bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of HRM-Analysis of the Melting Curves Obtained after Amplification of VNTR-Loci for Identification and Differentiation of Brucella Strains
Authors: Anisimova E. A. , Mirgazov D. A. , Dodonova E. A. , Elizarova I. A. , Pankova E. V. , Osyanin K. A.
Published: January 2024

The aim of the present study was to evaluate the effectiveness of analysis of the high resolution melting curves obtained after amplification of VNTR loci for the identification and differentiation of Brucella strains.

Materials and methods. 16 strains of Brucella species – B. canis (n=1), B. abortus (n=9), B. melitensis (n=2), B. suis (n=4) – of different geographical origin were used as objects of the research. The MLVA-typing was performed using conventional PCR followed by separation of amplicons in agarose gel and real-time PCR with post-amplification analysis of the curves of VNTR loci melting in the presence of intercalating dye SybrGreen. Bioinformatics analysis was conducted with the help of Vector NTI 9.1, Mega 11 software (MUSCLE algorithm). Phylogenetic analysis was carried out applying UPGMA method using the Mega 11 program.

Results and discussion. MLVA approach based on the analysis of the melting point curves of the obtained after amplification of VNTR-loci PCR fragments has shown that each of the 16 strains of Brucella is characterized by a unique melting temperature profile. PCR followed by electrophoresis has demonstrated that despite the high variability of the used VNTR sequences (h=0.48…0.74), only post-amplification melting curves of the Bru7, Bru9, Bru18, Bru21 loci had sufficient information content to determine the genetic polymorphism of the studied Brucella strains. Based on the results of phylogenetic analysis of the Bru7, Bru9, Bru18, Bru21 sequences, it has been found that the majority of the studied Brucella strains are distributed in the dendrogram in accordance with their taxonomic and geographical position. Thus, HRM analysis of melting curves obtained after amplification of the Bru7, Bru9, Bru18, Bru21 loci has the potential to be used for differentiating Brucella strains.
MLVA25 and CRISPR Genotypes of Yersinia pestis Strains from the Caspian Sandy Plague Focus
Authors: Goryunova P. A. , Eroshenko G. A. , Balykova A. N. , Kovrizhnikov A. V. , Shevchenko K. S. , Kukleva L. M. , Naryshkina E. A. , Chervyakova N. S. , Kutyrev V. V.
Published: January 2024

The aim of the work was to study the genetic diversity and spatial-temporal structure of Yersinia pestis in the Caspian sandy plague focus using MLVA25 and CRISPR typing methods.

Materials and methods. 98 Y. pestis strains isolated in the territory of the Caspian sandy plague focus in 1925–2015 were used in the study. Whole genome sequencing was performed on Ion GeneStudio S5 System (ThermoFisher Scientific) and MGI (DNBSEQ-G50RS) platforms. Fragment sequencing was conducted using “ABI PRISM 3500XL”. The search for VNTR and CRISPR loci with subsequent alignment of nucleotide sequences was carried out in the MEGA X program. The obtained sequences were entered into the created database in the Bionumerics v7.6 (Applied Maths) software. The phylogenetic tree was constructed using the UPGMA method.

Results and discussion. According to the results of MLVA25 and CRISPR analysis, 98 Y. pestis strains are divided into 60 genotypes (CS1 – CS60). Variability by 23 VNTR loci has been discovered. 7 new CRISPR spacers are described: 5 in YPa and 2 in YPb (size 31–33 bp, GC composition 34–58 %). The described spacers are designated as a108, a109, a110, a111, a112, b53, b54. The interrelation of changes in the copy number of VNTR loci depending on the place and time of isolation of strains has been revealed. The data obtained can be used to carry out molecular-genetic certification of the territory of the Caspian sandy plague focus and to study the routes and patterns of evolution and spatiotemporal circulation of Y. pestis populations in the Caspian plague foci.
The effects of trainers’ competence on employability of government polytechnic college graduates in Dire Dawa City, east-central Ethiopia
Authors: Geressu Birhane , Woldesemayat Zewdu Teshome
Published: January 2024

The need for competent and qualified trainers is of paramount importance for an effective technical training system that, in turn, helps to produce competent and employable graduates for the country’s economy. The purpose of this study is to investigate the effects of trainers' competence on the employability of polytechnic college graduates in Dire Dawa. The study employed a descriptive-correlational-explanatory research design with a quantitative research method. The sample for quantitative data consisted of 351 randomly selected graduates, trainees, trainers, and administrators. Both descriptive and inferential statistics were used to analyse the data. The findings revealed that trainers’ competence was positively correlated with graduates' employability. Specifically, predictors such as knowledge-related competence, assessment-related competence, skill-related competence, and managerial competence were found to have significant and positive effects on the employability of polytechnic college graduates in Dire Dawa. Therefore, the study recommends that the Dire Dawa city Labour Skill and Technology Development Bureau and Polytechnic colleges should give greater emphasis on improving trainers’ competence, which in turn enhances the employability of graduates.
Correlation Study of Rupture Risk in Intracranial Unruptured Aneurysms: Integration of Mannose-binding lectin、Hydrodynamics and Morphology
Authors: Dai Junxia , Li Zhiwei , Lin Qun , Cai Jianyong , Chen Xiaoxiang
Published: January 2024

