bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma
Authors: Xie Linshan , Kong Hui , Yu Jinjie , Sun Mengting , Lu Shaohua , Zhang Yong , Hu Jie , Du Fang , Lian Qiuyu , Xin Hongyi , Zhou Jian , Wang Xiangdong , Powell Charles A. , Hirsch Fred R. , Bai Chunxue , Song Yuanlin , Yin Jun , Yang Dawei 
Published: February 2024

AbstractBackgroundPatients who possess various histological subtypes of early‐stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early‐stage LUAD due to intratumour intricacy.MethodsWe included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single‐cell RNA sequencing (scRNA‐seq) was carried out on matched tumour and normal tissue. Three formalin‐fixed and paraffin‐embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP).ResultsUsing DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA‐seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = –.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD‐L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region.ConclusionsThese findings illustrate that assessing patient histological subtypes at the single‐cell level is feasible. Additionally, tumour endothelial cells that express PD‐L1 in stage IA LUAD suppress immune‐responsive CD8+ T cells.
Early investigation of a novel SI306 theranostic prodrug for glioblastoma treatment
Authors: Vagaggini Chiara , Petroni Debora , D'Agostino Ilaria , Poggialini Federica , Cavallini Chiara , Cianciusi Annarita , Salis Annalisa , D'Antona Lucia , Francesconi Valeria , Manetti Fabrizio , Damonte Gianluca , Musumeci Francesca , Menichetti Luca , Dreassi Elena , Carbone Anna , Schenone Silvia 
Published: February 2024

AbstractGlioblastoma multiforme (GBM) is one of the most aggressive malignancies with a high recurrence rate and poor prognosis. Theranostic, combining therapeutic and diagnostic approaches, arises as a successful strategy to improve patient outcomes through personalized medicine.Src is a non‐receptor tyrosine kinase (nRTK) whose involvement in GBM has been extensively demonstrated. Our previous research highlighted the effectiveness of the pyrazolo[3,4‐d]pyrimidine SI306 and its more soluble prodrug CMP1 as Src inhibitors both in in vitro and in vivo GBM models.In this scenario, we decided to develop a theranostic prodrug of SI306, ProSI‐DOTA(68Ga) 1, which was designed to target GBM cells after hydrolysis and follow‐up on the disease's progression and improve the therapy's outcome.First, the corresponding nonradioactive prodrug 2 was tested to evaluate its ADME profile and biological activity. It showed good metabolic stability, no inhibition of CYP3A4, suboptimal aqueous solubility, and slight gastrointestinal and blood‐brain barrier passive permeability. Compound 2 exhibited a drastic reduction of cell vitality after 72 h on two different GBM cell lines (GL261 and U87MG). Then, 2 was subjected to complexation with the radionuclide Gallium‐68 to give ProSI‐DOTA(68Ga) 1. The cellular uptake of 1 was evaluated on GBM cells, highlighting a slight but significant time‐dependent uptake. The data obtained from our preliminary studies reflect the physiochemical properties of 1. The use of an alternative route of administration, such as the intranasal route, could overcome the physiochemical limitations and enhance the pharmacokinetic properties of 1, paving the way for its future development.
Development and optimization of a novel environmental DNA‐based method for moor frog (Rana arvalis) monitoring and comparison with a commercial detection kit
Authors: Olli Suvi , Lampila Petri , Kvist Laura , Honka Johanna 
Published: February 2024

