bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency of pharmacogenomic variants affecting efficacy and safety of anti-cancer drugs in a south Asian population from Sri Lanka
Authors: Ranasinghe Priyanga , Sirisena Nirmala , Vishnukanthan Thuwaragesh , Ariadurai J. N. , Thilakarathne Sathsarani , Priyadarshani C. D. Nelanka , Bhagya Hendalage D. P. , Dissanayake Vajira H. W. 
Published: May 2024

Abstract
Background
Therapy with anti-cancer drugs remain the cornerstone of treating cancer. The effectiveness and safety of anti-cancer drugs vary significantly among individuals due to genetic factors influencing the drug response and metabolism. Data on the pharmacogenomic variations in Sri Lankans related to anti-cancer therapy is sparse. As current treatment guidelines in Sri Lanka often do not consider local pharmacogenomic variants, this study aimed to explore the diversity of pharmacogenomic variants in the Sri Lankan population to pave the way for personalized treatment approaches and improve patient outcomes.

Methods
Pharmacogenomic data regarding variant-drug pairs of genes CYP2D6, DPYD, NUDT15, EPAS1, and XRCC1 with clinical annotations labelled as evidence levels 1A-2B were obtained from the Pharmacogenomics Knowledgebase database. Their frequencies in Sri Lankans were obtained from an anonymized database that was derived from 541 Sri Lankans who underwent exome sequencing at the Human Genetics Unit, Faculty of Medicine, University of Colombo. Variations in DPYD, NUDT15, and EPAS1 genes are related to increased toxicity to fluoropyrimidines, mercaptopurines, and sorafenib respectively. Variations in CYP2D6 and XRCC1 genes are related to changes in efficacy of tamoxifen and platinum compounds, respectively. Minor allele frequencies of these variants were calculated and compared with other populations.

Results
MAFs of rs1065852 c.100 C > T (CYP2D6), rs3918290 c.1905 + 1G > A (DPYD), rs56038477 c.1236G > A (DPYD), rs7557402 c.1035–7 C > G (EPAS1), rs116855232 c.415 C > T (NUDT15*3), and rs25487 c.1196 A > G (XRCC1) were: 12.9% [95%CI:10.9–14.9], 1.5% [95%CI:0.8–2.2], 1.2% [95%CI:0.5–1.8], 37.7% [95%CI:34.8–40.6], 8.3% [95%CI:6.7–10.0], and 64.0% [95%CI:61.1–66.8], respectively. Frequencies of rs1065852 c.100 C > T (CYP2D6), rs7557402 c.1035–7 C > G (EPAS1), and rs25487 (XRCC1) were significantly lower in Sri Lankans, while frequencies of rs116855232 c.415 C > T (NUDT15*3) and rs56038477 c.1236G > A (DPYD) were significantly higher in Sri Lankans when compared to some Western and Asian populations.

Conclusion
Sri Lankans are likely to show lower toxicity risk with sorafenib (rs7557402 c.84,131 C > G) and, higher toxicity risk with fluoropyrimidines (rs56038477 c.1236G > A) and mercaptopurine (rs116855232 c.415 C > T), and reduced effectiveness with tamoxifen (rs1065852 c.100 C > T) and platinum compounds (rs25487). These findings highlight the potential contribution of these genetic variations to the individual variability in anti-cancer dosage requirements among Sri Lankans.
Kinetic studies on optimized extracellular laccase from Trichoderma harzianum PP389612 and its capabilities for azo dye removal
Authors: Abd El-latif Amira Saad , Zohri Abdel-Naser A. , El-Aref Hamdy M. , Mahmoud Ghada Abd-Elmonsef 
Published: May 2024

Abstract
Background
Azo dyes represent a common textile dye preferred for its high stability on fabrics in various harsh conditions. Although these dyes pose high-risk levels for all biological forms, fungal laccase is known as a green catalyst for its ability to oxidize numerous dyes.

Methods
Trichoderma isolates were identified and tested for laccase production. Laccase production was optimized using Plackett–Burman Design. Laccase molecular weight and the kinetic properties of the enzyme, including Km and Vmax, pH, temperature, and ionic strength, were detected. Azo dye removal efficiency by laccase enzyme was detected for Congo red, methylene blue, and methyl orange.

Results
Eight out of nine Trichoderma isolates were laccase producers. Laccase production efficiency was optimized by the superior strain T. harzianum PP389612, increasing production from 1.6 to 2.89 U/ml. In SDS-PAGE, purified laccases appear as a single protein band with a molecular weight of 41.00 kDa. Km and Vmax values were 146.12 μmol guaiacol and 3.82 μmol guaiacol/min. Its activity was stable in the pH range of 5–7, with an optimum temperature range of 40 to 50 °C, optimum ionic strength of 50 mM NaCl, and thermostability properties up to 90 °C. The decolorization efficiency of laccase was increased by increasing the time and reached its maximum after 72 h. The highest efficiency was achieved in Congo red decolorization, which reached 99% after 72 h, followed by methylene blue at 72%, while methyl orange decolorization efficiency was 68.5%.

