bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstacle Avoidance Model of Two‐Wheeled Vehicles for Nonrigid Obstacles Based on Social Forces
Authors: Zhou Dan , Hu Qingwei , Sun Xin , Gu Guobin , Li Wenyong , Wang Tao
Published: January 2024

To describe the microtrajectory change behavior of two‐wheeled vehicles when encountering nonrigid obstacles, this paper proposes an obstacle avoidance model of two‐wheeled vehicles for nonrigid obstacles based on the improved social force method. In the model, the obstacle avoidance characteristics of two‐wheeled vehicles for nonrigid obstacles and the safety operation requirements of two‐wheeled vehicles are considered. The calculation methods of the minimum boundary distance of avoidance and the boundary avoidance force range edge function are proposed based on the ultimate turning angle and boundary avoidance characteristics, respectively. The speed control and direction control behavior of the rider to the vehicle is abstracted as the form of social force, and the two‐wheeled vehicle/rider individual is subjected to the avoidance force and correction force perpendicular to the direction of the longitudinal axis of the vehicle body. The centrifugal trajectory obstacle avoidance motion obeying the Newtonian mechanics is studied based on the characteristics of the vehicle body turning angle change. Different traffic environments are constructed by MATLAB software and simulated according to the model running logic, and sensitivity analysis is performed based on the actual data collected in the survey. The simulation results show that, under the same conditions, compared with μi = 50N, when μi = 200N, the X‐axis displacement of the simulated vehicle in the avoidance process is shortened by 26.31%, and the body deflection angle increases by 50.75% at the end moment of the avoidance process. Compared with electric motorcycles, the displacement of the X‐axis in the avoidance process of the electric bicycle is shortened by 16.92%, and the body deflection angle at the end moment of the avoidance process is increased by 13.68%. The simulation results show that the model can well describe the trajectory change behavior characteristics of two‐wheeled vehicles/riders encountering nonrigid obstacles in real situations, and the obstacle avoidance model of two‐wheeled vehicles proposed in this paper is considered to be traffic justified.
Analysis of Age-Structured Mathematical Model of Malaria Transmission Dynamics via Classical and ABC Fractional Operators
Authors: Gizaw Ademe Kebede , Deressa Chernet Tuge
Published: January 2024

Malaria is a complex disease with many factors influencing the transmission dynamics, including age. This research analyzes the transmission dynamics of malaria by developing an age-structured mathematical model using the classical integer order and Atangana–Baleanu–Caputo fractional operators. The analysis of the model focused on several important aspects. The existence and uniqueness of solutions of fractional order were explored based on some fixed-point theorems,such as Banach and Krasnoselski. The Positivity and boundedness of the solutions were also investigated. Furthermore, through mathematical analysis techniques, we analyzed different types of stability results, and the results showed that the disease-free equilibrium point of the model is proved to be both locally and globally asymptotically stable if the basic reproduction number is less than one, whereas the endemic equilibrium point of the model is both locally and globally asymptotically stable if the basic reproduction number is greater than one. The findings from the sensitivity analysis revealed that the most sensitive parameters, essential for controlling or eliminating malaria are mosquito biting rate, density-dependent natural mortality rate, clinical recovery rate, and recruitment rate for mosquitoes. Numerical simulations are also performed to examine the behavior of the model for different values of the fractional-order alpha,and the result revealed that as the value α reduces from 1, the spread of the endemic grows slower. By incorporating these findings, this research helps to clarify the dynamics of malaria and provides information on how to create efficient control measures.
Are Highly Intelligent People More Likely to Tolerate Risk in China? Evidence from China Family Panel Studies
Authors: Zhang Jing , Liu Haijian , Xu Jiaming
Published: January 2024

Understanding the correlation between cognitive ability and risk preferences is crucial for promoting technological progress and innovation in China. This study aims to investigate this relationship using survey data from the China Family Panel Studies. The results reveal a significant positive correlation between cognitive ability and risk tolerance. These findings have important implications for understanding the relationship between cognitive ability and risk preferences, as well as for informing policy decisions in areas such as financial investments and entrepreneurship incentives.
A Baseline‐Free Electromechanical Impedance Resonance Method for Measuring the Modulus of Elasticity of Concrete Cubes Using Surface‐Bonded PZT Patches
Authors: Sha Xiong , Zhu Songye
Published: January 2024

The modulus of elasticity of concrete (Ec) is an essential parameter commonly used in concrete design, concrete curing monitoring, and deterioration evaluation and damage detection of concrete structures. A quick and reliable in situ determination of Ec helps in accurate decision‐making for construction and maintenance. The electromechanical impedance (EMI) technique using surface‐bonded lead zirconate titanate (PZT) patches (referred to as SBP) has become a popular nondestructive method for monitoring concrete structures due to ease of operations. The existing research mainly utilized baseline‐dependent approaches to monitor the changes (e.g., hardening or damage evolution) of concrete structures. However, relevant baselines are greatly influenced by the status of PZT sensors and bonding layers, limiting the practical applications of this technique. This paper presents a baseline‐free EMI resonance method for measuring Ec of concrete without using prior baseline data for the first time. Numerical and experimental studies on standard concrete cubes (100 mm in width) with SBP were conducted to examine the proposed method. A dimensionless physical quantity was first proposed to view the EMI signals. Then, resonance peaks highly related to concrete properties but insensitive to the status of the sensor system were selected, physically described, and correlated to the concrete parameters through numerical analyses. Finally, experimental validations, covering the measurement of Ec, repeatability of the chosen resonance peaks, and temperature effects, were conducted to illustrate the proposed method’s stability, accuracy, and sensitivity.
Preparation, Characterization, and Nutritional Analysis of Napham: An Indian Traditional Smoke-Dried-Fermented Fish Paste
Authors: Nath Kapil Deb , Nickhil C. , Borah Debasish , Pandiselvam R. , Deka Sankar Chandra
Published: January 2024

