bluuebunny/crossref_metadata_2025 huggingface dataset:
Durable antitumor response via an oncolytic virus encoding decoy-resistant IL-18
Authors: Cheng Yan , Zhao Yuanhui , Liu Yu , Zhang Yichi , Xu Dongge , Sun Weikang , Zhang Mengyu , Miao Yuqing , He Susu , Hou Yayi , Stupack Dwayne , Li Erguang
Published: December 2024

Background

Interleukin-18 (IL-18), or interferon (IFN)-γ-inducing factor, potentiates T helper 1 and natural killer cell activation as well as CD8+T-cell proliferation. Recombinant IL-18 has displayed limited clinical efficacy in part due to the expression of the decoy receptor, IL-18 binding protein (IL-18BP). A series of IL-18 variants that are devoid of IL-18BP binding, termed DR18 (decoy-resistant IL-18), was developed via directed evolution. We tested DR18 using oncolytic adenovirus (oAd) as a platform for delivery in syngeneic mouse tumor models.

Methods

oAd harboring wild-type IL-18 or DR18 (oAdDR18) was constructed by inserting IL-18 mutant into modified oAd backbone with Ad5/3 chimeric fiber. The delivery effect and IFN-γ induction were determined by ELISA. The antitumor efficiency of oAdDR18 was tested in CT26, B16BL6 and 4T1 tumor-bearing mice, or athymic nude mice and compared with recombinant DR18 protein (rDR18). 4T1 lung metastasis model was used to evaluate the antitumor efficiency of local and distant tumors. Antitumor memory and synergistic effect with an anti-programmed cell death protein-1 (PD-1) antibody was evaluated. The phenotypes of the immune cells in tumor microenvironment were analyzed by flow cytometry and immunohistochemistry.

Results

Mice received oAdDR18 maintained stable production of IL-18 and IFN-γ compared with those received rDR18. Intratumoral delivery of oAdDR18 significantly reduced tumor growth across several tumor models, but not in the athymic nude mouse model. Mice that had tumor remission showed antitumor memory. The antitumor effect was associated with intratumor infiltration of CD4+and CD8+T cells. DR18 delivered by oAd demonstrated long-lasting and enhanced antitumor activities against local and distant tumors compared with that received rDR18 or wild-type IL-18 delivered by oAd (oAdwtIL-18). oAdDR18 treatment also reduced 4T1 lung metastasis. In addition, combination of this virotherapy with immune checkpoint inhibitors (ICIs)

like the anti-PD-1 antibody further enhanced the antitumor activity as compared with respective monotherapy.

Conclusions

oAdDR18 demonstrates enhanced antitumor activities through the induction of stronger local and system immunities and modulation of the tumor microenvironment compared with those of oAdwtIL-18 and rDR18. A combination of oncolytic virotherapy with cytokine engineering would lead to cytokine-based therapeutics for cancer and other diseases.
Plasma arginine as a predictive biomarker for outcomes with immune checkpoint inhibition in metastatic colorectal cancer: a correlative analysis of the CCTG CO.26 trial
Authors: Ma Lucy X , Titmuss Emma , Loree Jonathan M , Jonker Derek J , Kennecke Hagen F , Berry Scott , Couture Felix , Ahmad Chaudhary E , Goffin John R , Kavan Petr , Harb Mohammed , Colwell Bruce , Samimi Setareh , Samson Benoit , Abbas Tahir , Aucoin Nathalie , Aubin Francine , Koski Sheryl , Tu Dongsheng , O’Callaghan Christopher , Chen Eric X
Published: December 2024

Background

Nutritional stress is a mechanism that allows tumor cells to evade the immune system. Arginine (ARG), an amino acid involved in immunomodulation, aids in regulating T-lymphocyte cell activity and the antitumor response. ARG deficiency in the tumor microenvironment can impair T-cell response while ARG supplementation may promote antitumor immune activity. In this exploratory post hoc analysis of the randomized phase II CO.26 trial, we investigated the role of plasma ARG in predicting response to immune checkpoint inhibitors (ICI) in patients with microsatellite stable refractory metastatic colorectal cancer (mCRC).

Methods

CO.26 randomized patients with refractory mCRC to durvalumab plus tremelimumab (D+T) versus best supportive care (BSC). Plasma ARG concentrations were determined from pretreatment blood samples using high-performance liquid chromatography-tandem mass spectrometry. The median plasma ARG value was used as a cut-off stratifying patients into ARG-high (≥10 700 ng/mL) versus ARG-low (<10 700 ng/mL) groups. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard models were used to analyze the prognostic and predictive impacts of ARG on OS.

Results

Of 180 patients enrolled in CO.26, 161 (N=114 treated with D+T and 47 BSC) had pretreatment blood samples for ARG analysis. There were no significant differences in baseline characteristics between patients included in this analysis and the total study patients, or between ARG-high and ARG-low patients. In the BSC arm, the median OS was 3.09 months for ARG-high versus 4.27 months for ARG-low patients (univariable HR 0.89 (0.49–1.65), p=0.72). In the D+T arm, the median OS was 7.62 months for ARG-high versus 5.27 months for ARG-low patients (univariable HR 0.68, (0.48–1.0], p=0.048). In ARG-high patients, D+T significantly improved OS (median OS 7.62 months with D+T vs 3.09 months BSC; HR 0.61 (0.37–0.99), p=0.047; adjusted p=0.042 for interaction). In ARG-low patients there was no OS benefit with D+T (median OS 5.27 months D+T vs 4.27 months BSC; HR 0.87 (0.52–1.46), p=0.61).