Conclusion
Trichoderma laccase can be used as an effective natural bio-agent for dye removal because it is stable and removes colors very well.
Molecular mechanisms of aging and anti-aging strategies
Authors: Li Yumeng , Tian Xutong , Luo Juyue , Bao Tongtong , Wang Shujin , Wu Xin 
Published: May 2024

AbstractAging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.
Time to improvement of pain, morning stiffness, fatigue, and disease activity in patients with ankylosing spondylitis treated with tofacitinib: a post hoc analysis
Authors: Navarro-Compán Victoria , Deodhar Atul , Bahiri Rachid , Bushmakin Andrew G. , Cappelleri Joseph C. , Rammaoui Jihane 
Published: May 2024

Abstract
Background
Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS.

Methods
This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16–48. Outcomes: nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1–6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points.

Results
269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4–8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8–24 (12–40) weeks with tofacitinib vs. 24–32 weeks (32 weeks–not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment.

Conclusions
Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment.

Trial registration
ClinicalTrials.gov, NCT03502616, 11 April 2018.
Development of scoring-assisted generative exploration (SAGE) and its application to dual inhibitor design for acetylcholinesterase and monoamine oxidase B
Authors: Lim Hocheol 
Published: May 2024

Abstract
De novo molecular design is the process of searching chemical space for drug-like molecules with desired properties, and deep learning has been recognized as a promising solution. In this study, I developed an effective computational method called Scoring-Assisted Generative Exploration (SAGE) to enhance chemical diversity and property optimization through virtual synthesis simulation, the generation of bridged bicyclic rings, and multiple scoring models for drug-likeness. In six protein targets, SAGE generated molecules with high scores within reasonable numbers of steps by optimizing target specificity without a constraint and even with multiple constraints such as synthetic accessibility, solubility, and metabolic stability. Furthermore, I suggested a top-ranked molecule with SAGE as dual inhibitors of acetylcholinesterase and monoamine oxidase B through multiple desired property optimization. Therefore, SAGE can generate molecules with desired properties by optimizing multiple properties simultaneously, indicating the importance of de novo design strategies in the future of drug discovery and development.

Scientific contribution
The scientific contribution of this study lies in the development of the Scoring-Assisted Generative Exploration (SAGE) method, a novel computational approach that significantly enhances de novo molecular design. SAGE uniquely integrates virtual synthesis simulation, the generation of complex bridged bicyclic rings, and multiple scoring models to optimize drug-like properties comprehensively. By efficiently generating molecules that meet a broad spectrum of pharmacological criteria—including target specificity, synthetic accessibility, solubility, and metabolic stability—within a reasonable number of steps, SAGE represents a substantial advancement over traditional methods. Additionally, the application of SAGE to discover dual inhibitors for acetylcholinesterase and monoamine oxidase B not only demonstrates its potential to streamline and enhance the drug development process but also highlights its capacity to create more effective and precisely targeted therapies. This study emphasizes the critical and evolving role of de novo design strategies in reshaping the future of drug discovery and development, providing promising avenues for innovative therapeutic discoveries.
Critical insights on “Association of the C allele of rs479200 in the EGLN1 gene with COVID‑19 severity in Indian population: a novel finding”
Authors: Deora Nimita , Agrohi Priya , Mallick Prashant K , Sinha Abhinav 
Published: May 2024

AbstractThe recent article by Harit et al. in Human Genomics reported a novel association of the C allele of rs479200 in the human EGLN1 gene with severe COVID-19 in Indian patients. The gene in context is an oxygen-sensor gene whose T allele has been reported to contribute to the inability to cope with hypoxia due to increased expression of the EGLN1 gene and therefore persons with TT genotype of EGLN1 rs479200 are more susceptible to severe manifestations of hypoxia. In contrast to this dogma, Harit et al. showed that the C allele is associated with the worsening of COVID-19 hypoxia without suggesting or even discussing the scientific plausibility of the association. The article also suffers from certain epidemiological, statistical, and mathematical issues that need to be critically elaborated and discussed. In this context, the findings of Harit et al. may be re-evaluated.
The neuropathological landscape of small vessel disease and Lewy pathology in a cohort of Hispanic and non-Hispanic White decedents with Alzheimer disease
Authors: Wang Hsin-Pei , Scalco Rebeca , Saito Naomi , Beckett Laurel , Nguyen My-Le , Huie Emily Z. , Honig Lawrence S. , DeCarli Charles , Rissman Robert A. , Teich Andrew F. , Mungas Dan M. , Jin Lee-Way , Dugger Brittany N. 
Published: May 2024

