bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia
Authors: Lane Andrew A. , Garcia Jacqueline S. , Raulston Evangeline G. , Garzon Jada L. , Galinsky Ilene , Baxter Emilie W. , Leonard Rebecca , DeAngelo Daniel J. , Luskin Marlise R. , Reilly Christopher R. , Stahl Maximilian , Stone Richard M. , Vedula Rahul S. , Wadleigh Martha M. , Winer Eric S. , Mughal Tariq , Brooks Christopher , Gupta Ira V. , Stevenson Kristen E. , Neuberg Donna S. , Ren Siyang , Keating Julia , Konopleva Marina , Stein Anthony , Pemmaraju Naveen 
Published: December 2023

Abstract
CD123, a subunit of the interleukin-3 receptor, is expressed on ∼80% of acute myeloid leukemias (AMLs). Tagraxofusp (TAG), recombinant interleukin-3 fused to a truncated diphtheria toxin payload, is a first-in-class drug targeting CD123 approved for treatment of blastic plasmacytoid dendritic cell neoplasm. We previously found that AMLs with acquired resistance to TAG were re-sensitized by the DNA hypomethylating agent azacitidine (AZA) and that TAG-exposed cells became more dependent on the antiapoptotic molecule BCL-2. Here, we report a phase 1b study in 56 adults with CD123-positive AML or high-risk myelodysplastic syndrome (MDS), first combining TAG with AZA in AML/MDS, and subsequently TAG, AZA, and the BCL-2 inhibitor venetoclax (VEN) in AML. Adverse events with 3-day TAG dosing were as expected, without indication of increased toxicity of TAG or AZA+/−VEN in combination. The recommended phase 2 dose of TAG was 12 μg/kg/day for 3 days, with 7-day AZA +/− 21-day VEN. In an expansion cohort of 26 patients (median age 71) with previously untreated European LeukemiaNet adverse-risk AML (50% TP53 mutated), triplet TAG-AZA-VEN induced response in 69% (n=18/26; 39% complete remission [CR], 19% complete remission with incomplete count recovery [CRi], 12% morphologic leukemia-free state [MLFS]). Among 13 patients with TP53 mutations, 7/13 (54%) achieved CR/CRi/MLFS (CR = 4, CRi = 2, MLFS = 1). Twelve of 17 (71%) tested responders had no flow measurable residual disease. Median overall survival and progression-free survival were 14 months (95% CI, 9.5-NA) and 8.5 months (95% CI, 5.1-NA), respectively. In summary, TAG-AZA-VEN shows encouraging safety and activity in high-risk AML, including TP53-mutated disease, supporting further clinical development of TAG combinations. The study was registered on ClinicalTrials.gov as #NCT03113643.
sBioSITe enables sensitive identification of the cell surface proteome through direct enrichment of biotinylated peptides
Authors: Garapati Kishore , Ding Husheng , Charlesworth M. Cristine , Kim Yohan , Zenka Roman , Saraswat Mayank , Mun Dong-Gi , Chavan Sandip , Shingade Ashish , Lucien Fabrice , Zhong Jun , Kandasamy Richard K. , Pandey Akhilesh 
Published: December 2023

Abstract
Background
Cell surface proteins perform critical functions related to immune response, signal transduction, cell–cell interactions, and cell migration. Expression of specific cell surface proteins can determine cell-type identity, and can be altered in diseases including infections, cancer and genetic disorders. Identification of the cell surface proteome remains a challenge despite several enrichment methods exploiting their biochemical and biophysical properties.

Methods
Here, we report a novel method for enrichment of proteins localized to cell surface. We developed this new approach designated surface Biotinylation Site Identification Technology (sBioSITe) by adapting our previously published method for direct identification of biotinylated peptides. In this strategy, the primary amine groups of lysines on proteins on the surface of live cells are first labeled with biotin, and subsequently, biotinylated peptides are enriched by anti-biotin antibodies and analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Results
By direct detection of biotinylated lysines from PC-3, a prostate cancer cell line, using sBioSITe, we identified 5851 peptides biotinylated on the cell surface that were derived from 1409 proteins. Of these proteins, 533 were previously shown or predicted to be localized to the cell surface or secreted extracellularly. Several of the identified cell surface markers have known associations with prostate cancer and metastasis including CD59, 4F2 cell-surface antigen heavy chain (SLC3A2) and adhesion G protein-coupled receptor E5 (CD97). Importantly, we identified several biotinylated peptides derived from plectin and nucleolin, both of which are not annotated in surface proteome databases but have been shown to have aberrant surface localization in certain cancers highlighting the utility of this method.