Conclusion

High baseline plasma ARG was predictive of improved OS in patients with mCRC treated with D+T. Further investigations are needed to validate ARG as a biomarker. Therapeutic approaches targeting the ARG pathway may augment ICI activity.

Trial registration number

NCT02870920.
Implementation of Energy-Efficient Approximate Computing via Recursive Multiplier in Error-Tolerant Applications
Authors: Karthikkumar M. , Kalaivani R.
Published: December 2024

Approximate computing (AC) in arithmetic logic has become a viable option in applications requiring error tolerance in energy-efficient architectures. AC relied on approximate arithmetic functions to reduce delay, area, and power consumption while sacrificing accuracy to reduce delay, power, and area. In this research, a novel two approximate recursive multipliers (RMul-1, RMul-2) and an approximate adder have been designed to reduce power consumption, area, and computational delay in error-tolerant systems. The recursive multipliers utilize a combination of NOR, AND, half adder, and full adder gates to achieve low power and area-efficient designs. Furthermore, to reduce time, the approximation adder uses an optimal combination of AND, OR, and MUX gates. Furthermore, the cadence RTL compiler synthesizes the proposed multiplier using 28[Formula: see text]nm technology, and it is compared to previous approximation multipliers. Image processing applications are simulated, and the performance of the proposed multipliers is verified using simulations using the Xilinx ISE 13.2 tool. The proposed RMul designs outperform current techniques by up to 30.3% in area, 20.2% in power, and 43.9% in delay, according to experimental results. In addition, the suggested multipliers outperform existing multipliers in terms of SSIM and PSNR.
Free Vibration Analysis of Mindlin Sectorial Plates by the Weak Form Quadrature Element Method
Authors: Liu He , Zhong Hongzhi
Published: December 2024

The weak form quadrature element method is applied to free vibration analysis of Mindlin sectorial plates. Sharp corner functions are introduced in the vicinity of the corner to eliminate the influence of stress singularity. The outer annular subdomain is analyzed according to weak form quadrature procedures. The continuity of displacement and rotation angles on the interface is enforced afterwards. For various combinations of boundary conditions and vertex angles, the first six nondimensional frequencies are computed by the present formulation. Comparative analysis against existing analytical and numerical results confirms the validity and efficiency of the proposed formulation for analyzing the free vibration behavior of Mindlin sectorial plates.
AdaptSel: Adaptive Selection of Biased and Debiased Recommendation Models for Varying Test Environments
Authors: Wang Zimu , Zou Hao , Liu Jiashuo , Wu Jiayun , Tian Pengfei , He Yue , Cui Peng
Published: December 2024

Recommendation systems are frequently challenged by pervasive biases in the training set that can compromise model effectiveness. To address this issue, various debiasing techniques have been developed to eliminate biases and produce debiased models. However, when encountering varying test environments, some data patterns manifested by the training data could be beneficial to the model’s performance. Completely removing biases may overlook the beneficial data patterns and consequently diminish recommendation accuracy. Thus, it is crucial to carefully integrate certain biases to optimize performance, while the ideal level of bias integration is highly dependent on the test environment. Moreover, these systems operate in dynamic scenarios where the test environments could vary, necessitating an adaptive integration strategy customized to the environment. Our research establishes that discrepancies in predictions of models can guide the selection of the most fitting model for specific situations. Building on this understanding, we present AdaptSel, a pioneering method for the adaptive selection of the superior model during the testing phase. Empirical evaluations substantiate the foundational assumptions of AdaptSel, accentuating its effectiveness in adaptively selecting the most suitable model for varying test environments.
The Query Complexity of Searching Trees with Permanently Noisy Advice
Authors: Boczkowski Lucas , Feige Uriel , Korman Amos , Rodeh Yoav
Published: December 2024

We consider a search problem on trees aiming to find a
treasure
that an adversary places at one of the nodes. The algorithm can query nodes and extract directional information from them. That is, each node holds a pointer, termed
advice
, to one of its neighbors. Ideally, this advice points to the neighbor that is closer to the treasure, however, with probability

\(q\)

this advice points to a uniformly random neighbor. Crucially, the advice is
permanent
, hence querying the same node again yields the same answer.

Let

\(\Delta\)

denote the maximal degree. Roughly speaking, we show that the expected number of queries incurs a phase transition when

\(q\)

is about

\(1/\sqrt{\Delta}\)

. In a recent paper, at TALG’21, we showed that if

\(q\)

is above the threshold then the expected number of queries is polynomial in

\(n\)

. Here, we prove that below the threshold, the expected number of queries is

\(\mathcal{O}(\sqrt{\Delta}\log\Delta\cdot\log^{2}n)\)

, which is tight up to an

\(\mathcal{O}(\log n)\)

factor when

\(\Delta\)

is small. We further show that this factor can be reduced to

\(\mathcal{O}(\log\log n)\)

in the case of regular trees and assuming that

\(q<c/\sqrt{\Delta}\)

for sufficiently small

\(c>0\)

. In addition, we study the case that the treasure must be found with some given probability. We show that for every fixed

\(\varepsilon,\delta>0\)

