bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights on cyclophosphamide metabolism and anticancer mechanism of action: A computational study
Authors: Dabbish Eslam , Scoditti Stefano , Shehata Mohammed N. I. , Ritacco Ida , Ibrahim Mahmoud A. A. , Shoeib Tamer , Sicilia Emilia 
Published: December 2023

AbstractThe oxazaphosphorine cyclophosphamide (CP) is a DNA‐alkylating agent commonly used in cancer chemotherapy. This anticancer agent is administered as a prodrug activated by a liver cytochrome P450‐catalyzed 4‐hydroxylation reaction that yields the active, cytotoxic metabolite. The primary metabolite, 4‐hydroxycyclophosphamide, equilibrates with the ring‐open aldophosphamide that undergoes β‐elimination to yield the therapeutically active DNA cross‐linking phosphoramide mustard and the byproduct acrolein. The present paper presents a DFT investigation of the different metabolic phases and an insight into the mechanism by which CP exerts its cytotoxic action. A detailed computational analysis of the energy profiles describing all the involved transformations and the mechanism of DNA alkylation is given with the aim to contribute to an increase of knowledge that, after more than 60 years of unsuccessful attempts, can lead to the design and development of a new generation of oxazaphosphorines.
Transient presence of stomatocytes: A clue to the diagnosis of overhydrated hereditary stomatocytosis in a child with beta‐thalassemia
Authors: Chen Yanhui , Lin Qile , Ni Wenpeng , Deng Kunyi , Li Lilian 
Published: December 2023

AbstractBackgroundOverhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis. Early and accurate diagnosis is essential for appropriate management and genetic counseling.MethodsWe present the case of a child with beta‐thalassemia and a history of multiple blood transfusions. Clinical presentation, laboratory findings, and genetic testing were reviewed. Peripheral blood smear examination and genetic analysis were performed.ResultsThe patient was admitted with severe anemia, and peripheral blood smear examination revealed the presence of up to 50% stomatocytes. Laboratory investigations showed abnormalities in red blood cell parameters, including decreased hemoglobin levels and increased mean corpuscular volume. Genetic testing identified a heterozygous mutation in the RHAG gene, confirming the diagnosis of OHSt. The presence of stomatocytes in the peripheral blood smear was transient, correlating with episodes of hemolysis and its control.
Association between endogenous plasma beta‐hydroxy‐beta‐methylbutyrate levels and frailty in community‐dwelling older people
Authors: Molina‐Baena Begoña , Carnicero Jose Antonio , Pereira Suzette L. , García‐García Francisco José , Santos‐Fandila Angela , Cabrera Ricardo Rueda , Rodríguez‐Mañas Leocadio 
Published: December 2023

AbstractBackgroundFrailty is a key element in healthy ageing in which muscle performance plays a main role. Beta‐hydroxy‐beta‐methylbutyrate (HMB) supplementation has shown favourable effects in modulating protein synthesis, improving muscle mass and function in interventional studies. Decreased age‐related endogenous HMB levels have been shown in previous studies. The aim of the present study is to assess whether there is an association between endogenous plasma HMB levels and frailty.MethodsData from 1290 subjects (56.98% women; mean ± standard deviation age 74.6 ± 5.95 years) from the Toledo Study for Healthy Aging were obtained. Participants had their frailty status qualified according to Fried's Frailty Phenotype (FFP) score and the Frailty Trait Scale in its 12‐domain version (FTS‐12). Plasma HMB levels were analysed by an ultrahigh‐performance liquid chromatography tandem mass spectrometry. Differences between groups (frail vs. non‐frail) were tested using Mann–Whitney U test, Kruskal–Wallis test and chi‐squared test. The association between HMB and frailty was assessed by multivariate linear and logistic regressions when frailty was analysed as continuous and binary, respectively. Models were adjusted by age, gender, comorbidity, body composition and protein intake.ResultsHMB levels were lower in those aged ≥75 years than in those aged 65–74 years, with an inverse linear relationship between age and HMB levels (β = −0.031; P = 0.018), mainly accounted by males (β = −0.062; P = 0.002). HMB levels were higher in men (0.238 ± 0.065 vs. 0.193 ± 0.051 ng/mL; P ≤ 0.001). HMB levels were significantly lower in frail than in non‐frail individuals: 0.204 ± 0.058 versus 0.217 ± 0.063 ng/dL (P = 0.001) according to the FFP and 0.203 ± 0.059 versus 0.219 ± 0.063 ng/mL (P < 0.001) according to FTS‐12. These differences showed a dose‐dependent profile when we compared them by quintiles of HMB (P for trend: 0.022; 0.012 and 0.0004, respectively, for FFP, FTS‐12 binary and FTS‐12 continuous). Variables associated with low HMB levels were body mass index, strength, exhaustion and weight loss. Frailty was associated with HMB levels in all the adjusted models, including the fully adjusted ones, no matter the tool used (odds ratio: 0.45 [0.26, 0.77] for FFP and 0.36 [0.20, 0.63] for FTS‐12 binary; β = −4.76 [−7.29, −2.23] for FTS‐12 score). This association was also observed when the analyses were done by quintiles, showing such association since Q4 (FFP), Q2 (FTS‐12 binary) and Q3 (FTS‐12 score). The associations were observed in the whole sample and in each gender.ConclusionsThere is an inverse association between HMB levels and frailty status. These findings support the design of targeted clinical trials to evaluate the effect of HMB supplementation in older frail people with low HMB levels.
Implication of grip strength assessment for the management of body weight in disability prevention in older adults
Authors: Zhang Shu , Otsuka Rei , Tange Chikako , Nishita Yukiko , Shimokata Hiroshi , Satake Shosuke , Arai Hidenori 
Published: December 2023