Napham, a unique smoked-dried-fermented fish paste, is a traditional delicacy prepared by the Assamese Bodo people. This research focuses on the process of Napham preparation and explores its nutritional benefits. To make Napham, sundried and smoked trash fishes, along with Alocasia macrorrhiza stems, are ground and stuffed into immature bamboo tubes, where they ferment for 2-3 months. Although Napham possesses a distinct taste and texture that may not appeal to everyone, the fermentation process significantly enhances its nutritional value by increasing its vitamin content, improving fatty acid profiles, and enhancing amino acid profiles. The study reveals that Napham is a remarkable source of protein (63.65 ± 0.83 g/100 g), potassium (667.87 ± 3.48 mg/kg), sodium (531.48 ± 3.43 mg/kg), and magnesium (56.23 ± 1.53 mg/kg). Napham contains both omega-3 and omega-6 fatty acids, including linoleic acid (10.10 ± 0.002%), α-linolenic acid (6.47 ± 0.062%), arachidonic acid (4.65 ± 0.031%), eicosapentaenoic acid (1.08 ± 0.007%), and docosahexaenoic acid (3.44 ± 0.036%). Furthermore, Napham is rich in essential amino acids such as methionine (227.407 µmol/L), isoleucine (478.525 µmol/L), leucine (797.944 µmol/L), valine (640.867 µmol/L), phenylalanine (320.573 µmol/L), lysine (1066.557 µmol/L), and histidine (104.525 µmol/L), complementing its nutritional profile.
Potential Locations of Strong Earthquakes in Bulgaria and the Neighbouring Regions
Authors: Gorshkov Alexander I. , Novikova Olga V. , Dimitrova Sonya Y. , Dimova Lyuba D. , Raykova Reneta B.
Published: January 2024

Information about potential earthquake sources is a key issue for seismic hazard assessment. This study presents the application of a phenomenological approach based on pattern recognition to determine the possible locations of strong earthquakes in the Bulgarian region. The technique assumes the origin of strong earthquakes in morphostructural nodes formed around the intersections of morphostructural lineaments identified by morphostructural zoning. For the territory of the Bulgaria and neighbouring regions, 178 nodes were defined in this work. The CORA-3 pattern recognition algorithm identified 59 seismogenic nodes analysing a set of geophysical and geological node’s characteristics. The identified seismogenic nodes are capable to generate earthquakes with magnitude equal to or greater than 6 and are located at the boundaries between the largest tectonic domains: Rila, Pirin, and Rhodope orogens; the Serbian-Macedonian massif; and in the Stara Planina belt. The set of characteristic features of seismogenic nodes indicates that the vicinity of potential nodes is characterized by a high contrast of neotectonic movements of the Earth’s crust and the presence of deep heterogeneities in the Earth’s crust. About 40% of the recognized nodes are not associated with any earthquakes, while the rest of the recognized seismogenic nodes are characterized by an area with a radius of 25 km where earthquakes are known to occur. Part of these “non active” seismogenic nodes are close to the historical events with magnitudes higher than 5.5 since the magnitude and location of historical events have large uncertainties. Another part of the seismogenic nodes may slightly change the location due to the uncertainties in morphostructural zonation. Other nodes may indicate unknown historical seismicity or paleoearthquakes. Defined M6+ seismogenic nodes can fill the potential gaps in the recorded seismicity on the territory of Bulgaria, thus to improve the seismic hazard assessment of the studied region.
Estimates of Inhaled and Deposited Doses following Exposure to Humidifier Disinfectant Containing Polyhexamethylene Guanidine (PHMG)
Authors: Kim Sunju , Yoon Chungsik
Published: January 2024

We estimated the inhaled and deposited dose in humans using the International Commission on Radiological Protection (ICRP) and multiple‐path particle dosimetry (MPPD) models following exposure to humidifier disinfectant containing polyhexamethylene guanidine (PHMG). The disinfectant has caused at least 1,810 deaths, with an odds ratio of lung injury of 47.3 (95% confidence interval: 6.1–369.7), because of its application in Korea. In this study, the Oxy product, which is regarded as the causative agent of most lung diseases, was sprayed into a cleanroom at normal (6.5 ppm in solution) and worst case (65 ppm in solution) dilutions; the airborne aerosol was monitored with direct reading instruments. Areas of deposition were divided into the head airway, tracheobronchial, and alveolar regions. Four dose scenarios were considered in this study: adults and children in both daily average and sleep conditions. Most PHMG aerosols were smaller than PM1 (96%). Number‐based concentration analysis showed that <100 nm nanoparticles comprised 81% and 69% of the aerosol when the 6.5 and 65 ppm solutions were used, respectively. In all scenarios, the number‐based deposited dose increased in the order of alveolar, tracheobronchial, and head airway regions; the mass‐based deposited dose increased in the order of the head airway, alveolar, and tracheobronchial regions. The deposited dose per unit body weight was higher in children than in adults in terms of both number‐ and mass‐based concentrations. When the humidifier was sprayed, the highest number‐based concentration was found at a particle size of 15.4 nm; the highest deposition fraction or dose by PM1 was observed in the pulmonary and head airways in both models.
Challenges in Emerging Vaccines and Future Promising Candidates against SARS‐CoV‐2 Variants
Authors: Ghildiyal Tanmay , Rai Nishant , Mishra Rawat Janhvi , Singh Maargavi , Anand Jigisha , Pant Gaurav , Kumar Gaurav , Shidiki Amrullah
Published: January 2024

