bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new CRISPR‐mediated Apc knockout allele leads to pyloric gland adenoma‐like gastric polyps in mice with C57BL/6;FVB/N mixed background
Authors: Uzun Sarp , Özcan Özge , Gök Ayşenur , Işık Aynur , Bakır Sinem , Günel‐Özcan Ayşen , Onbaşılar İlyas , Akyol Aytekin 
Published: February 2025

AbstractAdenomatous polyposis coli (APC) mutations are the most frequently identified genetic alteration in sporadic colorectal cancer (CRC) cases, and a myriad of genetically engineered Apc‐mutant CRC mouse models have been developed using various genetic manipulation techniques. The advent of the CRISPR/Cas9 system has revolutionized the field of genetic engineering and facilitated the development of new genetically engineered mouse models. In this study, we aimed to develop a novel Apc knockout allele using the CRISPR/Cas9 system and evaluate the phenotypic effects of this new allele in two different mouse strains. For this purpose, exon 16 of mouse Apc gene was targeted with a single‐guide RNA, and the mouse carrying an Apc frameshift mutation at codon 750 (Δ750) was chosen as the founder. The mutant FVB‐ApcΔ750 mice were backcrossed with wild‐type C57BL/6 mice, and the phenotypic effects of the knockout allele were evaluated in F8‐FVB‐ApcΔ750, F4‐B6;FVB‐ApcΔ750, and F1‐B6;FVB‐ApcΔ750 by a macroscopic and microscopic examination of the gastrointestinal system. The result showed that the mean polyp number was significantly higher in F4‐BL6;FVB‐ApcΔ750 than in F8‐FVB‐ApcΔ750. Intestinal polyposis was more prominent in F4‐BL6;FVB‐ApcΔ750, whereas a higher number of colon polyps than intestinal polyps were observed in F8‐FVB‐ApcΔ750. Additionally, F1‐BL6;FVB‐ApcΔ750 mixed background mice developed gastric polyps that morphologically resembled the pyloric gland adenoma of humans. In conclusion, we developed a novel CRISPR‐mediated Apc knockout allele using two mouse strains. We showed that this allele can exert a strain‐specific effect on the phenotype of mice and can cause gastric polyp formation.
Phylogeography of the Pacific Angel Shark (Squatina californica) in the Eastern Pacific
Authors: Alfonso‐González Massiel , Galván‐Magaña Felipe , Sotil Giovanna , Domínguez Omar Domínguez , Herrera Eduardo Espinoza , Díaz‐Jaimes Píndaro 
Published: February 2025

ABSTRACTSquatina californica is a near‐threatened angel shark distributed in coastal areas of eastern Pacific. Despite its wide distribution and the conservation threats, basic knowledge of the species populations, evolutionary history and genetic diversity is scarce. In this study, we use two mitochondrial genetic markers (Control Region of mtDNA and Cytochrome C Oxidase subunit I) to explore the species' phylogeography. We included samples from locations in the Southern Californian Pacific (SCP), the Gulf of California (GC) and the Southeast Pacific (SEP). We identified three populations of the Pacific Angel Shark, corresponding to the regions SCP, GC and SEP. These results show an antitropical distribution for the species, which may be a consequence of the climatic instability of Central America during the Pliocene. Additionally, we infer that the divergence of the SCP populations from those of the GC coincided closely with the formation of the Baja California Peninsula, without current migration through the southern end of the peninsula. Finally, we detected a signal of population expansion and substructure within the GC, probably promoted by environmental heterogeneity in this area. Our results indicate that the three populations identified herein should be considered separate management units, because they exhibited independent evolutionary histories that may influence their levels of resilience to fishing pressure.
Prevalence and risk factors of stress urinary incontinence in a 2023 Japanese community health survey ‐ differences between males and females
Authors: Haga Nobuhiro , Yoshida Mikako , Mitsui Takahiko , Sekido Noritoshi , Masumori Naoya , Omae Kenji , Saito Motoaki , Kubota Yasue , Sakakibara Ryuji , Takahashi Satoru 
Published: February 2025