AbstractBackgroundAlthough body mass index (BMI) and grip strength (GS) are both predictors of disability, their joint effect on predicting incident disability remains uncertain. We examined whether the effect of BMI on incident disability can be modulated by GS in community‐dwelling older people in Japan.MethodsA total of 1486 community‐dwellers in Japan (731 men and 755 women, aged 65–82 years) who participated in the 2nd to 7th waves of the National Institute for Longevity Sciences‐Longitudinal Study of Aging (NILS‐LSA) project, were followed up to 20 years. Twelve subgroups were created according to the intersections of GS (sex‐specific tertiles: low, intermediate, and high) and BMI (underweight 1, <18.5; underweight 2, 18.5–<21.5; normal, 21.5–<25.0; and overweight/obese, ≥25.0 kg/m2). Incident disability was defined as requiring care need level 1 or higher, as per the long‐term care insurance system in Japan. The hazard ratios (HR) and corresponding 95% confidence intervals (CI) of incident disability (the ‘high GS‐normal BMI’ subgroup was used as the reference) were calculated using a multivariable‐adjusted Cox proportional hazards model. The model was adjusted for baseline characteristics on sex, participation wave, smoking, depressive symptoms, total physical activity, disease history, education level, residential status, and energy intake.ResultsCompared with that for participants in the ‘high GS‐normal BMI’ group, the risk of incident disability was higher for participants in the ‘low GS‐normal BMI’, ‘low GS‐overweight/obese’, ‘intermediate GS‐underweight 1’ and ‘intermediate GS‐overweight/obese’ groups. The multivariable‐adjusted HR (95% CI) were 1.72 (1.27–2.32, P value<0.001), 1.81 (1.27–2.58, P value = 0.001), 2.42 (1.35–4.32, P value = 0.003) and 1.53 (1.06–2.20, P value = 0.023), respectively. The results did not change substantially when participants with disability occurring within 1 and 2 years of follow‐up were excluded, or when the competing events were death without incident disability or dementia.ConclusionsThe joint effect of BMI and GS was more pronounced in those of normal weight or overweight/obese status and low GS, along with underweight or overweight/obese status and intermediate GS in predicting disability. The lack of observed joint effect for those underweight with low GS was likely due to insufficient sample size. GS consideration is necessary for weight management in older adults, and interventions for individuals who are underweight or overweight/obese with adequate GS need not be prioritized for disability prevention.
Integrating reading and writing with STEAM/STEM: A systematic review on STREAM education
Authors: Sun Wang , Zhong Baichang 
Published: December 2023

