bluuebunny/crossref_metadata_2025_split huggingface dataset:
Search for germline gene variants in colorectal cancer families presenting with multiple primary colorectal cancers
Authors: Försti Asta , Ambrozkiewicz Filip , Marciniak Magdalena , Lubinski Jan , Hemminki Kari 
Published: December 2024

AbstractA double primary colorectal cancer (CRC) in a familial setting signals a high risk of CRC. In order to identify novel CRC susceptibility genes, we whole‐exome sequenced germline DNA from nine persons with a double primary CRC and a family history of CRC. The detected variants were processed by bioinformatics filtering and prioritization, including STRING protein–protein interaction and pathway analysis. A total of 150 missense, 19 stop‐gain, 22 frameshift and 13 canonical splice site variants fulfilled our filtering criteria. The STRING analysis identified 20 DNA repair/cell cycle proteins as the main cluster, related to genes CHEK2, EXO1, FAAP24, FANCI, MCPH1, POLL, PRC1, RECQL, RECQL5, RRM2, SHCBP1, SMC2, XRCC1, in addition to CDK18, ENDOV, ZW10 and the known mismatch repair genes. Another STRING network included extracellular matrix genes and TGFβ signaling genes. In the nine whole‐exome sequenced patients, eight harbored at least two candidate DNA repair/cell cycle/TGFβ signaling gene variants. The number of families is too small to provide evidence for individual variants but, considering the known role of DNA repair/cell cycle genes in CRC, the clustering of multiple deleterious variants in the present families suggests that these, perhaps jointly, contributed to CRC development in these families.
An Experimental Insight Into the Role of Agomelatine in Renal Ischemia/Reperfusion Injury
Authors: Aykora Damla , Bahar Mehmet Refik , Tanbek Kevser , Öztürk Dilara Altay , Karaca Elif , Sandal Süleyman , Tekin Suat 
Published: December 2024

ABSTRACTAcute kidney injury (AKI) is one of the leading causes of chronic kidney disease and accounts for 50%–75% of mortality following renal pathologies or organ transplantation. Ischemia‒reperfusion injury (IRI) involves an interrupted blood supply to organs and the kidney; IRI exacerbates AKI development. Owing to several pharmacological treatment methods, AKI still has a poor prognosis, and novel therapeutic options are needed. Agomelatine (AGM) is a melatonin receptor agonist (MT1 and MT2) with increased bioavailability and lipophilicity. In this study, we aimed to investigate the antioxidant and anti‐inflammatory effects of AGM in experimental renal IRI via long‐term and short‐term applications. Sixty male Sprague–Dawley rats were randomly divided into six groups (n = 10): the control, I/R, AGM20S, AGM40S, AGM20L, and AGM40L groups. Following the establishment of the renal IRI model, the rats received agomelatine at 20 and 40 mg/kg orally, and agomelatine solvent (hydroxyethylcellulose) was used as a vehicle. At the end of the experiment, blood samples and renal tissues were harvested for histopathological and biochemical analysis. Urea, creatinine, tumor necrosis factor (TNF‐α), and interleukin‐1 beta (IL‐1β) levels were measured in blood serum samples. Malondialdehyde (MDA) levels and increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and total glutathione (GSH) levels were measured in renal tissue supernatants. Our biochemical results indicated that AGM reduced creatinine, TNF‐α, IL‐1β, and malondialdehyde levels and increased SOD, CAT, GSHPx, and total GSH levels. Agolematine reduced infiltration, intratubular hemorrhage, and intratubular cast formation histopathologically. Our results suggest that AGM could be a potential therapeutic adjuvant agent for ischemia‒reperfusion injury in the kidney and several other organs.
In Silico Hybridization and Molecular Dynamics Simulations for the Identification of Candidate Human MicroRNAs for Inhibition of Virulent Proteins' Expression in Staphylococcus aureus
Authors: Tiwari Harshita , Saha Subhadip , Ghosh Monidipa 
Published: December 2024

