bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ring‐Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti‐Breast Cancer Evaluation
Authors: Zhu Jun‐Jie , Ai Yi , Wu Jun‐Hui , Zeng Chang‐Guang , Cui Zhen , Zhang Zheng‐Ping , Zhu Jia‐Yi , Wang Chang‐Qi , Zhong Hang 
Published: April 2024

AbstractThe endoperoxide group of artemisinins is universally accepted an essential group for their anti‐cancer effects. In this study, a series of D‐ring‐contracted artemisinin derivatives were constructed by combining ring‐contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty‐six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H‐NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA‐MB‐436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 μM, and its activity was approximately 1/3 of the positive control Palbociclib.
Chest pain in a patient with transthyretin cardiac amyloidosis: A case report
Authors: Xie Linfeng , Luo Suxin , Huang Bi 
Published: April 2024

Key Clinical MessagePatients with transthyretin cardiac amyloidosis (ATTR‐CM) commonly present with dyspnea, fatigue, and edema. In our case, the main presentation was exertional angina, which was atypical in patients with ATTR‐CM and should be paid more attention to.AbstractA 54‐year‐old woman was admitted with a complaint of exertional chest pain, and she had a history of hypertension. The results of the electrocardiogram and echocardiography revealed the clues of cardiac amyloidosis, and the patient was finally diagnosed with transthyretin cardiac amyloidosis, then she received tafamidis, and the symptoms improved significantly.
Osteoblastoma of the frontal sinus: A rare case presenting with seizures and pneumocephalus
Authors: Mallik Dattatraya , Chandrashekhar Nandyal , Rai Abhishek Kumar , Dhingra Saransh , Arora Gaurav , Gandhi Sapan , Scalia Gianluca , Chaurasia Bipin 
Published: April 2024

Key Clinical MessageOsteoblastoma of the frontal sinus, although rare, can manifest with seizures and pneumocephalus, underscoring the importance of thorough evaluation and complete surgical excision to prevent serious complications and ensure optimal patient outcomes.AbstractOsteoblastoma is an infrequent bone tumor, with origins typically in the vertebrae and long bones. While craniofacial involvement is rare, it may occur in regions such as the paranasal sinuses. We present a case of osteoblastoma located in the frontal sinus, an exceptionally uncommon site, resulting in seizures secondary to pneumocephalus. A 21‐year‐old male presented with a generalized tonic–clonic seizure and postictal confusion. Imaging studies revealed a well‐defined lesion in the left frontal sinus causing cortical breach, destruction of the posterior wall, and pneumocephalus. A total surgical excision was performed through bifrontal craniotomy. Histopathological analysis confirmed the diagnosis of osteoblastoma. Postoperative recovery was uneventful, with a follow‐up CT scan showing complete lesion excision. Osteoblastomas, especially in the cranial sinuses, are rare entities that may present asymptomatically but can lead to severe complications. The risk of recurrence underscores the importance of complete surgical resection for optimal patient outcomes.
A case of celiac plexus block causing iatrogenic Cushing's syndrome
Authors: Chindris Ana‐Maria , Rao Sarika N. , Chirila Razvan M. , Dumitrascu Adrian G. 
Published: April 2024

Key Clinical MessageTreatment with corticosteroids can lead to iatrogenic Cushing's syndrome when used for longer intervals and in high doses. Less common administration routes may conceal the exposure, raising the possibility of misdiagnosis and mismanagement.
Ionic Liquid‐Silver Catalysts for Acetylene Acetoxylation at Low‐Temperature
Authors: Zhuang Qi , Zhang Xunchao , Zhu Mingyuan , Dai Bin 
Published: April 2024

AbstractIt was crucial to develop a catalyst with high catalytic activity at low temperatures, as the zinc‐based catalysts were prone to deactivation in the high‐temperature reaction of acetylene acetoxylation, and Ionic liquid (IL)‐silver (Ag) catalysts were synthesized and applied in acetylene acetoxylation. The X‐ray diffraction, transmission electron microscopy, and X‐ray photoelectron spectroscopy characterizations displayed that Ag species were stabilized in the state of Ag+, and the dispersion of the Ag active species was effectively improved in supported‐ionic‐liquid‐phase (SILP) system. Furthermore, we prepared Ag‐IL liquid phase catalysts for catalyzing acetylene acetoxylation in liquid phase systems. It was demonstrated that the presence of ILs could effectively stabilize the Ag+ active site. The catalytic performance of the Ag‐IL/AC catalyst prepared in this article at a low temperature of 180 °C was 2.5 times that of the traditional Zn/AC catalyst. The development of low‐temperature catalysts would play a driving role in the development of acetylene acetoxylation.
In Situ Determination of the Potential Distribution within a Copper Foam Electrode in a Zinc‐Air/Silver Hybrid Flow Battery
Authors: Genthe Sascha , Arenas Luis F. , Becker Maik , Kunz Ulrich , Turek Thomas 
Published: April 2024