AbstractBackgroundScience, technology, reading and writing, engineering, art, and mathematics (STREAM) education is an emerging form of STEM/STEAM education. STEM education research focuses on how students acquire knowledge and skills. The potential of reading and writing to effectively support students in STEM education has been the focus of research. Although researchers have noted the role of language, they have not explored it in depth.Purpose/HypothesisThis paper presents a systematic review of STREAM education to clarify how reading/writing is integrated with STEM/STEAM education and explores the level of cognitive goals in instruction.Design/MethodBy searching for articles related to STREAM education up to 2021, we coded some important features of STREAM education and highlighted the correlations between two or more features.Results(i) STREAM education has developed rapidly in the past 3 years; (ii) Writing appeared in STEM education before reading, and the trend of research is spreading from college to lower school levels; (iii) The combination of reading and writing is better in primary school and is underemphasized in middle school; (iv) The cognitive goals of STREAM education in higher education are slightly higher overall than those before college; (v) Current studies focus on the reflection process of the course, while the main process deserves more attention; and (vi) reading/writing activities in the reflection process achieved the highest levels of cognition than in the entry and main processes.ConclusionThe integration of language activities (reading and writing) into STREAM education is a trend toward disciplinary integration, which helps develop students' cognition and form knowledge constructs.
Contextualization in engineering education: A scoping literature review
Authors: Kleine Marie Stettler , Zacharias Kari , Ozkan Desen 
Published: December 2023

AbstractBackgroundEngineering educators prepare students for responsible, ethical, and socially aware engineering practice by contextualizing engineering in a variety of ways. Recently, ABET and the NAE have prioritized engineers' ability to make judgments considering a variety of contexts and specifically advocated for building engineers' contextual competencies.PurposeEducators can often agree that contextualizing engineering work and problems is beneficial, while taking different approaches to that contextualization. It is important for engineering educators to know how their modes of contextualization compare with others, as well as how they define and achieve success.Scope/MethodThis scoping literature review answers two research questions: How are engineering educators contextualizing engineering through their programs, courses, and pedagogies? And what are the justifications, motivations, or desired ends of engineering educators' contextualization? The original search yielded 500 articles from pertinent engineering education venues. After detailed exclusion and inclusion criteria were applied, 104 relevant articles were analyzed.ResultsThese remaining articles were sorted into six modes of contextualization: context tools, professional skills, real‐world problems, design, sociotechnical thinking, and social impact. The categorization and analysis led to a complex understanding of the multiplicity of contextualization in engineering education.ConclusionsThe wide variety of modes of contextualization results in a variety of bettering strategies, or ways that these forms of pedagogy can improve engineering education, and, in turn, larger engineering contexts. We conclude that engineering content and context are “interactional” and co‐constructed, showing how different modes of contextualization demarcate different images of what engineering content and contexts are and ought to be.
Overfullness of edge‐critical graphs with small minimal core degree
Authors: Cao Yan , Chen Guantao , Jing Guangming , Shan Songling 
Published: December 2023

AbstractLet be a simple graph. Let and be the maximum degree and the chromatic index of , respectively. We call overfull if , and critical if for every proper subgraph of . Clearly, if is overfull then . The core of , denoted by , is the subgraph of induced by all its maximum degree vertices. We believe that utilizing the core degree condition could be considered as an approach to attack the overfull conjecture. Along this direction, we in this paper show that for any integer , if is critical with and , then is overfull.
Real‐life effectiveness of carfilzomib in patients with relapsed multiple myeloma receiving treatment in the context of early access: The CARMYN study
Authors: Laribi Kamel , Leleu Xavier , Texier Nathalie , Germain Raphaël , Touzeau Cyrille , Hammoud Mohammad , Payssot Alexandre , Schulmann Samantha , Le Calloch Ronan , Trebouet Adrien , Chaoui Driss , David Selva , Benbrahim Omar , Benramdane Riad , Charvet‐Rumpler Anne , Jadeau Christelle , Rouanet Eglantine , Decaux Olivier , Perrot Aurore 
Published: December 2023

AbstractThe real‐life retrospective observational study CARMYN aimed at investigating the long‐term efficacy and safety of carfilzomib in combination with dexamethasone and lenalidomide (KRd, 159 patients). These patients (62% in first and 38% in second relapse, median age 62 yo) were treated between 02/2014 and 02/2017. Most had been pre‐exposed to bortezomib (98.2%) and to an IMID (75.4%). At the time of collection, 90% had permanently discontinued carfilzomib. Data collection was conducted from January to July 2021 in 27 participating sites, after a median of 39 months follow‐up. For patients treated with KRd, an overall response rate of 78.4% translated in a median progression free survival (PFS) of 24.0 months (95% CI 18.8–27.6) and a median overall survival (OS) of 51.1 months (95% CI 41.3–not reached). Results were poorer but difficult to interpret in the small cohort of Kd recipients. The study is one of the longest real‐life studies of carfilzomib treatment in patients in first or second relapse. CARMYN confirmed the real‐life long‐term efficacy of carfilzomib in combination with lenalidomide and dexamethasone with results similar to those of clinical trials. The KRd regimen is thus an option to consider for late relapses in the current context of MM management.
‘Happy’ activists: Non‐governmental organization staff navigating the social movement/service provider divide in India
Authors: Mount Liz 
Published: December 2023

