bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system
Authors: Zhang Jun-Tao , Liu Xiao-Yu , Li Zhuolin , Wei Xin-Yang , Song Xin-Yi , Cui Ning , Zhong Jirui , Li Hongchun , Jia Ning
Published: March 2024

Silent information regulator 2 (Sir2) proteins typically catalyze NAD+-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD+ to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2–DSAD1 and DSR2–DSAD1–NAD+, as well as active DSR2–tube and DSR2–tube–NAD+ complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTDclosed or CTDopen. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTDclosed and activate Sir2 for NAD+ hydrolysis. DSAD1 binding to CTDopen allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD+ substrate catalysis in bacterial DSR2 anti-phage defense systems.
Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype
Authors: Chen Han-Yi , Hsieh Wan-Chen , Liu Yu-Chieh , Li Huei-Ying , Liu Po-Yo , Hsu Yu-Ting , Hsu Shao-Chun , Luo An-Chi , Kuo Wei-Chen , Huang Yi-Jhen , Liou Gan-Guang , Lin Meng-Yun , Ko Chun-Jung , Tsai Hsing-Chen , Chang Shu-Jung
Published: March 2024

Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention.
FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA
Authors: Liu Yaping , Reed Sarah C. , Lo Christopher , Choudhury Atish D. , Parsons Heather A. , Stover Daniel G. , Ha Gavin , Gydush Gregory , Rhoades Justin , Rotem Denisse , Freeman Samuel , Katz David W. , Bandaru Ravi , Zheng Haizi , Fu Hailu , Adalsteinsson Viktor A. , Kellis Manolis
Published: March 2024

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.
Combination of acalabrutinib with lenalidomide and rituximab in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma: a single-arm phase II trial
Authors: Park Changhee , Lee Ho Sup , Kang Ka-Won , Lee Won-Sik , Do Young Rok , Kwak Jae-Yong , Shin Ho-Jin , Kim Sung-Yong , Yi Jun Ho , Lim Sung-Nam , Lee Jeong-Ok , Yang Deok-Hwan , Jang Hun , Choi Byoungsan , Lim Jiwoo , Sun Choong Hyun , Byun Ja Min , Yoon Sung-Soo , Koh Youngil
Published: March 2024

Potential synergism between Bruton’s tyrosine kinase (BTK) inhibitor and lenalidomide in treating aggressive B-cell lymphoma has been suggested. Here, the authors report a single-arm phase II clinical trial of combination of acalabrutinib, lenalidomide and rituximab (R2A) in patients with aggressive relapsed/refractory aggressive (R/R) B-cell non-Hodgkin lymphoma (NHL). The primary endpoint of this study is objective response rate (ORR), and the secondary endpoints are complete remission (CR) rate, duration of response (DoR), progression-free survival (PFS) and overall survival (OS). A total of 66 patients are enrolled mostly with diffuse large B-cell lymphoma. The ORR is 54.5% and CR rate is 31.8% meeting the primary end point. The median DoR is 12.9 months, and 1-year PFS and OS rate is 33.1% and 67.5% respectively. Adverse events (AE) are manageable with the most frequent AE being neutropenia (31.8%). Patients with MYD88 mutations, subtypes known for NF-κB activation, and high BTK expression by immunohistochemistry respond well. Overall, these results show a significant efficacy of the R2A regimen in patients with aggressive R/R B-cell NHL, with exploratory biomarkers suggesting potential associations with response. (ClinicalTrials.gov 51 identifier: NCT04094142)
Monolithic back-end-of-line integration of phase change materials into foundry-manufactured silicon photonics
Authors: Wei Maoliang , Xu Kai , Tang Bo , Li Junying , Yun Yiting , Zhang Peng , Wu Yingchun , Bao Kangjian , Lei Kunhao , Chen Zequn , Ma Hui , Sun Chunlei , Liu Ruonan , Li Ming , Li Lan , Lin Hongtao
Published: March 2024

Monolithic integration of novel materials without modifying the existing photonic component library is crucial to advancing heterogeneous silicon photonic integrated circuits. Here we show the introduction of a silicon nitride etch stop layer at select areas, coupled with low-loss oxide trench, enabling incorporation of functional materials without compromising foundry-verified device reliability. As an illustration, two distinct chalcogenide phase change materials (PCMs) with remarkable nonvolatile modulation capabilities, namely Sb2Se3and Ge2Sb2Se4Te1, were monolithic back-end-of-line integrated, offering compact phase and intensity tuning units with zero-static power consumption. By employing these building blocks, the phase error of a push-pull Mach–Zehnder interferometer optical switch could be reduced with a 48% peak power consumption reduction. Mirco-ring filters with >5-bit wavelength selective intensity modulation and waveguide-based >7-bit intensity-modulation broadband attenuators could also be achieved. This foundry-compatible platform could open up the possibility of integrating other excellent optoelectronic materials into future silicon photonic process design kits.
Recent progress of artificial intelligence for liquid-vapor phase change heat transfer
Authors: Suh Youngjoon , Chandramowlishwaran Aparna , Won Yoonjin
Published: March 2024