AbstractThis work describes a novel methodology for measuring the potential distribution within the porous copper foam electrode of a zinc‐air/silver hybrid (ZASH) flow battery by using local potential probes. The suitability of dynamic hydrogen electrodes (DHEs) and a quasi‐reference electrode as probes is evaluated, with the latter chosen in view of stability. Liquid and solid‐phase potentials are recorded at varying applied current densities over multiple charge‐discharge cycles. Various zinc structures are found within specific overpotential ranges, with moss‐like structures appearing between 7.8 mV and 13.2 mV and the desired boulder structures in the range of 22 mV to 100 mV. Regardless of the current density, the highest liquid‐phase potentials are always measured in the outermost region of the porous foam near to the separator. In practice, this means that increasing the thickness of the copper foam over about 5 mm does not provide significant performance benefits. Conversely, solid‐phase potentials across the copper foam remain nearly uniform, resulting in negligible effects on local overpotential. The presented technique provides unique insights into the behavior of porous electrodes in electrochemical energy conversion technologies, facilitating the determination of the optimal properties for maximum efficiency, such as electrode thickness.
Structural Reconstruction Chemistry for Alkaline Oxygen Evolution Catalysts
Authors: Ma Peiyu , Jia Chuanyi , Zhang Zhirong , Bao Jun 
Published: April 2024

AbstractDeveloping efficient and stable catalysts for energy conversion processes such as alkaline oxygen evolution reaction is one of the key measures to solve the energy shortage problems. During alkaline oxygen evolution, several electrocatalysts would undergo structural reconstruction from the pre‐catalyst state to the real‐catalyst state. The structural reconstruction may modify the quantity and characterizations of the active sites, thus affecting the configuration and adsorption strength of the reaction key intermediates, which directly influence the activity and stability of the electrocatalysts. Understanding the structural transformation chemistry is essential for the rational design of highly efficient and stable electrocatalysts. In this review, we have deeply discussed the role and regulation strategies of structural reconstruction. Then, on this basis, we described some characterization technologies to probe the structural reconstruction of catalysts during alkaline OER. Finally, we put forward some views on the future research direction of this vital field.
Tagraxofusp, a first‐in‐class CD123‐targeted agent: Five‐year postapproval comprehensive review of the literature
Authors: Jen Wei‐Ying , Konopleva Marina , Pemmaraju Naveen 
Published: April 2024

AbstractTagraxofusp is a first‐in‐class CD123‐directed conjugate of an amended diphtheria toxin platform and recombinant interleukin 3. Binding and subsequent internalization of the drug result in cell death via disruption of intracellular protein synthesis. CD123 is a surface marker that is expressed in several hematological malignancies, especially blastic plasmacytoid dendritic cell neoplasm (BPDCN), where its expression is ubiquitous. A pivotal study of tagraxofusp in BPDCN resulted in its approval for the treatment of BPDCN, the first treatment approved for this indication. Since the introduction of tagraxofusp, research has focused on the management of adverse effects, combination therapy to improve outcomes in fit patients, and dosing and combination strategies to mitigate toxicities while preserving efficacy, especially among older patients. The successful targeting of CD123 in BPDCN has also encouraged research into a variety of other CD123‐positive hematological neoplasms, including acute myeloid leukemia (AML), and informed the development of other novel agents targeting CD123. This review examines the clinical data leading to the development and approval of tagraxofusp in BPDCN, how it is being used in combination to improve outcomes in BPDCN and AML, and its developing role in other hematological malignancies.
LC filter optimized design considering the effect on the power converter and capacitor lifetimes
Authors: Bolsi Pedro C. , Prado Edemar O. , Lenz João M. , Sartori Hamiltom C. , Pinheiro José R. 
Published: April 2024