ABSTRACTStaphylococcus aureus is a major threat to human health, causing infections that range in severity from moderate to fatal. The rising rates of antibiotic resistance highlight the critical need for new therapeutic techniques to combat this infection. It has been recently discovered that microRNAs (miRNAs) are essential for cross‐kingdom communication, especially when it comes to host‐pathogen interactions. It has been demonstrated that these short noncoding RNAs control gene expression in the gut microbiota, maintaining homeostasis; dysbiosis in this system has been linked to several diseases, including cancer. Our research attempts to use this understanding to target specific bacterial species and prevent severe diseases. In particular, we look for putative human miRNAs that can attach to virulent bacterial proteins' mRNA and prevent them from being expressed. In‐silico hybridization experiments were performed between 100 human miRNA sequences with varied expression levels in gram‐positive bacterial infections and five virulence factor genes. In addition, these miRNAs' binding properties were investigated using molecular dynamics (MD) simulations. Our findings demonstrate that human miRNAs can target and inhibit the expression of bacterial virulent genes, thereby opening up new paths for developing innovative miRNA‐based therapeutics. The implementation of MD simulations in our study not only improves the validity of our findings but also proposes a new method for constructing miRNA‐based therapies against life‐threatening bacterial infections.
Preclinical and Clinical Pharmacokinetics of JNJ‐75220795, an siRNA Therapeutic Targeting PNPLA3, for Metabolic Dysfunction‐Associated Steatohepatitis
Authors: Jeon Jae Yoon , Ayyar Vivaswath S. , Ouchi Shohei , Fabbrini Elisa , Koshkina Anastasiya , Prusakiewicz Jeffery J. , Dallas Jed , Yang Txheng , Jian Wenying , Kang Lijuan , Cofsky Korin , Rady Brian , Tamamura Ryo , Saito Yuki , Yamashita Aimi , Vaughan Tamisha , Wendel Susan , Makimura Hideo , Csonka Dénes , Goyal Navin 
Published: December 2024

AbstractJNJ‐75220795 or ARO‐PNPLA3 is an investigational small interfering ribonucleic acid agent conjugated with N‐acetyl‐d‐galactosamine that targets the PNPLA3 gene, currently being developed for metabolic dysfunction‐associated steatohepatitis (MASH). This study evaluated the pharmacokinetics (PK) profile of single subcutaneous doses of JNJ‐75220795 in preclinical species as well as in human subjects with homozygous or heterozygous PNPLA3 I148M mutation in two phase 1 studies—a first‐in‐human study in the United States and a first‐in‐Japanese study in Japan. Preclinical PK in rats and non‐human primates (NHP) showed a rapid systemic absorption and elimination following single subcutaneous doses. JNJ‐75220795 was predominantly distributed to the liver with peak liver concentrations reached at 4 h and still detectable at 672 and 336 h in rats and NHPs, respectively, with an apparent liver‐to‐plasma area under the curve (AUC) ratio of 2800 in rats. Consistent with the preclinical findings, clinical PK showed rapid systemic absorption and clearance in humans with median peak concentrations at 3.0–9.0 h and mean short half‐life of 3.4–6.2 h. Plasma PK exposure parameters including Cmax and AUC increased approximately dose proportionally. Kidney had the second highest tissue exposure following the liver in rats. Renal excretion was a significant but minor elimination pathway as approximately 15%–25% of the administered dose was recovered in urine. Based on the overall data, JNJ‐75220795 was primarily localized to the liver and exhibited sustained hepatic exposures, which confer prolonged pharmacodynamic effects in the target organ. The favorable PK profiles of single subcutaneous doses observed in the phase 1 studies support continued clinical development of JNJ‐75220795 for the treatment of MASH.
Extractive rectification using DES for benzene‐cyclohexane‐cyclohexene ternary azeotropic system
Authors: Haiou Wang , Yang Xu , Weihe Sang , Hao Li , Jing Fang 
Published: December 2024