Artificial intelligence (AI) is shifting the paradigm of two-phase heat transfer research. Recent innovations in AI and machine learning uniquely offer the potential for collecting new types of physically meaningful features that have not been addressed in the past, for making their insights available to other domains, and for solving for physical quantities based on first principles for phase-change thermofluidic systems. This review outlines core ideas of current AI technologies connected to thermal energy science to illustrate how they can be used to push the limit of our knowledge boundaries about boiling and condensation phenomena. AI technologies for meta-analysis, data extraction, and data stream analysis are described with their potential challenges, opportunities, and alternative approaches. Finally, we offer outlooks and perspectives regarding physics-centered machine learning, sustainable cyberinfrastructures, and multidisciplinary efforts that will help foster the growing trend of AI for phase-change heat and mass transfer.
Untargeted metabolomics-based network pharmacology reveals fermented brown rice towards anti-obesity efficacy
Authors: Barathikannan Kaliyan , Chelliah Ramachandran , Vinothkanna Annadurai , Prathiviraj Ragothaman , Tyagi Akanksha , Vijayalakshmi Selvakumar , Lim Min-Jin , Jia Ai-Qun , Oh Deog- Hwan
Published: March 2024

There is a substantial rise in the global incidence of obesity. Brown rice contains metabolic substances that can help minimize the prevalence of obesity. This study evaluated nine brown rice varieties using probiotic fermentation using Pediococcus acidilacti MNL5 to enhance bioactive metabolites and their efficacy. Among the nine varieties, FBR-1741 had the highest pancreatic lipase inhibitory efficacy (87.6 ± 1.51%), DPPH assay (358.5 ± 2.80 mg Trolox equiv./100 g, DW), and ABTS assay (362.5 ± 2.32 mg Trolox equiv./100 g, DW). Compared to other fermented brown rice and FBR-1741 varieties, UHPLC-Q-TOF-MS/MS demonstrated significant untargeted metabolite alterations. The 17 most abundant polyphenolic metabolites in the FBR-1741 variety and 132 putative targets were assessed for obesity-related target proteins, and protein interaction networks were constructed using the Cystoscope software. Network pharmacology analysis validated FBR-1741 with active metabolites in the C. elegans obesity-induced model. Administration of FBR-1741 with ferulic acid improved lifespan decreased triglycerides, and suppressed the expression of fat-related genes. The enhanced anti-obesity properties of FBR-1741 suggest its implementation in obesity-functional food.
Highly stable and immunogenic CMV T cell vaccine candidate developed using a synthetic MVA platform
Authors: Yll-Pico Marcal , Park Yoonsuh , Martinez Joy , Iniguez Angelina , Kha Mindy , Kim Taehyun , Medrano Leonard , Nguyen Vu H. , Kaltcheva Teodora , Dempsey Shannon , Chiuppesi Flavia , Wussow Felix , Diamond Don J.
Published: March 2024

Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.
Podocalyxin promotes the formation of compact and chemoresistant cancer spheroids in high grade serous carcinoma
Authors: Le Tran Ngoc , Wang Yao , Bilandzic Maree , Stephens Andrew , Nie Guiying
Published: March 2024

High grade serous carcinoma (HGSC) metastasises primarily intraperitoneally via cancer spheroids. Podocalyxin (PODXL), an anti-adhesive transmembrane protein, has been reported to promote cancer survival against chemotherapy, however its role in HGSC chemoresistance is unclear. This study investigated whether PODXL plays a role in promoting chemoresistance of HGSC spheroids. We first showed that PODXL was expressed variably in HGSC patient tissues (n = 17) as well as in ovarian cancer cell lines (n = 28) that are more likely categorised as HGSC. We next demonstrated that PODXL-knockout (KO) cells proliferated more slowly, formed less compact spheroids and were more fragile than control cells. Furthermore, when treated with carboplatin and examined for post-treatment recovery, PODXL-KO spheroids showed significantly poorer cell viability, lower number of live cells, and less Ki-67 staining than controls. A similar trend was also observed in ascites-derived primary HGSC cells (n = 6)—spheroids expressing lower PODXL formed looser spheroids, were more vulnerable to fragmentation and more sensitive to carboplatin than spheroids with higher PODXL. Our studies thus suggests that PODXL plays an important role in promoting the formation of compact/hardy HGSC spheroids which are more resilient to chemotherapy drugs; these characteristics may contribute to the chemoresistant nature of HGSC.
Expansion of thyroid surgical territory through 10,000 cases under the da Vinci robotic knife
Authors: Kim Jin Kyong , Lee Cho Rok , Kang Sang-Wook , Jeong Jong Ju , Nam Kee-Hyun , Chung Woong Youn
Published: March 2024