Background
The purpose of this study is to explore the interconnection between Mannose-Binding Lectin (MBL) and fluid dynamics in the context of rupture risk associated with intracranial unruptured aneurysms.
Methods
68 cases of intracranial unruptured aneurysms were selected from patients treated at Wenzhou Central Hospital between June 2020 and December 2022. Based on MBL concentrations, cases were categorized into three groups: <0.80 mg/L for the low concentration group, 0.80–1.10 mg/L for the moderate concentration group, and > 1.10 mg/L for the high concentration group. Geometric and computational fluid dynamics were employed to calculate morphological and hemodynamic parameters. PHASES score was calculated for each case to estimate rupture risk. Univariate and multivariate logistic regression analyses were conducted to investigate the relationship between morphological-hemodynamic patterns and MBL, as well as their association with rupture risk.
Results
Among them, there were 30 cases in the low concentration group (44.1%), 25 cases in the moderate concentration group (36.8%), and 13 cases in the high concentration group (19.1%). Size ratio, wall shear stress, velocity, low wall shear stress, and relative residence time (RRT) were identified as independent risk factors associated with elevated serum MBL concentration in intracranial unruptured aneurysms. With an increase in PHASES score, there is a significant rise in size-related parameters and the frequency of irregular shapes. Additionally, lower and oscillatory wall shear stress is observed, along with a lower intra-aneurysmal flow velocity and prolonged residence time, indicative of altered hemodynamic patterns. Simultaneously, there is a decrease in the proportion of low MBL concentrations, while the proportions of moderate and high MBL concentrations in aneurysms show a significant increase(P < 0.001).
Conclusions
The serum MBL concentration levels in patients with intracranial unruptured aneurysms are closely associated with their aneurysmal morphology and hemodynamics. Intracranial unruptured aneurysms at higher risk of rupture tend to exhibit larger and irregular shapes, characterized by fluid dynamics with low and variable wall shear stress. Additionally, these aneurysms show elevated serum MBL concentrations.
Climate Change Effects on the Sundarban Mangrove Ecosystem and Tiger Population Dynamics in the Indian Region
Authors: Barik Parthasarathi , Gouda KC
Published: January 2024

In this study, we investigate the impact of climate change, encompassing both natural and anthropogenic scenarios, on the Sundarban mangrove ecosystem—the world's largest natural low-lying mangrove habitat—and its implications for the Royal Bengal Tiger habitat. Situated along the Ganges River between India and Bangladesh, the Sundarban spans approximately 9,600 square km. Employing a multi-source approach, we analyze climate parameters from satellite and real observations, alongside data on mangrove and tiger populations from various sources. Our findings reveal a concerning decrease in mangrove coverage in the present decade, attributed to climate change factors such as rising temperatures, coastal storms, sea-level rise, high humidity, and inadequate rainfall, particularly during the monsoon period. Simultaneously, the Royal Bengal Tiger population in the region has dwindled from 250 in 1960 to a current estimation of 70–80, with the decline attributed to poaching, climate change, and habitat loss. The analysis underscores the interconnectedness of climate, mangrove health, and tiger population, indicating a pressing need for conservation efforts. The study provides critical insights for researchers and policymakers, enhancing our understanding of the complex dynamics between climate change and coastal biodiversity, with significant implications for mangrove ecosystems and tiger habitats. Furthermore, it emphasizes the potential migration of tiger populations from Sundarban to alternative regions due to habitat loss, emphasizing the urgency of addressing climate-induced threats to preserve these vital ecosystems.
A stochastic evolutionary game model of green credit participation behavior among banks and enterprises
Authors: Sun Hao , Feng Yuan
Published: January 2024

With the growing severity of environmental problems, green credit has become an important means of promoting low-carbon development, however, the motivation of banks and enterprises to participate in green credit is insufficient. In order to effectively guide banks and enterprises to actively participate in green credit, we constructed a stochastic evolutionary game model for banks and enterprises to participate in green credit, and analyzed the dynamic game relationship between banks and enterprises. Due to the uncertainty of the external environment, we introduce Gaussian white noise in the replicated dynamic equations, and finally, we use numerical simulation to describe the dynamic evolution trend of the two-dimensional game system. The results show that the stochastic disturbances from external uncertainties amplify the fluctuation range of the game between banks and enterprises and shortening the time to achieve a stable strategy. As enterprises’ fulfillment levels improve, the strategic choices of both banks and enterprises gradually converge to (implement, participate), with banks converging more swiftly. When the government provides certain subsidies, both banks and enterprises tend to opt for green credit, however, after subsidies reach a certain threshold, increasing them no longer significantly impacts strategic choices. An escalation in carbon trading prices also spurs enterprises to choose green credit.
Evaluating Treatment and Care Outcomes for Neuromuscular Diseases in a Pediatric Intermediate Care Setting
Authors: Brisca Giacomo , Strati Marina F. , Canzoneri Francesca , Mariani Marcello , Pirlo Daniela , Romanengo Marta , Tardini Giacomo , Brolatti Noemi , Buratti Silvia , Pedemonte Marina , Striano Pasquale , Bruno Claudio , Moscatelli Andrea
Published: January 2024