Since the COVID‐19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID‐19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS‐CoV‐2 variants of interest and variants of concern (VOCs). The keywords like COVID‐19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS‐CoV‐2, the safety and efficacy of COVID‐19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants.
Green Tea Leaves and Rosemary Extracts Selectively Induce Cell Death in Triple-Negative Breast Cancer Cells and Cancer Stem Cells and Enhance the Efficacy of Common Chemotherapeutics
Authors: Raad Chris , Raad Abby , Pandey Siyaram
Published: January 2024

While incredible medical advancements in chemotherapeutics development for cancer treatment have been made, the majority of these are not selective in their mechanism of action, leading to adverse effects. Given the systemic toxicity associated with these therapies, they are not well suited for long-term use. Natural health products, or NHPs, may provide a way to selectively target the oxidative and metabolic vulnerabilities in cancer cells. White tea (Camelia sinensis) and rosemary (Salvia rosmarinus) are two natural extracts that have been studied extensively for their medicinal properties. However, their anticancer activity and mechanism of action are yet to be fully elucidated. We have examined the extracts’ cancer cell-killing ability as well as their interactions with common chemotherapeutics in MDA-MB-231 cells, a triple-negative breast cancer cell line, in vitro. Cell death measurement, morphological and biochemical characterization of apoptotic cell death, mechanisms of action (mitochondrial depolarization and oxidative stress), and immunofluorescence assays to estimate the percentage of cancer stem cells (CSCs) were performed following treatment with Synthite tea extract (STE) and rosemary extract (RE), provided by Synthite Industries Limited alone and in combination with cisplatin and paclitaxel. The key findings in this study are that STE and RE alone demonstrated very efficient anticancer activity against TNBC, and more importantly, the administration of the extracts in conjunction with cisplatin and paclitaxel sensitizes cancer cells to achieve enhanced cell death. In addition, CSCs were found to be sensitive to treatment with STE alone and in combination with RE and exhibited greater sensitivity to combination therapies compared to chemotherapeutic alone. The significance of these observations is that STE and RE, well-tolerated NHPs, have the potential to enhance the efficacy of current chemotherapeutics when combined, as well as prevent relapse for TNBC.
Human Tumor–Associated Macrophages and Neutrophils Regulate Antitumor Antibody Efficacy through Lethal and Sublethal Trogocytosis
Authors: Singhal Sunil , Rao Abhishek S. , Stadanlick Jason , Bruns Kyle , Sullivan Neil T. , Bermudez Andres , Honig-Frand Adam , Krouse Ryan , Arambepola Sachinthani , Guo Emily , Moon Edmund K. , Georgiou George , Valerius Thomas , Albelda Steven M. , Eruslanov Evgeniy B.
Published: January 2024

The clinical benefits of tumor-targeting antibodies (tAb) are modest in solid human tumors. The efficacy of many tAbs is dependent on Fc receptor (FcR)–expressing leukocytes that bind Fc fragments of tAb. Tumor-associated macrophages (TAM) and neutrophils (TAN) represent the majority of FcR+ effectors in solid tumors. A better understanding of the mechanisms by which TAMs and TANs regulate tAb response could help improve the efficacy of cancer treatments. Here, we found that myeloid effectors interacting with tAb-opsonized lung cancer cells used antibody-dependent trogocytosis (ADT) but not antibody-dependent phagocytosis. During this process, myeloid cells “nibbled off” tumor cell fragments containing tAb/targeted antigen (tAg) complexes. ADT was only tumoricidal when the tumor cells expressed high levels of tAg and the effectors were present at high effector-to-tumor ratios. If either of these conditions were not met, which is typical for solid tumors, ADT was sublethal. Sublethal ADT, mainly mediated by CD32hiCD64hi TAM, led to two outcomes: (i) removal of surface tAg/tAb complexes from the tumor that facilitated tumor cell escape from the tumoricidal effects of tAb; and (ii) acquisition of bystander tAgs by TAM with subsequent cross-presentation and stimulation of tumor-specific T-cell responses. CD89hiCD32loCD64lo peripheral blood neutrophils (PBN) and TAN stimulated tumor cell growth in the presence of the IgG1 anti-EGFR Ab cetuximab; however, IgA anti-EGFR Abs triggered the tumoricidal activity of PBN and negated the stimulatory effect of TAN. Overall, this study provides insights into the mechanisms by which myeloid effectors mediate tumor cell killing or resistance during tAb therapy.

