes in global mean surface temperature (GMST), one must infer past temperatures for regions of the planet that lacked observations. While current global instrumental temperature datasets (GITDs) estimate different rates of warming for different regions of the planet, this non‐uniform warming is often modelled as residuals relative to underlying trends of spatially uniform warming. To better account for spatial non‐uniform trends in warming, a new GITD was created that used maximum likelihood estimation (MLE) to combine the land surface air temperature (LSAT) anomalies of non‐infilled HadCRUT5 with the sea surface temperature (SST) anomalies of HadSST4. This GITD better accounts for non‐uniform trends in warming in two ways. Firstly, the underlying warming trends in the model are allowed to vary spatially and by the time of year. Secondly, climatological differences between open‐sea and sea ice regions are used to better account for changes in sea ice concentrations (SICs). These improvements increase the estimate of GMST change from the late 19th century (1850–1900) to 2023 by 0.006°C and 0.079°C, respectively. Although, for the latter improvement, tests suggest that there may be an overcorrection by a factor of two and estimates of SICs for the late 19th century are a significant source of unquantified uncertainty. In addition, this new GITD has other improvements compared to the HadCRUT5 Analysis dataset, including correcting for a small underestimation of LSAT warming between 1961 and 1990, taking advantage of temporal correlations of observations, taking advantage of correlations between land and open‐sea observations, and better treatment of the El Niño Southern Oscillation (ENSO). Overall, the median estimate of GMST change from the late 19th century to 2023 is 1.548°C, with a 95% confidence interval of [1.449°C, 1.635°C].This paper suggests two improvements to better account for spatially non‐uniform warming in thermometer‐based global temperature datasets: allowing underlying warming trends in the dataset to vary spatially and by the time of year, and using differences between sea water temperatures and air temperatures above sea ice to better account for the impacts of melting sea ice. These improvements increase the estimate of the average amount of global warming since the late nineteenth century by several hundredths of a degree Celsius. [ABSTRACT FROM AUTHOR]

Mycoplasma bovis (M. bovis) infection is causing substantial economic losses to the global dairy industry including Egypt through its role as a major mastitis pathogen in cattle. The present study was aimed to evaluate loop-mediated isothermal amplification methods (LAMP) and real-time quantitative PCR (rt-qPCR) assays for detecting M. bovis in milk samples from cows (n=30) and buffaloes (n=20) with mastitis across different governorates in Egypt between January and March 2023. Both assays were compared to traditional culture and counter-immunoelectrophoresis (CIEP) methods. The results of the culture methods were 16 (32%), CIEP was 10 (20%), PCR was 16 (32%), LAMP was 18 (36%), and rt-qPCR based on Syber Green was 19 (38%), respectively. The sensitivity of rt-qPCR has the highest sensitivity (100%), specificity (91.17%), and accuracy (100%) (kappa coefficient of 0.856). While LAMP has sensitivity 93.75%, specificity 91.17%, and accuracy 98% (kappa coefficient of 0.811). However, the lowest detection rate was found in culture methods and CIEP. Our research effectively utilized LAMP and Sybr Green-based rt-qPCR assays for the rapid detection of M. bovis in bovine milk samples. However, further validation is necessary with a larger sample size. [ABSTRACT FROM AUTHOR]

This paper will provide a case study to show how the psychoanalyst can use the intuitive archetypal image from a client in the analytic process. The animal image occurred in the analysis has been amplified beyond personal, cultural, historical associations as a ¨fox¨ in modern China. The fox image represents an archetype of masculine energy emerged from female agency as the animal instinct to break through tradition and the limitations of culture and gender. [ABSTRACT FROM AUTHOR]