Conclusions
Detection of biotinylation sites on cell surface proteins using sBioSITe provides a reliable method for identifying cell surface proteins. This strategy complements existing methods for detection of cell surface expressed proteins especially in discovery-based proteomics approaches.
Ecological factors and parity mode correlate with genome size variation in squamate reptiles
Authors: Saha Anik , Bellucci Arianna , Fratini Sara , Cannicci Stefano , Ciofi Claudio , Iannucci Alessio 
Published: December 2023

Abstract
Background
Evidence of correlation between genome size, the nuclear haploid DNA content of a cell, environmental factors and life-history traits have been reported in many animal species. Genome size, however, spans over three orders of magnitude across taxa and such a correlation does not seem to follow a universal pattern. In squamate reptiles, the second most species-rich order of vertebrates, there are currently no studies investigating drivers of genome size variability. We run a series of phylogenetic generalized least-squares models on 227 species of squamates to test for possible relationships between genome size and ecological factors including latitudinal distribution, bioclimatic variables and microhabitat use. We also tested whether genome size variation can be associated with parity mode, a highly variable life history trait in this order of reptiles.

Results
The best-fitting model showed that the interaction between microhabitat use and parity mode mainly accounted for genome size variation. Larger genome sizes were found in live-bearing species that live in rock/sand ecosystems and in egg-laying arboreal taxa. On the other hand, smaller genomes were found in fossorial live-bearing species.

Conclusions
Environmental factors and species parity mode appear to be among the main parameters explaining genome size variation in squamates. Our results suggest that genome size may favour adaptation of some species to certain environments or could otherwise result from the interaction between environmental factors and parity mode. Integration of genome size and genome sequencing data could help understand the role of differential genome content in the evolutionary process of genome size variation in squamates.
StableDNAm: towards a stable and efficient model for predicting DNA methylation based on adaptive feature correction learning
Authors: Zhuo Linlin , Wang Rui , Fu Xiangzheng , Yao Xiaojun 
Published: December 2023

Abstract
Background
DNA methylation, instrumental in numerous life processes, underscores the paramount importance of its accurate prediction. Recent studies suggest that deep learning, due to its capacity to extract profound insights, provides a more precise DNA methylation prediction. However, issues related to the stability and generalization performance of these models persist.

Results
In this study, we introduce an efficient and stable DNA methylation prediction model. This model incorporates a feature fusion approach, adaptive feature correction technology, and a contrastive learning strategy. The proposed model presents several advantages. First, DNA sequences are encoded at four levels to comprehensively capture intricate information across multi-scale and low-span features. Second, we design a sequence-specific feature correction module that adaptively adjusts the weights of sequence features. This improvement enhances the model’s stability and scalability, or its generality. Third, our contrastive learning strategy mitigates the instability issues resulting from sparse data. To validate our model, we conducted multiple sets of experiments on commonly used datasets, demonstrating the model’s robustness and stability. Simultaneously, we amalgamate various datasets into a single, unified dataset. The experimental outcomes from this combined dataset substantiate the model’s robust adaptability.

Conclusions
Our research findings affirm that the StableDNAm model is a general, stable, and effective instrument for DNA methylation prediction. It holds substantial promise for providing invaluable assistance in future methylation-related research and analyses.
Association between cardiovascular risk factors and cognitive impairment in adults aged 60 years or older from Chile: a cross-sectional study
Authors: Souza-Lima Josivaldo , Matsudo Sandra Mahecha , Valdivia-Moral Pedro , Pérez Waldo , Drenowatz Clemens , Zenteno Jorge Sapunar , Ferrari Gerson 
Published: December 2023

Abstract
Background
Few studies in Latin America have examined the association between cardiovascular risk factors and cognitive impairment (CI) in a nationally representative sample. Therefore, this study aimed to estimate the prevalence of CI in a nationally representative sample of adults aged 60 years or older from Chile and to investigate the association between cardiovascular risk factors and CI.