Significance:

The elucidation of the conditions and mechanisms by which human FcR+ myeloid effectors mediate cancer cell resistance and killing during antibody treatment could help develop improved strategies for treating solid tumors.
Data from p53 Promotes Cell Survival due to the Reversibility of Its Cell-Cycle Checkpoints
Authors: Lukin Dana J. , Carvajal Luis A. , Liu Wen-jun , Resnick-Silverman Lois , Manfredi James J.
Published: January 2024

Abstract
The tumor suppressor p53 (TP53) has a well-studied role in triggering cell-cycle checkpoint in response to DNA damage. Previous studies have suggested that functional p53 enhances chemosensitivity. In contrast, data are presented to show that p53 can be required for cell survival following DNA damage due to activation of reversible cell-cycle checkpoints. The cellular outcome to DNA damage is determined by the duration and extent of the stimulus in a p53-dependent manner. In response to transient or low levels of DNA damage, p53 triggers a reversible G2 arrest, whereas a sustained p53-dependent cell-cycle arrest and senescence follows prolonged or high levels of DNA damage. Regardless of the length of treatment, p53-null cells arrest in G2, but ultimately adapt and proceed into mitosis. Interestingly, they fail to undergo cytokinesis, become multinucleated, and then die from apoptosis. Upon transient treatment with DNA-damaging agents, wild-type p53 cells reversibly arrest and repair the damage, whereas p53-null cells fail to do so and die. These data indicate that p53 can promote cell survival by inducing reversible cell-cycle arrest, thereby allowing for DNA repair. Thus, transient treatments may exploit differences between wild-type p53 and p53-null cells.

Implications: Although p53 status has been suggested as a clinical predictor of chemotherapeutic efficacy, studies to date have not always supported this. This study demonstrates that p53 is still an important determinant of cell fate in response to chemotherapy, under the appropriate treatment conditions. Mol Cancer Res; 13(1); 16–28. ©2014 AACR.
Data from Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis
Authors: Ligumsky Hagai , Rubinek Tami , Merenbakh-Lamin Keren , Yeheskel Adva , Sertchook Rotem , Shahmoon Shiri , Aviel-Ronen Sarit , Wolf Ido
Published: January 2024

Abstract
Klotho is a transmembrane protein containing two internal repeats, KL1 and KL2, both displaying significant homology to members of the β-glycosidase family. Klotho is expressed in the kidney, brain, and various endocrine tissues, but can also be cleaved and act as a circulating hormone. Klotho is an essential cofactor for binding of fibroblast growth factor 23 (FGF23) to the FGF receptor and can also inhibit the insulin-like growth factor-1 (IGF-1) pathway. Data from a wide array of malignancies indicate klotho as a tumor suppressor; however, the structure–function relationships governing its tumor suppressor activities have not been deciphered. Here, the tumor suppressor activities of the KL1 and KL2 domains were examined. Overexpression of either klotho or KL1, but not of KL2, inhibited colony formation by MCF-7 and MDA-MB-231 cells. Moreover, in vivo administration of KL1 was not only well tolerated but significantly slowed tumor formation in nude mice. Further studies indicated that KL1, but not KL2, interacted with the IGF-1R and inhibited the IGF-1 pathway. Based on computerized structural modeling, klotho constructs were generated in which critical amino acids have been mutated. Interestingly, the mutated proteins retained their tumor suppressor activity but showed reduced ability to modulate FGF23 signaling. These data indicate differential activity of the klotho domains, KL1 and KL2, in breast cancer and reveal that the tumor suppressor activities of klotho can be dissected from its physiologic activities.

Implications: These findings pave the way for a rational design of safe klotho-based molecules for the treatment of breast cancer. Mol Cancer Res; 13(10); 1398–407. ©2015 AACR.
Table S4 from Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel
Authors: Paiva Bruno , Manrique Irene , Rytlewski Julie , Campbell Timothy , Kazanecki Christian C. , Martin Nathan , Anderson Larry D. , Berdeja Jesús G. , Lonial Sagar , Raje Noopur S. , Lin Yi , Moreau Philippe , San-Miguel Jesús F. , Munshi Nikhil C. , Kaiser Shari M.
Published: January 2024

HR and P values for landmark PFS within first year
Table S3 from Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel
Authors: Paiva Bruno , Manrique Irene , Rytlewski Julie , Campbell Timothy , Kazanecki Christian C. , Martin Nathan , Anderson Larry D. , Berdeja Jesús G. , Lonial Sagar , Raje Noopur S. , Lin Yi , Moreau Philippe , San-Miguel Jesús F. , Munshi Nikhil C. , Kaiser Shari M.
Published: January 2024

CR and MRD on treated population
Figure S1 from Time-Dependent Prognostic Value of Serological and Measurable Residual Disease Assessments after Idecabtagene Vicleucel
Authors: Paiva Bruno , Manrique Irene , Rytlewski Julie , Campbell Timothy , Kazanecki Christian C. , Martin Nathan , Anderson Larry D. , Berdeja Jesús G. , Lonial Sagar , Raje Noopur S. , Lin Yi , Moreau Philippe , San-Miguel Jesús F. , Munshi Nikhil C. , Kaiser Shari M.
Published: January 2024

Consort Diagram
Supplementary Table S2 from ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma
Authors: Neri Paola , Barwick Benjamin G. , Jung David , Patton Jonathan C. , Maity Ranjan , Tagoug Ines , Stein Caleb K. , Tilmont Remi , Leblay Noemie , Ahn Sungwoo , Lee Holly , Welsh Seth J. , Riggs Daniel L. , Stong Nicholas , Flynt Erin , Thakurta Anjan , Keats Jonathan J. , Lonial Sagar , Bergsagel P. Leif , Boise Lawrence H. , Bahlis Nizar J.
Published: January 2024