AbstractObjectivesThe aim of the present epidemiological study was to evaluate the sex‐related prevalence of stress urinary incontinence (SUI) and the associated factors using data from the 2023 Japan Community Health Survey.MethodsWe investigated 3097 males and 3056 females aged 20–99 years. All participants answered web‐based questionnaires on their health status and lower urinary tract symptoms. Data on the frequency of SUI, comorbidities and health‐related behaviour were extracted. The Cochran‐Armitage trend test was used to evaluate the trend between the prevalence of SUI and age. Multivariate analysis was performed using logistic regression analysis to identify factors associated with SUI.ResultsSUI was consistently observed in about 10% of individuals in their 20s and 30s, including in males. There were no age‐related differences in the prevalence of SUI in males (P = 0.55). In females, the prevalence of SUI statistically significantly increased with age (P < 0.0001). The frequency of SUI was, however, low in both sexes. Drinking habits (OR, 1.43; 95% CI, 1.10–1.87) and frequent spicy food intake (OR, 1.55; 95% CI, 1.19–2.01) were associated with SUI only in males. Age (OR, 1.36; 95% CI, 1.13–1.62), BMI (OR, 1.87; 95% CI, 1.50–2.32) and history of vaginal delivery (OR, 2.15; 95% CI, 1.77–2.63) were only associated with SUI in females.ConclusionsAlthough the frequency of SUI was low in both sexes, the correlation between the prevalence of SUI and age was different between both sexes. Female SUI might involve weakness of the pelvic floor muscle, while male SUI might be affected by health‐related behaviours.
First‐in‐human safety, tolerability, pharmacokinetics and pilot food‐effect study of the candidate antimalarial compound MMV367
Authors: Kuemmerle Andrea , Singh Nand , Gossen Denis , Janin Annick , Sharma Raman , Cahn Anthony , Gibson Rachel A. , Menakuru Somasekhara R. , Lambourne Erin , Dove Tom , Gamo Francisco‐Javier , Sanz Laura , Bestgen Benoit , Chalon Stephan 
Published: February 2025

AbstractAimTo evaluate the safety, tolerability and pharmacokinetics in healthy participants of orally administered MMV367 (GSK3772701), a novel antimalarial interfering with Plasmodium falciparum acyl coenzyme A synthetase 10/11 function.MethodsThis first‐in‐human study enrolled 47 healthy male and female participants. Part 1 was a randomised, double‐blind, placebo‐controlled study in which four sequential fasted cohorts received MMV367 single ascending doses (100, 300, 750 and 1500 mg) or placebo (six active, two placebo per cohort). Part 2 was a randomised, open‐label crossover (fed‐fasted) pilot food‐effect study of MMV367 440 mg (n = 8). In Part 3 MMV367 400 mg was administered once daily for 3 days in a single cohort (six active, two placebo).ResultsTreatment‐emergent adverse events (TEAEs) occurred in 36.8% (14/38) of participants receiving MMV367 vs 44.4% (4/9) with placebo. There were two MMV367‐related TEAEs, and no serious or severe TEAEs or clinically relevant changes in electrocardiograms, vital signs or laboratory tests. In Part 1 (fasted), maximum plasma concentrations occurred between 2.0 and 5.0 h post dose, with a geometric mean half‐life of 16.5‐18.4 h. Approximate dose proportionality was demonstrated across the dose range (100‐1500 mg). In Part 2, MMV367 relative bioavailability (fed vs fasted) was 161.4% (90% confidence interval 148.3, 175.6) for maximum observed concentration (Cmax), 130.4% (122.2, 139.1) for the area under the curve (AUC) until the last measurable concentration and 132.9% (124.1, 142.3) for AUC extrapolated to infinity. In Part 3, geometric mean day 1:3 exposure ratios (geometric co‐efficient of variability) were 1.9 (4.9%) for Cmax and 2.1 (7.7%) for the AUC for the defined interval between doses after once‐daily dosing for 3 days.ConclusionsMMV367 demonstrated acceptable safety, tolerability and pharmacokinetic profiles supporting further development as an antimalarial drug.
Inequities in the Time to Colon Cancer Diagnosis Among Individuals With Severe Psychiatric Illness
Authors: Gorodensky Jonah H. , Davis Laura , Griffiths Rebecca , Ayonrinde Oyedeji , Webber Colleen , Hanna Timothy P. , Coburn Natalie , Mahar Alyson L. 
Published: February 2025