Methods
Data from the cross-sectional 2016–2017 National Health Survey of Chile, which included 2031 adults (63.7% women) was used. Body mass index, metabolic syndrome (blood pressure, triglycerides, fasting glucose or treatment for diabetics, waist circumference, and HDL cholesterol), risk of cardiovascular disease (history and measured variables, using the Framingham risk score), tobacco use, and physical activity were measured. CI was assessed using the Mini-Mental Status Examination (MMSE).

Results
Overall, the prevalence of CI was 12.2% at the national level. Significant differences in CI were observed by age, education level, risk of cardiovascular disease, and smoking. High risk of cardiovascular disease was associated with higher odds of CI (OR: 2.04; 95%CI: 1.20–3.45) compared to low risk. Smoking was significantly associated with a lower likelihood of CI (OR: 0.56; 95%CI: 0.36–0.87) compared to never smoking. Body mass index, metabolic syndrome, and physical activity were not associated with CI.

Conclusions
This study provided additional support for previous findings on the relationship between cognitive decline and an elevated risk of cardiovascular disease. Worse CI was associated with the group with the highest risk of cardiovascular disease, and the presence of lifestyle factors, such as obesity and physical inactivity, exacerbate this relationship, but not being a current smoker.
Individual and combined associations of sarcopenia, osteoporosis and obesity with frailty in a multi-ethnic asian older adult population
Authors: Heng Matthew Wong Yu , Chan Aurora W. D. , Man Ryan E. K. , Fenwick Eva K. , Chew Samuel T. H. , Tay Laura , Sien Ng Yee , Ng David , Koh Frederick H. , Yong Eu-Leong , Gupta Preeti , Lamoureux Ecosse L. 
Published: December 2023

Abstract
Background
We explored the relationships between sarcopenia (SP), osteoporosis (OP), obesity (OB), (alone and in combination) with physical frailty (PF) in a multi-ethnic, population-based study of Asians aged ≥ 60 years.

Methods
Participants were enrolled from the PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study (PIONEER) study. PF was defined using the modified Fried phenotype; SP using the Asian Working Group for Sarcopenia 2019; OP using bone mineral density scores; and OB using the fat mass index. Modified Poisson regression models investigated the associations between exposures and PF, and the relative excess rates of PF due to interactions (RERI) to determine synergistic or antagonistic interactions.

Results
Of the 2643 participants, 54.8% was female; and 49.8%, 25.1%, 25.0% were Chinese, Indians, and Malays, respectively. 25%, 19.0% and 6.7% participants had OB only, SP only, and OP only, respectively. A total of 356 (17.5%), 151 (7.4%) and 97 (4.8%) had osteosarcopenia (OSP), sarcopenic obesity (SOB) and osteo-obesity (OOB), respectively; while 70 (3.5%) had all 3 morbid conditions (osteosarcopenic obesity, OSO). Both SP only and OB only were strongly associated with increased rates of PF (RR: 2.53, 95% CI: 1.95, 3.29; RR: 2.05, 95% CI: 1.58, 2.66 respectively); but not OP. Those with OSP, OOB and SOB were also associated with high risks of PF (RR: 2.82, 95% CI: 2.16, 3.68; RR: 2.34, 95% CI: 1.69, 3.23; and RR: 2.58, 95% CI: 1.95, 3.41, respectively) compared to robust individuals. Critically, individuals with OSO had the highest relative risk of having PF (RR: 3.06, CI: 2.28, 4.11). Only the sarcopenia-obesity interaction was significant, demonstrating negative synergism (antagonism). The concurrent presence of SP and OB was associated with a 100% lower rate of PF compared to the sum of the relatively rates of SP only and OB only.