List of antibodies used in this study.
Supplementary Data 7 from ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma
Authors: Neri Paola , Barwick Benjamin G. , Jung David , Patton Jonathan C. , Maity Ranjan , Tagoug Ines , Stein Caleb K. , Tilmont Remi , Leblay Noemie , Ahn Sungwoo , Lee Holly , Welsh Seth J. , Riggs Daniel L. , Stong Nicholas , Flynt Erin , Thakurta Anjan , Keats Jonathan J. , Lonial Sagar , Bergsagel P. Leif , Boise Lawrence H. , Bahlis Nizar J.
Published: January 2024

Genes whose expression are associated with ETV4 in NDMM and in RRMM patients enrolled in the CoMMpass study.
Supplementary Data 4 from ETV4-Dependent Transcriptional Plasticity Maintains MYC Expression and Results in IMiD Resistance in Multiple Myeloma
Authors: Neri Paola , Barwick Benjamin G. , Jung David , Patton Jonathan C. , Maity Ranjan , Tagoug Ines , Stein Caleb K. , Tilmont Remi , Leblay Noemie , Ahn Sungwoo , Lee Holly , Welsh Seth J. , Riggs Daniel L. , Stong Nicholas , Flynt Erin , Thakurta Anjan , Keats Jonathan J. , Lonial Sagar , Bergsagel P. Leif , Boise Lawrence H. , Bahlis Nizar J.
Published: January 2024

JASPAR transcription factor binding motifs enriched in IKZF1-bound regions in RPMI8226 cells where the cognate transcription factor was expressed at greater than 1 FPKM and the FDR enrichment significance P ≤ 10e-10.
Table S4 from A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML
Authors: Chen Lanpeng , Pronk Eline , van Dijk Claire , Bian Yujie , Feyen Jacqueline , van Tienhoven Tim , Yildirim Meltem , Pisterzi Paola , de Jong Madelon M.E. , Bastidas Alejandro , Hoogenboezem Remco M. , Wevers Chiel , Bindels Eric M. , Löwenberg Bob , Cupedo Tom , Sanders Mathijs A. , Raaijmakers Marc H.G.P.
Published: January 2024

Table S4 Differentially expressed genes and transcriptional programs (GSEA Hallmark) in BMSCs from AML vs. BMSCs from NBM (scRNAseq)
Table S3 from A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML
Authors: Chen Lanpeng , Pronk Eline , van Dijk Claire , Bian Yujie , Feyen Jacqueline , van Tienhoven Tim , Yildirim Meltem , Pisterzi Paola , de Jong Madelon M.E. , Bastidas Alejandro , Hoogenboezem Remco M. , Wevers Chiel , Bindels Eric M. , Löwenberg Bob , Cupedo Tom , Sanders Mathijs A. , Raaijmakers Marc H.G.P.
Published: January 2024

Supplementary Table 3. Differentially expressed genes in the NBM BMSC cluster 0 vs. other BMSC clusters
Supplementary Figure 1-9 from A Single-Cell Taxonomy Predicts Inflammatory Niche Remodeling to Drive Tissue Failure and Outcome in Human AML
Authors: Chen Lanpeng , Pronk Eline , van Dijk Claire , Bian Yujie , Feyen Jacqueline , van Tienhoven Tim , Yildirim Meltem , Pisterzi Paola , de Jong Madelon M.E. , Bastidas Alejandro , Hoogenboezem Remco M. , Wevers Chiel , Bindels Eric M. , Löwenberg Bob , Cupedo Tom , Sanders Mathijs A. , Raaijmakers Marc H.G.P.
Published: January 2024

Fig S1-S9
Supplementary Table 4 from Neoadjuvant CD40 Agonism Remodels the Tumor Immune Microenvironment in Locally Advanced Esophageal/Gastroesophageal Junction Cancer
Authors: Soto Maira , Filbert Erin L. , Yang Hai , Starzinski Stephanie , Starzinski Alec , Gin Marissa , Chen Brandon , Le Phi , Li Tony , Bol Brandon , Cheung Alexander , Zhang Li , Hsu Frank J. , Ko Andrew , Fong Lawrence , Keenan Bridget P.
Published: January 2024

Gene lists for gene scores.
Supplementary Figure 2 from Neoadjuvant CD40 Agonism Remodels the Tumor Immune Microenvironment in Locally Advanced Esophageal/Gastroesophageal Junction Cancer
Authors: Soto Maira , Filbert Erin L. , Yang Hai , Starzinski Stephanie , Starzinski Alec , Gin Marissa , Chen Brandon , Le Phi , Li Tony , Bol Brandon , Cheung Alexander , Zhang Li , Hsu Frank J. , Ko Andrew , Fong Lawrence , Keenan Bridget P.
Published: January 2024

Supplementary Figure 2
A Novel Homozygous ACBD5 Variant in an Emerging Peroxisomal Disorder Presenting with Retinal Dystrophy and a Review of the Literature
Authors: Hasturk Berfin Ayla , Cinar Çisem , Zubarioglu Tanyel , Tiryaki-Demir Semra , Cansever Mehmet Serif , Kiykim Ertugrul , Kalaycı Yigin Aysel , Yalcinkaya Cengiz , Aktuglu-Zeybek Cigdem
Published: January 2024