With the progress of robotic transaxillary thyroid surgery (RTTS), the indications for this procedure have gradually expanded. This study presents the insights gained from performing 10,000 RTTS cases at a single institution, along with the expansion of indications over time. RTTS was performed on 10,000 patients using the da Vinci robot system between October 2007 and April 2023 at the Yonsei University Health System, Seoul, Korea. Among 10,000 patients, 9461 (94.0%) were diagnosed with thyroid cancer, whereas 539 (5.4%) had either a benign thyroid nodule or Graves’ disease. Surgical procedures were performed using four-arm-based robots (da Vinci S, Si, or Xi) for 8408 cases (84.1%), with the remaining 1592 cases (15.9%) being performed using the da Vinci SP surgical robotic system. Notably, for 53 patients with nodules ≥ 5 cm, which were not included in the eligibility criteria of the previous study, RTTS was performed safely without significant complications. The most common postoperative complication was transient hypoparathyroidism (37.91%), and recurrence occurred in 100 patients with thyroid cancer (1.1%). In conclusion, RTTS appears safe and feasible from both surgical and oncological perspectives, and the spectrum of indications suitable for RTTS surgery is progressively expanding.
Domestic wastewater treatment by Pistia stratiotes in constructed wetland
Authors: Ali Majid , Aslam Ambreen , Qadeer Abdul , Javied Sabiha , Nisar Numrah , Hassan Nayyer , Hussain Afzal , Ali Basharat , Iqbal Rashid , Chaudhary Talha , Alwahibi Mona S. , Elshikh Mohamed S.
Published: March 2024

The objective of the study was to evaluate the performance of Pistia stratiotes for treatment of domestic wastewater in a free surface water flow constructed wetland. The objective of the study was to evaluate contaminants removal efficiency of the constructed wetland vegetated with P. stratiotes in treatment of domestic wastewater against Hydraulic retention time (HRT) of 10, 20 and 30 days was investigated. This asks for newer and efficient low-cost nature-based water treatment system which along with cost takes into consideration the sustainability of the ecosystem. Five constructed wetland setups improved the wastewater quality and purify it significantly by reducing the TDS by 83%, TSS by 82%, BOD by 82%, COD by 81%, Chloride by 80%, Sulfate by 77%, NH3 by 84% and Total Oil and Grease by 74%. There was an increase in pH of about 11.9%. Color and odor of wastewater was also improved significantly and effectively. It was observed that 30 days’ HRT was optimum for the treatment of domestic wastewater. The final effluent was found to be suitable as per national environmental quality standards and recycled for watering plants and crop irrigation but not for drinking purposes. The treatment in constructed wetland system was found to be economical, as the cost of construction only was involved and operational and maintenance cost very minimal. Even this research was conducted on the sole purpose of commuting the efficiency of pollutant removal in short span time.
Characterization of the complete mitochondrial genome of Spirobolus grahami (Diplopoda: Spirobolidae) with phylogenetic analysis
Authors: Zhang Wenwen , Gan Tianyi , Xu Tangjun , Wang Peng , Tai Jingzhe , Ma Fangzhou
Published: March 2024

Diplopoda is one of the most diverse and important groups of soil arthropods, but little research has been done on their phylogenetic relationship and evolution. Here, we sequenced and annotated the complete mitochondrial genomes of Spirobolus grahami. The total mitogenome of S. grahami was typical circular, double-stranded molecules, with 14,875 bp in length, including 13 protein-coding genes, 22 tRNAs, two rRNAs, and one control region. Base composition analysis suggested that the mitochondrial sequences were biased toward A and T, with A + T content of 58.68%. The mitogenomes of S. grahami exhibited negative AT and positive GC skews. Most of the 13 PCGs had ATN as the start codon, except COX1 start with CGA, and most PCGs ended with the T stop codon. The dN/dS values for most PCGs were lower than 1, suggesting that purifying selection was likely the main driver of mitochondrial PCG evolution. Phylogenetic analyses based on 13 PCGs using BI and ML methods support the classification of genus Spirobolus and Tropostreptus. Glomeridesmus spelaeus is distantly related to the other Diplopoda species.
Entrepreneurial education and its role in fostering sustainable communities
Authors: Suguna M. , Sreenivasan Aswathy , Ravi Logesh , Devarajan Malathi , Suresh M. , Almazyad Abdulaziz S. , Xiong Guojiang , Ali Irfan , Mohamed Ali Wagdy
Published: March 2024