Background
Neuromuscular disorders (NMDs) represent a complex group requiring specialized care, often straddling the needs between general pediatric wards and Intensive Care Units (ICUs). Our research focuses on the role of a newly established pediatric Intermediate Care Unit (IMCU) in this context.
Methods
We conducted a single-center retrospective observational study, encompassing patients with NMDs admitted to the newly established pediatric IMCU at IRCCS Istituto Giannina Gaslini, Genoa, Italy, from January 2021 to June 2023. The study assessed demographics, clinical characteristics, therapeutic management, length of stay, and outcomes including mortality 28 days post-discharge.
Results
Sixty-three patients (median age 12, female 58.7%) were included. The majority of admissions were due to neurological issues (39.7%) and respiratory complications (22%), with a significant proportion of patients requiring initiation or potentiation of respiratory support (59%). Factors such as the presence of tracheostomy (p = 0.021), the need for antibiotics (p = 0.025), and parenteral nutrition (p = 0.026) were associated with ICU admissions while steroid treatment (p = 0.047) increased IMCU stay.
Conclusions
The establishment of the IMCU has shown promising results in managing NMDs patients, serving as a crucial step-down unit for ICU patients and a step-up unit for those with worsening conditions in low-intensity care units. It has led to decreased ICU admissions and shorter ICU stays, suggesting potential healthcare costs and patient comfort benefits. The study underscores the importance of pediatric IMCUs in providing specialized care for children with NMDs, balancing the need for intensive monitoring and treatment in a less intensive setting than an ICU.
LightGBM-Based Stochastic Modeling for River Dust-Raising Alert
Authors: Ho Chih Chao , Chang Chih Hsiung
Published: January 2024

To enhance the accuracy of Taiwan's existing river dust-raising alert system, which exclusively depends on wind speed predictions, this study combines hydrological, meteorological, air quality information with LightGBM to establish a stochastic model for forecasting PM10 exceedance probabilities. The flexible probability information can effectively reduce the risk of poor decision-making caused by concentration deterministic forecast errors. LightGBM, a boosting-based ensemble learning algorithm, employs a depth-constrained leaf-wise growth strategy, speeding up training, reducing memory consumption, and shortening training time. The results of model training and validation demonstrate good performance in terms of accuracy, recall, and specificity metrics. This signifies that the model effectively predicts the occurrence of actual dust-raising events. In comparison to the current dust-raising alert mechanism, the model can significantly reduce unnecessary dust alerts and lightening the workforce's burden. Moreover, this model effectively forecasts dust events under low to moderate wind speed conditions, providing decision-makers with crucial support data for proactive dust control deployment.
Single-cell RNA-seq reveals TCR clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in NOD mice
Authors: Robben Michael , Islam Md ZOhorul , Zimmerman Sam , Weidanz Jon , Ordovas-Montanes Jose , Kostic Aleksandar , Luber Jacob
Published: January 2024

T cells primarily drive the autoimmune destruction of pancreatic beta cells in Type 1 diabetes (T1D). However, the profound yet uncharacterized diversity of the T cell populations in vivo has hindered obtaining a clear picture of the T cell changes that occur longitudinally during T1D onset. This study aimed to identify T cell clonal expansion and distinct transcriptomic signatures associated with T1D progression in Non-Obese Diabetic (NOD) mice. Here we profiled the transcriptome and T cell receptor (TCR) repertoire of T cells at single-cell resolution from longitudinally collected peripheral blood and pancreatic islets of NOD mice using single-cell RNA sequencing technology. Surprisingly, we detected a considerable high frequency of islet-matching T cell clones in the peripheral circulation and blood-matching T cell clones in the islets. Our analysis showed that transcriptional signatures of the T cells are associated with the matching status, suggesting potential future applications of T cell clonal biomarkers for early prediction of diabetic onset using peripheral T cells. In addition, we discovered a high frequency of transcriptionally distinct double negative (DN) T cells that likely play a major role in creating an immunosuppressive environment in the pancreas that protects from inflammatory damage. This study provides a single-cell level transcriptome and TCR repertoire atlas of T cells in NOD mice and opens the door for more research into the causes of type 1 diabetes and inflammatory autoimmune disease using mouse models.
Arctic Climate Feedback Response to Local Sea-Ice Concentration and Remote Sea Surface Temperature Changes in PAMIP Simulations
Authors: Jenkins Matthew T. , Dai Aiguo , Deser Clara
Published: January 2024