Introduction: Acyl-CoA binding domain containing 5 (ACBD5) deficiency is a newly defined inborn peroxisomal disorder with only 7 patients reported to date. Herein, we report a patient with ACBD5 deficiency who was diagnosed after a complicated diagnostic process. Case Presentation: A 6-year-old male patient was admitted with complaints of neuromotor regression and visual disturbances. He had spastic paraparesis dominated with axial hypotonic posturing and horizontal nystagmus. His very-long-chain fatty acid levels were within normal ranges with a slightly elevated C26:0/C22:0 ratio. Brain magnetic resonance imaging revealed white matter involvement. Clinical exome sequencing displayed a novel homozygous intronic splice site variant (c.936 + 2T>G) in the ACBD5 (NM_145698.5) gene. Conclusion: With this report, a novel variant in ACBD5 deficiency was described. Macular dystrophy was demonstrated with optical coherence tomography imaging for the first time in the literature in ACBD5 deficiency. In order to contribute to the knowledge about the clinical, biochemical, and genetic spectrum of ACBD5 deficiency, new patients need to be defined.
Association of Cancer and Its Interaction with Conventional Risk Factors on Cardiovascular Disease Risk
Authors: Suzuki Yuta , Kaneko Hidehiro , Okada Akira , Matsuoka Satoshi , Kashiwabara Kosuke , Fujiu Katsuhito , Michihata Nobuaki , Jo Taisuke , Takeda Norifumi , Morita Hiroyuki , Node Koichi , Yasunaga Hideo , Komuro Issei
Published: January 2024

Introduction: We sought to examine the association of cancer history with the incidence of individual cardiovascular disease events and to clarify whether the history of cancer modifies the relationship between conventional cardiovascular risk factors and incident cardiovascular disease. Methods: This retrospective cohort study used the JMDC Claims Database, including 3,531,683 individuals. The primary endpoint was the composite cardiovascular disease outcome, which included myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Results: During a follow-up, 144,162 composite endpoints were recorded. Individuals with a history of cancer had a higher risk of developing composite cardiovascular disease events (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.22–1.29). The HRs for myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation were 1.11 (95% CI 0.98–1.27), 1.15 (95% CI 1.10–1.20), 1.11 (95% CI 1.05–1.18), 1.39 (95% CI 1.34–1.44), and 1.22 (95% CI 1.13–1.32), respectively. Individuals who required chemotherapy for cancer had a higher risk of developing cardiovascular disease. Although conventional risk factors (e.g., overweight/obesity, hypertension, and diabetes) were associated with incident composite cardiovascular disease even in individuals with a history of cancer, the total population-attributable fractions of conventional risk factors were less in individuals with a history of cancer. Conclusion: Individuals with a history of cancer (particularly those requiring chemotherapy) have a higher risk of cardiovascular disease. Traditional risk factors are important in the development of cardiovascular disease in individuals with and without a history of cancer. In individuals with a history of cancer, however, the total population-attributable fractions of conventional risk factors decreased.
Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133
+
TRPV4
high
Endothelial Subpopulation in Regulating Flow-Induced Vascular Tone in Mice
Authors: Mao Aiqin , Zhang Ka , Kan Hao , Gao Mengru , Wang Zhiwei , Zhou Tingting , Shao Jing , He Dongxu
Published: January 2024

BACKGROUND:

Single-cell RNA-Seq analysis can determine the heterogeneity of cells between different tissues at a single-cell level. Coronary artery endothelial cells (ECs) are important to coronary blood flow. However, little is known about the heterogeneity of coronary artery ECs, and cellular identity responses to flow. Identifying endothelial subpopulations will contribute to the precise localization of vascular endothelial subpopulations, thus enabling the precision of vascular injury treatment.

METHODS:

Here, we performed a single-cell RNA sequencing of 31 962 cells and functional assays of 3 branches of the coronary arteries (right coronary artery/circumflex left coronary artery/anterior descending left coronary artery) in wild-type mice.

RESULTS:

We found a compendium of 7 distinct cell types in mouse coronary arteries, mainly ECs, granulocytes, cardiac myocytes, smooth muscle cells, lymphocytes, myeloid cells, and fibroblast cells, and showed spatial heterogeneity between arterial branches. Furthermore, we revealed a subpopulation of coronary artery ECs, CD133
+
TRPV4
high
ECs. TRPV4 (transient receptor potential vanilloid 4) in CD133
+
TRPV4
high
ECs is important for regulating vasodilation and coronary blood flow.

CONCLUSIONS:

Our study elucidates the nature and range of coronary arterial cell diversity and highlights the importance of coronary CD133
+
TRPV4
high
ECs in regulating coronary vascular tone.
Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation
Authors: Dzobo Kim E. , Cupido Arjen J. , Mol Barend M. , Stiekema Lotte C.A. , Versloot Miranda , Winkelmeijer Maaike , Peter Jorge , Pennekamp Anne-Marije , Havik Stefan R. , Vaz Frédéric M. , van Weeghel Michel , Prange Koen H.M. , Levels Johannes H.M. , de Winther Menno P.J. , Tsimikas Sotirios , Groen Albert K. , Stroes Erik S.G. , de Kleijn Dominique P.V. , Kroon Jeffrey
Published: January 2024

BACKGROUND:

Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a).

METHODS:

Untargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The atherogenicity of the observed Lp(a)-associated lipids was tested ex vivo in primary human monocytes by RNA sequencing, ELISA, Western blot, and transendothelial migratory assays. Using immunofluorescence staining and single-cell RNA sequencing, the phenotype of macrophages was investigated in human atherosclerotic lesions.

