bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physicochemical and Biological Evaluation of gem‐Difluorinated Saturated Oxygen Heterocycles as Bioisosteres for Drug Discovery
Authors: Melnykov Kostiantyn P. , Liashuk Oleksandr S. , Holovach Serhii , Shatnia Valeriia , Horbenko Artur , Lesyk Dmytro , Melnyk Varvara , Skrypnik Daniil , Beshtynarska Anna , Borysko Petro , Viniichuk Oleksandr , Grygorenko Oleksandr O. 
Published: December 2024

AbstractA comprehensive study on the physicochemical properties of gem‐fluorinated O‐heterocyclic substituents is reported. Systematic additive effects of introducing O‐ and gem‐CF2 group introduction on acidic properties (pKa) of the corresponding carboxylic acids/protonated primary amines were demonstrated. The impact of the O/CF2 moieties on lipophilicity (LogP) was found to be complex; significant mutual influence of the corresponding polar moieties governed the compound's overall properties in this case. Biological evaluation of MAPK kinase inhibitors incorporating the title substituents demonstrated their utility as promising fragments for bioisosteric replacements in drug discovery campaigns.
Subclinical Myocardial Dysfunction Assessment Using Speckle Tracking Echocardiography in Patients With Psoriasis: A Pilot Meta‐Analysis
Authors: Jain Hritvik , Jain Jyoti , Dey Debankur , Modi Rishika , Alomari Omar , Ahmed Mushood , Singh Jagjot , Odat Ramez M. , Ahmed Raheel , Nashwan Abdulqadir J. 
Published: December 2024

ABSTRACTIntroductionPsoriasis is a systemic inflammatory disease associated with elevated cardiovascular risk due to inflammatory and oxidative stress. Two‐dimensional speckle‐tracking echocardiography (2D‐STE) can detect both regional and global myocardial strain. Impairment of ventricular strain can assist in the early detection of myocardial dysfunction. Subclinical myocardial dysfunction in psoriasis has not yet been elucidated with inconsistent results.MethodsA systematic literature search of various databases was conducted to identify studies comparing global longitudinal strain (GLS) and global circumferential strain (GCS) between patients with psoriasis and healthy controls. Standardized mean differences (SMD) with 95% confidence intervals (CI) were pooled using the inverse‐variance random‐effects model in Review Manager Software Version 5.4.1.ResultsEleven studies with 879 participants (501 patients with psoriasis and 378 healthy controls) were included. Psoriasis was associated with a statistically significant reduction in GLS [SMD: –1.04; 95% CI: –1.45, –0.62; p < 0.00001] and GCS [SMD: –0.66; 95% CI: –1.27, –0.05; p = 0.03] compared to healthy controls.ConclusionThis study demonstrated that patients with psoriasis are at an elevated risk of subclinical myocardial dysfunction, as shown by the reduced GLS and GCS. Early assessment of subclinical impairment in psoriasis will allow targeted intervention and may mitigate future adverse cardiovascular events. Prospective studies with larger sample sizes are warranted to validate these results.
Contemporary trends in utilization of metastasectomy in the era of targeted and immunotherapies
Authors: Passman Jesse E. , Kallan Michael J. , Roberson Jeffrey L. , Ginzberg Sara P. , Amjad Wajid , Soegaard Ballester Jacqueline M. , Tortorello Gabriella , Fraker Douglas , Karakousis Giorgos C. , Bartlett Edmund K. , Wachtel Heather 
Published: December 2024

AbstractBackgroundMetastasectomy is a useful adjunct in the management of metastatic cancer. Widespread adoption of novel targeted and immunotherapies has improved the survival profiles of multiple malignancies, which has potentially altered the role of metastasectomy. This study aimed to characterize trends in metastasectomy across five primary cancers eligible for these therapies.MethodsThe National Inpatient Sample was used to identify patients who underwent metastasectomy in the United States (2016–2021). Patients with procedure codes for resection of the lung, liver, adrenal gland, brain, or small bowel and concurrent diagnosis codes for secondary malignant neoplasm of that site were included. Subjects were subcategorized by primary malignancy: colorectal cancer, lung cancer, breast cancer, melanoma, or renal cancer. Sample weights were used to produce national estimates, which were incidence adjusted by primary malignancy. Trends in utilization were calculated with average annual percent change (AAPC) and linear regression coefficients.ResultsColorectal cancer was the most frequent indication for metastasectomy (n = 57,644 cases), followed by lung cancer (n = 55,090 cases), breast cancer (n = 12,616 cases), renal cancer (n = 8427 cases), and melanoma (n = 5658 cases). Utilization of metastasectomy increased over the study period for breast cancer (AAPC, +10.6%; p = .013) and melanoma (AAPC, +8.3%; p = .040) but did not change for lung cancer (AAPC, −1.6%; p = .26), colorectal cancer (AAPC, +0.3%; p = .83), or renal cancer (AAPC, +2.3%; p = .36).ConclusionsBetween 2016 and 2021, utilization of metastasectomy increased significantly for melanoma and breast cancer. The role of metastasectomy will likely continue to develop as new treatment protocols improve survival profiles for patients with metastatic disease.
Improving survival for patients with metastatic non–small cell lung cancer in the immunotherapy era
Authors: Zhang David , Rohatgi Anjali 
Published: December 2024