Local and remote processes have been suggested to drive Arctic amplification (AA) – the enhanced warming of the Arctic region relative to other areas under increased greenhouse gases. We use Polar Amplification Model Intercomparison Project (PAMIP) simulations with changes in Arctic sea-ice with fixed global sea surface temperature (SST), or changes in global SST with fixed Arctic sea-ice to untangle the climate response to Arctic sea-ice loss or SST-induced warming, respectively. In response to Arctic sea-ice loss, the surface albedo feedback activates in summer mainly to increase oceanic heat uptake, leading to weak summertime warming. During winter, Arctic sea-ice loss greatly enhances oceanic heat release, which produces Arctic bottom-heavy warming and triggers positive lapse rate and cloud feedbacks, leading to large AA. In contrast, enhanced atmospheric energy convergence into the Arctic becomes the dominant contributor to relatively small AA under global SST-induced warming. Water vapor feedback contributes to Arctic warming but opposes AA due to larger tropical than Arctic moistening under SST-induced warming with fixed Arctic sea-ice. We also find top-heavy to uniform (bottom-heavy) Arctic warming and moistening in the Arctic mid-upper (lower) troposphere in the SST (Arctic sea-ice) perturbation runs, producing a negative-neutral (positive) Arctic lapse rate feedback, respectively. Lastly, we show that the responses to global SST or polar SIC perturbations are linearly separable. Our results suggest that large AA is caused primarily by sea-ice loss and resultant local changes in surface fluxes, while increased poleward energy transport can only produce weak AA under fixed sea ice.
Fabricating Pentaazatetraethylene Modified Sulfonated Polyacrylamide for Dye Adsorption from Aqueous Media: Isotherms and Kinetics Models
Authors: Karimi Seyed Yaghoub , Marofi Safar , Zare Mohamad Ali
Published: January 2024

In this study, pentaazatetraethylene modified sulfonated polyacrylamide (PAm-SO3-N5) was synthesized and used as a novel efficient adsorbent to remove Calmagite from aqueous media. To this end, a central composite design (CCD) was applied to reduce the number of reaction variables (i.e., adsorbent concentration, temperature, initial concentration, and pH) on Calmagite removal. The results showed that calmagite was entirely adsorbed by the PAm-SO3-N5 within 30 min. In addition, a pseudo-second-order (PSO) model was prepared as the optimum formula to fit the kinetics information. The modeling results revealed that film diffusion and adsorption are rate-limiting stages to remove the dyes. Using a Langmuir isotherm to fit the equilibrium data, the highest equilibrium adsorption was calculated to be 1,732.5 mg/g. In the present study, the ΔH value indicates that the adsorption is of chemical type. Also, the negative sign of ΔS° shows that PAm-SO3-N5 removes Calmagite during a relatively stable process with randomness in the system. The increase in ΔG° values with increasing temperature indicates a descending trend in the feasibility degree of Calmagite adsorption. Eventually, recycling the adsorbent for 7 cycles to adsorb calmagite dye showed no remarkable activity loss.
Repeatability of 18F-FDG uptake in metastatic bone lesions of breast cancer patients and implications for accrual to clinical trials
Authors: Muzi Mark , Peterson Lanell M. , Specht Jennifer M. , Hippe Daniel S. , Novakova-Jiresova Alena , Lee Jean H. , Kurland Brenda F. , Mankoff David A. , Obuchowski Nancy , Linden Hannah M. , Kinahan Paul E.
Published: January 2024

BACKGROUND
Standard measures of response such as Response Evaluation Criteria in Solid Tumors are ineffective for bone lesions, often making breast cancer patients with bone-dominant metastases ineligible for clinical trials with potentially helpful therapies. In this study we prospectively evaluated the test-retest uptake variability of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) in a cohort of breast cancer patients with bone-dominant metastases to determine response criteria. The thresholds for 95% specificity of change versus no-change were then applied to a second cohort of breast cancer patients with bone-dominant metastases.
In this study, nine patients with 38 bone lesions were imaged with 18F-FDG in the same calibrated scanner twice within 14 days. Tumor uptake was quantified as the maximum tumor voxel normalized by dose and body weight (SUVmax) and the mean of a 1-cc maximal uptake volume normalized by dose and lean-body-mass (SULpeak). The asymmetric repeatability coefficients with confidence intervals of SUVmax and SULpeak were used to determine limits of 18F-FDG uptake variability. A second cohort of 28 breast cancer patients with bone-dominant metastases that had 146 metastatic bone lesions was imaged with 18F-FDG before and after standard-of-care therapy for response assessment.
RESULTS
The mean relative difference of SUVmax in 38 bone tumors of the first cohort was 4.3%. The upper and lower asymmetric limits of the repeatability coefficient were 19.4% and -16.3%, respectively. The 18F-FDG repeatability coefficient confidence intervals resulted in the following patient stratification for the second patient cohort: 11-progressive disease, 5-stable disease, 7-partial response, and 1-complete response with three inevaluable patients. The asymmetric repeatability coefficients response criteria changed the status of 3 patients compared to standard the standard Positron Emission Tomography Response Criteria in Solid Tumors of ±30% SULpeak.
CONCLUSIONS
In evaluating bone tumor response for breast cancer patients with bone-dominant metastases using 18F-FDG uptake, the repeatability coefficients from test-retest studies show that reductions of more than 17% and increases of more than 20% are unlikely to be due to measurement variability. Serial 18F-FDG imaging in clinical trials investigating bone lesions from these patients, such as the ECOG-ACRIN EA1183 trial, benefit from confidence limits that allow interpretation of response.
Visualization of blood-brain barrier disruption in septic mice with the new method based on in vivo imaging technology
Authors: Zhang Haisong , Ai Yuhang , Zhang Xiaolei , Deng Fuxing , Jiang Shiwei , Xie Shucai , Peng Milin , Chen Wei , Hu Jiyun , Deng Songyun , Zhang Lina
Published: January 2024