AbstractMoor frogs (Rana arvalis) are protected by the European Union's Habitats Directive, often making them a target for environmental impact assessments. However, moor frog detection with the traditional method using their mating calls is difficult, time‐consuming, and limited to the short mating season. Environmental DNA (eDNA)‐based methods could be beneficial in moor frog detection since moor frogs are shy and co‐occurring common frogs (R. temporaria) are morphologically similar. Additionally, eDNA‐based methods could even extend the detection period of moor frogs. We tested two different DNA isolation methods and two different eDNA detection methods, Sanger sequencing and quantitative PCR (qPCR), and compared the results to the traditional mating call survey method. In addition, we tested whether linear polyacrylamide treatment would improve eDNA detection. We sampled 27 sites in Finland, of which moor frogs were detected in 17 sites by traditional acoustic survey method, in 20 sites with Sanger sequencing‐based eDNA method, and in 21 sites with qPCR‐based eDNA method. We sampled water bodies during and 3–4 weeks after the end of the mating season. Our results show that both tested eDNA methods (Sanger sequencing and qPCR) can be used to detect moor frogs and extend the moor frog detection period by at least 3–4 weeks, but qPCR slightly outperforms Sanger sequencing. Linear polyacrylamide treatment did not improve the results. Detection probabilities were similar or higher with the eDNA‐based methods than with the traditional survey method, as moor frogs were also detected in water bodies in which mating calls were not heard. Based on our results, eDNA‐based detection methods can be highly beneficial in monitoring the presence of moor frogs and can be used to complement traditional surveys.
Distinguishing heart failure with reduced ejection fraction from heart failure with preserved ejection fraction: A phenomics approach
Authors: van Essen Bart J. , Tharshana Ganash N. , Ouwerkerk Wouter , Yeo Poh Suan Daniel , Sim David , Jaufeerally Fazlur , Ong Hean Yee , Ling Lieng Hsi , Soon Dinna Kar Nee , Lee Shao Guang Sheldon , Leong Gerard , Loh Seet Yoong , San Tan Ru , Ramachandra Chrishan J. , Hausenloy Derek J. , Liew Oi Wai , Chong Jenny , Voors Adriaan A. , Lam Carolyn S.P. , Richards A. Mark , Tromp Jasper 
Published: February 2024

AbstractAimPathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets.Methods and resultsWe report data from a representative subcohort of the prospective Singapore Heart Failure Outcomes and Phenotypes (SHOP), including patients with HFrEF (EF <40%, n = 217), HFpEF (EF ≥50%, n = 213), and age‐ and sex‐matched controls without HF (n = 216). We measured 92 biomarkers using a proximity extension assay and assessed cardiac structure and function in all participants using echocardiography. We used multi‐block projection to latent structure analysis to integrate clinical, echocardiographic, and biomarker variables. Candidate biomarker targets were cross‐referenced with small‐molecule and drug databases. The total cohort had a median age of 65 years (interquartile range 60–71), and 50% were women. Protein profiles strongly discriminated patients with HFrEF (area under the curve [AUC] = 0.89) and HFpEF (AUC = 0.94) from controls. Phenomics analyses identified unique druggable inflammatory markers in HFpEF from the tumour necrosis factor receptor superfamily (TNFRSF), which were positively associated with hypertension, diabetes, and increased posterior and relative wall thickness. In HFrEF, interleukin (IL)‐8 and IL‐6 were possible targets related to lower EF and worsening renal function.ConclusionWe identified pathophysiological mechanisms related to increased cardiac wall thickness parameters and potentially druggable inflammatory markers from the TNFRSF in HFpEF.
Chemical Structure Elucidation in the Development of Inorganic Drugs: Evidence from Ru‐, Au‐, As‐, and Sb‐based Medicines
Authors: Lance‐Byrne Alissa , Lindquist‐Kleissler Brent , Johnstone Timothy C. 
Published: February 2024