Establishing sustainable communities requires bridging the gap between academic knowledge and societal requirements; this is where entrepreneurial education comes in. The first phase involved a comprehensive review of the literature and extensive consultation with experts to identify and shortlist the components of entrepreneurship education that support sustainable communities. The second phase involved Total Interpretative Structural Modelling to explore or ascertain how the elements interacted between sustainable communities and entrepreneurial education. The factors are ranked and categorized using the Matrice d'impacts croises multiplication appliquee an un classement (MICMAC) approach. The MICMAC analysis classifies partnerships and incubators as critical drivers, identifying Student Entrepreneurship Clubs and Sustainability Research Centers as dependent elements. The study emphasizes alumni networks and curriculum designs as key motivators. The results highlight the critical role that well-designed entrepreneurial education plays in developing socially conscious entrepreneurs, strengthening communities, and generating long-term job prospects. The study provides a valuable road map for stakeholders dedicated to long-term community development agendas by informing the creation of strategic initiatives, curriculum updates, and policies incorporating entrepreneurial education.
Predicting the dispersal and invasion dynamics of ambrosia beetles through demographic reconstruction and process-explicit modeling
Authors: Fadda Lucas A. , Osorio-Olvera Luis , Ibarra-Juárez Luis A. , Soberón Jorge , Lira-Noriega Andrés
Published: March 2024

Evaluating potential routes of invasion of pathogens and vectors of sanitary importance is essential for planning and decision-making at multiple scales. An effective tool are process-explicit models that allow coupling environmental, demographic and dispersal information to evaluate population growth and range dynamics as a function of the abiotic conditions in a region. In this work we simulate multiple dispersal/invasion routes in Mexico that could be taken by ambrosia beetles and a specific symbiont, Harringtonia lauricola, responsible for a severe epiphytic of Lauraceae in North America. We used Xyleborus bispinatus Eichhoff 1868 as a study subject and estimated its demography in the laboratory in a temperature gradient (17, 20, 26, 29, 35 °C), which we then used to parameterize a process-based model to estimate its metapopulation dynamics. The maximum intrinsic growth rate of X. bispinatus is 0.13 with a thermal optimum of 26.2 °C. The models suggest important regions for the establishment and dispersal the states of Veracruz, Chiapas and Oaxaca (high host and secondary vectors diversity), the Isthmus of Tehuantepec (connectivity region), and Michoacán and Jalisco (important avocado plantations). The use of hybrid process-based models is a promising tool to refine the predictions applied to the study of biological invasions and species distributions.
Comparing episodic memory outcomes from walking augmented reality and stationary virtual reality encoding experiences
Authors: Pastor Alvaro , Bourdin-Kreitz Pierre
Published: March 2024

Episodic Memory (EM) is the neurocognitive capacity to consciously recollect personally experienced events in specific spatio-temporal contexts. Although the relevance of spatial and temporal information is widely acknowledged in the EM literature, it remains unclear whether and how EM performance and organisation is modulated by self-motion, and by motor- and visually- salient environmental features (EFs) of the encoding environment. This study examines whether and how EM is modulated by locomotion and the EFs encountered in a controlled lifelike learning route within a large-scale building. Twenty-eight healthy participants took part in a museum-tour encoding task implemented in walking Augmented Reality (AR) and stationary Virtual Reality (VR) conditions. EM performance and organisation were assessed immediately and 48-hours after trials using a Remember/Familiar recognition paradigm. Results showed a significant positive modulation effect of locomotion on distinctive EM aspects. Findings highlighted a significant performance enhancement effect of stairway-adjacent locations compared to dead-end and mid-route stimuli-presentation locations. The results of this study may serve as design criteria to facilitate neurocognitive rehabilitative interventions of EM. The underlying technological framework developed for this study represents a novel and ecologically sound method for evaluating EM processes in lifelike situations, allowing researchers a naturalistic perspective into the complex nature of EM.
Myofascial trigger point (MTrP) size and elasticity properties can be used to differentiate characteristics of MTrPs in lower back skeletal muscle
Authors: Tsai P. , Edison J. , Wang C. , Sefton J. , Manning K. Q. , Gramlich M. W.
Published: March 2024

Myofascial trigger points (MTrPs) are localized contraction knots that develop after muscle overuse or an acute trauma. Significant work has been done to understand, diagnose, and treat MTrPs in order to improve patients suffering from their effects. However, effective non-invasive diagnostic tools are still a missing gap in both understanding and treating MTrPs. Effective treatments for patients suffering from MTrP mediated pain require a means to measure MTrP properties quantitatively and diagnostically both prior to and during intervention. Further, quantitative measurements of MTrPs are often limited by the availability of equipment and training. Here we develop ultrasound (US) based diagnostic metrics that can be used to distinguish the biophysical properties of MTrPs, and show how those metrics can be used by clinicians during patient diagnosis and treatment. We highlight the advantages and limitations of previous US-based approaches that utilize elasticity theory. To overcome these previous limitations, we use a hierarchical approach to distinguish MTrP properties by patients’ reported pain and clinician measured palpation. We show how US-based measurements can characterize MTrPs with this approach. We demonstrate that MTrPs tend to be smaller, stiffer, and deeper in the muscle tissue for patients with pain compared to patients without pain. We provide evidence that more than one MTrP within a single US-image field increases the stiffness of neighboring MTrPs. Finally, we highlight a combination of metrics (depth, thickness, and stiffness) that can be used by clinicians to evaluate individual MTrPs in combination with standard clinical assessments.
Innovative dead-time correction and background subtraction for neutron multiplicity measurements using neural networks
Authors: Garcia-Duarte Jeremias , Mishnayot Yonatan , Tamashiro Aaron S. , Lawrence Jackson R. , Harke Jason T.
Published: March 2024