AbstractBACKGROUNDBenzene, cyclohexane, and cyclohexene are ternary azeotropic systems, which cannot achieve high‐purity separation by ordinary distillation, but this issue can be solved by extractive distillation. Deep Eutectic Solvents (DES) is a ‘green solvent’ that has emerged in recent years and is often used as an extractant.RESULTSIn this study, the COSMO‐SAC solvation model was used to calculate the infinite dilution activity coefficients (γ∞) of DES with different compositions to screen suitable DES, and the effect was demonstrated by vapor–liquid equilibrium experiment (VLE). In addition, the effect of intermolecular interactions was explored in this study by means of independent gradient (IGM) equivalence plot, and process simulations were carried out by means of Aspen Plus software.CONCLUSIONVLE experiments showed that the combination of DES extractants tetrabutylphosphonium bromide: levulinic acid (1:4) and tetrabutylammonium bromide: cyclobutyl sulfone (1:4) could break the azeotropic relationship of benzene, cyclohexane, and cyclohexene ternary systems. In addition, using Aspen process simulation to compare the screened DES extractant with the industrially used dimethylacetamide (DMAC) extractant, the use of the screened DES extractant was able to reduce the condenser and reboiler energy consumption by 14.93%. © 2024 Society of Chemical Industry (SCI).
Selective Electrophile‐Promoted Cyclization Reactions of Lapachol and Evaluation of Bioactive Naphthoquinones Against Cancer Cell Lines
Authors: Omdim Irene Nadege , Eyong Kenneth Oben , Ouahouo Blandine Marlysse Wache , Ketsemen Herve Landry , Werner Thomas , Kamdem Michael Hermann K. , Ndinteh Derek Tantoh , Folefoc Gabriel Ngosong , Rajkumar Abhinav , Morales Kayla , Taube Joseph , Baskaran Sundarababu 
Published: December 2024

ABSTRACTCyclic ether‐fused tricyclic naphthoquinones are major pharmacophores because of their biological activities. The methodology of construction is either by inter or intra‐molecular cyclization of functionalized naphthoquinones. This reaction includes a wide range of reagents from classical Brønsted to Lewis acids. The choice of appropriate reagent and reaction conditions against the substrate is the key to accomplishing the regio‐ and/or stereo‐selective synthesis of these compounds, though it seems difficult at first glance to decide how because numerous numbers of actual examples have been presented. To have a deeper insight into the mechanism of cyclization under acid conditions, lapachol 1 was subjected to electrophilic entities: Brønsted acids (H2SO4, HCl, H3PO4, HNO3, HCOOH, CH3COOH, HOOCCH2COOH), Lewis acids (AlCl3, FeCl3, ZnCl2) nitrogenous cations (NO+, NO2+), carbocation (CH3CO+), neutral polarized molecules (CH3COCl, CH3COOCH3), neutral polarizable molecules (Br2, I2), oxidant promoted cyclization (DDQ, CAN, Peroxides), and reaction conditions. A series of Naphthoquinones based on the Isoprenyl‐1,4‐naphthoquinone (Lapachol), naphtho[1,2‐b]furan‐4,5‐dione (nor β‐lapachone), naphtho[2,3‐b]pyran‐5,10‐dione (α‐lapachone), naphtho[1,2‐b]pyran‐5,6‐dione (β‐lapachone), and naphtho[2,3‐b]furan‐4,9‐dione (2‐acetyl furonaphthoquinone) skeletons were selectively synthesized. By looking at our result, there are characteristic trends of cyclized adducts depending on which reagents were used. The synthesized compounds were evaluated for their biological activity against the MDA‐MB‐231 breast cancer, HT‐29 MTX colon cancer, and non‐transformed mammary epithelial cell lines at concentrations of 1 μM, 10 μM, and 100 μM. The result indicated that lapachol and β‐lapachone skeletons were the most active at 10 μM and 100 μM especially 3‐hydroxy‐β‐lapachone 8 with interesting growth stimulatory effect on cancer cell lines, but not the non‐transformed cells.
Synthesis of Photochromic Lactone‐Fused Naphthopyrans With Extended Visible Light Absorption
Authors: Ferreira Nuno , Sousa Céu M. , Coelho Paulo J. 
Published: December 2024

ABSTRACTThe synthesis of new photochromic lactone‐fused naphthopyrans substituted with arylethenyl groups is discussed. Brief exposure of solutions of these colorless compounds to the UV light results in the generation of intense hues, which spontaneously return to the uncolored state within seconds after removing the light source. As anticipated, introducing the ethenyl bonds caused a bathochromic shift in the absorption spectrum of the opened colored photoisomers, however, due to non‐uniform absorption across the visible spectrum, the perceived color ranged from red to brownish‐red.
Ecological Restoration Enhances the Stability and Associated Organic Carbon of Soil Aggregates in a Tibetan Alpine Meadow
Authors: Ma Zhiwen , Liu Xiang , Qin Wenping , Wang Shengzhong 
Published: December 2024