Conclusion
The prevalence of SP, OB and OP, alone and combined, is substantial in older Asians and their early identification is needed to mitigate the risk of frailty. OB may interact with SP in an antagonistic manner to moderate rates of frailty. Further longitudinal studies are needed to address causality and mechanistic underpinnings our findings.
Resilience in caregivers of people with mild-to-moderate dementia: findings from the IDEAL cohort
Authors: Martyr Anthony , Rusted Jennifer M. , Quinn Catherine , Gamble Laura D. , Collins Rachel , Morris Robin G. , Clare Linda 
Published: December 2023

Abstract
Objectives
A novel model of resilience was tested in caregivers of people with mild-to-moderate dementia and was extended to explore whether including self-efficacy, optimism, and self-esteem improved its predictive value.

Design
Cross-sectional.

Setting
Data from the IDEAL cohort were used.

Participants
The study comprised 1222 caregivers of people with dementia.

Measurements
A composite resilience score was calculated from five measures. Multivariable regressions were used to investigate factors associated with resilience.

Results
Greater resilience was associated with being older, being male, and caregiving for older people with dementia. Greater resilience was also observed when people with dementia had fewer functional difficulties and/or fewer neuropsychiatric symptoms, there was a stronger dyadic relationship, and the caregiver had fewer social restrictions, less neuroticism, and greater perceived competence. Surprisingly, caregiver self-efficacy, optimism, and self-esteem were unrelated to resilience.

Conclusion
Caregivers of people with mild-to-moderate dementia generally scored well for resilience. Resilience was associated with both the personal characteristics of caregivers and level of care need among people with dementia. Future work is needed to determine whether the caregivers in this cohort appeared resilient because the care recipients had relatively low care needs and consequently placed fewer demands on caregiver well-being than would be the case where dementia is more advanced.
Association between elevated serum transaminase and moderately increased albuminuria: a cross-sectional study in western Tokushima, Japan
Authors: Fukuda Shoichi , Shirase Ukyo , Ogimoto Shigeru , Nakagawa Mai , Nakagawa Kazumi , Tominaga Ayumu , Morioka Hisayoshi 
Published: December 2023

Abstract
Background
This study aimed to identify the factors relating to moderately increased albuminuria among middle-aged and older individuals in Japan.

Methods
We conducted specific health examinations in which we measured albuminuria levels, and administered a questionnaire survey to record participants’ lifestyles in western Tokushima Prefecture, Japan. A total of 1,660 people whose albuminuria was less than 300 mg/g creatinine (Cr) were analyzed. We divided participants into two groups—those with normal albuminuria (< 30 mg/gCr) and those with moderately increased albuminuria (≥ 30 mg/gCr, > 300 mg/gCr)—and compared their characteristics. To investigate all relevant factors, we conducted a multivariate logistic regression analysis.

Results
The moderately increased albuminuria group were significantly older and had, among them, significantly higher percentages of a body mass index (BMI) ≥ 25 kg/m2, diabetes, hypertension, and mild liver disorder (aspartate transaminase ≥ 31 U/L or alanine aminotransferase ≥ 31 U/L or gamma-glutamyl transferase ≥ 51 U/L). (p < 0.01) In a multivariate logistic regression analysis that used microalbuminuria as an independent variable, we found the adjusted odds ratio (AOR) and 95% confidence interval (CI) to be significantly higher among individuals with diabetes (AOR: 2.04, 95% CI: 1.40–2.99); hypertension (AOR: 1.90, 95% CI: 1.36–2.65); BMI ≥ 25 kg/m2 (AOR: 1.76, 95% CI: 1.27–2.44); and mild liver disorder (AOR: 1.54, 95% CI: 1.10–2.18).

Conclusions
In addition to diabetes, hypertension, and BMI ≥ 25 kg/m2, this study found that among the middle-aged and older general population living in western Tokushima Prefecture, there were cases of mild liver disorder (elevated serum transaminase), which independently associated with moderately increased albuminuria. Therefore, in health checkups targeting the general population, there is a need to consider measuring albuminuria, even in those who have only mild liver dysfunction (health guidance level).