AbstractStructure elucidation plays a critical role across the landscape of medicinal chemistry, including medicinal inorganic chemistry. Herein, we discuss the importance of structure elucidation in drug development and then provide three vignettes that capture key instances of its relevance in the development of biologically active inorganic compounds. In the first, we describe the exploration of the biological activity of the trinuclear Ru compound called ruthenium red and the realization that this activity derived from a dinuclear impurity. We next explore the development of Au‐based antitubercular and antiarthritic drugs, which features a key step whereby ligands were discovered to bind to Au through S atoms. The third exposition traces the development of As‐based antiparasitic drugs, a key step of which was the realization that the reaction of arsenic acid and aniline does not produce an anilide of arsenic acid, as originally thought, but rather an amino arsonic acid. These case studies provide the motivation for an outlook in which the development of Sb‐based antiparasitic drugs is described. Although antileishmanial pentavalent antimonial drugs remain in widespread use to this day, their chemical structures remain unknown.
Synthesis of glycophospholipid conjugates with mono‐ and disaccharides by enzymatic transphosphatidylation
Authors: Barchan Nikolina , Adlercreutz Patrick 
Published: February 2024

AbstractPhospholipids, PLs, are interesting and highly abundant amphiphilic molecules, which self‐assemble into 3D nanostructures that have big interest as formulation excipients in, for example, pharma industry. However, the structures that are formed by naturally occurring PLs usually suffer from rigidity problems, and the nanostructures have to be modified in various ways for improved stability. One such approach is by the conjugation of saccharides to the PL head group. In this study, we investigate reaction conditions for the scalable phospholipase D–catalyzed transphosphatidylation reaction for the synthesis of glycophospholipids. Biphasic reaction systems with different solvents are compared with a purely aqueous system with PLs dispersed as vesicles. The investigations showed that use of the biphasic system containing chloroform and a glucose/phosphatidylcholine ratio of 50, in combination with carefully selected enzyme concentration and reaction time, led to an optimized process without any hydrolytic side reaction for the synthesis of phosphatidyl glucose. The reaction system was then applied to a variety of different mono‐ and disaccharides for the synthesis of a range of different glycophospholipids, resulting in yields up to 85% of phosphatidyl monosaccharides and 35% of disaccharides.Practical Application: Phospholipids and other polar lipids are of great scientific interest as formulation excipients. The chemical structures of lipids used for such applications have major impact on the properties of the self‐aggregated systems. Synthesis of new phospholipids with modified head groups can tremendously widen the portfolio of available choices of formulation excipients and make it possible to make customized formulations with the desired properties. The introduction of saccharides in the hydrophilic part of the phospholipid alters the chemistry of head group and its interaction with surrounding water in vesicle systems and should therefore have a significant effect on its formulating properties compared to natural phospholipids.
Hypervalent Iodine(III)‐Catalysis Using Sulfoxide Oxidant for the Dehydrogenative Cycloisomerization‐Arylation Reaction of 2‐Propargyl 1,3‐Dicarbonyl Compounds
Authors: Umakoshi Yuki , Tsubouchi Akira , Yoshimura Akira , Saito Akio 
Published: February 2024

AbstractWe report herein an unprecedented hypervalent iodine(III)‐catalysis using the activated sulfoxide. Since the present catalytic systems promote the dehydrogenative cycloisomerization‐arylation reaction of 2‐propargyl 1,3‐dicarbonyl compounds with aromatics, this report also provides one of the few methods for iodine(III)‐catalyzed intermolecular carbon‐carbon bond formation of aromatics.
Throwing cold water on muscle growth: A systematic review with meta‐analysis of the effects of postexercise cold water immersion on resistance training‐induced hypertrophy
Authors: Piñero Alec , Burke Ryan , Augustin Francesca , Mohan Adam E. , DeJesus Kareen , Sapuppo Max , Weisenthal Max , Coleman Max , Androulakis‐Korakakis Patroklos , Grgic Jozo , Swinton Paul A. , Schoenfeld Brad J. 
Published: February 2024