ABSTRACTIntroductionEarly colon cancer detection is critical for improving outcomes. The diagnostic interval is a useful approach to conceptualizing time‐to‐diagnosis within the healthcare system and understanding the diagnostic journey. Adults with severe psychiatric illness (SPI) are less likely to participate in cancer screening and more likely to be diagnosed with advanced cancers. We investigated the association between having an SPI and the colon cancer diagnostic interval.MethodsWe conducted a cross‐sectional study of adults diagnosed with colon cancer in Ontario, Canada between 2007 and 2019 using administrative health data. Individuals with healthcare encounters consistent with pre‐existing major depression, schizophrenia, bipolar disorder, or other non‐organic psychotic illnesses were considered as having SPI. Individuals with an SPI‐related hospitalization were categorized as having an inpatient SPI; the rest were considered outpatient. We calculated the diagnostic interval as the number of days from first colon cancer‐related healthcare encounter to cancer diagnosis. Diagnostic pathways were assessed descriptively, including whether diagnosis was made symptomatically or with no symptom recorded. Quantile regression (stratified by symptom status) was used to quantify the association between SPI status and the diagnostic interval.ResultsWe identified 42,143 individuals with colon cancer: 40,884 with no history of mental illness, 835 with a history of outpatient SPI, and 424 with inpatient SPI. Adults with SPI were significantly more likely to be diagnosed symptomatically (inpatient: 89.9%, outpatient: 86.6%, no SPI: 80.9%, p < 0.001). Individuals with SPI experienced a significantly longer median symptomatic diagnostic interval and a similar median diagnostic interval when diagnosed with no symptom recorded, relative to those without a history of mental illness. After adjusting for covariates, the median symptomatic diagnostic interval was 48 days longer (95% CI 28, 68) among individuals with outpatient SPI and 55 days longer (95% CI 28, 82) among individuals with inpatient SPI compared to those with no SPI.ConclusionIndividuals with SPI were more likely to be diagnosed symptomatically and had longer symptomatic diagnostic intervals than those without. This study represents a first step in targeting and improving cancer diagnostic processes for individuals with SPI.
Periorbital Purpura: A Key Finding in Identifying Hematological Disorders
Authors: Ono Ryohei , Iwahana Togo , Aoki Kaoruko , Kato Hirotoshi , Kobayashi Yoshio 
Published: February 2025

ABSTRACTPeriorbital purpura, also known as “raccoon eyes,” is the key finding in identifying hematological disorders such as amyloid light chain amyloidosis, multiple myeloma, or monoclonal gammopathy of undetermined significance.
Characterization of Recombinant Unspecific Peroxygenase from Candolleomyces aberdarensis through Crystallographic and Substrate Selectivity Studies
Authors: Menés-Rubio Andrea , Fernandez-Garcia Ángela , Monterrey Dianelis T. , de Santos Patricia Gomez , Sánchez-Moreno Israel , Sanz-Aparicio Julia , Alcalde Miguel 
Published: February 2025

Fungal unspecific peroxygenases (UPOs) are remarkable biocatalysts for the selective oxygenation of non‐activated C‐H bonds. Here, we describe a crystallographic and substrate selectivity study of an UPO ortholog from Candolleomyces (Psathyrella) aberdarensis (PabUPO‐II). The recombinant enzyme produced in yeast was crystallized and complexed with a representative panel of substrates, including alkanes, fatty acids and norisoprenoids, the crystals diffracting at a resolution up to 2 Å. PabUPO‐II combines structural features of canonical long and short UPOs, presenting a hybrid heme channel and a flexible catalytic Glu212 that adopts two alternate conformations, proximal and distal to the substrates. The positioning of substrates at the heme channel in soaking experiments was complemented with a characterization of the enzymatic reactions. With alkanes and fatty acids, PabUPO‐II carried out oxygenations at ω‐2 and ω‐1 but when forcing the reaction with dicarboxylic acids, α‐ and β‐hydroxylations were detected. Reactions with the α‐ionone and α‐damascone norisoprenoids produced major oxygenations at the cyclohexene and at the vinylic aliphatic chain, respectively. Taken together, PabUPO‐II shares structural and functional similarities with both long and short UPOs, opening avenues for future engineering endeavors.
Supramolecular Polymers for Drug Delivery
Authors: Zhang Xinyue , Zhuo Jiaxin , Wang Dali , Zhu Xinyuan 
Published: February 2025

AbstractSupramolecular polymers are constructed through highly reversible and directionally specific non‐covalent interactions between monomer units. This unique feature enables supramolecular polymers to undergo controlled structural reconfiguration and functional transformation in response to external stimuli, imparting them with high environmental responsiveness and self‐healing properties. In particular, supramolecular polymers exhibit several specific advantages compared to conventional polymers, such as inherent degradability, the ease of preparation and the incorporation of functional units, and smart responsiveness to various biological stimuli. These characters make supramolecular polymers promising candidates for intelligent drug delivery systems in complex biological environments. In this review, we comprehensively summarize the latest developments and representative achievements of supramolecular polymers in drug delivery fields, focusing primarily on the design and synthesis, the properties and functionalities, and the practical applications of supramolecular polymers in small molecule drug delivery, gene therapy, and protein delivery. Finally, we highlight future research directions, focusing on multifunctionality, adaptability, and personalized therapy. We focus on recent studies that address key challenges in the field, providing rational polymer design, important properties, functionality, and understanding delivery strategies. These developments are expected to advance supramolecular polymers as new platforms of intelligent drug delivery systems, offering innovative solutions for the treatment of complex diseases.
Catalytic Aerobic Oxidation of p‐Methoxybenzyl (PMB) Ethers to Aldehydes or Ketones
Authors: Zhang Qian , Qian Hui , Ma Shengming 
Published: February 2025