, if

\(q<1/\Delta^{\varepsilon}\)

then there exists a search strategy that with probability

\(1-\delta\)

finds the treasure using

\((\delta^{-1}\log n)^{O(\frac{1}{\varepsilon})}\)

queries, whereas

\((\delta^{-1}\log n)^{\Omega(\frac{1}{\varepsilon})}\)

queries are necessary.
Prediction of Major Adverse Coronary Events Using the Coronary Risk Score in Women
Authors: Romero-Farina Guillermo , Aguadé-Bruix Santiago , Ferreira-González Ignacio
Published: December 2024

The COronary Risk Score in WOmen (ie, CORSWO) accurately stratified the risk for major adverse coronary events into four levels (low, moderate, high, and very high).
Cardiovascular function and autonomic regulation in urethane-anesthetized and conscious mice
Authors: Vasileva Anastasiia , Flores Laura D. M. , Vasilyev Mikhail , Buckman Michelle A. , DeRuisseau Lara R. , Tomasson Michael H. , Bates Melissa L.
Published: December 2024

This investigation documents cardiovascular outcomes in mice receiving urethane anesthesia, emphasizing sex as a biological variable, and considering oxygen supplementation during anesthesia. This is the first report of M-curve analysis in rodents as a heart rate-independent variability analysis.
An Experimental Investigation on the Characteristics of Excavation‐Induced Failure of Rocks Surrounding a Shaft
Authors: Liu Huanxin , An Zhihai , Liu Xingquan , Wang Xi , Liu Zhen
Published: December 2024

A series of true triaxial compression (TTC) tests was conducted on granite specimens to investigate their fracture behavior. The granite was sampled from a 1500‐m‐deep exploration borehole located on the Sanshandao gold field in Shandong Province, China, where a 1915‐m deep vertical shaft was planned. Under true triaxial stress, the fracture of the granite specimen shows anisotropic characteristics, which is manifested as different strains in the three directions of the specimen, and the macroscopic fractures formed are parallel to the direction of maximum principal stress σ1 and intermediate principal stress σ2. In addition, the effects of the intermediate principal stress σ2 and the minimum principal stress σ3 on the fracture of granite specimen are different. A higher σ2 causes the post‐peak curve of the granite specimen to develop toward a Class‐II type of curve, and the failure mode develops toward splitting failure, while a higher σ3 causes the post‐peak curve of the granite specimen to develop toward a Class‐I type of curve, and the failure mode develops toward shear failure. In particular, under the stress regime whereby σ3 = 0, σ2 = 40 MPa, it simulates the tangential stress adjustment process when the shaft is excavated to a depth of 1000 m. The fracture mode of the granite specimen and the post‐peak curve characteristics both indicate that the shaft excavation to this depth has the risk of inducing a strain burst.
Acellular Appendix Vermiform Mucinous Neoplasm
Authors: Tsikouras Panagiotis , Tsalikidis Christos , Oikonomou Efthymios , Kouroupi Maria , Nikolettos Konstantinos , Bothou Anastasia , Nalmpanti Theopi , Kritsotaki Nektaria , Kotanidou Sonia , Iatrakis Georgios , Nikolettos Nikolaos
Published: December 2024

Appendiceal neoplasms are usually asymptomatic or associated with mild, nonspecific symptoms. Due to the rarity of the disease and the lack of specific symptoms, this clinical entity escapes the diagnostic consideration of the gynecologist, when women come in with right iliac fossa pain. A case is presented of a 56‐year‐old woman with a mass in the right small pelvis, which was preoperatively diagnosed as originating from the ovary. An exploratory laparotomy followed in which the uterus and appendages were found to be macroscopically normal, while the mass described above came from the appendix, extended into the anatomical area of the right accessory, and was in contact with the atrophic right ovary. The appendix vermiformis was removed intact. The final pathologic examination confirmed an acellular mucinous tumor of the appendix. Accurate preoperative diagnosis of mucoceles is extremely difficult to make. The formation is discovered in a random imaging test, and the diagnosis is confirmed only intraoperatively.
“Oh, We Don’t Want the Men Around.” The Experience of Men in Nursing During Prelicensure Labor and Delivery Clinical Rotation
Authors: Iheduru-Anderson Kechi , Agomoh Chimezie J.
Published: December 2024

Background: The nursing profession has traditionally been dominated by females, with male nurses comprising a small minority. The labor and delivery unit is one area of nursing that is particularly associated with female care providers. Male nursing students face unique challenges and experiences while completing their clinical rotations in this setting. Understanding these challenges is vital to help support them during their clinical rotation. With the nursing shortage being a global concern, all students must be supported to achieve academic success, regardless of gender.

Purpose: This study uses social role theory to explore the experiences of male nursing students during their clinical rotations in the L&D unit.

Method: This study used a phenomenological qualitative approach to gather data through in‐depth interviews with male nursing students who had completed their labor and delivery unit clinical rotations. The data were thematically analyzed.

Findings: The analysis identified five main themes: Culture, Exclusion from the Learning Experience, Different Expectations for Men in Labor and Delivery Units, Men are not Equipped to Deal with Emotions in Labor and Delivery Units, and (Mis)interpretation of Touch.

