bluuebunny/crossref_metadata_2025_split huggingface dataset:
MYC Inhibition Potentiates CD8+ T Cells Against Multiple Myeloma and Overcomes Immunomodulatory Drug Resistance
Authors: Davis Lorraine N. , Walker Zachary J. , Reiman Lauren T. , Parzych Sarah E. , Stevens Brett M. , Jordan Craig T. , Forsberg Peter A. , Sherbenou Daniel W. 
Published: May 2024

Abstract

Purpose:
Immunomodulatory drugs (IMiDs), such as lenalidomide and pomalidomide, are a cornerstone of multiple myeloma (MM) therapies, yet the disease inevitably becomes refractory. IMiDs exert cytotoxicity by inducing cereblon-dependent proteasomal degradation of IKZF1 and IKZF3, resulting in downregulation of the oncogenic transcription factors IRF4 and MYC. To date, clinical IMiD resistance independent of cereblon or IKZF1/3 has not been well explored. Here, we investigated the roles of IRF4 and MYC in this context.

Experimental Design:
Using bone marrow aspirates from patients with IMiD-naïve or refractory MM, we examined IKZF1/3 protein levels and IRF4/MYC gene expression following ex vivo pomalidomide treatment via flow cytometry and qPCR. We also assessed exvivo sensitivity to the MYC inhibitor MYCi975 using flow cytometry.

Results:
We discovered that although pomalidomide frequently led to IKZF1/3 degradation in MM cells, it did not affect MYC gene expression in most IMiD-refractory samples. We subsequently demonstrated that MYCi975 exerted strong anti-MM effects in both IMiD-naïve and -refractory samples. Unexpectedly, we identified a cluster of differentiation 8+ (CD8+ T) cells from patients with MM as crucial effectors of MYCi975-induced cytotoxicity in primary MM samples, and we discovered that MYCi975 enhanced the cytotoxic functions of memory CD8+ T cells. We lastly observed synergy between MYCi975 and pomalidomide in IMiD-refractory samples, suggesting that restoring MYC downregulation can re-sensitize refractory MM to IMiDs.

Conclusions:
Our study supports the concept that MYC represents an Achilles’ heel in MM across disease states and that MYCi975 may be a promising therapeutic for patients with MM, particularly in combination with IMiDs.
Empowering Women in Labor Market: a Comprehensive Analysis of Recent Legal Developments in the Kingdom of Saudi Arabia
Authors: Polok Beata Maria 
Published: May 2024

Abstract
This survey examines the legal developments in Saudi Arabia following the announcement of the Vision 2030 reform plan in 2016. While the primary goal of Vision 2030 is to reduce the country’s dependence on oil and diversify the economy, it has also had a significant impact on women’s rights and empowerment. Legislative changes have been enacted to promote women’s participation in both public and private life, aligning with the core principles of Vision 2030. This Survey analyzes the specific legal reforms aimed at empowering women, including measures to facilitate access to the job market. Additionally, it explores developments related to women’s driving rights, gender segregation, anti-harassment laws, and the new Personal Status Law. These reforms indirectly contribute to women’s empowerment across private and public spheres.
Hermetia illucens larvae fat vs coconut oil to obtain free lauric acid-rich products by chemical or enzymatic hydrolysis
Authors: Vázquez L. , Hurtado-Ribeira R. , López de Haro C.S. , Martin D. 
Published: May 2024

Abstract
Lauric acid is present in various vegetable fats and has been shown to be beneficial for human health and well-being. The interest in the properties of this fatty acid has led to an increase in the production and consumption of oils rich in lauric acid, primarily coconut oil. Despite being less known, there is an atypical animal source of lauric acid that can be considered more sustainable and that has levels of this fatty acid comparable to coconut oil, as the case of the larvae of the edible insect black soldier fly (Hermetia illucens) is. Due to the fact that some of the bioactive properties of lauric acid are linked to its free form, and also to facilitate subsequent concentration processes, the release of the fatty acid from the triacylglycerols present in fats becomes necessary. In this study, chemical and enzymatic hydrolysis for transforming both lauric acid-rich fats into a product rich in free fatty acids (FFA) were investigated. Different variables were studied, such as reaction time and the amount of catalyst used, resulting in maximum conversions to FFA in the case of chemical hydrolysis in just 20 min for both fats. Furthermore, the efficiency of the lipase Eversa® Transform 2.0 in generating a lauric acid-rich product from both oils was demonstrated, but in this case, a longer time was needed. The products obtained through both types of hydrolysis contained high percentages of free lauric acid, also exhibiting high stability against oxidation. This makes H. illucens larvae fat a comparable and alternative source to coconut oil to produce lauric-acid rich products useful for different applications.
Accuracy of Polarimetric Radar ZDR Estimates: Implications for the Quantitative Observation of Meteorological and Nonmeteorological Echoes
Authors: May Peter T. , Guyot Adrien , Protat Alain , Curtis Mark 
Published: May 2024