AbstractThe purpose of this paper was to systematically review the literature and perform a meta‐analysis of the existing data on the effects of postexercise cold water immersion (CWI) coupled with resistance training (RT) on gains in measures of muscle growth. To locate relevant studies, we comprehensively searched the PubMed/MEDLINE, Scopus, and Web of Science databases. A total of 8 studies met the inclusion criteria; all investigated CWI as the means of cold application. Preliminary analyses conducted on noncontrolled effect sizes provided strong evidence of hypertrophic adaptations with RT that were likely to be at least small in magnitude (SMD0.5 = 0.36 [95% CrI: 0.10–0.61]; p (>0) = 0.995, p (>0.1) = 0.977). In contrast, noncontrolled effect sizes provided some evidence of hypertrophic adaptations with CWI + RT that were likely to be small to negligible in magnitude (SMD0.5 = 0.14 [95% CrI: −0.08–0.36]; p (>0) = 0.906, p (>0.1) = 0.68). The primary analysis conducted on comparative effect sizes provided some evidence of greater relative hypertrophic adaptations with RT compared to CWI + RT (cSMD0.5 = −0.22 [95% CrI: −0.47 to 0.04]) with differences likely to be greater than zero (p (<0) = 0.957) and of at least a small magnitude of effect (p (<−0.1) = 0.834). Meta‐regression did not indicate a potential moderation effect of training status ( = −0.10 [95% CrI: −0.65 to 0.43] p < 0) = 0.653). In conclusion, based on the current data, the application of CWI immediately following bouts of RT may attenuate hypertrophic changes. Given the overall relatively fair to poor quality of the studies examined, the results of the current study should be interpreted with some caution.
Can redistributive policies promote reconciliation beyond its scope? The impact of inequality reduction programs on peacebuilding in Colombia
Authors: Rincón‐Unigarro Camilo , Joel‐Bustos Angie , Pérez‐Farfán Katherine , Velosa‐Campos Astrid , López‐López Wilson 
Published: February 2024

AbstractTransitional justice jurisdictions aim to promote reconciliation. Although previous research focuses on truth commissions, the reconciliatory role of redistributive justice is less clear. This article investigated the association of conditional cash transfers and victims’ reparation with demand for redistribution, belief in forgiveness, support for the peace process and community participation in Colombia. We analysed three nationally representative samples of the Latin American Public Opinion Project (LAPOP) surveys in 2011 (Study 1; n = 1503), 2016 (Study 2; n = 1563) and 2018 (Study 3; n = 1663). Consistently across studies, conditional cash transfers (and not victim reparation programs) predicted higher community participation, with little effect on other reconciliation indicators. Further, redistribution is indirectly associated with other reconciliation indicators through community participation, supporting the observation that transitional justice relates to reconciliation when it satisfies a need for agency and empowerment. We discuss how the null effects of the victim reparation program suggesting context‐specific constraints.
Current progress in quantifying and monitoring instream large wood supply and transfer in rivers
Authors: Ruiz‐Villanueva Virginia , Aarnink Janbert , Ghaffarian Hossein , Gibaja del Hoyo Javier , Finch Bryce , Hortobágyi Borbála , Vuaridel Marceline , Piégay Hervé 
Published: February 2024

AbstractLarge wood drives both the form and function of gravel‐bed rivers draining forested basins. Previously overlooked benefits of wood in rivers are now widely recognized. Together with flow and sediment regimes, the wood regime controls rivers' physical and ecological integrity. Yet large quantities of wood transported during floods can pose additional hazards, potentially damaging infrastructures like bridges or dams and exacerbating flooding. However, unlike the water and sediment regimes intensively studied over the past decades, the instream wood regime or budgeting has been only recently defined and thus is still rarely quantified. The instream wood budget describes the cascading processes from supply or recruitment, entrainment, and transport to deposition, storage and decay (i.e., fragmentation or decomposition). These processes show high spatial and temporal variability but can be characterized by magnitude, frequency, timing, duration and mode. Instream wood budgeting is challenging, primarily because of the lack of observations, monitoring stations, and standardized protocols to acquire data. This contribution reviews the most recent advances to quantify the different instream wood budget components, notably the wood supply, and transfer. Case studies showing applications of biogeochemistry, videography, artificial intelligence, numerical modelling or tracking illustrate the current progress. Because critical challenges remain, we identify and describe some of them and discuss how the wood in riverine sciences may develop in the future.
Improvement of MQTT semantic to minimize data flow in IoT platforms based on distributed brokers
Authors: Kamoun Karim , Hmissi Fatma , Ouni Sofiane , Ouni Sonia 
Published: February 2024