Conclusion: This study explored the experiences of male nursing students during their clinical rotations in the labor and delivery unit. The findings will add to the body of knowledge on gender and nursing education and provide valuable insight into the experiences of male nursing students, which can be used to support and improve nursing education in this area.
Primary Breast Malignancy in Children and Adolescents: A Population‐Based Study
Authors: He Guorong , Shen Nan , Zhao Lingling , Liu Xian , Zhang Caiyun
Published: December 2024

Purpose: Primary breast cancer in children and adolescents is extremely uncommon and presents with different characteristics from those found in adult women. We aimed to conduct a population‐based cohort study to predict overall survival (OS) in pediatric patients with breast cancer.

Methods: Demographic and clinicopathological data on pediatric breast cancer patients were obtained from the Surveillance, Epidemiology, and End Results database (2000–2019). The survival rates were measured using the Kaplan–Meier method. Univariate survival analysis used the log‐rank test, while multivariate analysis used Cox proportional hazards regression to identify factors influencing OS. Furthermore, we created a nomogram to predict OS in pediatric patients.

Results: A total of 115 pediatric patients were analyzed, with a median age at diagnosis of 18 years (range: 2–19 years). In terms of tumor grade, 27 (23.4%) patients had well or moderately differentiated tumors and 32 (27.8%) had poorly or undifferentiated tumors. The predominant histological type was phyllodes tumor, accounting for 36.5%, followed by infiltrating duct carcinoma at 31.3%, and other types at 32.2%. The SEER and M stages were substantial independent indicators of OS. A nomogram was created to predict OS in pediatric breast cancer patients.

Conclusions: Our findings confirmed that the SEER stage and M stage were the most critical predictors of OS in pediatric patients with breast cancer. By focusing on this rare demographic, our study fills an important gap in the literature, as there are few comprehensive studies available that explore a prognosis in pediatric breast cancer.
Epidemiology and Molecular Identification of Coenurus cerebralis in Sheep and Goats in Mpwapwa District, Tanzania: Factors to Consider in Control Plans
Authors: Philipo Veneranda , Lupindu Athumani Msalale , Nzalawahe Jahashi Saidi
Published: December 2024

Cerebral coenurosis is a significant disease that affects sheep and goats worldwide. Studies conducted in northern and southern Tanzania have determined its magnitude and determinants. However, limited information from other regions of the country hinders the development of comprehensive national control plans. This study was conducted to determine the prevalence, knowledge, risk factors, and molecular identity of Coenurus cerebralis in sheep and goats in Mpwapwa District, Tanzania, in order to establish the preliminary status of the disease in the central regions. Data were collected through postmortem examinations of 84 sheep and 295 goat heads for cysts, polymerase chain reaction (PCR) and sequencing for species identification, and a structured questionnaire of 303 small ruminant keepers for knowledge and identification of risk factors. The overall prevalence of cerebral coenurosis in sheep and goats was 13.5% (95% confidence interval (CI) 10.3–17.2). In goats, the prevalence of cerebral coenurosis was comparatively higher 15.9% (95% CI 11.9–20.6) than in sheep 4.8% (95% CI 1.3–11.8) (p = 0.008). Multivariate logistic regression analysis identified the origin of sheep and goats (Chipogoro: odds ratio (OR) = 7.54, 95% CI 1.96–28.97, and Iwondo: OR = 3.90, 95% CI 1.04–14.61) as a risk factor. The average knowledge score among small ruminant keepers on disease detection was 60.7%, on disease infection cycle and control was 10.85%, and on zoonotic potential was 1.39%. Phylogenetic analysis of Cytochrome C oxidase subunit I (CO1) gene partial nucleotide sequences revealed the two distinct clusters of Taenia multiceps, one from Saudi Arabia in 2021 and another from Egypt in 2018, Peru in 2017, and China in 2016. These findings suggest cerebral coenurosis is locally widespread and highlight the importance of considering animal movement patterns, livestock keeper’s knowledge, and good husbandry practices when planning for control measures of cerebral coenurosis.
Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma
Authors: Ford Catriona A. , Koludrovic Dana , Centeno Patricia P. , Foth Mona , Tsonou Elpida , Vlahov Nikola , Sphyris Nathalie , Gilroy Kathryn , Bull Courtney , Nixon Colin , Serrels Bryan , Munro Alison F. , Dawson John C. , Carragher Neil O. , Pavet Valeria , Hornigold David C. , Dunne Philip D. , Downward Julian , Welch Heidi C.E. , Barry Simon T. , Sansom Owen J. , Campbell Andrew D.
Published: December 2024

Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma recurrence, and suppressing metastatic progression. Here, we used genetically engineered mouse models and patient-derived BRAFV600E-driven melanoma cell lines to dissect the role of PREX2 in melanomagenesis and response to therapy. Although PREX2 was dispensable for the initiation and progression of melanoma, its loss conferred sensitivity to clinically relevant therapeutics targeting the MAPK pathway. Importantly, genetic and pharmacologic targeting of PI3Kβ phenocopied PREX2 deficiency, sensitizing model systems to therapy. These data reveal a druggable PREX2/RAC1/PI3Kβ signaling axis in BRAF-mutant melanoma that could be exploited clinically.

Significance: Cotargeting the MAPK and the PREX2/RAC1/PI3Kβ pathways has remarkable efficacy and outperforms monotherapy MAPK inhibition in BRAF-mutant melanoma, supporting the potential of this combination therapy for treating metastatic melanoma.
Biomarkers of Exposure to Nicotine and Selected Toxicants in Individuals Who Use Alternative Tobacco Products Sold in Japan and Canada from 2018 to 2019
Authors: Miller Connor R. , Schneller-Najm Liane M. , Leigh Noel J. , Agar Thomas , Quah Anne CK. , Cummings K. Michael , Fong Geoffrey T. , O’Connor Richard J. , Goniewicz Maciej L.
Published: December 2024

Background:

Comparisons of nicotine and toxicant exposures between people who use different alternative tobacco products remain underexplored.