AbstractCerebrovascular and α-synuclein pathologies are frequently observed alongside Alzheimer disease (AD). The heterogeneity of AD necessitates comprehensive approaches to postmortem studies, including the representation of historically underrepresented ethnic groups. In this cohort study, we evaluated small vessel disease pathologies and α-synuclein deposits among Hispanic decedents (HD, n = 92) and non-Hispanic White decedents (NHWD, n = 184) from three Alzheimer’s Disease Research Centers: Columbia University, University of California San Diego, and University of California Davis. The study included cases with a pathological diagnosis of Intermediate/High AD based on the National Institute on Aging– Alzheimer’s Association (NIA-AA) and/or NIA-Reagan criteria. A 2:1 random comparison sample of NHWD was frequency-balanced and matched with HD by age and sex. An expert blinded to demographics and center origin evaluated arteriolosclerosis, cerebral amyloid angiopathy (CAA), and Lewy bodies/Lewy neurites (LBs/LNs) with a semi-quantitative approach using established criteria. There were many similarities and a few differences among groups. HD showed more severe Vonsattel grading of CAA in the cerebellum (p = 0.04), higher CAA density in the posterior hippocampus and cerebellum (ps = 0.01), and increased LBs/LNs density in the frontal (p = 0.01) and temporal cortices (p = 0.03), as determined by Wilcoxon’s test. Ordinal logistic regression adjusting for age, sex, and center confirmed these findings except for LBs/LNs in the temporal cortex. Results indicate HD with AD exhibit greater CAA and α-synuclein burdens in select neuroanatomic regions when compared to age- and sex-matched NHWD with AD. These findings aid in the generalizability of concurrent arteriolosclerosis, CAA, and LBs/LNs topography and severity within the setting of pathologically confirmed AD, particularly in persons of Hispanic descent, showing many similarities and a few differences to those of NHW descent and providing insights into precision medicine approaches.
Understanding science data literacy: a conceptual framework and assessment tool for college students majoring in STEM
Authors: Qiao Cuilan , Chen Yuqing , Guo Qing , Yu Yunwei 
Published: May 2024

Abstract
Background
In the era defined by the fourth paradigm of science research, the burgeoning volume of science data poses a formidable challenge. The established data-related requisites within science literacy now fall short of addressing the evolving needs of researchers and STEM students. Consequently, the emergence of science data literacy becomes imperative. However, notwithstanding the escalating importance of science data literacy, a comprehensive definition and conceptual framework are still elusive, posing challenges to effective assessment.

Results
This study analyzes the science literacy frameworks of six international organizations and countries, including the OECD, and reviews 16 data literacy-related literature sources identified using the PRISMA process. We also consider the characteristics of science data. Based on these sources, we clarify the connotation of science data literacy and construct a tailored conceptual framework for college students majoring in STEM. The framework undergoes two rounds of Delphi method refinement to enhance its applicability. Subsequently, we created and piloted a set of questions using physics, astronomy, geography, and other STEM subjects as examples to assess science data literacy. The revised assessment tool was then used in a formal test with 198 university students, employing Rasch modeling to evaluate its effectiveness. The tool’s validity in assessing science data literacy was confirmed.

Conclusions
This study offers a systematic and comprehensive conceptual framework for science data literacy tailored to STEM undergraduates. Endorsed by experts, the framework outlines essential literacies for STEM students in handling science data. The developed assessment tool enables educators to measure students’ science data literacy levels and serves as a scientific guide to enhance their competencies in this area.
Ultra-low foetal radiation exposure in 18F-FDG PET/CT imaging with a long axial field-of-view PET/CT system
Authors: Smith Charlotte L. C. , Yaqub Maqsood , Wellenberg Ruud H. H. , Knip Jelijn J. , Boellaard Ronald , Zwezerijnen Gerben J. C. 
Published: May 2024

Abstract
Purpose
Long axial field-of-view (LAFOV) PET/CT systems enable PET/CT scans with reduced injected activities because of improved sensitivity. With this study, we aimed to examine the foetal radiation dose from an 18F-FDG PET/CT scan on a LAFOV PET/CT system with reduced injected activity.

Methods
Two pregnant women were retrospectively included and received an 18F-FDG PET/CT scan on a LAFOV PET/CT system with an intravenous bolus injection of 0.30 MBq/kg. Foetal radiation exposure from the PET was estimated using dose conversion factors from three published papers. Radiation exposure from the CT scans was estimated using CT-Expo.