Abstract
This paper considers theoretical and observed uncertainties in the estimates of ZDR and ρHV(0) using data from an operational S-band radar and a mobile X-band radar. Cases of widespread uniform precipitation including bright-band, clear air, and ash echoes from forest fires are all considered in order to obtain a wide range of ρHV(0) values as this along with the radar frequency and spectrum width determines the uncertainties. The theoretical uncertainties in these parameters provide a good estimate of the lower bound of the standard deviations of the observed values where these have been estimated using the adjacent data to the target pixel. The implications for the accuracy of precipitation estimation, particle identification, and estimates of drop-size distributions are discussed.

Significance Statement
High-quality quantitative precipitation and particle size/classification retrievals using weather radar are strongly dependent on the accuracy of ZDR and ρHV(0). This paper examines the theoretical limits to the measurement accuracy and verifies these limits with radar data at 10- and 3-cm wavelengths.
A Review of a Traditional Chinese Medicine Formula for Treating Insomnia with  Depression: Wendan Decoction
Authors: Kong Lingyuan , He Xinyi , Li Xiuyang 
Published: May 2024

Background: The relationship between insomnia and depression is complex and two-way. Long-term insomnia may cause, maintain, and aggravate depression, and with the development of the disease, depression patients will also experience insomnia symptoms. Oral medication is currently the main treatment for insomnia with depression (ID). Drugs such as Estazolam have good anti-anxiety and insomnia effects, high safety, and relatively small side effects. They are widely used in the treatment of ID in clinics, but some patients still have adverse reactions or low efficacy when taking Estazolam and other drugs. In recent years, Chinese herbal medicine and TCM prescriptions for the treatment of mental illness have been more and more accepted and studied by international scholars. The efficacy of Wendan Decoction (WDD) has been tested by ancient China for nearly 1,400 years, and with the development of modern pharmacological research, it is widely used in the treatment of insomnia and depression. Purpose: Therefore, based on the understanding of ID in TCM, this article discusses the pharmacodynamic effect of WDD, and based on existing clinical and experimental studies, comprehensively analyzes the clinical observation, mechanism of action, and pharmacological effect of WDD in the treatment of ID, to provide more clinical experience and experimental theoretical support for WDD in the treatment of ID. Methods: Retrieve Chinese and English literature on the treatment of ID with WDD from databases such as Web of Science, etc. Conclusion: WDD has good therapeutic effects on ID.
Sickle Cell Disease Has No Impact on 10-Year Cumulative Incidence and Indications for Revision Lumbar Fusion
Authors: Seibold B. Tanner , Ramesh Abhisri , Parel Philip M. , Quan Theodore , Ranson Rachel A. , Mesfin Addisu , Patel Tushar Ch. 
Published: May 2024