Methods:

This cross-sectional, multicountry study analyzed urinary metabolites of nicotine, tobacco-specific nitrosamines [4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK)], and volatile organic compounds (acrolein, acrylamide, and acrylonitrile) among established users (n = 550) in Japan and Canada. Participants exclusively or concurrently used nicotine vaping products (NVP; Canada only), heated tobacco products (HTP; Japan only), and combustible cigarettes (CC; Japan and Canada) or abstained (Japan and Canada).

Results:

All product groups showed substantial nicotine exposure. Both HTPs and NVPs exposed exclusive users to lower toxicant levels than exclusive CC use. Canadian participants who exclusively used NVPs exhibited lower NNK and acrolein exposure but higher acrylamide exposure than Japanese participants who exclusively used HTPs. Concurrent use of CCs alongside alternative products exposed users to higher toxicant levels compared with exclusive use of either alternative product.

Conclusions:

Exclusive use of alternative tobacco products results in significant nicotine exposure but substantially lower toxicant exposure compared with exclusive CC use. People who use HTPs in Japan may experience higher exposure to nicotine and certain toxicants (NNK and acrolein) than people who use NVPs in Canada. Concurrent use results suggest that partially substituting CCs with alternative products may reduce toxicant exposure but to a lesser extent than completely transitioning to alternative products.

Impact:

Exposure patterns between two popular alternative tobacco products differ. The overall toxicant exposure from these products is lower than from CCs, providing critical data for regulatory decisions and public health considerations.
Aberrantly Expressed Mitochondrial Lipid Kinase, AGK, Activates JAK2–Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy
Authors: Mamidi Murali K. , Sinha Sutapa , Mendez Mariana T. , Sanyal Tapojyoti , Mahmud Hasan , Kay Neil E. , Gupta Mamta , Xu Chao , Vesely Sara K. , Mukherjee Priyabrata , Holter Chakrabarty Jennifer , Ghosh Asish K.
Published: December 2024

Purpose:

Although the B-cell receptor (BCR) signal plays a critical role in chronic lymphocytic leukemia (CLL) cell survival and a target of current therapies (ibrutinib targets Bruton’s tyrosine kinase; idelalisib targets PI3Kδ), contribution of the cytokine-driven JAK2 pathway to the “CLL cell-survival signaling network” is largely undefined.

Experimental Design:

Patients with CLL were enrolled to investigate expression/activation of JAK2 and acylglycerol kinase (AGK), and their functional implication in primary CLL cell survival. A series of biochemical and molecular biology assays were employed to uncover the underlying mechanism.

Results:

We detected that compared with normal B cells, CLL cells aberrantly express constitutively active JAK2. Mechanistically, HSP90 forms a chaperoning complex with JAK2, resulting in its aberrant accumulation in CLL cells. We also discovered aberrant upregulation of a novel mitochondrial lipid kinase, AGK, which remains complexed with HSP90 in CLL cells activating JAK2. Although AGK is typically mitochondrial, we detected its nuclear localization in association with JAK2 in some CLL cells. Functionally, JAK2 phosphorylates its noncanonical substrate, histone H3(Y41), but not STAT3, activating transcription of diverse sets of genes in a patient-specific manner. Additionally, JAK2 activates the BCR signal in CLL cells via LYN/Bruton’s tyrosine kinase axis. Targeted inhibition of JAK2 as monotherapy, or in combination with the BCR inhibitors or venetoclax (a BCL2 inhibitor), induced apoptosis synergistically in CLL cells.

Conclusions:

These findings suggest that aberrantly expressed AGK activates JAK2, independent of cytokine, leading to activation of diverse sets of gene transcription in CLL cells. Combined targeting of JAK2 and BCR signals or BCL2 may be effective in some patients with CLL.
Roles of Necroptosis, Apoptosis, and Inflammation in Colorectal Carcinogenesis: A Longitudinal Human Study
Authors: Su Timothy , Zhu Xiangzhu , Li Yong , Yu Chang , Deng Xinqing , Shubin Eugene , Hou Lifang , Zhao Jing , Fan Lei , Zhang Heping , Murff Harvey J. , Ness Reid M. , Shrubsole Martha J. , Dai Qi
Published: December 2024