ABSTRACTFencing and reseeding are two widely implemented ecological restoration strategies aimed at rehabilitating degraded grasslands globally. However, their effects on soil aggregates have been insufficiently explored. Employing the space‐for‐time substitution approach, we collected intact soils from a degraded alpine meadow, a fenced alpine meadow (natural restoration), a reseeded alpine meadow (interventional restoration), and an undegraded alpine meadow on the eastern Tibetan Plateau. Our main objective was to assess how the composition, stability, and associated organic carbon content of soil water‐stable aggregates responded to a 12‐year restoration effort in degraded alpine meadows. The results revealed that both restoration measures enhanced plant biomass, the levels of soil carbon, nitrogen, and phosphorus, as well as the concentrations of microbial phospholipid fatty acids. In contrast, these measures had a minimal effect on soil bulk density and glomalin‐related soil protein, while causing a reduction in soil pH. Post‐restoration, the mass proportion of macroaggregates increased notably by 66.45%–71.18%, whereas that of microaggregates and silt‐clay particles exhibited decreasing trends. The mean weight diameter and geometric mean diameter of the aggregates also significantly enhanced following restoration, indicating improvements in soil structural health and stability. However, the restored paddocks still showed lower aggregate stability than the undegraded paddock, suggesting that a longer restoration period may be required to fully recover the degraded soil structure. The aggregate‐associated organic carbon content significantly increased after reseeding but showed a negligible response to fencing alone. Nevertheless, both restoration measures improved the organic carbon stock within macroaggregates and its contribution to soil total organic carbon. Soil pH, total nitrogen content, and plant biomass were identified as key factors influencing the composition and associated organic carbon content of aggregates during restoration. Our findings indicate that ecological restoration enhances the stability and associated organic carbon accumulation of soil aggregates, primarily by promoting the formation of macroaggregates in degraded alpine meadows on the Tibetan Plateau.
A neural network to create super‐resolution MR from multiple 2D brain scans of pediatric patients
Authors: Benitez‐Aurioles Jose , Osorio Eliana M. Vásquez , Aznar Marianne C. , Van Herk Marcel , Pan Shermaine , Sitch Peter , France Anna , Smith Ed , Davey Angela 
Published: December 2024

AbstractBackgroundHigh‐resolution (HR) 3D MR images provide detailed soft‐tissue information that is useful in assessing long‐term side‐effects after treatment in childhood cancer survivors, such as morphological changes in brain structures. However, these images require long acquisition times, so routinely acquired follow‐up images after treatment often consist of 2D low‐resolution (LR) images (with thick slices in multiple planes).PurposeIn this work, we present a super‐resolution convolutional neural network, based on previous single‐image MRI super‐resolution work, that can reconstruct a HR image from 2D LR slices in multiple planes in order to facilitate the extraction of structural biomarkers from routine scans.MethodsA multilevel densely connected super‐resolution convolutional neural network (mDCSRN) was adapted to take two perpendicular LR scans (e.g., coronal and axial) as tensors and reconstruct a 3D HR image. A training set of 90 HR T1 pediatric head scans from the Adolescent Brain Cognitive Development (ABCD) study was used, with 2D LR images simulated through a downsampling pipeline that introduces motion artifacts, blurring, and registration errors to make the LR scans more realistic to routinely acquired ones.The outputs of the model were compared against simple interpolation in two steps. First, the quality of the reconstructed HR images was assessed using the peak signal‐to‐noise ratio and structural similarity index compared to baseline. Second, the precision of structure segmentation (using the autocontouring software Limbus AI) in the reconstructed versus the baseline HR images was assessed using mean distance‐to‐agreement (mDTA) and 95% Hausdorff distance. Three datasets were used: 10 new ABCD images (dataset 1), 18 images from the Children's Brain Tumor Network (CBTN) study (dataset 2) and 6 “real‐world” follow‐up images of a pediatric head and neck cancer patient (dataset 3).ResultsThe proposed mDCSRN outperformed simple interpolation in terms of visual quality. Similarly, structure segmentations were closer to baseline images after 3D reconstruction. The mDTA improved to, on average (95% confidence interval), 0.7 (0.4–1.0) and 0.8 (0.7–0.9) mm for datasets 1 and 3 respectively, from the interpolation performance of 6.5 (3.6–9.5) and 1.2 (1.0–1.3) mm.ConclusionsWe demonstrate that deep learning methods can successfully reconstruct 3D HR images from 2D LR ones, potentially unlocking datasets for retrospective study and advancing research in the long‐term effects of pediatric cancer. Our model outperforms standard interpolation, both in perceptual quality and for autocontouring. Further work is needed to validate it for additional structural analysis tasks.
Fast Solution of Sylvester‐Structured Systems for Spatial Source Separation of the Cosmic Microwave Background
Authors: Pham Dung , Soodhalter Kirk M. , Wilson Simon 
Published: December 2024