AbstractIn the Global South, non‐governmental organizations (NGOs) face criticism; staff employ strategies to mitigate it. What happens when NGO staff express different levels of awareness about such criticism? How are these differences shaped by whether staff identify themselves as ‘community’ members the NGO serves or ‘non‐community’ members whose work serves the community? How do these identities impact NGOs? Through an 18‐month ethnographic study at a large NGO in Bangalore, India, I show that NGO staff members' identification as ‘community’ or ‘non‐community’ members shapes their perceptions of the NGO, their work and the NGO's work. I trace these differing perceptions to mission creep.
MR Assessed Changes of Renal Sinus Fat in Response to Glucose Regulation in West European and South Asian Patients With Type 2 Diabetes
Authors: Lin Ling , Dekkers Ilona A. , Tao Qian , Paiman Elisabeth H.M. , Bizino Maurice B. , Jazet Ingrid M. , Lamb Hildo J. 
Published: December 2023

BackgroundEthnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI‐quantified renal sinus fat volume could be a potential biomarker to help investigate the changes of DKD risk in response to glucose regulation.PurposeTo evaluate whether the effect of glucose‐lowering treatment on renal sinus fat volume differed in West Europeans (WE) compared to South Asians (SA), and whether ethnic‐related difference exists regarding the effect of liraglutide on renal sinus fat.Study TypeRetrospective.PopulationNinety‐three patients with type 2 diabetes mellitus, including 47 WE (27 males) aged 59.3 ± 6.5 years, and 46 SA (19 males) aged 54.4 ± 9.8 years.Field Strength/Sequence3.0 T dual‐echo fast gradient‐echo pulse sequence using two‐point Dixon technique with a phase‐correction algorithm.AssessmentChanges of renal sinus fat volume were measured by a radiologist (LL) with 4‐years' experience, and were compared between the two ethnic groups, together with glycemic level, metabolic risk factors and renal function. The effects of liraglutide were assessed.Statistical TestsNormality of the data was visually evaluated by histograms and Q–Q plots. Within‐group and between‐group differences were analyzed using paired t‐tests and analysis of covariance. Associations were analyzed by person's correlation and multiple linear regression models.ResultsRenal sinus fat decreased in SA patients (Δ% = −7.6% ± 14.8%), but increased in WE patients (Δ% = 5.0% ± 13.1%), with a significant difference between the two ethnic groups. In the WE group, the increase of sinus fat volume was significant in the placebo subgroup (Δ% = 6.8% ± 12.5%), in contrast to the nonsignificant increase in the liraglutide subgroup (Δ% = 3.0% ± 13.8%, P = 0.444).Data ConclusionRenal sinus fat accumulation responds differently to glucose regulation, showing a reduction in SA patients in contrast to a persistent accumulation in WE patients. A trend of less accumulation of sinus fat in WE patients receiving liraglutide has been observed.Evidence Level4Technical EfficacyStage 4
Genome sequencing reveals molecular epidemiological characteristics and new recombinations of adenovirus in Beijing, China, 2014−2019
Authors: Li Maozhong , Li Jing , Kang Lu , Gong Cheng , Luo Ming , Wang Xue , Guan Xuejiao , Tong Yigang , Huang Fang 
Published: December 2023

AbstractTo investigate the molecular epidemiological characteristics and genetic variations of human adenovirus (HAdV) in acute respiratory tract infections in Beijing. Whole‐genome sequencing and phylogenetic analyses were performed for 83 strains of HAdV with different types in Beijing from 2014 to 2019. The clinical characteristics of HAdV infection were analyzed statistically. HAdV‐B was divided into four genotypes, including B3 (n = 11), B7 (n = 13), B14 (n = 4), and B55 (n = 2). HAdV‐C was divided into three genotypes, including C1 (n = 14), C2 (n = 13), and C5 (n = 10). In HAdV‐C, nine recombinant adenovirus strains were identified in type 1, and seven recombinant strains were found in type 2. In type 1, we found three newly emerged intraspecific recombinant strains (A47, A48, and A52) collected in 2017, 2018, and 2019, respectively. In addition, the previously reported recombinant strains of HAdV‐C1 showed more severe disease than other strains of HAdV‐C, causing severe community‐acquired pneumonia in both the elderly and children. Continuous population‐wide molecular epidemiological surveillance of HAdV is essential for the prevention and control of respiratory infectious diseases.
Spatial patterns of torrential rain in the Haihe River Basin and the corresponding large‐scale circulation
Authors: Cheng Shanjun , Li Mingcong , Wang Shanshan , Liang Sujie 
Published: December 2023