AbstractThis work presents an LC filter design methodology that considers the optimization of the converter as a whole: filter, semiconductor switches, and DC bus. The optimization is made in light of the system losses, volume, and the capacitors lifetime, discussing the advantages and disadvantages of decisions in the parametric design of the filter (of the values of L and C). The technology of components and construction challenges are considered in the design. The manuscript guides the design process of the filter in two steps: first, by providing the means to perform the parametric sweep of possible filter designs, according to the converter specifications and other restrictions; second, by describing how the hardware design is carried out and indicating the models and methods that are being used. Individualized analyses for each part of the converter system are made, and using the proposed methodology, three design examples are provided and analyzed, each choosing the filter parameters with different objectives: minimum volume, maximum capacitor lifetime, or maximum efficiency. Results show that using Kool M
material results in the lowest filter volumes and losses. It is also shown that for the DC bus design, there is a compromise between volume and lifetime, with a greater number of capacitors increasing both attributes. By designing the system using the proposed methodology, the minimum volume is achieved at an operating point that differs from the individual minimum volumes of the filter and the inverter, and the lifetime is only 1.78% than the maximum lifetime point.
SARS‐CoV‐2‐infected human airway epithelial cell cultures uniquely lack interferon and immediate early gene responses caused by other coronaviruses
Authors: Wang Ying , Thaler Melissa , Salgado‐Benvindo Clarisse , Ly Nathan , Leijs Anouk A , Ninaber Dennis K , Hansbro Philip M , Boedijono Fia , van Hemert Martijn J , Hiemstra Pieter S , van der Does Anne M , Faiz Alen 
Published: April 2024

AbstractObjectivesSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a member of a class of highly pathogenic coronaviruses. The large family of coronaviruses, however, also includes members that cause only mild symptoms, like human coronavirus‐229E (HCoV‐229E) or OC43 (HCoV‐OC43). Unravelling how molecular (and cellular) pathophysiology differs between highly and low pathogenic coronaviruses is important for the development of therapeutic strategies.MethodsHere, we analysed the transcriptome of primary human bronchial epithelial cells (PBEC), differentiated at the air–liquid interface (ALI) after infection with SARS‐CoV‐2, SARS‐CoV, Middle East Respiratory Syndrome (MERS)‐CoV and HCoV‐229E using bulk RNA sequencing.ResultsALI‐PBEC were efficiently infected by all viruses, and SARS‐CoV, MERS‐CoV and HCoV‐229E infection resulted in a largely similar transcriptional response. The response to SARS‐CoV‐2 infection differed markedly as it uniquely lacked the increase in expression of immediate early genes, including FOS, FOSB and NR4A1 that was observed with all other coronaviruses. This finding was further confirmed in publicly available experimental and clinical datasets. Interfering with NR4A1 signalling in Calu‐3 lung epithelial cells resulted in a 100‐fold reduction in extracellular RNA copies of SARS‐CoV‐2 and MERS‐CoV, suggesting an involvement in virus replication. Furthermore, a lack in induction of interferon‐related gene expression characterised the main difference between the highly pathogenic coronaviruses and low pathogenic viruses HCoV‐229E and HCoV‐OC43.ConclusionOur results demonstrate a previously unknown suppression of a host response gene set by SARS‐CoV‐2 and confirm a difference in interferon‐related gene expression between highly pathogenic and low pathogenic coronaviruses.
Relationship of plasma biomarkers to digital cognitive tests in Alzheimer's disease
Authors: Toniolo Sofia , Zhao Sijia , Scholcz Anna , Amein Benazir , Ganse‐Dumrath Akke , Heslegrave Amanda J. , Thompson Sian , Manohar Sanjay , Zetterberg Henrik , Husain Masud 
Published: April 2024

AbstractINTRODUCTIONA major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale—robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD.METHODSWe used a novel web‐based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p‐tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352).RESULTSPatients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p‐tau181. The combination of p‐tau181 and the single best‐performing digital test achieved high accuracy in group classification.DISCUSSIONThese findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease.Highlights
This is the first study comparing online digital testing to plasma biomarkers.
Alzheimer's disease patients and two independent cohorts of elderly controls were assessed.
Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p‐tau)181.
Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance.
The best cognitive metric performed at par to p‐tau181 in group classification.
YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance
Authors: Yang Jian , Chen Yawen , He Yang , Da Mingxu 
Published: April 2024