RESULTS:

Compared with healthy individuals with low/normal Lp(a) levels (median, 7 mg/dL [18 nmol/L]; n=13), individuals with elevated Lp(a) levels (median, 87 mg/dL [218 nmol/L]; n=12) demonstrated an increase in lipid species, particularly diacylglycerols (DGs) and lysophosphatidic acid (LPA). DG and the LPA precursor lysophosphatidylcholine were enriched in the Lp(a) fraction. Ex vivo stimulation with DG(40:6) demonstrated a significant upregulation in proinflammatory pathways related to leukocyte migration, chemotaxis, NF-κB (nuclear factor kappa B) signaling, and cytokine production. Functional assessment showed a dose-dependent increase in the secretion of IL (interleukin)-6, IL-8, and IL-1β after DG(40:6) and DG(38:4) stimulation, which was, in part, mediated via the NLRP3 (NOD [nucleotide-binding oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome. Conversely, LPA-stimulated monocytes did not exhibit an inflammatory phenotype. Furthermore, activation of monocytes by DGs and LPA increased their transendothelial migratory capacity. Human atherosclerotic plaques from patients with high Lp(a) levels demonstrated colocalization of Lp(a) with M1 macrophages, and an enrichment of CD68
+
IL-18
+
TLR4
+
(toll-like receptor) TREM2
+
(triggering receptor expressed on myeloid cells) resident macrophages and CD68
+
CASP1
+
(caspase) IL-1B
+
SELL
+
(selectin L) inflammatory macrophages compared with patients with low Lp(a). Finally, potent Lp(a)-lowering treatment (pelacarsen) resulted in a reduction in specific circulating DG lipid subspecies in patients with cardiovascular disease with elevated Lp(a) levels (median, 82 mg/dL [205 nmol/L]).

CONCLUSIONS:

Lp(a)-associated DGs and LPA have a potential role in Lp(a)-induced monocyte inflammation by increasing cytokine secretion and monocyte transendothelial migration. This DG-induced inflammation is, in part, NLRP3 inflammasome dependent.
Estimation of Distribution Algorithm for Grammar-Guided Genetic Programming
Authors: Criado Pablo Ramos , Rolanía D. Barrios , de la Hoz David , Manrique Daniel
Published: January 2024

Genetic variation operators in grammar-guided genetic programming are fundamental to guide the evolutionary process in search and optimization problems. However, they show some limitations, mainly derived from an unbalanced exploration and local-search trade-off. This paper presents an estimation of distribution algorithm for grammar-guided genetic programming to overcome this difficulty and thus increase the performance of the evolutionary algorithm. Our proposal employs an extended dynamic stochastic context-free grammar to encode and calculate the estimation of the distribution of the search space from some promising individuals in the population. Unlike traditional estimation of distribution algorithms, the proposed approach improves exploratory behavior by smoothing the estimated distribution model. Therefore, this algorithm is referred to as SEDA, smoothed estimation of distribution algorithm. Experiments have been conducted to compare overall performance using a typical genetic programming crossover operator, an incremental estimation of distribution algorithm, and the proposed approach after tuning their hyperparameters. These experiments involve challenging problems to test the local search and exploration features of the three evolutionary systems. The results show that grammar-guided genetic programming with SEDA achieves the most accurate solutions with an intermediate convergence speed.
Socratic Heterodoxy? Ontological Commitment in the Hippias Major
Authors: Driscoll Sean
Published: January 2024

The question of ontological commitment in Plato’s Hippias Major has been important in disputes over the dialogue’s place in the corpus, its meaning, and its authenticity. But this question seems to have been settled—the Hippias Major is not committed to the ‘forms.’ Such an ontological conclusion has been vigorously defended, but its defenses rest on a problematic meta-ontological framework. This paper suggests a more adequate framework and brings more evidence to the evaluation of the question of ontological commitment in the Hippias Major. It concludes that the dialogue is indeed committed to some kind of form.
Bringing Climate Change to Strasbourg. The Convention and Healthy Environment Claims
Authors: den Exter André
Published: January 2024

Climate change profoundly impacts all aspects of human life, including health. International fora and nation States recognise the importance of urgently cutting greenhouse gas emissions as a primary cause of global warming. States’ commitment to alter climate change has resulted in several treaty documents referring explicitly to human rights obligations. But what exactly are States’ obligations under climate change treaty law and other human rights treaties? And what is the judiciary’s role when confronted with the right to health violations and systemic deficiencies relating to climate change? Can climate change litigation give individual citizens a remedy to right to health violations and reduce the impact of climate change?
Research on the Lacquered Channel Figurine Excavated from a Han Tomb in Tianhui
Authors: Zhou Qi , Yu Catherine Xin Xin
Published: January 2024

Apart from the seven medical treatises excavated from Laoguanshan Tomb M3, there were also medical artifacts: an iron mortar and pestle for medicine, remains of plants that seem to be medicine, and a tiny figurine decorated with red and white lacquered lines. In accordance with the Han period funerary practice of “serving the dead as serving the living” (shi si ru shi sheng 事死如事生), these funerary medical artifacts are likely related to the profession and daily life of the tomb’s occupier, in this case, very probably a medical official. This article introduces the lacquer figurine and the “channels” (jingmai 經脈) it illustrates in relation to roughly contemporaneous textual accounts of similar channels that have been excavated from tombs that were sealed in the Western Han (202 BCE–9 CE) period, as well as to accounts in the medical classics that were passed down and printed over one thousand years later than the date of the Laoguanshan tomb.
Reflections on Bian Que in Religious and Medical Traditions in Early China
Authors: Ochs Shelley
Published: January 2024