AbstractAn efficient and highly selective aerobic oxidation of p‐methoxybenzyl ethers to aldehydes or ketones with Fe(NO3)3 ⋅ 9H2O and TEMPO as catalysts at 25 °C has been developed. This method is compatible with versatile functional groups: adamantyl, ether, alkynyl, and alkenyl, etc. Due to the mild nature of the reaction conditions, even the highly sensitive optically active aldehydes with an easily racemized α‐chiral center could be formed from optically active PMB ethers without racemization. Other protecting groups of hydroxyl group remained intact during the current aerobic oxidation. The catalytic protocol has been successfully applied to synthesis of (R)‐tert‐butyldimethylsilyl hept‐1‐en‐6‐yn‐4‐yl ether, which is the key intermediate for the total synthesis of natural product, (−)‐6‐O‐methylcitreoisocoumarin.
Nitrile‐tolerant Iridium‐catalysed Hydrogen Isotope Exchange
Authors: Knight Nathan M. L. , Anderson David E. , Mulrainey Paul T. , Paterson Laura C. , Lindsay David M. , Tuttle Tell , Kerr William J. 
Published: February 2025

AbstractIsotopically labelled molecules are vital tools within drug discovery and are used extensively to assess a given candidate's absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile. Related to this, transition metal‐catalyzed hydrogen isotope exchange (HIE) has become a prominent technique for the rapid and selective late‐stage installation of a deuterium or tritium label. Despite having a generally wide applicability, the current state‐of‐the‐art in this specific field is limited when particularly co‐ordinating motifs are present within a given molecule to be labelled. For example, the exceptional binding strength and sterically unencumbered nature of the nitrile functionality leads to inhibition of catalyst turnover, and has hindered the development of efficient methods for the HIE of nitrile‐containing molecules. Herein, in silico solvent binding energy parameter approaches have been disclosed which have facilitated the discovery of uniquely tolerant neutral iridium catalyst species that demonstrate a significantly lower binding strength with nitrile functionality. In turn, we describe the first effective nitrile‐tolerant HIE methodology enabled via ortho‐directed C(sp2)−H activation using air‐ and moisture‐stable iridium pre‐catalysts of the type Ir(COD)(NHC)Cl under an atmosphere of deuterium gas. This methodology proceeds under mild and practically accessible reaction conditions with a range of directing groups, including heterocycles, ketones, and amines, with this class of catalyst also shown to be applicable towards bioactive molecules, resulting in products with high levels of isotopic labelling.
Circularly Polarized MIMO Antenna System for Millimeter Wave 5G Applications Using Characteristic Mode Theory
Authors: Modak Sumon , Farooq Umar , Lokam Anajaneyulu 
Published: February 2025

ABSTRACTThis study introduces a quad‐port multi‐input multi‐output antenna design specifically suited for fifth‐generation wireless technology. The antenna geometry is characterized by a flower‐shaped configuration, featuring five petals complemented by a circular slot, positioned in the ground plane to improve operational bandwidth. The effective realization of wide‐band characteristics has been studied utilizing the analysis of characteristic modes. The design antenna demonstrates simulated performance parameters that cover the millimeter‐wave frequency band from 25.6 to 32.4 GHz, delivering a maximum gain of 6.1 dBi and ensuring minimum port isolation of > 15 dB across all ports. In addition, a circular stub is purposefully positioned over the slot to facilitate circular polarization radiation behavior at 26.3 GHz, exhibiting an axial ratio bandwidth of 0.5 GHz (26–26.5 GHz). Further, the proposed antenna design is subjected to validation encompassing diversity metrics. The proposed antenna structure is successfully fabricated, and its performance is experimentally validated. A comprehensive comparative analysis is then conducted to evaluate its alignment with the simulated results.
Scarecrow‐Shaped Antenna Optimization Using Machine Learning Algorithms
Authors: Bhavani S. , Raviteja B. , Shanmuganantham T. 
Published: February 2025