Study Design Retrospective Cohort Study. Objectives Patients with sickle cell disease (SCD) experience distinct physiological challenges that may alter surgical outcomes. There has been no research establishing 10-year lumbar fusion (LF) implant survivorship rates among individuals with SCD. This study aims to determine the 10-year cumulative incidence and indications for revision LF between patients with and without SCD. Methods A national database was queried to identify patients with and without SCD who underwent primary LF. SCD patients undergoing LF were propensity-score matched in a 1:4 ratio by age, gender, and Charlson Comorbidity Index (CCI) to a matched LF control. In total, 246 SCD patients were included along with 981 and 100,000 individuals in the matched and unmatched control cohorts, respectively. Kaplan-Meier survival analysis was utilized to determine the 10-year cumulative incidence rates of revision LF. Furthermore, multivariable analysis using Cox proportional hazard modeling was performed to compare indications for revisions and surgical complications between cohorts including hardware removal, drainage and evacuation, pseudoarthrosis, and mechanical failure. Results No significant differences were found in the cumulative incidence of 10-year all-cause revision LF between patients in the SCD cohort and either of the control cohorts ( P > .05 for each). Additionally, there were no significant differences between the SCD cohort and either of the control cohorts in regards to the indications for revision or surgical complications in LF ( P > .05 for each). Conclusions This study indicates that SCD patients do not have increased risk for revision LF, nor any of its indications.
CRISPR-based gene expression platform for precise regulation of bladder cancer
Authors: Zhan Tianying , Li Xiao , Liu Jiumin , Ye Chujin 
Published: May 2024

AbstractThe development of compact CRISPR systems has facilitated delivery but has concurrently reduced gene editing efficiency, thereby limiting the further utilization of CRISPR systems. Enhancing the efficiency of CRISPR systems poses a challenging task and holds significant implications for the advancement of biotechnology. In our work, we report a synthetic dual-antibody system that can stably exist in the intracellular environment, specifically inhibiting the functions of NF-κB and β-catenin. This not only elevates the transgenic expression of the CRISPR system by suppressing the innate immune response within cells to enhance the gene editing efficiency but also demonstrates a notable tumor inhibitory effect. Based on the specific output expression regulation of CRISPR-CasΦ, we constructed a CRISPR-based gene expression platform, which includes sensor modules for detecting intracellular β-catenin and NF-κB, as well as an SDA module to enhance overall efficiency. In vitro experiments revealed that the CRISPR-based gene expression platform exhibited superior CDK5 expression inhibition efficiency and specific cytotoxicity towards tumor cells. In vitro experiments, we found that CRISPR-based gene expression platforms can selectively kill bladder cancer cells through T cell-mediated cytotoxicity. Our design holds significant assistant potential of transgene therapy and may offer the capability to treat other diseases requiring transgene therapy.
Antibiotic-induced microbiome depletion promotes intestinal colonization by Campylobacter jejuni in mice
Authors: Chen Haohao , Zhang Yanfang , Pan Yi , Wu Lin , Wang Wenqian , Zhang Hui , Lou Hongqiang 
Published: May 2024

Abstract
Background
To establish a method to induce Campylobacter jejuni colonization in the intestines of C57BL/6 mice through antibiotic-induced microbiome depletion.

Results
Fifty-four female C57BL/6 mice were divided into the normal, control, and experimental groups. The experimental group was administered intragastric cefoperazone sodium and sulbactam sodium (50 mg/mL) for 2 days; then, the experimental and control mice were intragastrically administered 200 µL C. jejuni, which was repeated once more after 2 days. Animal feces were collected, and the HipO gene of C. jejuni was detected using TaqMan qPCR from day 1 to day 14 after modeling completion. Immunofluorescence was used to detect intestinal C. jejuni colonization on day 14, and pathological changes were observed using hematoxylin and eosin staining. Additionally, 16S rDNA analyses of the intestinal contents were conducted on day 14. In the experimental group, C. jejuni was detected in the feces from days 1 to 14 on TaqMan qPCR, and immunofluorescence-labeled C. jejuni were visibly discernable in the intestinal lumen. The intestinal mucosa was generally intact and showed no significant inflammatory-cell infiltration. Diversity analysis of the colonic microbiota showed significant inter-group differences. In the experimental group, the composition of the colonic microbiota differed from that in the other 2 groups at the phylum level, and was characterized by a higher proportion of Bacteroidetes and a lower proportion of Firmicutes.

Conclusions
Microbiome depletion induced by cefoperazone sodium and sulbactam sodium could promote long-term colonization of C. jejuni in the intestines of mice.
Morphological and genetic characterization of jackfruit (Artocarpus heterophyllus) in the Kayunga and Luwero districts of Uganda
Authors: Gwokyalya Racheal , Nanteza Ann , Wagaba Henry , Kayondo Siraj Ismail , Kazigaba Dan , Nakabonge Grace 
Published: May 2024

Abstract
Background
Jackfruit (Artocarpus heterophyllus) is an economically valuable fruit tree in Uganda. However, the production of jackfruit in Uganda is low. Additionally, because of deforestation, genetic erosion of the resource is predicted before its exploitation for crop improvement and conservation. As a prerequisite for crop improvement and conservation, 100 A. heterophyllus tree isolates from the Kayunga and Luwero districts in Uganda were characterized using 16 morphological and 10 microsatellite markers.