The article by Wang et al. demonstrates that immune checkpoint inhibitor therapy has increased survival for patients with metastatic non–small cell lung cancer, although the increases in overall survival and progression‐free survival are typically less than demonstrated in randomized controlled trials. These discrepancies are likely caused by lower rates of immune checkpoint inhibitor therapy in the real world compared to clinical trial populations and by differences in patient characteristics.
The 2021 US Preventive Services Task Force lung cancer screening eligibility criteria disproportionately exclude younger Black patients with lung cancer
Authors: Potter Alexandra L. , Kuhan Sangkavi , Senthil Priyanka , Mansur Arian , Haridas Chinmay , Srinivasan Deepti , Kumar Arvind , Zheng Wei , Warner Erica T. , Yang Chi‐Fu Jeffrey 
Published: December 2024

AbstractBackgroundThe 2021 US Preventive Services Task Force (USPSTF) lung cancer screening guideline may continue to exclude many younger Black individuals who have not yet accumulated enough smoking pack‐years to be eligible for screening. The objective of this study was to evaluate the proportions of Black and White patients with lung cancer, stratified by age at diagnosis, who would have been eligible for lung cancer screening.MethodsIncident lung cancer cases among Black and White individuals aged 50–80 years with a smoking history in the Southern Community Cohort Study (SCCS) were identified for analysis. The proportions of Black and White individuals, stratified by age at diagnosis, who would have qualified for screening under the 2013 and 2021 USPSTF guidelines were calculated.ResultsA total of 1856 individuals met inclusion criteria. Compared to the 2013 USPSTF guideline, the 2021 USPSTF guideline significantly increased the proportions of Black and White patients with lung cancer who would have qualified for screening in all age groups evaluated. However, under the 2021 USPSTF guideline, there remained a notable racial disparity in lung cancer screening eligibility, particularly among younger patients with lung cancer. Only 47.4% and 61.9% of Black patients aged 50–54 and 50–59 years, respectively, would have qualified for screening under the 2021 USPSTF guideline compared to 80.3% and 88.8% of White patients aged 50–54 and 50–59 years, respectively. With increasing age, the racial disparity in lung cancer screening eligibility between Black and White patients with lung cancer was reduced, and there were no longer any statistically significant differences in screening eligibility between Black and White patients with lung cancer aged 70–74 and 75–80 years. Of Black individuals aged 50–54 and 55–59 years who were ineligible for screening, 100% and 97.5% were ineligible because they had smoked fewer than 20 pack‐years, respectively.ConclusionsThis analysis of SCCS participants with lung cancer found that the 2021 USPSTF eligibility criteria disproportionately exclude many younger Black individuals with lung cancer, primarily because they have too few smoking pack‐years.
In Vivo Bioluminescence Imaging of Tumor Progression in the Lewis Lung Carcinoma Orthotopic Mouse Model: A Comparison Between the Tail Vein Injection and Intranasal Instillation Methods
Authors: Yamada‐Hara Miki , Takahashi Naoki , Byun Ji Won , Zeng Liping , Wang Zhihe , Tanaka Arisachi , Malakoutikhah Zahra , Hayashi Tomoko , Webster Nicholas J. G. , Raz Eyal , Bertin Samuel 
Published: December 2024