An ultrasensitive electrochemical biosensor to detect trace Hg2+ in environmental samples was developed utilizing nanogold-decorated magnetic reduced graphene oxide (MrGO-AuNPs), exonuclease III-assisted target cycle (Exo III-ATC) and hybridization chain reaction (HCR) synergistic triple signal amplification. The MrGO-AuNPs is a superior carrier for capture DNA (cDNA) and acts as magnetic media for automatic separation and adsorption. This innovative utilization of the magnetism and improved sensing efficiency obviates the need for direct modification and repeated polishing of the working electrode. Additionally, the three DNA hairpins (cDNA, methylene blue (MB) labeled HP1 and HP2) further contribute to biosensor specificity and selectivity. When cDNA captures Hg2+, it activates Exo III-ATC due to the formation of a sticky end in the cDNA stem via thymine-Hg2+-thymidine (T-Hg2+-T), this leads to the hydrolysis of self-folded cDNA by Exo III-ATC to form "key" DNA (kDNA). The kDNA subsequently initiates HCR, resulting in massive super-sandwich structures (kDNA-[HP1/HP2]n carrying signaling molecules on MrGO-AuNPs, and this overall structure serves as a signal probe (SP). Leveraging magnetic adsorption, the SP was automatically adsorbed onto the magneto-glass carbon electrode (MGCE), generating an amplified signal. This biosensor's detection limit (LOD) was 3.14 pmol/L, far below the limit of 10 nmol/L for mercury in drinking water set by the US EPA. The biosensor also showed excellent selectivity when challenged by interfering ions, and the results of its application in actual samples indicate that it has good potential for practical applications in environmental monitoring. [ABSTRACT FROM AUTHOR]

We present the first comprehensive study for signal growth in transmission lines (TL) with purely time-modulated characteristic impedance [Formula: see text] (infinite superluminality). This study pioneers the investigation into the effects of varying the cell’s electrical length and the impact of loss on momentum bandgaps and amplification levels. It also thoroughly examines how time-modulated transmission line truncation by a static load influences the sensitivity of amplification gain to the relative phase between the incoming signal and modulation, comparing these findings with the case of parametric amplification. Varying [Formula: see text] is accomplished by loading TLs with a sinusoidally time-modulated capacitor (TMC). The study starts with a simple lumped model cell to facilitate understanding of the phenomena. Following this, transmission lines are introduced, and the effects of incorporating loss are examined. To accomplish this, three models are investigated: a lossless L-C TL lumped model loaded with a shunt lossless TMC and a TL loaded with a shunt lossless and lossy TMC. Dispersion diagrams are plotted and momentum bandgaps are identified at a modulation frequency double the signal frequency. Within the momentum bandgap, only imaginary frequencies are found and correlated to momentum bandgap width and signal growth level. Signal growth is confirmed using harmonic balance and transient simulations, and the results are consistent with the dispersion diagram outcomes.

Miniature inverted-repeat transposable elements (MITEs) constitute a class of class II transposable elements (TEs) that are abundant in plant genomes, playing a crucial role in their evolution and diversity. Barley (Hordeum vulgare), the fourth-most important cereal crop globally, is widely used for brewing, animal feed, and human consumption. However, despite their significance, the mechanisms underlying the insertion or amplification of MITEs and their contributions to barley genome evolution and diversity remain poorly understood. Through our comprehensive analysis, we identified 32,258 full-length MITEs belonging to 2,992 distinct families, accounting for approximately 0.17% of the barley genome. These MITE families can be grouped into four well-known superfamilies (Tc1/Mariner-like, PIF/Harbinger-like, hAT-like, and Mutator-like) and one unidentified superfamily. Notably, we observed two major expansion events in the barley MITE population, occurring approximately 12-13 million years ago (Mya) and 2-3 Mya. Our investigation revealed a strong preference of MITEs for gene-related regions, particularly in promoters, suggesting their potential involvement in regulating host gene expression. Additionally, we discovered that 7.73% miRNAs are derived from MITEs, thereby influencing the origin of certain miRNAs and potentially exerting a significant impact on post-transcriptional gene expression control. Evolutionary analysis demonstrated that MITEs exhibit lower conservation compared to genes, consistent with their dynamic mobility. We also identified a series of MITE insertions or deletions associated with domestication, highlighting these regions as promising targets for crop improvement strategies. These findings significantly advance our understanding of the fundamental characteristics and evolutionary patterns of MITEs in the barley genome. Moreover, they contribute to our knowledge of gene regulatory networks and provide valuable insights for crop improvement endeavors.