ABSTRACTImplementation of many statistical methods for large, multivariate data sets requires one to solve a linear system that, depending on the method, is of the dimension of the number of observations or each individual data vector. This is often the limiting factor in scaling the method with data size and complexity. In this paper, we illustrate the use of Krylov subspace methods to address this issue in a statistical solution to a source separation problem in cosmology where the data size is prohibitively large for direct solution of the required system. Two distinct approaches, adapted from techniques in the literature, are described: one that uses the method of conjugate gradients directly to the Kronecker‐structured problem and another that reformulates the system as a Sylvester matrix equation. We show that both approaches produce an accurate solution within an acceptable computation time and with practical memory requirements for the data size that is currently available.
An Outdoor Walking Program for Immigrant Muslim Older Adults: A Community‐Based Participatory Intervention
Authors: Salma Jordana , Yamamoto Shelby , Salbach Nancy M , Barclay Ruth , Jones Allyson 
Published: December 2024

ABSTRACTAimTo explore Muslim immigrant older adults' experiences of a modified community‐based outdoor walking program and identify factors that facilitate or hinder program acceptance and participation.DesignAn exploratory qualitative description single‐group pilot study was designed and implemented in three phases: (1) pre‐intervention focus group interviews; (2) intervention implementation with tracking of physical activity levels using personal activity monitors; and (3) postintervention individual interviews.MethodsParticipants were recruited using a convenience sampling strategy in a mosque in Edmonton, Canada, in June 2019. After focus group discussions with participants, walking sessions were conducted for 10 weeks in a local accessible park with required amenities such as benches and restrooms. A fitness instructor delivered the weekly program that was followed by individual semistructured interviews to explore participants' satisfaction and program acceptance. Content analysis was used for qualitative data and sociodemographic, health and physical activity level (via step counts) data was documented for all participants.ResultsThirteen participants with a mean age of 66.9 years completed the program. The majority of participants led a sedentary lifestyle. Participants identified three motivators that increased program satisfaction, which were socialising with peers, having a fitness instructor, and using Fitbit activity trackers. Difficulties with transportation and lack of appropriate educational components were areas for improvement that could enhance acceptability of the program.ConclusionsThis study suggests that early incorporation of older immigrants' preferences increases acceptance of physical activity programs.ImplicationsNurses' engaging in healthy lifestyle support for older immigrants can identify the influences on positive uptake of physical activity programs in this population.ImpactImmigrant Muslim older adults lack access to evidence‐based physical activity programming that meets their cultural and religious preferences. This study provides some insights into ways to engage this population in similar programs.Patient or Public ContributionCommunity‐dwelling older adults who participated in this study completed focus groups and interviews and engaged in the 10‐week pilot intervention. Their input informed the modifications to the intervention.
A Feasibility Study on the Use of UV‐Curable Resins for Long‐Acting Monitoring Microneedle Substrates
Authors: Jia Baoling , Xia Tiandong , Wang Xiaohui , Xu Yangtao , Li Bei 
Published: December 2024

ABSTRACTMicroneedle (MN) has significant potential for transdermal glucose monitoring. However, challenges remain in selecting suitable materials for long‐acting monitoring MN. In this study, precise solid UV‐curable resin MN patches were fabricated using a synergistic combination of the micromolding method and the UV‐curing procedure, as an alternative to the previous 3D printing. The properties of the UV‐cured resin MN patches prepared using this method were evaluated and characterized, focusing on their potential for long‐acting monitoring. The results demonstrated that the UV‐curable resin MN patches exhibited superior shape stability, very low cytotoxicity, minimal skin irritation, and a fracture force of approximately 2.289 N/needle. Following immersion in 37°C PBS for different days, the shape and mass changed negligibly, and the fracture force still reached half of the original values after 21 days. UV‐curable resin is a highly promising substrate for MN, and the study provides a new material selection strategy for long‐acting monitoring of MN development.