The number of neutrons emitted from a nuclear reaction plays a crucial role in various fields, including nuclear theory, nuclear nonproliferation, nuclear energy and nuclear criticality safety. Accurate determination of neutron multiplicities requires the application of several corrections, with dead-time correction and background subtraction being particularly significant. These corrections become more challenging for neutron detectors with time-dependent neutron capture. In this work, we perform a comprehensive study of three existing methods used for dead-time correction and background subtraction in neutron detectors with time-dependent neutron capture. The methods were tested for dead-times in the range from 0 to 1 μs using a Monte Carlo model simulating the dead-time and background effects in the standard neutron multiplicity probability distribution of $$^{252}$$

252

Cf. The previous methods showed larger than desired uncertainty or systematic trade off. Those uncertainties prompted the development of a novel approach using neural networks trained with data from Monte Carlo simulations. The Neural Network method enabled the correction of neutron multiplicity probabilities more accurately than the other methods with fractional errors smaller than 3% for multiplicities around the peak of $$^{252}$$

252

Cf. A similar approach using neural networks could be applied to problems where the system being studied can be accurately simulated without having an accurate analytical description available. The neural network method presented in this paper can be easily expanded if multiplicities greater than 10 are expected.
The prognostic value and model construction of inflammatory markers for patients with non-small cell lung cancer
Authors: Xu Wanting , Liu Xinya , Yan Ci , Abdurahmane Gulinurayi , Lazibiek Jiayina , Zhang Yan , Cao Mingqin
Published: March 2024

The aim of this study was to investigate and analyse the predictive value of systemic inflammatory markers based on peripheral blood biomarkers for the prognosis of non-small cell lung cancer (NSCLC) patients. Based on a retrospective monitoring cohort of 973 NSCLC patients from an Affiliated Tumor Hospital from 2012 to 2023. The log-rank test and Cox proportional risk regression model were used to identify independent prognostic inflammatory markers. Subsequently, a nomogram prediction model was constructed and evaluated. The results of multivariate Cox regression analysis showed that patients with high NLR group (HR = 1.238, 95% CI 1.015–1.510, P = 0.035), and high CAR group (HR = 1.729, 95% CI 1.408–2.124, P < 0.001) were risk factors affecting the prognosis of NSCLC patients. The nomogram that includes age, tumor stage, smoking history, BMI, NLR, and CAR can effectively predict the prognosis of NSCLC patients.The inflammatory markers NLR and CAR, which combine inflammatory and nutritional status, are effective predictors of the prognosis of NSCLC patients. The combination of clinical information and these easily accessible inflammatory markers has significant research value for prognostic assessment, clinical treatment, and follow-up monitoring of NSCLC patients.
Cancer testis antigen MAGEA3 in serum and serum-derived exosomes serves as a promising biomarker in lung adenocarcinoma
Authors: Gan Yuhan , Kang Yanli , Zhong Ruifang , You Jianbin , Chen Jiahao , Li Ling , Chen Jinhua , Chen Liangyuan
Published: March 2024