ABSTRACTIn this article, scarecrow‐shaped antenna with a Rogers RT6002 substrate with a permittivity of 2.94 and a thickness of 1 mm is presented. It is operating from 3.5 to 12 GHz frequency band. The next generation of wireless communication networks will make extensive use of machine learning (ML). It is anticipated that the growth of various communication‐based applications will improve coverage and spectrum efficiency when compared with traditional systems. A wide range of domains, including antennas, can benefit from the application of ML to generate solutions. Scarecrow‐shaped antenna is optimized using machine learning algorithms decision tree, random forest, XGBoost regression, K‐nearest neighbor (KNN), and light gradient boosting regression (LGBR). The antenna's return loss, gain, and directivity were predicted in this work. The KNN achieved the highest accuracy in the prediction of return loss. Hence, proposed antenna is suitable for flexible wireless communication systems, IoT, 5G, and 6G.
Point‐ConNet: Integrated Power Allocation and Target Assignment for Efficient Multi‐Target Tracking in Distributed Radar Networks
Authors: Karthik V. , Priya M. , Ramkumar M. , Nagarajan Sathish Kumar 
Published: February 2025

ABSTRACTThe technique of using radar or other sensing devices to simultaneously monitor and track the positions of several moving objects is known as multiple target tracking or MTT. The challenge is to efficiently follow many targets in distributed radar networks by optimizing combined power allocation, resource allocation, and radar target assignment. This publication proposes an efficient deep‐learning strategy for Joint Power Resource Allocation and Radar Target Assignment (JPRA‐RTA) in distributed radar networks with ground‐based transmitters and aerial receivers. The method has two phases: (i) Point‐wise Activations Steerable Convolutional Neural Networks (Point‐ConNet) with Narwhal Optimizer for joint power allocation and radar target assignment, and (ii) Hybrid Snow Geese Alpine Skiing Optimization (Hyb‐SGASO), for resource allocation. First, the JPRA‐RTA problem is converted into a regression problem solvable by Point‐ConNet with the Narwhal Optimizer, enhancing computational efficiency, accuracy, fast convergence, and scalability. After optimizing power and radar target assignment, Hyb‐SGASO is used to optimize remaining resources like communication bandwidth, ensuring balanced and efficient resource use. Thus, the proposed Point‐ConNet‐ Hyb‐SGASO method is implemented in Python and the method's performance is evaluated using metrics such as power consumption, spectral capacity, spectral efficiency, energy efficiency, tracking frame accuracy, cumulative distribution function (CDF), Mean Square Error (MSE), and Root Mean Square Error (RMSE), demonstrating significant improvements over traditional approaches. Thus, the proposed Point‐Connet‐Hyb‐SGASO approach has achieved 18.76%, 23.04%, 28.06%, and 17.67% lower NMSE, 33.78%, 31.09%, 28.76%, and 24.89% higher energy efficiency compared with other conventional approaches like SDP‐LHS‐IPSOTS, ITPRS‐LADMM, BCRLB‐PSO, and SCA‐RWO methods respectively.
Cytologic Histotyping of Gynecologic Malignancies in Peritoneal Fluids Is Reliable When Compared to Its Corresponding Surgical Specimen
Authors: Sabljic Thomas , Lou Si Kei (Sandy) 
Published: February 2025

ABSTRACTBackgroundCytologic examination of peritoneal fluid (PTFL) often represents the first and only pathologic specimen available to guide management of gynecologic malignancies (GMs). This study examines the cytohistologic correlation between histotyping of GM in PTFL and its corresponding surgical specimen (SS).MethodsThe study retrospectively identified positive PTFL with a GM between 2017 and 2022. Cytologic specimens (CSs) that were obtained after or concurrently with its diagnostic SS (biopsy/resection) were excluded. Root cause analysis of discordant cases was performed by reviewing morphology, specimen characteristics, and immunophenotype of CS.ResultsGM affected 55.8% (502/899) of malignant PTFL, of which 15.7% (79)/22.3% (112) was the only/initial diagnostic sample, respectively. Compared to SS, when a subtype was rendered on CS (91.9%), the concordance rate is 91.2% (almost perfect agreement, K = 0.842). Factors contributing to incorrect/inadequate subtyping include specimen limitations (low volume and/or cellularity), cytopathologist preference, and insufficient immunophenotyping. In seven patients (1.4%), the CS was able to render a more definitive diagnosis than its preceding nondiagnostic SS due to the paucity of lesional cells.ConclusionWhen compared to SS, histotyping of GM in PTFL is reliable and, at times, can be more definitive than its surgical counterpart. In some cases, subtyping is limited by extrinsic factors (i.e., specimen limitations). In other cases, the responsible cytopathologist prefers not to subtype despite supportive morphologic and immunohistochemical features. This highlights an opportunity for improvement in the diagnosis/subtyping of GM in PTFL, which may be the initial or only diagnostic specimen prior to patient treatment.