AbstractMetastasis remains a leading cause of cancer‐related mortality, yet its study has been constrained by the lack of reliable animal models that faithfully replicate this complex process. Syngeneic models for studying lung cancer metastasis are limited, with the Lewis lung carcinoma (LLC) model being the most commonly employed. The conventional LLC orthotopic model involves injecting LLC cells intravenously (i.v.) via the tail vein into syngeneic C57BL/6 mice. However, this model has significant drawbacks, such as tumor development in multiple anatomical sites, incomplete lung tumor penetrance, and challenges in monitoring lung tumor growth. This article highlights the advantages of using luciferase‐expressing LLC cells combined with bioluminescence imaging (BLI) to quantify tumor progression in live animals. We demonstrate that both white‐ and black‐furred C57BL/6 mice can be used for BLI. Finally, we propose that intranasal (i.n.) instillation of LLC cells offers a valuable alternative to the traditional i.v. tail vein injection method, particularly for its simplicity and improved reproducibility. Although the LLC i.n. model does not recapitulate the metastasis process via the blood vascular route, it is an effective model for studying tumor seeding within the lungs and is particularly useful for analyzing the impact of the lung microenvironment on tumor initiation and progression. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Lewis lung carcinoma intravenous injection methodSupport Protocol: In vivo bioluminescence imagingBasic Protocol 2: Lewis lung carcinoma intranasal instillation method
Boosting Photocatalytic Selective Oxidation of 5‐Hydroxymethylfurfural to 2,5‐Diformylfuran via Atomically Bridged Indium in In‐SnS2
Authors: Putta Rangapppa Akkammagari , Xue Wenhua , Chowdhury Anirban , Liu Yixuan , Lee Jong‐Min , Zhao Jun 
Published: December 2024

AbstractThe photocatalytic conversion of biomass‐based platform molecules, such as 5‐hydroxymethylfurfural (HMF), holds significant importance for the utilization of biomass resources. This study focuses on the unique ability of atomically bridged indium (In) atoms that encourages inactive SnS2 surface and steer the selective HMF oxidation process under solar light. Experimental results suggest that In confined SnS2 structure provides not only favorable sites and electronic structures for the synergistic activation of HMF/O2 but also benefit in charge carrier dynamics, thus influencing the overall activity and selectivity of the SnS2 catalyst. In addition, in‐situ spectroscopy and density functional theory (DFT) analysis uncovered the multifunctional role of In sites in promoting the key steps of the catalytic process, from reactive oxygen species (ROS) generation to regulated adsorption/activation of *HMF which serves as the rate limiting step of the overall HMF oxidation process. Consequently, the optimized In‐SnS2‐0.75 photocatalyst demonstrated excellent photo oxidation performance, reaching a high HMF conversion efficiency, yield, and selectivity of 91.2, 73 and 80 % respectively, in just two hours of the reaction. This study highlights the strategic approach of rationally designed catalytic systems in order to tune the ROS and the product distribution of the HMF oxidation process.
Application of Human Papillomavirus‐DNA Test on Salivary Gland Fine Needle Aspiration Cytology Samples Confirms the Absence of the Virus in Primary Neoplasms and Demonstrates for the First Time Its Presence in Salivary Intraglandular Cysts
Authors: Cozzolino Immacolata , Ronchi Andrea , Montella Marco , Ruggiero Raffaella , Cappiello Rosaria , Savarese Giovanni , Colella Giuseppe , Franco Renato 
Published: December 2024

ABSTRACTBackgroundThe correlation between Human Papillomavirus (HPV) and salivary gland neoplasms is still controversial. Data in the literature are conflicting, reporting the presence of the HPV‐DNA in a significant percentage of cases or none. We investigated the presence of HPV in a series of salivary gland neoplasms using fine needle aspiration cytology (FNAC) samples to explore its potential oncogenic role in salivary gland tumor development.MethodsThe study included 66 salivary gland lesions from 65 patients. For all cases, residual cytological material in the needle hub, once direct smears were obtained, was fixed by rinsing the needle in Cytolyt hemolytic and preservative solution (Hologic Inc. Marlborough, MA 01752 USA). The samples fixed in the Cytolyt hemolytic and preservative solution (Hologic Inc. Marlborough, MA 01752 USA) were centrifuged at 252 g, then the sediment was transferred to the Preservcyt solution and used for the detection of HPV‐DNA.ResultsWe found evidence of the presence of HPV in two salivary intraglandular cysts lined by squamous cell epithelium. Furthermore, we also found HPV in three metastatic oropharyngeal squamous cell carcinomas (SCC) located in the parotid gland. Regarding primary salivary gland tumors, the HPV test produced negative results in all cases.ConclusionHPV testing produced negative results in all primary salivary gland tumors, failing to confirm the potential involvement of HPV infection in the pathogenesis of salivary gland tumors. Instead, the presence of HPV DNA in samples of salivary intraglandular cysts, never reported before, may be an interesting fact, which however requires further evaluation.
Heme Oxygenase‐1 Overexpression Activates the IRF1/DRP1 Signaling Pathway to Promote M2‐Type Polarization of Spinal Cord Microglia
Authors: Lin Wenping , Cai Ziming , Liang Jinzhu , Miao Ping , Ruan Ye , Li Pian , Lin Shuhui , Tian He , Yu Qinghe , He Xu 
Published: December 2024