Cancer testis antigen (CTA) Melanoma Antigen Gene A3 (MAGEA3) were overexpressed in multiple tumor types, but the expression pattern of MAGEA3 in the serum of lung adenocarcinoma (LUAD) remains unclear. Clinically derived serum and serum exosome samples were used to assess the mRNA expression of MAGEA3 and MAGEA4 by qRT-PCR, and serum MAGEA3 and MAGEA4 protein expression were evaluated by ELISA in total 133 healthy volunteers’ and 289 LUAD patients’ serum samples. An analysis of the relationship of the mRNA and protein expression of MAGEA3 and MAGEA4 with clinicopathologic parameters was performed and the diagnostic value of MAGEA3 and MAGEA4 was plotted on an ROC curve. In addition, the correlation of MAGEA3 mRNA with infiltrating immune cells was investigated through TIMER, the CIBERSORT algorithm and the TISIDB database. Expression of serum and serum exosome MAGEA3 and MAGEA4 mRNA were significantly higher in LUAD patients than in healthy donors. MAGEA3 mRNA associated with tumor diameter, TMN stage, and NSE in LUAD serum samples, and MAGEA3 mRNA correlated with N stage in serum-derived exosomes, possessing areas under the curve (AUC) of 0.721 and 0.832, respectively. Besides, serum MAGEA3 protein levels were elevated in LUAD patients, and were closely related to stage and NSE levels, possessing AUC of 0.781. Further analysis signified that the expression of MAGEA3 mRNA was positive correlation with neutrophil, macrophages M2, dendritic cells resting, and eosinophilic, but negatively correlated with B cells, plasma cells, CD8 + T cells, CD4 + T cells, Th17 cells, macrophages and dendritic cells. Collectively, our results suggested that the MAGEA3 expression in mRNA and protein were upregulated in LUAD, and MAGEA3 could be used as a diagnostic biomarker and immunotherapy target for LUAD patients.
5-Methylcytosine immunohistochemistry for predicting cutaneous melanoma prognosis
Authors: Meevassana Jiraroch , Varophas Shananya , Prabsattru Piyawan , Kamolratanakul Supitcha , Ruangritchankul Komkrit , Kitkumthorn Nakarin
Published: March 2024

There is a correlation between DNA methylation and the diseased stage and poor survival. 5-methylcytosine (5-mC) is one of the epigenetic modifications of bases that researchers focus on. Staining with 5-mC immunohistochemistry was used to examine pathological samples taken from individuals diagnosed with cutaneous melanoma. Between Breslow levels 2 and 4, there was a significant difference in the H-score of 5-mC expression (p = 0.046). A significant reduction in 5-mC expression H-scores was seen in patients who were diagnosed with ulcers (p = 0.039). It was shown that patients with low 5-mC had a significantly worse overall survival rate (p = 0.027).
Integrated smart dust monitoring and prediction system for surface mine sites using IoT and machine learning techniques
Authors: Tripathi Abhishek Kumar , Aruna Mangalpady , Parida Satyajeet , Nandan Durgesh , Elumalai P. V. , Prakash E. , Isaac JoshuaRamesh Lalvani Joshua Stephen Chellakumar , Rao Koppula Srinivas
Published: March 2024

The mining industry confronts significant challenges in mitigating airborne particulate matter (PM) pollution, necessitating innovative approaches for effective monitoring and prediction. This research focuses on the design and development of an Internet of Things (IoT)-based real-time monitoring system tailored for PM pollutants in surface mines, specifically PM 1.0, PM 2.5, PM 4.0, and PM 10.0. The novelty of this work lies in the integration of IoT technology for real-time measurement and the application of machine learning (ML) techniques for accurate prediction based on recorded dust pollutants data. The study's findings indicate that PM 1.0 pollutants exhibited the highest concentration in the atmosphere of the ball clay surface mine sites, with the stockyard site registering the maximum levels of PM pollutants (28.45 µg/m3, 27.89 µg/m3, 26.17 µg/m3, and 27.24 µg/m3, respectively) due to the dry nature of clay materials. Additionally, the research establishes four ML models—Decision Tree (DT), Gradient Boosting Regression (GBR), Random Forest (RF), and Linear Regression (LR)—for predicting PM pollutant concentrations. Notably, Random Forest demonstrates superior performance with the lowest Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) at 1.079 and 1.497, respectively. This comprehensive solution, combining IoT-based monitoring and ML-based prediction, contributes to sustainable mining practices, safeguarding worker well-being, and preserving the environment.
Modification mechanism of calcium lignosulfonate on cementing cement
Authors: Zou Quanle , Wang Weizhi , Wang Xin
Published: March 2024

During the construction of coalbed methane extraction wells, cementing cement sheath is crucial for the stability and sealing of surface wells. One effective method to enhance these properties is the addition of lignosulfonate. However, the mechanism of the effect of calcium lignosulfonate on the whole process of cement hydration is still unclear. In this paper, the water distribution and variation characteristics of calcium lignosulfonate modified cement paste were revealed by low-field nuclear magnetic resonance technology, and the hydration ion experiment of modified cement was carried out to obtain the variation characteristics of hydration ions of modified cementing cement. Finally, the formation mechanism of hydration products was clarified by analyzing the phase change of modified cement stone. The results indicate that the cement paste’s hydration process can be divided into four stages: dissolution, crystallization, acceleration, and decline. During the dissolution stage, calcium lignosulfonate’s air entraining effect maintains the cement paste in a stable suspension state. In the crystallization stage, calcium lignosulfonate’s electro-repulsion delays the formation of hydration products and the hydration process. During the acceleration stage, the addition of calcium lignosulfonate reduces bound water formation in the cement slurry’s flocculation structure, and the released filled water participates more in the hydration reaction, reducing the total relaxation signal’s increasing trend. In the decline stage, the cement paste has solidified, and the system’s water is primarily in the porous medium. The research results have practical guiding significance for the addition of calcium lignosulfonate in cementing operations.
Effect of vegetable consumption with chewing on postprandial glucose metabolism in healthy young men: a randomised controlled study
Authors: Kamemoto Kayoko , Tataka Yusei , Hiratsu Ayano , Nagayama Chihiro , Hamada Yuka , Kurata Koji , Chiyoda Michiko , Ito Machi , Miyashita Masashi
Published: March 2024