Results
The results from the morphological analysis revealed variations in tree height, diameter at breast height (DBH), and crown diameter, with coefficient of variation (CV) values of 20%, 41%, and 33%, respectively. Apart from the pulp taste, variation was also observed in qualitative traits, including tree vigor, trunk surface, branching density, tree growth habit, crown shape, leaf blade shape, fruit shape, fruit surface, flake shape, flake color, flake flavor and pulp consistency/texture. Genotyping revealed that the number of alleles amplified per microsatellite locus ranged from 2 to 5, with an average of 2.90 and a total of 29. The mean observed (Ho) and expected (He) heterozygosity were 0.71 and 0.57, respectively. Analysis of molecular variance (AMOVA) indicated that 81% of the variation occurred within individual trees, 19% among trees within populations and 0% between the two populations. The gene flow (Nm) in the two populations was 88.72. The results from the ‘partitioning around medoids’ (PAM), principal coordinate analysis (PCoA) and genetic cluster analysis further revealed no differentiation of the jackfruit populations. The Mantel test revealed a negligible correlation between the morphological and genetic distances.

Conclusions
Both morphological and genetic analyses revealed variation in jackfruit within a single interbreeding population. This diversity can be exploited to establish breeding and conservation strategies to increase the production of jackfruit and hence boost farmers’ incomes. However, selecting germplasm based on morphology alone may be misleading.
Comparative mineral and biochemical characterization of Citrus reticulata fruits and leaves to citrus canker pathogens, Xanthomonas axonopodis
Authors: Nawaz Rab , Ghani Abdul , Nadeem Muhammad , Abbas Toqeer , Shah Anis Ali , Shaffique Shifa , Elansary Hosam O. , Moussa Ihab Mohamed 
Published: May 2024

AbstractPakistan’s economy greatly benefits from citrus production since these fruits are sold and consumed all over the world. Although citrus fruits are easy to cultivate, they are susceptible to diseases caused by bacteria, viruses, and fungi. These challenges, as well as difficulties in obtaining the proper nutrients, might negatively impact fruit yields and quality. Citrus canker is another complicated problem caused by the germ Xanthomonas axonopodis. This germ affects many types of citrus fruits all over the world. This study looked closely at how citrus canker affects the leaves and the quality of the fruit in places like Sargodha, Bhalwal, Kotmomin, and Silanwali, which are big areas for growing citrus in the Sargodha district. What we found was that plants without the disease had more chlorophyll in their leaves compared to the sick plants. Also, the healthy plants had better amounts of important minerals like calcium, magnesium, potassium, and phosphorus in their fruits. But the fruits with the disease had too much sodium, and the iron levels were a bit different. The fruits with the disease also didn’t have as much of something that protects them called antioxidants, which made them more likely to get sick. This study helps us understand how citrus canker affects plants and fruit, so we can think of ways to deal with it.
Patterns and driving factors of functional traits of desert species with different elevational distributions in the Tibetan Plateau and adjacent areas
Authors: Hu Ya , Li Xiangyun , Wang Shaokun , Lv Peng , Yue Ping , Chen Min , Zuo Xiaoan 
Published: May 2024