ABSTRACTMicroglia‐mediated neuroinflammatory responses have a critical function in the spinal cord injury (SCI) mechanism, and targeted modulation of microglia activity has emerged as a new therapeutic strategy for SCI. Heme oxygenase 1(HO‐1) regulates the close dynamic crosstalk between oxidative stress and inflammatory responses. This investigation aimed to study the molecular pathways by which HO‐1 regulates the inflammatory response of microglia. We cultivated primary rat spinal cord microglia and BV2 cell lines and used lipopolysaccharide (LPS) to stimulate microglia to establish an in vitro model. The adeno‐associated virus (AAV) was used to induce HO‐1 overexpression to observe the effects of HO‐1 overexpression on microglia survival, morphological changes, microglia activation, inflammatory cytokines secretion, mitochondrial dynamics, and nucleotide‐binding oligomerization domain‐like receptor protein (NLRP3) inflammatory complex and nuclear factor‐κB (NF‐κB) signaling pathways. It was found that HO‐1 overexpression was successfully induced using an AAV on microglia in vitro. HO‐1 overexpression increased microglia survival and reduced microglia apoptosis in the inflammatory microenvironment. Overexpressed HO‐1 inhibited microglia M1‐type polarization, downregulated the NF‐κB signaling pathway, inhibited NLRP3 inflammatory complex activation, and reduced the secretion of inflammatory factors. Overexpressed HO‐1 maintained the stability of mitochondrial dynamics and inhibited excessive mitochondrial cleavage. Further experiments showed that overexpression of HO‐1 activated the interferon regulatory factor 1 (IRF1)/dynamin‐related protein 1 (DRP1) signaling pathway, thereby promoting microglia M2‐type polarization and improving neuronal survival. This study demonstrates that HO‐1 activates the IRF1/DRP1 axis, promoting M2 polarization in microglia and attenuating neuroinflammation by suppressing the NF‐κB signaling pathway. These outcomes offer new visions and important clues for effectively managing SCI in the clinic.
The Incremental Growth of Data Infrastructure in Ecology (1980–2020)
Authors: Baker Karen S. , Millerand Florence 
Published: December 2024

ABSTRACTAfter decades of growth, a research community's network information system and data repository were transformed to become a national data management office and a major element of data infrastructure for ecology and the environmental sciences. Developing functional data infrastructures is key to the support of ongoing Open Science and Open Data efforts. This example of data infrastructure growth contrasts with the top‐down development typical of many digital initiatives. The trajectory of this network information system evolved within a collaborative, long‐term ecological research community. This particular community is funded to conduct ecological research while collective data management is also carried out across its geographically dispersed study sites. From this longitudinal ethnography, we describe an Incremental Growth Model that includes a sequence of six relatively stable phases where each phase is initiated by a rapid response to a major pivotal event. Exploring these phases and the roles of data workers provides insight into major characteristics of digital growth. Further, a transformation in assumptions about data management is reported for each phase. Investigating the growth of a community information system over four decades as it becomes data infrastructure reveals details of its social, technical, and institutional dynamics. In addition to addressing how digital data infrastructure characteristics change, this study also considers when the growth of data infrastructure begins.
The Environmental Light Characteristics of Forest Under Different Logging Regimes
Authors: Coetzee Bernard W. T. , van Zyl Layla 
Published: December 2024

ABSTRACTLight is a fundamental attribute and key abiotic driver in forest ecosystems. Although the ecological effects of light itself is well studied, capturing the complex parameters that constitute the whole light environment remain an intricate research endeavor. Here, we apply the newly introduced environmental light field (ELF) technique in Kibale National Park, Uganda. We captured whole light scenes with repeat photography and processed it to measure both the spectral composition of light in the red‐green‐blue range, as well as its variation, or “contrast‐span”, using the newly introduced International System of Units (SI); “lit”. We compare across major and globally common utilized forest types—primary, secondary, and selectively logged areas, as well as a completely cleared area as a control. We find that the ELF system is able to effectively capture key aspects of the local light environment across the range of forest types. The distribution of light intensity and its spectral composition across our study is hardly uniform, with primary forest and a clearing showing two orders of magnitude difference in light. Blue light predominates the sky areas of the clearing, indicating the Rayleigh scattering of sunlight in the atmosphere. In general, radiance decrease with increasing intactness of the forest, and selectively logged and primary forest show the most similar environmental light characteristics. Owing to its ability to capture fine scale variations in light across elevation gradients, their spectral characteristics, as well as their intensities, the ELF system should become a useful tool in better quantifying light in ecology. In particular, we discuss its potential use in restoration ecology.
Duration of sodium zirconium cyclosilicate treatment and continuation of RAASi therapy after a hyperkalaemia episode
Authors: Pollack Charles V. , Arroyo David , Kanda Eiichiro , Lázaro Ignacio José Sánchez , Lesén Eva , Franzén Stefan , Gray Christen M. , Lipińska Anna , Murohara Toyoaki , Rastogi Anjay 
Published: December 2024