Although thorough chewing lowers postprandial glucose concentrations, research on the effectiveness of chewing vegetables in different forms on postprandial glucose metabolism remains limited. This study examined the effects of vegetables consumed in solid versus puree forms on postprandial glucose metabolism. Nineteen healthy young men completed two 180-min trials on separate days in a random order: the chewing trial involved the consumption of shredded cabbage with chewing and the non-chewing trial involved the consumption of pureed cabbage without chewing. Energy jelly was consumed immediately after the consumption of shredded or puree cabbage. Blood samples were collected at 0, 30, 45, 60, 90, 120 and 180 min. Circulating concentrations of glucose, insulin, total glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) concentrations were measured from the plasma. Although plasma glucose concentrations did not differ between the trials, the plasma insulin and GIP incremental area under the curve values were higher in the chewing than in the non-chewing trial. Postprandial total GLP-1 concentrations were higher in the chewing than in the non-chewing trial at 45, 60 and 90 min. This study demonstrates that consuming shredded cabbage while chewing enhances postprandial incretin secretion but has no effect on postprandial glucose concentration.

Trial registration: Clinical trial registration ID.: UMIN000052662, registered 31 October 2023.
Data-driven normative values based on generative manifold learning for quantitative MRI
Authors: Attyé Arnaud , Renard Félix , Anglade Vanina , Krainik Alexandre , Kahane Philippe , Mansencal Boris , Coupé Pierrick , Calamante Fernando
Published: March 2024

In medicine, abnormalities in quantitative metrics such as the volume reduction of one brain region of an individual versus a control group are often provided as deviations from so-called normal values. These normative reference values are traditionally calculated based on the quantitative values from a control group, which can be adjusted for relevant clinical co-variables, such as age or sex. However, these average normative values do not take into account the globality of the available quantitative information. For example, quantitative analysis of T1-weighted magnetic resonance images based on anatomical structure segmentation frequently includes over 100 cerebral structures in the quantitative reports, and these tend to be analyzed separately. In this study, we propose a global approach to personalized normative values for each brain structure using an unsupervised Artificial Intelligence technique known as generative manifold learning. We test the potential benefit of these personalized normative values in comparison with the more traditional average normative values on a population of patients with drug-resistant epilepsy operated for focal cortical dysplasia, as well as on a supplementary healthy group and on patients with Alzheimer’s disease.
The cyclooxygenase-2 upregulation mediates production of PGE2 autacoid to positively regulate interleukin-6 secretion in chronic rhinosinusitis with nasal polyps and polyp-derived fibroblasts
Authors: Shieh Jiunn-Min , Tsai Yih-Jeng , Ma Ming-Chieh , Chen Chih-Li , Wu Wen-Bin
Published: March 2024

Chronic rhinosinusitis (CRS) can be traditionally classified as CRSwNP [with nasal polyps (NPs)] and CRSsNP (without NPs) based on the clinical phenotypes but recently suggested to be classified by the endotypes. We have identified overexpression of the cyclooxygenase-2 (COX-2) gene in NP tissues of Taiwanese CRSwNP patients. Therefore, in this study, we sought to investigate its protein expression/location/distribution in NP specimens and explore its roles in nasal polyposis. The COX-2 protein and mRNA expression was found higher in NPs than that in the control and CRSsNP patients’ nasal tissues, mainly located at the epithelium and subepithelial stroma. Consistently, the CRS-related peptidoglycan (PGN) and bradykinin provoked COX-2 mRNA and protein upregulation in the human NP-derived fibroblasts and caused PGE2, thromboxane A2 (TXA2), and interleukin (IL-6) secretion in culture medium. Further analysis revealed that the PI3K/Akt activation and COX-2 induction were necessarily required for PGN-induced IL-6 production/secretion and the induced PGE2, but not TXA2, was speculated to affect IL-6 protein trafficking and production. Finally, the IL-6 increase observed in vitro could also be detected in NP tissues. Collectively, we demonstrated here that COX-2 protein and IL-6 are overexpressed in human NP tissues. In response to PGN challenge, the PI3K/Akt activation and COX-2-mediated PGE2 autacoid correlates with extracellular IL-6 protein trafficking/production in NP-derived fibroblasts, which can additionally contribute to the production of Th17-related cytokines such as IL-17 and TNF-α. This study also suggests COX-2 as a special biomarker for CRSwNP endotyping and may highlight the importance of COX-2 inhibitors in treating CRSwNP.
Unraveling the complex interplay between obesity and vitamin D metabolism
Authors: Alzohily Bashar , AlMenhali Asma , Gariballa Salah , Munawar Nayla , Yasin Javed , Shah Iltaf
Published: March 2024