Initial analysis of the contents of the Laoguanshan manuscripts shows there is an emphasis on a number of healing principles and techniques that have been associated with Bian Que: puncturing the mai-channels to heal disease; diagnosis based on examining the appearance and palpating multiple sites on the body; reverence for the mantic arts, and the superior physician who can correctly “determine whether [the patient] will live or die.” These characteristics have been ascribed to Bian Que across a number of domains: through non-medical texts that describe cases or anecdotes, passages in the received medical literature ascribed to a person or lineage with this name, and material evidence from Han dynasty mortuary art. Widespread references to Bian Que in medical and non-medical works indicate that citing the name constituted a recognizable and potent mode of establishing authority. Although we cannot completely reconstruct the medical practices of a person, clan, or mode of authority called “Bian Que,” the traces that remain substantiate claims that a set of ideas and practices associated with Bian Que was revered as efficacious healing worthy of study and transmission.
Techniques for Piercing the Mai Recorded in the Laoguanshan Han Tomb Bamboo Slips
Authors: Gu Man , Zhou Qi , Liu Changhua , Ochs Shelley
Published: January 2024

The text discussed in this paper is part of the collection of bamboo slip medical manuscripts excavated from the Laoguanshan Han tomb outside of Chengdu, Sichuan Province, China, in 2012. We have given it the title Piercing Methods based on its contents. This text provides invaluable new material for understanding the historical development of Chinese medicine and acupuncture over the course of the Han dynasty (202 BCE–220 CE). We combine analyses of excavated manuscripts, received texts, and excavated artifacts to reconstruct the piercing methods from the early Han presented in this text. Three primary sets of techniques and associated piercing tools have been identified: mai piercing, division piercing, and piercing water (swelling), although only the first technique that concerns treating the mai is dealt with comprehensively in this article.
A Brief Introduction to the Horse Medical Manuscript from the Tianhui Laoguanshan Han Tomb
Authors: Yang Dolly
Published: January 2024

One of the most important archaeological finds excavated from the Tianhui Laoguanshan Han tombs in 2012–13 was a manuscript on horse medicine, dated around the third century BCE. Prior to the discovery of this highly specialized veterinary text, only a handful of horse recipes from the Qin and Han periods had been found, and a sixth-century CE agricultural treatise, Essential Techniques for the Common People, was generally regarded as the earliest surviving source of extensive veterinary material, including various medical treatments for horses. Although the Laoguanshan manuscript – given the modern title Book of Treating Horses by the Team for Collating the Medical Bamboo Slips Excavated from the Han Tombs in Tianhui Town, Chengdu – has suffered significant damage, it nevertheless gives us an insight into the knowledge and treatments for horses during the Qin and early Han periods. A variety of ways of treating horses are recorded in Treating Horses, including herbal remedies, piercing, cauterization, hot packs, bandages, massage, and bathing. The use of gold needles is also mentioned in this text, echoing the gold and silver sewing needles excavated from Liu Sheng’s (d. 113 BCE) tomb in Mancheng, Hebei Province. This paper offers a short introduction to this valuable text on horse medicine by examining the content of its fragments, including names of ailments, symptoms of certain diseases, etiologies, and treatment methods. The discovery of Treating Horses challenges the established view that horse treatment methods in ancient China were predominantly herbal and that techniques of bleeding and cauterization recorded in Essential Techniques were brought to China from elsewhere, together with the introduction of Buddhism. The paper argues that the “foreign influence” had already occurred at a much earlier date, in the form of interactions with nomadic tribes such as the Scythians, the horsemen par excellence of classical antiquity.
Three new species of the genus Odontomutilla Ashmead, 1899 (Hymenoptera: Mutillidae) from India
Authors: TERINE JOSHUA B. , KUMAR GIRISH P.
Published: January 2024

Three new species of velvet ant, Odontomutilla jaferpaloti sp. nov. (India: Karnataka), O. vishwanathi sp. nov. (India: Karnataka), and O. himalayensis sp. nov. (India: Uttarakhand), are described and illustrated. Diagnostic features of these new species, to separate them from similar species are provided. The updated key to the species of India is given.
An Analysis of the Lagged Relationship between Anomalies of Precipitation and Soil Moisture and Its Potential Role in Agricultural Drought Early Warning
Authors: Cammalleri C. , McCormick N. , Spinoni J. , Nielsen-Gammon J. W.
Published: January 2024

The standardized precipitation index (SPI) is the most commonly used index for detecting and characterizing meteorological droughts, and it is also extensively used as a proxy variable for soil moisture anomalies (SMA) for the purpose of monitoring agricultural drought in absence of long-term soil moisture observations. However, the potential capability of SPI to warn of the time-lagged soil water deficit—following the well-known “drought cascade” effect—is often overlooked in agricultural drought studies. In this research, a time-lagged correlation analysis is used to evaluate the relationship between the SMA dataset, generated as part of the Global Drought Observatory of the European Union’s Copernicus Emergency Management Service, and a set of SPIs derived from the ERA5 reanalysis produced by the European Centre for Medium-Range Weather Forecasts. The possibility to achieve an optimal agreement between SPI and SMA that also preserves the early warning skills of SPI is evaluated. The results suggest that if only the correlation between SPI and SMA is considered, the maximum agreement is usually obtained with a zero lead time (almost 80% of the cases), with SPI-3 representing the best option in about 40% of the grid cells at global scale. By also accounting for the benefits of a positive lead time, short accumulation periods tend to be favored, with SPI-1 being the optimal choice in about one-half of the cases, and 10–20 days of lead time in more than 90% of the grid cells is achieved without any significant reduction in either correlation or skill in drought extreme detection.