Introduction. It has been established that the presence of homologous recombination deficiency in a breast tumor is associated with the effectiveness of treatment. But despite the high chemosensitivity of the tumor to DNA-damaging agents, complete pathological responses to treatment are very rare. And this process may be based on a change in the somatic status of BRCA1, that is, a reversion and return of the wild-type allele occurs and the DNA repair function is restored.Aim. To evaluate changes in the presence of chromosomal aberrations and the expression profile of the main genes of homologous recombination in cell models of breast cancer under the influence of cisplatin and docetaxel.Materials and methods. The study was conducted on breast cancer tumor cell cultures: MCF-7, MDA-MB-231 and MDA-MB-468. A cell model of drug resistance was obtained for two drugs: cisplatin and docetaxel. RNA and DNA were isolated from cell suspension using the RNeasy Plus Mini Kit and QIAamp DNA Mini Kit (Qiagen, Germany), respectively. The expression level of homologous recombination genes was assessed using reverse transcription polymerase chain reaction. To assess the presence of chromosomal aberrations, microarray analysis was performed on DNA chips.Results. Restoration of normal copy number for the BRCA1, CDK12, CHEK1 and RAD51D genes in MCF-7 under the influence of cisplatin was shown. For BRCA2 and PALB2, amplifications were detected. A statistically significant increase in the expression of the BRCA1 (p = 0.04), BRCA2 (p = 0.02), PALB2 (p = 0.01) and RAD51D (p = 0.05) genes was also shown. MDAMB-231 shows that all identified loci with deletions, where the BRCA2, BARD1, CHEK2, PALB2 and RAD54L genes are localized, are restored to normal copy number by cisplatin. The appearance of amplifications was registered for BRCA1, BRIP1, FANCL, RAD51B, PARP1. A similar result was shown for docetaxel. An increase in the expression level is typical for the genes BRCA1 (p = 0.02), BRCA2 (p = 0.02), CHEK2 (p = 0.05), FANCL (p = 0.04), PALB2 (p = 0.05), RAD51C (p = 0.02), PARP1 (p = 0.02), which corresponds to the appearance of amplifications. In the MDA-MB-468 cell culture, an increase in the copy number of only the BRCA1 gene is observed. The effect of docetaxel has no effect on this cell culture. The level of BRCA1 expression increases in direct proportion to the duration of drug action.Conclusion. Thus, the study showed that under the influence of cisplatin, reversion of not only homologous recombination gene mutations, but also other disorders can occur.

Background. Millet is one of the main cereal crops with a wide area of cultivation. Over the past decade, there has been a significant increase in the consumption of millet and its processed products. As a result, the breeding of cultivars with high consumer properties is becoming relevant, requiring knowledge of the genetic diversity of germplasm accessions to identify donors of valuable agronomic traits and select parental forms using ISSR markers.Materials and methods. The analysis with 8 ISSR primers included 21 accessions of Panicum miliaceum L. of various origin from the VIR collection. The DNA of each accession was isolated by the CTAB method, and ISSR analysis was performed in a ­BioRad T100 Thermal Cycler. Statistical processing was made in the DARwin program (version 6.0.21).Results and conclusion. Eight primers were used to amplify 116 fragments, 62 (53.4%) of which turned out to be polymorphic. To assess the effectiveness of the analyzed primers and identify the polymorphism of millet, basic indicators of their informativeness were calculated and assessed by quantifying four marker parameters. Average PIC (0.27–0.36), EMR (1.38–14.5) and MI (0.12–4.87) values were obtained for most ISSR primers. Four ISSR primers had high Rp values (3.52–6.76) and were the most informative for genotyping. The selected ISSR markers were used to assess the genetic variability of the accessions and identify them. The values of genetic distances (GD) were 0.05–0.21. It was shown that four ISSR markers with the best informativeness values provided sufficient polymorphism to assess the genetic diversity of the analyzed P. miliaceum genotypes and could be recommended for identification of the variability in the genome of millet accessions.