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.
Supervised representation learning based on various levels of pediatric radiographic views for transfer learning
Authors: Kyung Sunggu , Jang Miso , Park Seungju , Yoon Hee Mang , Hong Gil-Sun , Kim Namkug
Published: March 2024

Transfer learning plays a pivotal role in addressing the paucity of data, expediting training processes, and enhancing model performance. Nonetheless, the prevailing practice of transfer learning predominantly relies on pre-trained models designed for the natural image domain, which may not be well-suited for the medical image domain in grayscale. Recognizing the significance of leveraging transfer learning in medical research, we undertook the construction of class-balanced pediatric radiograph datasets collectively referred to as PedXnets, grounded in radiographic views using the pediatric radiographs collected over 24 years at Asan Medical Center. For PedXnets pre-training, approximately 70,000 X-ray images were utilized. Three different pre-training weights of PedXnet were constructed using Inception V3 for various radiation perspective classifications: Model-PedXnet-7C, Model-PedXnet-30C, and Model-PedXnet-68C. We validated the transferability and positive effects of transfer learning of PedXnets through pediatric downstream tasks including fracture classification and bone age assessment (BAA). The evaluation of transfer learning effects through classification and regression metrics showed superior performance of Model-PedXnets in quantitative assessments. Additionally, visual analyses confirmed that the Model-PedXnets were more focused on meaningful regions of interest.
Cigarette craving in virtual reality cue exposure in abstainers and relapsed smokers
Authors: Schröder Benedikt , Kroczek Agnes , Kroczek Leon O. H. , Ehlis Ann-Christine , Batra Anil , Mühlberger Andreas
Published: March 2024

Cue exposure therapy (CET) in substance-use disorders aims to reduce craving and ultimately relapse rates. Applying CET in virtual reality (VR) was proposed to increase its efficacy, as VR enables the presentation of social and environmental cues along with substance-related stimuli. However, limited success has been reported so far when applying VR-CET for smoking cessation. Understanding if effects of VR-CET differ between future abstainers and relapsing smokers may help to improve VR-CET. Data from 102 participants allocated to the intervention arm (VR-CET) of a recent RCT comparing VR-CET to relaxation in the context of smoking cessation was analyzed with respect to tolerability, presence, and craving during VR-CET. Cue exposure was conducted in four VR contexts (Loneliness/Rumination, Party, Stress, Café), each presented twice. Relapsed smokers compared to abstainers experienced higher craving during VR-CET and stronger craving responses especially during the Stress scenario. Furthermore, lower mean craving during VR-CET positively predicted abstinence at 6-month follow-up. Attempts to improve smoking cessation outcomes of VR-CET should aim to identify smokers who are more at risk of relapse based on high craving levels during VR-CET. Specifically measuring craving responses during social stress seems to be well suited to mark relapse. We propose to investigate individualized treatment approaches accordingly.
Paternal DDT exposure induces sex-specific programming of fetal growth, placenta development and offspring’s health phenotypes in a mouse model
Authors: Chen Elaine , da Cruz Raquel Santana , Nascimento Aallya , Joshi Meghali , Pereira Duane Gischewski , Dominguez Odalys , Fernandes Gabriela , Smith Megan , Paiva Sara P. C. , de Assis Sonia
Published: March 2024

Mounting evidence suggests that environmentally induced epigenetic inheritance occurs in mammals and that traits in the progeny can be shaped by parental environmental experiences. Epidemiological studies link parental exposure to environmental toxicants, such as the pesticide DDT, to health phenotypes in the progeny, including low birth and increased risk of chronic diseases later in life. Here, we show that the progeny of male mice exposed to DDT in the pre-conception period are born smaller and exhibit sexual dimorphism in metabolic function, with male, but not female, offspring developing severe glucose intolerance compared to controls. These phenotypes in DDT offspring were linked to reduced fetal growth and placenta size as well as placenta-specific reduction of glycogen levels and the nutrient sensor and epigenetic regulator OGT, with more pronounced phenotypes observed in male placentas. However, placenta-specific genetic reduction of OGT only partially replicates the metabolic phenotype observed in offspring of DDT-exposed males. Our findings reveal a role for paternal pre-conception environmental experiences in shaping placenta development and in fetal growth restriction. While many questions remain, our data raise the tantalizing possibility that placenta programming could be a mediator of environmentally induced intergenerational epigenetic inheritance of phenotypes and needs to be further evaluated.