AbstractThe classification of torrential rain is crucial to the flood mitigation and water resources, but the relevant research in the Haihe River Basin (HRB) is lacking. In this study, 156 regional torrential rain events from 1972 to 2022 were classified into two types using cluster analysis: eastern type and southern type. The eastern type is the typical torrential rain in the HRB, accounting for 61.5% of the total days, whereas the southern type mainly occurs in the piedmont plain with larger intensity and scope, which would pose more severe hazards. Corresponding large‐scale circulation patterns of the two types reveal a clear relationship between the HRB torrential rain and ascending motion, associated with the anomalies of low‐level moisture convergence and upper‐level wind divergence. The anomalous upper‐level divergence is accompanied by the northward expansion of South Asian High and intensified westerly jets. In the eastern type, strong low‐pressure anomalies north of Lake Baikal at mid‐level produce anomalous northwesterlies. The cold air from mid–high latitudes encounters enhanced southwesterly moist air accompanied by the northward expansion of Western Pacific Subtropical High (WPSH), resulting in the low‐level moisture convergence. In the southern type, the low‐level anomalous convergence is caused by a relatively weak cyclonic anomaly and significantly strengthened southeasterly moisture from the Pacific. The enhancement of southwesterlies results from the cooperative effect of the remarkably northwesterly WPSH and low‐pressure anomalies in South China Sea. As a whole, the eastern type is the result of convergence of cold air and southwesterly moisture driven by a dipole pattern at mid–high latitudes, whereas the southern type is mainly attributed to the accumulation of abundant southeasterly water vapour. This classification can identify high‐risk areas for torrential rain in the HRB and contribute to the forecast skills of extreme precipitation.
Aptamer‐Modified Tetrahedral DNA Nanostructures as Drug Delivery System for Cancer Targeted Therapy
Authors: Zhao Ruirui , Bai Yunfeng , Guo Yujing , Feng Feng , Shuang Shaomin 
Published: December 2023

AbstractImproving the selective delivery and uptake efficiency of chemotherapeutic drugs remains a challenge for cancer‐targeted therapy. In this work, a DNA tetrahedron is constructed as a targeted drug delivery system for efficient delivery of doxorubicin (Dox) into cancer cells. The DNA tetrahedron is composed of a tetrahedral DNA nanostructure (TDN) with two strands of AS1411 aptamer as recognition elements which can target the nucleolin protein on the cell membrane of cancer cells. The prepared DNA tetrahedron has a high drug‐loading capacity and demonstrates pH‐responsive Dox release properties. This enables efficient delivery of Dox into targeted cancer cells while reducing side effects on nontarget cells. The proposed drug delivery system exhibits significant therapeutic efficacy in vitro compared to free Dox. Accordingly, this work provides a good paradigm for developing a targeted drug delivery system for cancer therapy based on DNA tetrahedrons.
RoeNet: Predicting discontinuity of hyperbolic systems from continuous data
Authors: Tong Yunjin , Xiong Shiying , He Xingzhe , Yang Shuqi , Wang Zhecheng , Tao Rui , Liu Runze , Zhu Bo 
Published: December 2023

AbstractPredicting future discontinuous phenomena that are unobservable from training data sets has long been a challenging problem in scientific machine learning. We introduce a novel paradigm to predict the emergence and evolution of various discontinuities of hyperbolic partial differential equations (PDEs) based on given training data over a short window with limited discontinuity information. Our method is inspired by the classical Roe solver [P. L. Roe, J Comput Phys., vol. 43, 1981], a basic tool for simulating various hyperbolic PDEs in computational physics. By carefully designing the computing primitives, the data flow, and the novel pseudoinverse processing module, we enable our data‐driven predictor to satisfy all the essential mathematical criteria of a Roe solver and hence deliver accurate predictions of hyperbolic PDEs. We demonstrate through various examples that our data‐driven Roe predictor outperforms original human‐designed Roe solver and deep neural networks with weak priors in terms of accuracy and robustness.