Necroptosis triggers an inflammatory cascade associated with antimicrobial defense. No prospective human study has yet explored the role of necroptosis in colorectal cancer development. We conducted quantitative analysis of biomarkers for necroptosis [transient receptor potential cation channel subfamily M member 7 (TRPM7) and phosphorylated mixed lineage kinase domain-like protein], inflammation [cyclooxygenase-2 (COX-2)], apoptosis [BCL2-associated X (BAX) and terminal deoxynucleotidyl transferase dUTP nick end labeling], and cell proliferation (Ki67). This was done using tissue microarray biospecimens from the Cooperative Human Tissue Network and rectal biopsies from a longitudinal study within the Personalized Prevention of Colorectal Cancer Trial. In the human colorectal adenoma–carcinoma sequence, we observed an inverse expression trend between BAX and TRPM7; TRPM7 decreased from normal mucosa to small and large adenomas but significantly increased in early colorectal cancer stages (Ptrend = 0.004). It maintained high levels through all cancer stages. An increased COX-2 intensity in the epithelium was noted during tumorigenesis (Ptrend = 0.02) and was significantly associated with an elevated risk of metachronous polyps (odds ratio = 3.04; 95% confidence interval, 1.07–8.61; Ptrend = 0.02). The combined composite index scores of TRPM7 and COX-2 were strongly linked to 6- to 47-fold increased risks for metachronous adenoma/serrated polyps, whereas combined scores of phosphorylated mixed lineage kinase domain-like protein or TRPM7 with BAX were associated with an 11.5- or 13.3-fold elevated risk for metachronous serrated polyps. In conclusion, our findings suggest that COX-2 expression within normal-looking colorectal mucosa is significantly associated with an increased risk of metachronous colorectal polyp. Furthermore, our results propose the hypothesis that synergistic interactions among necroptosis, inflammation, and apoptosis could play a pivotal role in human colorectal tumorigenesis.

Prevention Relevance: Our findings suggest that COX-2 expression and combined scores of COX-2, TRPM7, and BAX hold promise for predicting the risk of metachronous polyps and could potentially serve as a tool for assessing the effectiveness of chemopreventive agents in preventing colorectal cancer during intervention trials.
Clinical and Genomic Prediction of Coronary Artery Disease Subtypes
Authors: Liou Lathan , García-González Judit , Wu Hei Man , Wang Zhe , Hoggart Clive J. , Kontorovich Amy R. , Kovacic Jason C. , O’Reilly Paul F.
Published: December 2024

BACKGROUND:

Coronary artery disease (CAD) is a complex, heterogeneous disease with distinct etiological mechanisms. These different etiologies may give rise to multiple subtypes of CAD that could benefit from alternative preventions and treatments. However, so far, there have been no systematic efforts to predict CAD subtypes using clinical and genetic factors.

METHODS:

Here, we trained and applied statistical models incorporating clinical and genetic factors to predict CAD subtypes in 26 036 patients with CAD in the UK Biobank. We performed external validation of the UK Biobank models in the US-based All of Us cohort (8598 patients with CAD). Subtypes were defined as high versus normal LDL (low-density lipoprotein) levels, high versus normal Lpa (lipoprotein A) levels, ST-segment–elevation myocardial infarction versus non–ST-segment–elevation myocardial infarction, occlusive versus nonocclusive CAD, and stable versus unstable CAD. Clinical predictors included levels of ApoA, ApoB, HDL (high-density lipoprotein), triglycerides, and CRP (C-reactive protein). Genetic predictors were genome-wide and pathway-based polygenic risk scores (PRSs).

RESULTS:

Results showed that both clinical-only and genetic-only models can predict CAD subtypes, while combining clinical and genetic factors leads to greater predictive accuracy. Pathway-based PRSs had higher discriminatory power than genome-wide PRSs for the Lpa and LDL subtypes and provided insights into their etiologies. The 10-pathway PRS most predictive of the LDL subtype involved cholesterol metabolism. Pathway PRS models had poor generalizability to the All of Us cohort.

CONCLUSIONS:

In summary, we present the first systematic demonstration that CAD subtypes can be distinguished by clinical and genomic risk factors, which could have important implications for stratified cardiovascular medicine.
Socioeconomic Disparities in Rate of Poststroke Dementia: A Nationwide Cohort Study
Authors: Vestergaard Sigrid Breinholt , Valentin Jan Brink , Dahm Christina C. , Gottrup Hanne , Johnsen Søren P. , Andersen Grethe , Mortensen Janne Kærgård
Published: December 2024

BACKGROUND:

Socioeconomic disparities exist in acute stroke care as well as in long-term stroke outcomes. We aimed to investigate whether socioeconomic status was associated with the rate of poststroke dementia (PSD).

METHODS:

This was a nationwide register-based cohort study including all patients with incident ischemic or hemorrhagic stroke in Denmark from 2010 to 2020. Socioeconomic status was defined by prestroke income, education, and employment. PSD was defined as a dementia diagnosis in the National Patient Registry or a dispensed prescription of dementia medication after a stroke. PSD incidence rates were compared between socioeconomic status groups using Poisson regression.

RESULTS:

A total of 98 489 patients with incident stroke without a diagnosis of prestroke dementia were identified and followed for a median (IQR) of 4.2 (IQR, 2.1–7.3) years. Median age was 72 (62–80) years, 56% were male, 5.1% were immigrants, and 86% had ischemic stroke. Dementia was diagnosed in 5680 patients at a median of 2.4 (IQR, 0.9–4.8) years after stroke (incidence rate=12.1/1000 person-years). After adjusting for age, sex, and immigrant status, PSD rates were 1.24 (1.15–1.34) times higher for low income compared with high income, 1.11 (1.03–1.20) times higher for low education compared with high education, and 1.57 (1.38–1.77) times higher for patients without employment compared with patients with employment. Further adjustments for stroke severity, cohabitation, and comorbidities showed similar results. Stratified analyses showed that the socioeconomic disparities in PSD rates were more pronounced among women, immigrants, and patients <70 years of age.