Trial registration
N/A.
Refining gastric cancer staging: examining the interplay between number and anatomical location of metastatic lymph nodes - a retrospective multi-institutional study
Authors: Jeon Chul-Hyo , Park Ki Bum , Lee Hayemin , Kim Dong Jin , Seo Ho Seok , Lee Junhyun , Jun Kyung Hwa , Kim Jin Jo , Lee Han Hong 
Published: December 2023

Abstract
Background
The current gastric cancer staging system relies on the number of metastatic lymph nodes (MLNs) for nodal stage determination. However, incorporating additional information such as topographic status may help address uncertainties. This study evaluated the appropriateness of the current staging system and relative significance of MLNs based on their anatomical location.

Methods
Patients who underwent curative gastrectomy for gastric cancer between 2000 and 2019 at six Catholic Medical Center-affiliated hospitals were included. Lymph node-positive patients were classified into the perigastric (stations 1–6, group P) or extragastric (stations 7–12) groups. The extragastric group was further subdivided into the near-extragastric (stations 7–9, group NE) and far-extragastric (stations 10–12, group FE) groups.

Results
We analyzed the data of 3,591 patients with positive lymph node metastases. No significant survival differences were found between group P and the extragastric group in each N stage. However, in N1 and N2, group FE showed significantly worse survival than the other groups (p = 0.013 for N1, p < 0.001 for N2), but not in N3. In the subgroup analysis, group FE had a significantly lower overall survival in N2, regardless of the cancer location.

Conclusions
Our large-scale multi-institutional big data analysis confirmed the superiority of the current numerical nodal staging system for gastric cancer. Nonetheless, in N1 and N2 in which there is an upper limit on metastatic nodes, attention should be paid to the potential significance of topographic information for specific nodal stations.
Prevalence of lifestyle cardiovascular risk factors and estimated framingham 10-year risk scores of adults with psychotic disorders compared to controls at a referral hospital in Eldoret, Kenya
Authors: Kwobah Edith , Koen Nastassja , Mwangi Ann , Atwoli Lukoye , Stein Dan J. 
Published: December 2023

Abstract
Introduction
Lifestyle factors such as smoking, alcohol use, suboptimal diet, and inadequate physical activity have been associated with increased risk of cardiovascular diseases. There are limited data on these risk factors among patients with psychosis in low- and middle-income countries.

Objectives
This study aimed to establish the prevalence of lifestyle cardiovascular risk factors, and the 10-year cardiovascular risk scores and associated factors in patients with psychosis compared to controls at Moi Teaching and Referral Hospital in Eldoret, Kenya.

Methods
A sample of 297 patients with schizophrenia, schizoaffective disorder, or bipolar mood disorder; and 300 controls matched for age and sex were included in this analysis. A study specific researcher-administered questionnaire was used to collect data on demographics, antipsychotic medication use, smoking, alcohol intake, diet, and physical activity. Weight, height, abdominal circumference, and blood pressure were also collected to calculate the Framingham 10-year Cardiovascular Risk Score (FRS), while blood was drawn for measurement of glucose level and lipid profile. Pearson’s chi-squared tests and t-tests were employed to assess differences in cardiovascular risk profiles between patients and controls, and a linear regression model was used to determine predictors of 10-year cardiovascular risk in patients.

Results
Compared to controls, patients with psychosis were more likely to have smoked in their lifetimes (9.9% vs. 3.3%, p = 0.006) or to be current smokers (13.8% vs. 7%, p = 0.001). Over 97% of patients with psychosis consumed fewer than five servings of fruits and vegetables per week; 78% engaged in fewer than three days of vigorous exercise per week; and 48% sat for more than three hours daily. The estimated 10-year risk of CVD was relatively low in this study: the FRS in patients was 3.16, compared to 2.93 in controls. The estimated 10-year cardiovascular risk in patients was significantly associated with female sex (p = 0.007), older patients (p < 0.001), current tobacco smoking (p < 0.001), and metabolic syndrome (p < 0.001).

Conclusion
In the setting of Eldoret, there is suboptimal physical exercise and intake of healthy diet among patients with psychosis and controls. While the estimated risk score among patients is relatively low in our study, these data may be useful for informing future studies geared towards informing interventions to promote healthy lifestyles in this population.