AbstractAimsRenin–angiotensin–aldosterone system inhibitors (RAASi) are foundational in the management of heart failure (HF) and chronic kidney disease (CKD) but increase the risk of hyperkalaemia. To facilitate continuation of RAASi therapy, guidelines suggest managing hyperkalaemia using newer potassium binders such as sodium zirconium cyclosilicate (SZC). This observational study describes the likelihood of continued RAASi therapy by duration of SZC treatment.MethodsThe study population included non‐dialysis‐dependent adults diagnosed with HF and/or CKD who initiated outpatient SZC treatment while receiving RAASi therapy. Patients were identified using healthcare registers and claims data from the United States, Japan and Spain. SZC treatment duration was described using the Kaplan–Meier method. Hernán's clone–censor–weight (CCW) approach, using principles of trial emulation, was applied to evaluate the likelihood of continued RAASi therapy at specific time points by distinct SZC treatment durations, using a weighted Kaplan–Meier method and Z‐tests.ResultsThe study included 7980 patients, from the United States (n = 4849), Japan (n = 2759) and Spain (n = 372). Across the three countries, mean patient age was 73.1–75.0 years, 53.2%–66.4% of patients were male, 39.0%–75.0% had HF and 76.9%–95.3% had CKD. Between Days 30 and 120, the percentage of patients remaining on SZC treatment decreased from 36.5% to 12.8% in the United States, from 63.8% to 33.7% in Japan, and from 81.9% to 65.0% in Spain. In the United States, patients who continued SZC treatment beyond 30 days had a higher likelihood of continuing RAASi therapy for up to 90 days (P < 0.001), and continuing SZC treatment beyond 60 days was superior for continuing RAASi therapy for up to 6 months (P < 0.001), versus earlier SZC discontinuation. At 120 days, the likelihood of remaining on RAASi therapy was 69%–70% for SZC treatment durations exceeding 60 days, versus 59% for shorter durations (1–30 days) (P < 0.001). Similar patterns were observed in Japan. At 120 days, the likelihood of remaining on RAASi therapy was 86%–87% for SZC treatment durations exceeding 90 days, versus 82% for shorter SZC treatment durations (1–30 days) (P < 0.05). The CCW analyses were not deemed feasible in the Spanish dataset due to the smaller initial sample size and few patients having a relatively short SZC treatment duration.ConclusionsPatients with longer SZC treatment experience sustained protection against RAASi discontinuation, and the risk of RAASi discontinuation resumes once SZC is discontinued.
Hydrogenation of 1‐Octene Using Homogenous Pyrazolyl Nickel(II) Complexes as Pre‐Catalysts: Experimental and Computational Studies
Authors: Olaoye Oluwasegun E. , Oyetunji Olayinka A. , Demissie Taye B. , Darkwa James 
Published: December 2024

AbstractWe present the synthesis, characterization, and catalytic activities of four bis(pyrazolyl)nickel(II) complexes (1–4) in the hydrogenation of 1‐octene. Characterization techniques, such as Fourier‐transform infrared spectroscopy, electrospray ionization‐mass spectrometry, elemental analysis, single‐crystal X‐ray diffraction, and density functional theory calculations (DFT) were employed. These complexes exhibited significant catalytic activities for olefin hydrogenation under mild experimental conditions. The tert‐butyl‐substituted bis(pyrazolyl)nickel(II) complex 2 demonstrated the highest conversion of 1‐octene to n‐octane. The catalyst's recyclability was demonstrated over multiple cycles with minimal activity loss. Catalytic evaluations involved optimizing parameters such as temperature, pressure, and reaction time. Homogeneity tests confirmed the homogeneous nature of these catalytic systems. The reaction mechanism was studied using DFT calculations. The results demonstrate the efficacy of the nickel(II) complexes in enabling the hydrogenation of 1‐octene.