AbstractVariations in functional traits serve as measures of plants’ ability to adapt to environment. Exploring the patterns of functional traits of desert plants along elevational gradients is helpful to understand the responses and adaptation strategies of species to changing environments. However, it is unknown whether the relationship between functional traits and elevation is affected by differences in the species’ elevational distributions (elevation preference and species’ range). Importantly, most researches have concerned with differences in mean trait values and ignored intraspecific trait variation. Here, we measured functional traits of desert plants along a wide elevational gradient in the Tibetan Plateau and adjacent areas and explored functional trait patterns over elevation in species with different elevational distributions. We decomposed trait variation and further investigated characterizations of intraspecific variation. Ultimately, the main drivers of trait variation were identified using redundancy analysis. We found that species’ elevational distributions significantly influenced the relationship of functional traits such as plant height, leaf dry matter content, leaf thickness, leaf nitrogen and carbon content with elevation. Species with a lower elevational preference showed greater trait variation than species with a higher elevational preference, suggesting that species that prefer high elevation are more conservative facing environmental changes. We provide evidence that interspecific trait variation in leaf thickness and leaf carbon content decreased with increasing species’ range, indicating that increased variations in resistance traits within species make greater responsiveness to environmental changes, enabling species a wider range. Elevation, temperature and precipitation were the main drivers of trait variation in species with a low elevational preference, while the effect of precipitation on trait variation in species with a high elevational preference was not significant. This study sheds new insights on how plants with different elevational distributions regulate their ecological strategies to cope with changing environments.
The potential range of west Asian apple species Malus orientalis Uglitzk. under climate change
Authors: Walas Łukasz , Alipour Shirin , Haq Shiekh Marifatul , Alamri Saud 
Published: May 2024

AbstractThe wild relatives of cultivated apples would be an ideal source of diversity for breeding new varieties, which could potentially grow in diverse habitats shaped by climate change. However, there is still a lack of knowledge about the potential distribution of these species. The aim of the presented work was the understand the impacts of climate change on the potential distribution and habitat fragmentation of Caucasian crab apple (Malus orientalis Uglitzk.) and the designation of areas of high interest according to climatic conditions. We used the MaxEnt models and Morphological-Spatial Analysis (MSPA) to evaluate the potential distribution, suitability changes, habitat fragmentation, and connectivity throughout the species range in Turkey, Armenia, Georgia, Russia, and Iran. The results revealed that the potentially suitable range of M. orientalis encompasses 858,877 km², 635,279 km² and 456,795 km² under the present, RCP4.5 and RCP8.5 scenario, respectively. The range fragmentation analysis demonstrated a notable shift in the edge/core ratio, which increased from 50.95% in the current scenario to even 67.70% in the future. The northern part of the range (Armenia, northern Georgia, southern Russia), as well as the central and western parts of Hyrcania will be a core of the species range with suitable habitats and a high connectivity between M. orientalis populations and could work as major refugia for the studied species. However, in the Zagros and central Turkey, the potential range will shrink due to the lack of suitable climatic conditions, and the edge/core ratio will grow. In the southern part of the range, a decline of M. orientalis habitats is expected due to changing climatic conditions. The future outlook suggests that the Hyrcanian forest and the Caucasus region could serve as important refuges for M. orientalis. This study helps to understand spatial changes in species’ range in response to climate change and can help develop conservation strategies. This is all the more important given the species’ potential use in future breeding programs aimed at enriching the gene pool of cultivated apple varieties.
High-density genetic map construction and QTL mapping of a zigzag-shaped stem trait in tea plant (Camellia sinensis)
Authors: Liu Dingding , Ye Yuanyuan , Tang Rongjin , Gong Yang , Chen Si , Zhang Chenyu , Mei Piao , Chen Jiedan , Chen Liang , Ma Chunlei 
Published: May 2024

AbstractThe highly unique zigzag-shaped stem phenotype in tea plants boasts significant ornamental value and is exceptionally rare. To investigate the genetic mechanism behind this trait, we developed BC1 artificial hybrid populations. Our genetic analysis revealed the zigzag-shaped trait as a qualitative trait. Utilizing whole-genome resequencing, we constructed a high-density genetic map from the BC1 population, incorporating 5,250 SNP markers across 15 linkage groups, covering 3,328.51 cM with an average marker interval distance of 0.68 cM. A quantitative trait locus (QTL) for the zigzag-shaped trait was identified on chromosome 4, within a 61.2 to 97.2 Mb range, accounting for a phenotypic variation explained (PVE) value of 13.62%. Within this QTL, six candidate genes were pinpointed. To better understand their roles, we analyzed gene expression in various tissues and individuals with erect and zigzag-shaped stems. The results implicated CsXTH (CSS0035625) and CsCIPK14 (CSS0044366) as potential key contributors to the zigzag-shaped stem formation. These discoveries lay a robust foundation for future functional genetic mapping and tea plant genetic enhancement.