bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Can Ingredients-Based Forecasting Be Learned? Disentangling a Random Forest’s Severe Weather Predictions
Authors: Mazurek Alexandra C. , Hill Aaron J. , Schumacher Russ S. , McDaniel Hanna J. 
Published: December 2024

Abstract
Machine learning (ML)–based models have been rapidly integrated into forecast practices across the weather forecasting community in recent years. While ML tools introduce additional data to forecasting operations, there is a need for explainability to be available alongside the model output such that the guidance can be transparent and trustworthy for the forecaster. This work makes use of the algorithm tree interpreter (TI) to disaggregate the contributions of meteorological features used in the Colorado State University Machine Learning Probabilities (CSU-MLP) system, a random forest–based ML tool that produces real-time probabilistic forecasts for severe weather using inputs from the Global Ensemble Forecast System. TI feature contributions are analyzed in time and space for CSU-MLP day 2 and day 3 individual hazard (tornado, wind, and hail) forecasts and day 4 aggregate severe forecasts over a 2-yr period. For individual forecast periods, this work demonstrates that feature contributions derived from TI can be interpreted in an ingredients-based sense, effectively making the CSU-MLP physically interpretable. When investigated in an aggregate sense, TI illustrates that the CSU-MLP system’s predictions use meteorological inputs in ways that are consistent with the spatiotemporal patterns seen in meteorological fields that pertain to severe storm climatology. A discussion on how these insights could benefit forecast operations more broadly is also provided.

Significance Statement
Machine learning tools are becoming more common in weather forecasting settings, and there is a need to provide information to meteorologists on how machine learning models make their predictions in real time. Severe weather forecasts made by an operational machine learning model are deconstructed into meteorological components in a way that offers physically insightful context to the model’s predictions. The results show that the machine learning model uses the input meteorological fields to make predictions that resemble various aspects of severe storm climatology and environments. This work presents an avenue for using explainable artificial intelligence in operational weather forecasting by illustrating a method that could provide trust, transparency, and confidence in machine learning–based forecast guidance.
Association of pulmonary artery capacitance with long-term outcomes in acute coronary syndrome patients with left ventricular systolic dysfunction
Authors: Hsieh Shu-Yun , Yeh Jih-Kai , Huang Yu-Chang , Chen Dong-Yi , Ho Ming-Yun , Chen Chun-Chi , Hsieh I-Chang , Hsieh Ming-Jer 
Published: December 2024

Objective Hemodynamic monitoring via right heart catheterization (RHC) is critical for managing acute coronary syndrome (ACS) patients with heart failure or cardiogenic shock. However, the prognostic value of RHC-derived hemodynamic indices in ACS patients with left ventricular systolic dysfunction (LVSD) but without heart failure or shock remains uncertain. Methods A retrospective cohort study included 1151 consecutive ACS patients who underwent RHC during hospitalization from 2007 to 2016. After excluding patients with shock, pulmonary edema, and severe valvular disease, 750 ACS patients with LVSD and ejection fraction < 50% were analyzed. Major adverse cardiovascular events (MACEs), including myocardial infarction and all-cause mortality, were followed for five years. Cox regression identified predictors of MACEs, adjusting for comorbidities, treatments, and hemodynamic indices, including pulmonary arterial capacitance (PAC). Results After a mean follow-up of 4.0 ± 1.7 years, 113 (15.1%) patients experienced MACEs. Multivariate analysis showed that independent predictors included prior stroke, calcified coronary lesions, and PAC. Patients in the lowest PAC tertile (≤2.89 ml/mmHg) had significantly higher risks of myocardial infarction (adjusted hazard ratio [HR]: 3.74; 95% confidence interval [CI]: 1.55–9.07; p = .003), all-cause mortality (adjusted HR: 2.55; 95% CI: 1.27–5.10; p = .008), and MACEs (adjusted HR: 2.35; 95% CI: 1.25–4.42; p = .008) compared to those in the highest tertile (>4.43 ml/mmHg). Discussion The study demonstrated that PAC is a notably strong hemodynamic parameter with independent long-term prognostic value in ACS patients with LVSD, who do not present with shock or heart failure. This is the first study to establish the prognostic significance of hemodynamic indices obtained from RHC in this population, extending the clinical relevance of RHC from high-risk to intermediate-risk ACS populations. Conclusions The use of RHC to assess hemodynamic indices, including PAC, during index hospitalization in this population may enhance long-term risk stratification and improve outcome prediction.
Enhancing the quality and consumer satisfaction of dragon fruit beverage production: The effects of geological origin and processing conditions
Authors: Pham Thinh Van , Cao Thuy Xuan , Le Ngoc Thi Hong , Pham Ai Minh , Trinh Hung Tuan , Nguyen Dat Tien , Hoang Anh Le Tuan , Bui Minh Quang , Nguyen Tung Ngoc , Truong Minh Ngoc , Hoang Tao Minh 
Published: December 2024

Objectives In this study, the impacts of various processing parameters on the quality and consumer satisfaction of dragon fruit beverages were investigated in order to establish an informative framework for the manufacturing of commercial dragon fruit beverages, focusing on health benefits and safety for consumers, and sensory appeal of the products. Methods This study employed various analytical methods to quantify some important phytochemical compounds in dragon fruit juice such as total and reducing sugars, vitamin C, betacyanins, anthocyanins, polyphenol, and so forth. This study also employed the Box–Behnken response surface experimental design to optimize various processing parameters for quality and consumer satisfaction, which include enzymatic pectin hydrolysis parameters and formulation for dragon fruit energy drink. Results The results from this study indicated a causal relationship between geological origin and some important characteristics of dragon fruit juice, emphasizing the need to track the source of fruits to ensure consistent quality of juice products. This study also systematically determined the impacts of various enzymatic hydrolysis, thermal sterilization, and formulation parameters on both nutrition content and sensory aspects of dragon fruit beverages, while also successfully optimized these parameters for the best outcomes. Conclusion This study had successfully achieved the objective of establishing a valuable framework for the manufacturing of commercial dragon fruit beverages, focusing on health benefits and safety for consumers, and sensory appeal of the products.
Perceptions of digitally supported home exercise for people with Parkinson's disease: A qualitative study
Authors: Sedhed Jenny , Johansson Hanna , Åkesson Elisabet , Franzén Erika , Leavy Breiffni 
Published: December 2024

Background Digitally supported home exercise offers the potential to expand accessibility to rehabilitation. However, little is known about how people with Parkinson's disease experience performing home exercise programs using digital delivery. Objective To explore and describe how people with Parkinson's disease perceive digital home-based exercise that is not supported in real-time, and how it affected their everyday lives. Methods This study was qualitative in nature, using qualitative content analysis with an inductive approach. In-depth, individual, semi-structured interviews were held with 14 participants with Parkinson's disease. Results Two overarching themes were formed: “Active agency in the face of uncertainty” and “The home – safe space or disability on display”. The overarching themes were formed by four themes: 1) resisting the disease - a hope and a burden, 2) interpreting mixed messages, 3) home exercise – consideration and responsibility, and 4) the social context - judgement and support. Participants with Parkinson's disease believe that home exercise enables them to actively counter the disease, and this belief serves as both a source of hope but also a burden. Although perceived as advantageous, digitally supported home exercise may also incur becoming vulnerable to exposing one's disability. Conclusions People with Parkinson's disease struggle to reconcile their beliefs about exercise with that which is encouraged or discouraged by those around them. Exercise in the home involves a dynamic interplay between achieving self-directed goals while trying to balance social consideration and maintaining integrity of identity.