Results
Foetal radiation dose from the PET scan ranged between 0.11 and 0.44 mGy. Foetal radiation exposure from the CT scan ranged between < 0.10 – 0.90 mGy depending if the foetus was included in the field-of-view.

Conclusion
Foetal radiation dose could be reduced to < 1.5 mGy when scanning pregnant patients on a LAFOV PET/CT system. The radiation dose to the foetus was reduced significantly in our study due to the increased sensitivity of the LAFOV PET/CT system.
How do emotions affect giving? Examining the effects of textual and facial emotions in charitable crowdfunding
Authors: Lu Baozhou , Xu Tailai , Fan Weiguo 
Published: May 2024

AbstractDrawing on emotional contagion theory and language-mediated association theory, this study develops a research model to examine how textual and facial emotions affect charitable crowdfunding performance. We use computer-aided techniques to extract and measure specific textual and facial emotions in pitches. The proposed model is tested via regression analysis with a sample of 1372 campaigns collected from the largest charitable crowdfunding platform in China—Tencent Gongyi. Moreover, we conducted a fuzzy-set qualitative comparative analysis to examine the complementarity of textual and facial emotions, which supplements the regression analysis results. Our findings show that both textual and facial emotions can impact funding outcomes. However, the effects of specific emotions vary: some (e.g., textual sadness and facial anger) are positive, some (e.g., textual anger and facial fear) are negative, and others (e.g., textual fear, textual disgust, and facial sadness) are insignificant. Moreover, facial emotions complement textual emotions in their effects on funding outcomes. This research outlines a framework to offer a more detailed and comprehensive understanding of emotions in charitable crowdfunding. It also contributes to existing research by revealing the vital but complex role of emotions in the persuasive process of prosocial behaviors and by uncovering the different cognitive mechanisms underlying the impacts of textual and facial emotions.
Predictive model for post-induction hypotension in patients undergoing transcatheter aortic valve implantation: a retrospective observational study
Authors: Noto Kohei , Uchida Satoshi , Kinoshita Hirotaka , Takekawa Daiki , Kushikata Tetsuya , Hirota Kazuyoshi 
Published: May 2024

Abstract
Purpose
Post-induction hypotension (PIH) is an independent risk factor for prolonged postoperative stay and hospital death. Patients undergoing transcatheter aortic valve implantation (TAVI) are prone to develop PIH. This study aimed to develop a predictive model for PIH in patients undergoing TAVI.

Methods
This single-center retrospective observational study included 163 patients who underwent TAVI. PIH was defined as at least one measurement of systolic arterial pressure <90 mmHg or at least one incident of norepinephrine infusion at a rate >6 µg/min from anesthetic induction until 20 min post-induction. Multivariate logistic regression analysis was performed to develop a predictive model for PIH in patients undergoing TAVI.

Results
In total, 161 patients were analyzed. The prevalence of PIH was 57.8%. Multivariable logistic regression analysis showed that baseline mean arterial pressure ≥90 mmHg [adjusted odds ratio (aOR): 0.413, 95% confidence interval (95% CI): 0.193–0.887; p=0.023] and higher doses of fentanyl (per 1-µg/kg increase, aOR: 0.619, 95% CI: 0.418–0.915; p=0.016) and ketamine (per 1-mg/kg increase, aOR: 0.163, 95% CI: 0.062–0.430; p=0.002) for induction were significantly associated with lower risk of PIH. A higher dose of propofol (per 1-mg/kg increase, aOR: 3.240, 95% CI: 1.320–7.920; p=0.010) for induction was significantly associated with higher risk of PIH. The area under the curve (AUC) for this model was 0.802.

Conclusion
The present study developed predictive models for PIH in patients who underwent TAVI. This model may be helpful for anesthesiologists in preventing PIH in patients undergoing TAVI.
Junction formation rates, residence times, and the rate of plastic flow in FCC metals
Authors: Zhang Yurui , Sills Ryan B. 
Published: May 2024

AbstractDuring plastic flow in metals, dislocations from slip systems with different glide planes collide to form junctions. After being in-residence within the dislocation network for some period of time, these junctions then break, thereby liberating the attached dislocation lines. In this work we use random forest discrete dislocation dynamics simulations to quantify the junction formation rate and junction residence time as a function of stress for all junction types in face-centered cubic metals. We then relate these quantities to the dislocation link-length distribution, which is found to exhibit an exponential form. This enables us to quantify the mean junction strength and also the slip system interaction coefficients. Finally, using the link-length model we obtain a flow rule for our systems which is physics-based with all parameters determined from DDD simulations. The insights here provide a path forward for a dislocation network theory of plastic flow based on the link-length distribution.