Objectives
Dynamic monitoring of the blood-brain barrier (BBB) functional status in septic mice can helps to explore the pathological mechanisms. Therefore, we proposed a new method for monitoring BBB permeability and apply it to the detection of sepsis models.
Methods
The new method involves the construction of an optical cranial window and in vivo imaging. We performed dynamic monitoring of BBB permeability and cerebral blood flow (CBF) in cecal ligation puncture (CLP) and endotoxemia (LPS) mice.
Results
The sensitivity and accuracy of this method were higher than those of Evans blue evaluation. The increase of BBB permeability in CLP group mice was relatively mild and correlated with overall survival (OS), and the damage was irreversible. Contrarily, BBB damage in the LPS group was more acute and severe, unrelated to OS, but recoverable. The CBF decreased significantly in both model mouse groups 24 hours after modeling, but only the CBF proportion decrease in the LPS group was significantly correlated with the increased value of BBB permeability. Within 24 hours after both models were established, the decrease in blood flow in the digestive organs occurred earlier than in the brain and kidneys, and the decrease in small intestine blood flow in the LPS group progressed faster.
Conclusion
We have successfully demonstrated the feasibility of our novel method to detect BBB permeability in mice. Our results revealed a significant difference in the BBB permeability change trend between the CLP and LPS model mice when survival curves were consistent. Notably, the CLP model mice demonstrated a closer resemblance to clinical patients. Our findings suggest that early-stage brain tissue hypoperfusion has a greater impact on BBB function damage in endotoxemia mice, which is related to the faster progression of blood flow redistribution.
MIR4435-2HG: A Novel Biomarker for Triple-Negative Breast Cancer Diagnosis and Prognosis, Driving Tumor Progression through EMT by JNK/c-Jun and p38 MAPK Signaling Pathway Activation
Authors: Gu Peng , Ding Wentao , Zhu Wenting , Shen Ling , Yan Bin , Zhang Lei , Wang Wei , Wang Ruitao , Wang Wenhao , Wang Yanhao , Sun Xing
Published: January 2024

Background
Breast cancer has the highest incidence rate and causes the most fatalities among all female cancers worldwide. Triple-negative breast cancer (TNBC) is known for its strong invasiveness and higher rates of recurrence. In this research, we aimed to identify MIR4435-2HG as a promising long non-coding RNA (lncRNA) biomarker and therapeutic target for TNBC.
Methods
Utilizing clinicopathological information and transcriptome data from The Cancer Genome Atlas (TCGA) database, we assessed the clinical relevance of MIR4435-2HG in breast cancer through univariate and multivariate COX regression, receiver operating characteristic (ROC) analysis, as well as Kaplan-Meier survival analysis. To investigate the biological role of MIR4435-2HG in TNBC, we conducted gene set enrichment analysis (GSEA), as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Additionally, we constructed and validated a nomogram to predict disease-free survival (DFS). Both the R package “pRRophetic” and the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm were employed to forecast the sensitivity to different therapeutics between the high- and low-MIR4435-2HG groups. We employed single-cell RNA sequencing analysis and tumor microenvironment infiltration analysis to investigate the potential involvement of MIR4435-2HG in the TNBC tumor microenvironment. Cellular biological behaviors were assessed utilizing CCK-8, transwell assays, and wound-healing assays. Furthermore, we performed RNA-seq, qRT-PCR, and western blotting analyses to elucidate and confirm the specific mechanisms underlying MIR4435-2HG-mediated TNBC progression.
Results
In our study, we have identified MIR4435-2HG as a significant diagnostic and prognostic factor for TNBC. We observed that MIR4435-2HG is widely expressed and might have a significant impact on the reshaping of the TNBC tumor microenvironment. Patients with breast cancer in the high-MIR4435-2HG group may show reduced sensitivity to cisplatin, doxorubicin, and gemcitabine and have an increased propensity for immune escape. Notably, MIR4435-2HG predominantly enhances the migratory and invasive capabilities of TNBC cells through the epithelial-mesenchymal transition (EMT) process. Mechanistically, we validated that MIR4435-2HG activates the JNK/c-Jun and p38 MAPK signaling pathway in TNBC.
Conclusions
Our findings highlight the significant potential of MIR4435-2HG as a highly promising biomarker for TNBC. Targeting MIR4435-2HG could represent an appealing therapeutic approach to suppress TNBC metastasis.
Pediatric acute myeloid leukemia with t(8;21) and KIT mutation treatment with avapritinib post-stem cell transplantation: a case report
Authors: Wang Qingwei , Hu Yixin , Gao Li , Zhang Senlin , Lu Jun , Li Bohan , Li Jie , Yao Yanhua , Cheng Shengqin , Xiao Peifang , Hu Shaoyan
Published: January 2024