The ground consists of many layers of soil with different properties. The propagation speed and path of seismic waves are affected by different soil layers. It is necessary to understand that layered soil exhibits different dynamic behaviors and responses under the action of seismic waves. This study utilized weathered soil and silica sand as materials to create multi-layered soil conditions with varying degrees of compaction. By conducting a 1 g shaking-table test on multi-layered soil, the interactions and influences between different soil layers under different earthquake conditions were observed. The approach of our numerical analysis aimed to complement the experimental results and provide an in-depth understanding of the dynamic behavior of multi-layered soil surfaces during seismic events. The acceleration results achieved with the ABAQUS and DEEPSOIL models for multi-layered soil were in good agreement with the experimental results. By comparing the stress–strain curves, the deformation mechanisms under different constitutive models in the numerical analysis were studied. The results of this study show that the amplification effect of seismic waves is related to the number of soil layers and the degree of compaction of the soil layers. This indicates that multi-layered soil ground and the behavior of the soil layers play an important role in the propagation and impact of seismic waves, and this amplification effect is of great significance in the design of actual seismic disaster risk assessments. [ABSTRACT FROM AUTHOR]

This essay honors the creative work of Sanae Kawai and her collaborators who produced a remarkable documentary film called Ripples of Physis. Viewers are invited to witness the ancient Japanese art and craft of karakami as practiced by the Senda family. For over four-hundred years, they have continued making paper by hand, imprinted with wood block patterns born of the interplay between the elemental world and human hands inspired by the power and mystery of the Infinite. The slow pacing of the film conveys a sense of the eternal as does the resonant sound produced by contemporary composer Fred Frith. As a result, viewers become part of a reverberating system. Theories of emergence as well as contemporary ideas from neuroscience are offered as guiding principles for understanding the film and for analytic practice. Psychoanalytic and Jungian understandings of the unconscious are differentiated from the procedural nonconscious, which is imagined as a scaffold for the emergence of forces from both the personal and collective levels activated through environmental interchange. Intersubjectivity and inner-subjectivity are discussed along with what can be a Jungian contribution to psychoanalytic thinking by considering interobjectivity, intuitively understood as "moments of meeting" at the fundamental archetypal level. The film, in itself, has a quiet healing presence that goes far beyond words and is a testament to the value and profound meaning of Jungian amplification through art and craft. [ABSTRACT FROM AUTHOR]

Bone regeneration is a complex multicellular process involving the recruitment and attachment of osteoprogenitors and their subsequent differentiation into osteoblasts that deposit extracellular matrixes. There is a growing demand for synthetic bone graft materials that can be used to augment these processes to enhance the healing of bone defects resulting from trauma, disease or surgery. P-15 is a small synthetic peptide that is identical in sequence to the cell-binding domain of type I collagen and has been extensively demonstrated in vitro and in vivo to enhance the adhesion, differentiation and proliferation of stem cells involved in bone formation. These events can be categorized into three phases: attachment, activation and amplification. This narrative review summarizes the large body of preclinical research on P-15 in terms of these phases to describe the mechanism of action by which P-15 improves bone formation. Knowledge of this mechanism of action will help to inform the use of P-15 in clinical practice as well as the development of methods of delivering P-15 that optimize clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives To elucidate the mechanism of tigecycline resistance in Escherichia coli that is mediated by the tet (A) variant gene. Methods E. coli strain 573 carried a plasmid-borne tet (A) variant gene, tentatively designated tet (A)TIG, that conferred decreased tigecycline susceptibility (MIC 0.5 mg/L). When exposed to increasing concentrations of tigecycline (0.25–8 mg/L), mutants growing at 2, 4 and 8 mg/L were obtained and sequenced. Copies of plasmid and tet (A)TIG relative to the chromosomal DNA in the mutants were determined by WGS and quantitative PCR (qPCR). Expression of tet (A)TIG in the mutants was evaluated by RT–qPCR. The tet (A)TIG-carrying plasmids were visualized by S1-PFGE and Southern blot hybridization. PCR served for the detection of a tet (A)TIG-carrying unconventional circularizable structure (UCS). Results Tigecycline resistance with maximum MICs of 16 mg/L was seen in E. coli mutants selected in the presence of tigecycline. Compared with the parental strain, the relative copy number and transcription level of tet (A)TIG in the mutants increased significantly in the presence of 2, 4 and 8 mg/L tigecycline, respectively. With increasing tigecycline selection pressure, the tet (A)TIG-carrying plasmids in the mutants increased in size, correlating with the number of tandem amplificates of a ΔTn As1 -flanked UCS harbouring tet (A)TIG. These tandem amplificates were not stable in the absence of tigecycline. Conclusions Tigecycline resistance is due to the tandem amplification of a ΔTn As1 -flanked tet (A)TIG-carrying plasmid-borne segment in E. coli. The gain/loss of the tandem amplificates in the presence/absence of tigecycline represents an economic way for the bacteria to survive in the presence of tigecycline. [ABSTRACT FROM AUTHOR]