CONCLUSIONS:

Low socioeconomic status measured by prestroke income, education, and employment status was associated with higher rates of PSD. These socioeconomic disparities extended beyond what could be explained by common PSD risk factors.
Untangling the morphological and genetic variation of two endemic lizards from the coastal sand dunes of Northeastern Brazil
Authors: Fazolato Cecil , Barreto Silvia , Felgueiras Napoli Marcelo , Sequeira Fernando , Batalha-Filho Henrique
Published: December 2024

Studies in the Neotropical region consistently highlight high levels of endemism and biodiversity. However, challenges persist, particularly in uncovering the cryptic diversity among species. Various approaches are needed to address this, including morphological, genetic, and environmental data. This study focused on genetic and morphological variation in three endemic, sympatric lizard species: Tropidurus hygomi, Glaucomastix abaetensis, and Glaucomastix itabaianensis in the coastal sand dunes of Northeastern Brazil. These lizards are confined to sandy Pleistocene-formed environments with limited distribution. While earlier research revealed substantial genetic diversity, gaps remained in distribution sampling, morphological data, and understanding the correlation between this variation and environmental factors. We aimed to identify genetic clusters to assess the alignment of phenotypic differences with these clusters and explore potential relationships between climatic and geographical factors and morphometric variations. We utilized mtDNA data to assess population clusters. Geometric and linear morphometrics were employed to analyze morphological data, which was then correlated with climatic information. Results unveiled genetic and morphological variations signifying the presence of cryptic diversity. Our analyses also highlighted the influence of geography and climate on morphometric variations. These findings underscore hidden diversity and a complex evolutionary history within the confined Pleistocene sand dunes. Further genomic analyses could contribute to comprehending these patterns and enhancing the conservation strategies for these endangered species.
Mission Creep: Enduring Race-Place Schemata of California’s Colonial Settlements
Authors: Erickson Brad
Published: December 2024

This article traces contemporary patterns of housing and homelessness to colonial geographies as race-place schemata: historic and ongoing relationships to territory that articulate and impose white supremacy while stimulating resistance to it. These phenomena are approached through the four fields of anthropology, placing a contemporary ethnography of gentrification/displacement in Oakland in conversation with the archeological record of colonization. The demographic tracking of human populations through census instruments and discourses of biological distancing suggest implications for biological anthropology, and socio-linguistic analysis is applied to colonial naming practice. Intended as an essay-length land acknowledgement and critical interrogation of contemporary white spatial entitlement, this research centers the capacity of territorial aesthetics and the geographic organization of the Spanish imperial project to produce continuing place-based dominance over colonized peoples through dispossession of their lands, containment of their populations, assimilation and erasure of their life ways, and surveillance over and defense against their resistance.
Beyond Islam: Rethinking Central Asia’s Religious Identity through Pre-Islamic Traditions
Authors: Mohiuddin Asif
Published: December 2024

This essay explores the intricate dynamics of Central Asian religious identity in the context of global and local changes. It examines the interactions between Islam and local pre-Islamic traditions, with a primary focus on R. Charles Weller’s book titled, Pre-Islamic Survivals in Muslim Central Asia: Tsarist, Soviet, and Post-Soviet Ethnography in World Historical Perspective. Through a comprehensive assessment of the book, the essay investigates the survival and evolution of pre-Islamic traditions within Central Asia’s Muslim communities. The book contributes to the field of Central Asian studies by offering a specialised analysis and shedding light on the formation of religious history and identity in Central Asia.
Humanitarian Borders and Asylum in Mexico: Using Soft Power to Control Mobility
Authors: Cortés Maisonave Almudena , Benincasa Valentina
Published: December 2024

Drawing on the anthropological debates surrounding humanitarian borders, this article analyses the functioning of the humanitarian border in central Mexico. More specifically, it focuses on the state of Puebla as a case study that casts light on the ways in which the humanitarian border operates in states located far from geographic borders, which are frequently overlooked in discourse and action on migration and asylum in Mexico. Based on ethnographic research in Puebla between 2019 and 2022, we analyse how the state has been incorporated into the international humanitarian circuit by being made responsible for handling asylum seekers and refugees who have been relocated from the south of the country. Against this backdrop, a humanitarian border comprising two dimensions has emerged: a hard border governed by securitarian control measures and a soft border managed by humanitarian actors. In this article, we will analyse the soft humanitarian border.
The Effects of Chilling on Antioxidant Enzyme System and Related Gene Expression Levels in Sweet Corn Seeds with Different Germination Characteristics
Authors: Wang Tingzhen , Wu Zhenxing , Chen Jianjian , Li Fangjian , Lv Guihua
Published: December 2024

Sweet corn is a vegetable and grain dual-use crop with high economic value and industrial advantages. Low temperature stress significantly reduces the germination rate of sweet corn seeds, which has a negative impact on both quality and yield. This study used the chilling sensitive sweet corn inbred line 20hi111 and the chilling tolerant sweet corn inbred line T135 as experimental materials to measure the MDA (malondialdehyde) and H2O2 content, CAT, POD, and SOD enzyme activities, and enzyme gene expression patterns during seed germination under low temperature (10°C) and normal temperature (25°C) treatments. The research results indicated that during low-temperature germination, the H2O2 content and CAT activity of 20hi111 were generally higher than those of T135, while the POD and SOD activities and MDA content were generally lower than those of T135. There was no strict consistency between gene expression and enzyme activity. At low temperature, the expression of ZmCAT1 and ZmCAT3 in 20hi111 was significantly higher than T135, while there was no significant difference in ZmPOD1. In 20hi111, ZmPOD3 was first lower and then higher than T135, and ZmSOD3 and ZmSOD9 were lower than T135 under low temperature treatment. In this study, the activity of antioxidant enzymes and the expression of antioxidant enzyme-related genes in sweet corn inbred lines with different germination characteristics under low temperature were analyzed, which provided some theoretical basis for cultivating sweet corn varieties with low temperature tolerance.
Impact of Islamic Art on the Architectural Design of Mosques in Amman
Authors: Al-Tamimi Sakher , Pankina Marina
Published: December 2024