AbstractMessage queuing telemetry transport (MQTT) is an application layer protocol that enables effective device communication in the Internet of Things (IoT). MQTT operates according to a publish‐subscribe model, where a broker receives messages from the publishers and then forwards them to the subscribers. However, existing cloud‐based MQTT brokers lead to network bottlenecks due to the large number of devices that interact with them. Therefore, mist computing is involved, where the MQTT brokers are deployed closer to the IoT devices and the workload is distributed across multiple brokers. Nevertheless, the distributed mist‐based MQTT architecture introduces serious issues caused by the massive volume of flow exchanged by IoT devices. In this article, we introduce MQTT‐SD to address these issues. MQTT‐SD enhances MQTT protocol syntax with fusion semantic aggregation. It accomplishes MQTT topic fusion on the MQTT broker side with consideration of topics' distribution. We carried out extensive simulation and emulation to demonstrate MQTT‐SD efficacy. The results show that MQTT‐SD reduces MQTT flow and has the lowest traffic load compared to MQTT+ and MQTT‐MFA.
Bias‐adjusted and downscaled humidex projections for heat preparedness and adaptation in Canada
Authors: Chow Kenneth Kin Cheung , Sankaré Housseyni , Diaconescu Emilia P. , Murdock Trevor Q. , Cannon Alex J. 
Published: February 2024

AbstractTo help with preparedness efforts of Canadian public health and safety systems for adaptation to climate change, the humidity index (humidex) and three threshold‐based humidex indices (annual number of days with humidex greater than 30, 35 and 40) were computed for a multi‐model ensemble of climate change projections, over Canada. The ensemble consists of one run from each 19 Coupled Model Intercomparison Project Phase 6 (CMIP6) global climate models and offers historical simulations starting in 1950 and future projections out to 2100 following Shared Socioeconomic Pathways (SSPs): SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5. Each ensemble member was bias‐adjusted and statistically downscaled using the Multivariate bias correction—N‐dimensional probability density function transform (MBCn) with hourly data from ERA5‐Land as the target dataset and following a method proposed by Diaconescu et al. (2023; International Journal of Climatology, 43, 837) to calculate humidex from daily climate model outputs. This paper details the steps for data production including evaluation of the target historical gridded data and selection of downscaling method and presents some of the resulting humidex projections at the end of the century.
Revealing genomic heterogeneity and commonality: A penalized integrative analysis approach accounting for the adjacency structure of measurements
Authors: Wang Xindi , Jiang Yu , Sun Yifan 
Published: February 2024

AbstractAdvancements in high‐throughput genomic technologies have revolutionized the field of disease biomarker identification by providing large‐scale genomic data. There is an increasing focus on understanding the relationships among diverse patient groups with distinct disease subtypes and characteristics. Complex diseases exhibit both heterogeneity and shared genomic factors, making it essential to investigate these patterns to accurately detect markers and comprehensively understand the diseases. Integrative analysis has emerged as a promising approach to address this challenge. However, existing studies have been limited by ignoring the adjacency structure of genomic measurements, such as single nucleotide polymorphisms (SNPs) and DNA methylations. In this study, we propose a structured integrative analysis method that incorporates a spline type penalty to accommodate this adjacency structure. We utilize a fused lasso type penalty to identify both heterogeneity and commonality across the groups. Extensive simulations demonstrate its superiority compared to several direct competing methods. The analysis of The Cancer Genome Atlas melanoma data with DNA methylation measurements and GENEVA diabetes data with SNP measurements exhibit that the proposed analysis lead to meaningful findings with better prediction performance and higher selection stability.