Background: While targeted therapy has become the standard treatment for certain non-small-cell lung cancer (NSCLC) patients with gene mutation positivity, there remains a lack of enough reports of the efficacy of mesenchymal–epithelial transition (MET) alterations in the real world. Objectives: We aimed to explore the efficacy and toxicity of targeted therapy in NSCLC patients with different types of MET alterations and hope to provide more clinical medication guidance. Design: Designed different subgroups to compare the efficacy and safety of targeted therapy in NSCLC patients with MET alterations. Methods: We conducted analyses on the efficacy and safety of mesenchymal–epithelial transition factor-tyrosine kinase inhibitor (MET-TKI) therapy in NSCLC patients with MET alterations. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 criteria, and both progression-free survival (PFS) and overall survival were determined using the Kaplan–Meier method. Results: Our study encompassed 116 NSCLC patients with MET alterations, including MET ex14 skipping mutation (n = 50), MET primary amplification (amp) (n = 25), and secondary amp (n = 41). Among treated patients, 34 achieved a partial response, while 52 exhibited stable disease. The overall response rate for the entire cohort was 29.31%, with a disease control rate of 74.14%. A significant difference was observed in the median PFS among patients with MET ex14 skipping mutation, MET primary amplification (amp), and secondary amp (10.4 versus 6.6 versus 4.5 months, p = 0.002). In all, 69 patients experienced drug-related adverse effects, with the most common being peripheral edema (35.34%), nausea and vomiting (21.55%), and fatigue (10.34%). In total, 29 patients (25%) encountered drug-related adverse reactions of grade 3 or higher. Conclusion: MET-TKI therapy works better for MET ex14 skipping mutation than other types of MET gene alteration. In the two MET amplified groups, the secondary amp was less effective. This study may provide more research support for the treatment of these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This work investigated the impact of Hippo signaling pathways in the development of ovarian cancer. In order to investigate, the signatures relevant to Hippo signaling pathway were collected from the molecular signatures database, and the expression patterns of these signatures were explored in the mRNA expression profiles of ovarian cancer cohorts. The findings of this study demonstrate that the Hippo signaling pathway signatures are dysregulated significantly in serous subtype-specific ovarian carcinogenesis compared to other subtype ovarian cancers. The receiver operating characteristic curve using the Hippo gene set and its associated gene expressions could predict the serous subtype cancers with greater specificity and sensitivity. Furthermore, the cBioPortal database's high-grade serous ovarian cancer profile examined the Hippo gene set for mutation analysis. The Hippo signaling pathway genes are amplified significantly in grade three and stage three or severe fourth-type ovarian cancers. Furthermore, the Dependency Map plot results prove that these genes are amplified extensively across ovarian cancer cell lines. Additionally, analyses of the overall survival curve plot results also demonstrated that these gene expressions exhibit poor survival patterns associated with highly expressed conditions of serous subtypes of ovarian cancer patients. Among women, ovarian cancer ranks as the fifth most common cause of cancer-related deaths. This study examined the impact of Hippo signaling pathway on ovarian carcinogenesis. Therefore, the signatures related to Hippo signaling pathway were derived from the molecular signatures database (MSigDB) and were used for further analysis. The Z score-based pathway activation scoring method was employed to investigate the expression patterns of these signatures in the mRNA expression profiles of ovarian cancer cohorts. Compared to other subtype tumors, the results of this study show that the Hippo signaling pathway signatures are dysregulated prominently in serous subtype-specific ovarian carcinogenesis. A receiver operating characteristic (ROC) curve-based results of the Hippo gene set, yes-associated protein 1 (YAP1), and mammalian sterile 20-like kinases 1 (MST1) genes can predict the serous subtype tumors by higher specificity and sensitivity with significant areas under the curve values also further reconfirmed these signaling dysregulations. Moreover, these gene sets were studied further for mutation analysis in the profile of high-grade serous ovarian adenocarcinoma in the cBioPortal database. The OncoPrint results reveal that these Hippo signaling pathway genes are amplified highly during the grade three and stage third or fourth of serous type ovarian tumors. In addition, the results of the Dependency Map (DepMap) plot also clearly show that these genes are amplified significantly across the ovarian cancer cell lines. Finally, overall survival (OS) curve plot investigations also revealed that these gene expressions show poor survival patterns linked to highly expressed conditions in serous subtypes of ovarian cancer patients with significant p-values (p < 0.05). Thus, the current finding would help to develop the targeted therapies treatment for serous subtype ovarian carcinogenesis. [ABSTRACT FROM AUTHOR]