Acute myeloid leukemia (AML) with t(8;21) (q22;q22), which forms RUNX1::RUNX1T1 fusion gene, is classified as a favorable-risk group. However, the presence of mutations in KITexon 17 results in an adverse prognosis in this group. Avapritinib, a novel tyrosine kinase inhibitor, was designed to target KIT mutation. We report a retrospective study of four pediatric patients with AML with t(8:21) and KIT exon 17 mutation who were treated with avapritinib. Three of these patients failed to demethylate drugs and donor lymphocyte infusion targeting RUNX1::RUNX1T1-positivity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Three patients with RUNX1::RUNX1T1positivity had turned negative after 1, 2, and 7 months of avapritinib treatment and remained so during follow-up, while one patient retained the lowest relative value for months. The common adverse effect of avapritinib is neutropenia, which is well-tolerated. This case series indicates that avapritinib may be effective and safe for preemptive treatment of children with AML with t(8;21) and KIT mutation after allo-HSCT, providing a treatment option for preventing relapse after allo-HSCT.
Homoclinic bifurcations and chaotic dynamics in a bistable vibro-impact SD oscillator under Gaussian white noise
Authors: Jia Lele , Li Shuangbao , Kou Liying , Wu Kongran
Published: January 2024

This paper studies the effect of Gaussian white noise on homoclinic bifurcations and chaotic dynamics of a bistable vibro-impact SD oscillator. Firstly, the SD oscillator is reproduced and generalized by installing a slider on a fixed rod so that the slider is connected by a pair of linear springs initially pre-compressed in the vertical direction to achieve bistble vibration characteristic, two screw nuts are installed on the rod as two adjustable bilateral rigid constraints to generate vibro-impact. A discontinuous dynamical equation with a map defined on switching boundaries to represent velocity loss during each collision is derived to describe the vibration pattern of the bistable vibro-impact SD oscillator through studying the persistence of the unique unperturbed non-smooth homoclinic structure. Secondly, the general framework of random Melnikov process for a class of bistable vibro-impact systems under Gaussian white noise is simply derived and employed through the corresponding Melnikov function to obtain the necessary parameter thresholds for homoclinic tangency and possible chaos of the bistable vibro-impact SD oscillator. Thirdly, the effectiveness of a semi-analytical prediction by the Melnikov function is verified through the lagest Lyapunov exponent, bifurcation series, and 0 − 1 test. In addition, the sensitivity to the initial values of chaos is verified by the fractal of attractor basins, and the influence of the Gaussian white noise on periodic and chaotic structures is studied through Poincaré mapping to show rich dynamical geometric structures.
Variable Effects of Experimental Sea-Level Rise Conditions and Invasive Species on California cordgrass
Authors: Gonzalez Julie , Ferner Matthew C. , Grosholz Edwin D.
Published: January 2024

Sea-level rise (SLR) will produce unprecedented changes in tidal marsh systems that already cope with daily tidal perturbations, disturbances from storms, and salinity changes from droughts and runoff events. Additionally, negative impacts from non-native invasive species may alter marsh plants’ susceptibility to SLR stressors like inundation and salinity. Increasingly, tidal marsh communities must tolerate both changes in the physical environment from SLR and invasive species impacts. To assess the response of a threatened tidal marsh cordgrass (Spartina foliosa) to both stressors, we implemented a field experiment in San Francisco Bay, CA, USA, exposing cordgrass to a treatment that extended tidal inundation projected with SLR using a recently developed in situ method. At one of two field sites, we also enclosed the cordgrass with or without the invasive European green crab, Carcinus maenas. We found that cordgrass responded negatively to longer inundation, although these effects varied by site and year. In higher inundation treatments, cordgrass survival increased with increasing surface elevation of the plot. Cordgrass survival was lower in the presence of invasive crabs relative to controls. We did not find interacting effects of increased inundation and green crab presence on any response variables, which highlights the need to consider how latent or sequential effects of multiple stressors may affect ecosystems. This study demonstrates significant biological responses to invasive species and inundation. Evaluating relative effects and timing of multiple stressors, especially those induced by climate change and invasive species, will help us to manage threatened ecological communities in a changing world.
VBP1 promotes tumor proliferation as a part of the hypoxia-related signature in esophageal squamous cell carcinoma
Authors: Miao Huikai , Gao Wuyou , Zhong Leqi , Li Hongmu , Chen Dongni , Xu Chunmei , Wen Zhesheng , Chen Youfang
Published: January 2024

Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor in East Asia. Hypoxia, a hallmark of solid tumors, significantly alters redox homeostasis inside tumor microenvironment. This alteration drives tumor proliferation, invasion, and metastasis, leading to poor prognostic outcomes. However, the role of hypoxia-related genes in ESCC remains poorly understood. We employed RNA sequencing to identify differentially expressed genes in ESCC. Clinical data, transcriptome profiles, and a hypoxia-related gene set were extracted from open-source databases. A prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression, which was then validated through Cox regression analysis. Within this prognostic model, we pinpointed and investigated a key hypoxia-related gene affecting prognosis. The gene's expression was validated using real-time PCR and immunohistochemistry in both esophageal carcinoma and normal tissues. Tumor proliferation was examined through in vitro and in vivo assays, including the Cell Counting Kit-8, EdU, colony formation, and subcutaneous tumor models. A robust four-gene prognostic model (VBP1, BGN, CDKN1A, and PPFIA1) was successfully constructed and validated. Among these, VBP1 emerged as a key gene, exhibiting high expression levels that correlated with poor prognosis in ESCC. Functional experiments confirmed that VBP1 significantly accelerated tumor proliferation both in vitro and in vivo. VBP1 is identified as a pivotal gene within the hypoxia-related prognostic signature, and it significantly promotes tumor proliferation in ESCC.
The effect of social alienation on stigma among in-patients with stroke: A cross-sectional study
Authors: Wu Yu , Liu Jian , Fornah Lovel , Zhao Jun , Wu Shicai
Published: January 2024