Objectives: This article aims to highlight and study traditional and contemporary Islamic Art in Jordanian mosques. Methods:. Comparative analysis of Islamic Art concerning the mosque architecture in Amman, analysis of theoretical works on this topic, and historical approach. The study will also include a study of mosques in Amman. Results: When designing new mosques, architects need to study not only traditions, design experience, the space-planning solution of the mosque, and the functional organization of space but also the meaning of ornaments. The ornaments on the facade and interior, as well as various art objects in the interior, are the most expressive differences that indicate that the building belongs to the culture of Islam and forms a religion. Conclusions: Islamic art and architecture in Jordan have deep roots in the history of the religion. Many buildings and structures were built during the reign of the Umayyads, Abbasids, and other dynasties, who left their mark on architecture and design. Islamic sculptures and decorations also reflect Jordan's culture and heritage richness.
China and G7 in the Current Context of the World Trading
Authors: Gonchar Nicholas , Dovzhyk Olena , Zhokhin Anatoly , Kozyrski Wolodymyr , Makhort Andrii
Published: December 2024

The paper analyses trade between the most developed economies of the world. The analysis is based on the previously proposed model of international trade. This model of international trade is based on the theory of general economic equilibrium. The demand for goods in this model is built on the import of goods by each of the countries participating in the trade. The structure of supply of goods in this model is determined by the structure of exports of each country. It is proved that in such a model, given a certain structure of supply and demand, there exists a so-called ideal equilibrium state in which the trade balance of each country is zero. Under certain conditions on the structure of supply and demand, there is an equilibrium state in which each country have a strictly positive trade balance. Among the equilibrium states under a certain structure of supply and demand, there are some that differ from the ones described above. Such states are characterized by the fact that there is an inequitable distribution of income between the participants in the trade. Such states are called degenerate. In this paper, based on the previously proposed model of international trade, an analysis of the dynamics of international trade of 8 of the world's most developed economies is made. It is shown that trade between these countries was not in a state of economic equilibrium. The found relative equilibrium price vector turned out to be very degenerate, which indicates the unequal exchange of goods on the market of the 8 studied countries. An analysis of the dynamics of supply to the market of the world's most developed economies showed an increase in China's share. The same applies to the share of demand.
Valuation of State-Owned Enterprises in the Process of Privatisation in Ethiopia: Procedures and Methods
Authors: Asres Habtamu
Published: December 2024

Real property valuation is a vital component in the privatization of state-owned enterprises (SOEs). In Ethiopia, real property valuation is a difficult task as there is a lack of skilled manpower in the field, no adequate real estate market, and legal gaps in valuation. In addition literatures are scant about how real property valuation is done. Therefore, this study examines real property valuation procedures and challenges in the process of privatization of state-owned enterprises (SOEs) in Ethiopia. To achieve the objective of the study, qualitative research approach is applied. The target populations of the study were appraisers who participated in the valuation of SOEs. A purposive sampling technique was used to select respondents. Primary data were collected from appraisers using key informant interview (KII). Document review from different secondary sources was employed to triangulate the KIIs. The data were analyzed using thematic grouping and narration. The study found that for profitable enterprises Depreciated Replacement Cost (DRC) and Discounted Cash Flow (DCF) methods have been applied while for loss-making enterprises the DRC method has been used. These methods are selected based on the preceding three years of data. Moreover, these valuation methods are not applied in a proper way and the basis of selecting these methods are unjustifiable. The valuation result of SOEs, do not reported in a standard valuation reports formats. Lack of skilled manpower, inappropriate use of the valuation approaches, inappropriate base for selecting techniques of valuation, and organizational inefficiency are the key problems faced during valuation. To improve the situation market principles should be applied in the valuation of SOEs for privatization purposes in Ethiopia. These can be achieved by introducing strong institutions responsible for valuation regulations at the central level.
Forensic Analysis of a Good Universal Education in a Secular Culture as a Sign of Justice for the Need for a Better Future
Authors: Fénélus Saint-Luc
Published: December 2024

This article presents an analysis of the reality and the way of transmitting education based on the teaching of the Catholic faith in a culture or this secular as a sign of justice in a world of discard, taking into account the cultural value of education in our country, as well as his contributions to society, covering historical and modern characteristics of this political polemic in relation. The article consists of a bibliographic and exploratory research, with a view to raising concerns in situations presented with certain practical solutions in the application of learning in the seminar on a topic of paramount importance. In this way, the research provides a comparison between the characteristics of teaching or education starting from the educational process today in a certain place close to the parish where I am working; addresses themes inherent to the educational process regarding the origin of knowledge, the relationship between faith and science, teaching methods, worldviews, the role of religion in society and its implications for public and private education and culture, going over the Christianity's action in the History of Education and addresses this as social justice. Demonstrating that Christianity itself, not only maintains a relationship with education, but also constitutes an educational process, with objectives similar to the objectives of secular education.