TFEB -amplified renal cell carcinoma (RCC), which belongs to the MITF family of RCC, is characterized by genomic amplification at the 6p21.1 locus where the TFEB gene is located. The vascular endothelial growth factor A and cyclin D3 genes are also located at this same locus. When tumors lack classic morphologic features, they may be classified as "RCC not otherwise specified (NOS)." However, it is increasingly important to accurately diagnose the RCC subtype to define the patient's individual prognosis and select the subsequent therapeutic modalities, which now include targeted agents. Therefore, knowledge of the diagnostic features of TFEB -altered RCCs, such as t(6;11) RCCs and TFEB -amplified RCCs, is critical for identifying these tumors. Herein, we present an interesting case of TFEB -amplified RCC that was initially diagnosed as RCC NOS on biopsy of a renal tumor in a community practice setting with available molecular findings demonstrating CCND3 amplification. The genetic abnormality was "accidentally" detected due to the amplification of the colocated CCND3 gene at the 6p21 locus of the TFEB gene on a limited genetic sequencing panel. This case highlights the importance of molecular tests in accurately diagnosing RCC and carefully interpreting molecular findings in the context of histomorphologic features. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare the performance of direct amplification of viral nucleic acid from transport medium to extracted nucleic acid for polymerase chain reaction (PCR), sequencing, and genotyping applications. Methods XpressAmp lysate and extracted total nucleic acid from viral transport medium containing nasopharyngeal specimens were evaluated across different molecular applications to determine performance characteristics. Results SARS-CoV-2 quantitative PCR and angiotensin-converting enzyme (ACE) genotyping assays worked well with XpressAmp lysate, almost equal with or better than extracted nucleic acid in some specimens. However, XpressAmp completely failed to perform in next-generation sequencing for strain typing. Both protocols failed to detect ACE2 expression in viral transport medium. Conclusion Direct amplification of viral nucleic acid from viral transport medium containing nasopharyngeal specimen works well for molecular assays with low thresholds of quality; however, it does have limitations with assays that require high quality nucleic acid for input. Use of the XpressAmp protocol significantly improves turnaround time and allows for easy ramp-up of PCR and genotyping assays. [ABSTRACT FROM AUTHOR]