Backgroud Stigma adversely affects the rehabilitation among in-patients with stroke, which decreases the motivation and functional improvement during rehabilitation in patients with stroke. The study aims to investigate the influencing factors of stigma. Methods The study design is a cross-sectional survey. A total of 220 in-patients with stroke completed demographic information, the generalized social alienation scale, and the stroke stigma scale. Multiple linear regression analysis was used to evaluate the impact of the diverse factors on stigma. Results The findings indicate that there were moderate scores on stigma among in-patients with stroke. Age(B=−2.105, P < 0.001), level of education[Junior high school(B = 1.545, P = 0.040), senior high school or technical secondary school(B = 3.480, P < 0.001), Undergraduate or junior college(B = 3.716, P < 0.001), and graduate(B = 5.483, P < 0.001)] and social alienation(B = 0.158, P < 0.001) were all significantly associated with stigma in patients with stroke. Conclusions To address stigma among in-patients with stroke, efforts should be directed towards reducing social alienation among younger patients and those with higher levels of education.
WITHDRAWN: Cross-scale modeling of Microencapsulated self-healing composite with multiphase medium and their damage competition behavior
Authors: Yin Haipeng , Li Youtang , Huang Hua
Published: January 2024

Constructing a high-fidelity cross-scale numerical model is the primary challenge in the multiscale analysis of multiphase medium composites. Considering the limitations of the Finite Element Method (FEM) in the study of the dynamic damage problem of non-homogeneous and discontinuous materials, the Discrete Element Method (DEM) is used in this study to build a three-medium multiscale numerical model containing aggregates, matrix, and microcapsules. Further, the dynamic damage problem of microcapsules embedded in self-healing composites and the damage competition issues between the microcapsules and the matrix are investigated. The results indicate that (1) The damage evolution process, the location of maximum damage, and the final damage pattern of microcapsule embedded in the matrix and exposed to the ideal environment differed considerably. (2) The effect of microcapsule volume fraction on the mechanical strength of the matrix in self-healing composites is not linearly negatively correlated, but instead, there is a non-linear relationship, which is highly dependent on the strength ratio of the microcapsule to the matrix. (3) In self-healing composites, damage competition between the microcapsules and the matrix has a decisive influence on triggering the self-healing mechanism. (4) To obtain a better self-healing effect, the microcapsule volume fraction in the self-healing composites should not exceed 1.5%, and the mechanical strength pre-maintenance should not be more than 95% of the failure strength. The multiphase medium & multiscale analysis method proposed in this study also provides a new approach for visualizing the progressive dynamic damage problem in self-healing composites.
Energy Confinement of Mode-Localised Sensors
Authors: Chang Honglong , Zhang Zhao , Li Han , Hou Cheng , Hao Yongcun
Published: January 2024

Energy confinement is one of the significant features of the mode-localised phenomenon and is also the secret behind the high sensitivity of mode-localised sensors. Surprisingly, limited attention has been directed towards comprehensively elucidating the phenomenon of energy confinement within a specific resonator in weakly coupled resonators through detailed physical analysis. In this paper, a novel concept of modal dominance is proposed for the first time to elucidate the energy confinement of mode-localised sensors. The mode frequencies of the weakly coupled resonant system are dominated by the natural frequencies of the resonators in the system and the relationship between the two frequencies determines the resonant states, and then the amplitudes of the resonators. When perturbations break the system symmetry, the resonator in resonance acquires the larger amplitude while the amplitude of the out-of resonance resonator decreases. The concept of modal dominance is illustrated comprehensively and experimentally proved.
Age-related loss of intestinal barrier integrity plays an integral role in Thymic involution and T cell ageing
Authors: Conway Jessica , DeJong Erica N , White Andrea Andrea J , Dugan Ben , Rees Nia Paddison , Parnell Sonia M , Lamberte Lisa , Sharma-Oates Archana , Sullivan Jack , Mauro Claudio , Schaik Willem van , Anderson Graham , Bowdish Dawn M E , Duggal Niharika A
Published: January 2024

The intestinal epithelium serves as a physical and functional barrier against harmful substances, preventing their entry into the circulation and subsequent induction of a systemic immune response. Gut barrier dysfunction has recently emerged as a feature of ageing linked to declining health, and increased intestinal membrane permeability has been shown to promote heightened systemic inflammation in aged hosts. Concurrent with age-related changes in the gut microbiome, the thymic microenvironment undergoes a series of morphological, phenotypical and architectural alterations with age, including disorganisation of the corticomedullary junction, increased fibrosis, increased thymic adiposity and the accumulation of senescent cells. However, a direct link between gut barrier dysbiosis and thymic involution leading to features of immune ageing has not been explored thus far. Herein, we identify several strong associations between enhanced microbial translocation and the peripheral accumulation of terminally differentiated, senescent and exhausted T cells and the compensatory expansion of regulatory T cells in older adults. Most importantly, we confirm a direct effect of mucosal permeability on the regulation of thymic ageing and hyperactivation of the immune system by demonstrating that aged germ-free mice are protected from age-related intestinal membrane permeability. Together, these findings establish a mechanism by which gut barrier dysfunction drives systemic activation of the immune system during ageing, via causing thymic involution, extending our understanding of the consequences of intestinal membrane permeability and opening up the possibility for the use of microbiome-based interventions to restore immune homeostasis in older adults.
Self-injury functions mediate the association between anxiety and self-injury frequency among depressed Chinese adolescents: Gender differences
Authors: Zhao Yunhan , Zhao Xudong , Zhou Yongjie , Liu Liang
Published: January 2024

Background
Non-suicidal self-injury (NSSI) has become a common clinical problem that severely threatens the mental and physical health of Chinese adolescents. This study explores the mediation effects of NSSI functions on the relationship between anxiety and NSSI frequency among depressed Chinese adolescents as well as the gender differences in the mediating effects.
Methods
In this study, a cross-sectional survey method was used to obtain data of 1773 adolescent patients with major depression disorders from over 20 specialized psychiatric hospitals across multiple provinces in China. A self-designed questionnaire for demographic information, the NSSI function assessment scale, and the generalized anxiety disorder scale were employed to investigate demographic data, NSSI frequency, NSSI functions, and anxiety and to analyze the mediating effects of NSSI functions on the association between anxiety and NSSI frequency among adolescents of different genders.
Results
A total of 316 male patients and 1457 female patients were investigated. Female patients had a higher NSSI frequency (Z = 3.195, P = 0.001) and higher anxiety scores than did male patients (Z = 2.714, P = 0.007). Anxiety had a stronger positive predictive effect on the NSSI frequency in females (OR = 1.090) than in males (OR = 1.064). For male patients, the emotion regulation function in NSSI motivation played a full mediating role in the association between anxiety and NSSI frequency. For female patients, the emotion regulation and social avoidance functions in NSSI functions played a partial mediating role between anxiety and NSSI frequency.
Conclusions
There are gender differences in the mediating role of NSSI functions of depressed adolescents in the association between anxiety and NSSI frequency. When experiencing anxiety, males may engage in NSSI behaviors as a means to regulate their emotions. For females, anxiety can directly predict NSSI frequency, and they may attempt NSSI to alleviate part of their anxiety and achieve the purpose of rejecting others. In the face of anxiety among depressed adolescents of different genders, developing different emotional regulation methods and behavioral regulation strategies may be critical in preventing their NSSI behaviors.
MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program
Authors: Lewis Kimberly A. , Stroebel Benjamin , Zhang Li , Aouizerat Bradley , Mattis Aras , Flowers Elena
Published: January 2024

The Diabetes Prevention Program (DPP) randomized controlled trial demonstrated that metformin treatment reduced progression to type 2 diabetes (T2D) by 31% compared to placebo in adults with prediabetes. Circulating micro-ribonucleic acids (miRs) are promising biomarkers of T2D risk, but little is known about their associations with metformin regimens for T2D risk reduction. We compared the change in 24 circulating miRs from baseline to 2 years in a subset from DPP metformin intervention (n = 50) and placebo (n = 50) groups using Wilcoxon signed rank tests. Spearman’s correlations were used to evaluate associations between miR change and baseline clinical characteristics. Multiple linear regression was used to adjust for covariates. The sample was 73% female, 17% Black, 13% Hispanic, and 50 ± 11 years. Participants were obese, normotensive, prediabetic, and dyslipidemic. Change in 12 miR levels from baseline to 2 years was significantly different in the metformin group compared with placebo after adjusting for multiple comparisons: six (let-7c-5p, miR-151a-3p, miR-17-5p, miR-20b-5p, miR-29b-3p, and miR-93-5p) were significantly upregulated and six (miR-130b-3p, miR-22-3p, miR-222-3p, miR-320a-3p, miR-320c, miR-92a-3p) were significantly downregulated in the metformin group. These miRs help to explain how metformin is linked to T2D risk reduction, which may lead to novel biomarkers, therapeutics, and precision-health strategies.
Research on WSN coverage optimization of improved dung beetle algorithm in 3D environment
Authors: Xiaodong Wang , yang yijie , Yuqi LV , Chang LIU , Xuanzhong Chen , Bo Xie , Qingwen DU
Published: January 2024

Aiming at the difficulties in node deployment optimization of wireless sensor networks and the establishment of low-energy wireless sensor networks, this paper proposes an optimization scheme based on improved dung beetle optimization algorithm. Firstly, random sine-cosine perturbation strategy and uniform distribution dynamic reverse strategy are adopted to expand the algorithm search space, and then nonlinear and random perturbation strategy is adopted to improve the convergence factor. Finally, the local search strategy of Sparrow search algorithm is adopted to enhance the development ability of the algorithm. The benchmark function test of the algorithm and the optimization of wireless sensor node coverage are carried out. The results show that the algorithm has a good convergence speed and accuracy compared with other excellent algorithms, effectively improves the network coverage, and the optimized node distribution is more uniform.