AbstractThe role of YTHDF2 in gastric cancer (GC) is controversial. Due to the limitations of technical difficulty and experimental period, research on completely knocking out YTHDF2 is rare. Therefore, further investigations are still needed to clarify the YTHDF2's clinical significance and biological function in GC. To carry out the investigation, an analysis was performed on the expression levels of YTHDF2 in both publicly available databases and samples obtained from patients with gastric cancer. Based on the complete knockout of YTHDF2 using the CRISPR‐Cas9 system, in vivo and in vitro experiments were conducted to analyze the effects of YTHDF2 on tumor formation, radiotherapy and chemoradiotherapy resistance in GC. Our investigation revealed an increase in YTHDF2 levels in GC tissues, which was found to be associated with a negative prognosis. Under hypoxic conditions, high expression of YTHDF2 enhanced the invasion of gastric cancer cells, and high expression of YTHDF2 was associated with HIF‐1a. YTHDF2 facilitated gastric cancer cell growth in vitro and in vivo. Moreover, the results of the present study demonstrated that YTHDF2 mediated the expression of CyclinD1 and stability of CyclinD1 mRNA. CyclinD1 knockdown inhibited YTHDF2‐mediated GC cell proliferation whereas CyclinD1 overexpression ameliorated YTHDF2 knockdown‐induced inhibition of GC progression. Furthermore, YTHDF2 also promoted resistance to DDP and CTX chemotherapy, along with radiotherapy treatment for GC cells. The findings suggested that YTHDF2 expression accelerated GC progression through a potential mechanism involving CyclinD1 expression, and enhanced chemoradiotherapy resistance. This indicated that YTHDF2 could be a promising prognostic biomarker and therapeutic target for individuals diagnosed with GC.
Single and multiple inhibitors of the biosynthesis of 5‐, 12‐, 15‐lipoxygenase products derived from cinnamyl‐3,4‐dihydroxy‐α‐cyanocinnamate: Synthesis and structure–activity relationship
Authors: Touaibia Mohamed , Chiasson Audrey Isabel , Robichaud Samuel , Doiron Jérémie A. , Hébert Mathieu P. A. , Surette Marc E. 
Published: April 2024

AbstractThe involvement of lipoxygenases in various pathologies, combined with the unavailability of safe and effective inhibitors of the biosynthesis of their products, is a source of inspiration for the development of new inhibitors. Based on a structural analysis of known inhibitors of lipoxygenase products biosynthesis, a comprehensive structure–activity study was carried out, which led to the discovery of several novel compounds (16a‐c, 17a) demonstrating promising potency to inhibit the biosynthesis of products of 5‐, 12‐ and 15‐LO. Compounds 16b and 16c outperformed zileuton (1), the only FDA‐approved 5‐LO inhibitor, as well as known inhibitors such as caffeic acid phenethyl ester (CAPE (2)) and cinnamyl‐3,4‐dihydroxy‐α‐cyanocinnamate (CDC (4)). However, the introduction of a cyano group at the α‐position of the carbonyl abolished the activity. Compounds 16a and 17a also inhibited the biosynthesis of 12‐ and 15‐LO products. Compounds 16a, 17a far surpassed baicalein, a known 12‐LO inhibitor, as inhibitors of 12‐LO products biosynthesis. Compound 17a and CDC (4) showed equivalent inhibition of LO products, proposing that the double bond in the ester moiety is not necessary for the inhibitory activity. The introduction of the cyano group, as in compound 17a, at the α‐position of the carbonyl in compound 16a significantly reduced the inhibitory activity against the biosynthesis of 15‐LO products. In addition to the interactions with residues His372 and Phe421 also found with zileuton and CAPE, compounds 16a and 16c each interact with residue His367 as shown by molecular docking. This new interaction may explain their high affinity with the 5‐LO active site.
Assessment for shallow and large tunnel construction in weak ground conditions: Application of tunnel boring machines
Authors: Karahan Servet , Gokceoglu Candan 
Published: April 2024

AbstractWith recent technological advancements, tunnel boring machines (TBM) have developed and exhibited high performance in large diameters and weak ground conditions. Tunnels are crucial structures that significantly influence the timelines of highway and railway projects. Therefore, the construction of tunnels with TBMs becomes a preferred option. In this study, a comparative analysis between TBM and the New Austrian Tunneling Method (NATM) for tunnel construction is performed in the construction of the T1 tunnel with a diameter of 13 m, which is the longest tunnel in the Eşme‐Salihli section of Ankara‐İzmir High‐Speed Railway Project (Türkiye). The selection of TBM type, measures taken in problematic sections, and application issues of TBM are discussed. The impact of correct description of geological and geotechnical conditions on both selection and performance of TBM is presented. An earth pressure balanced type TBM is chosen for the construction of the T1 tunnel. Because of the additional engineering measures taken before excavation in problematic areas, the tunnel was completed with great success within the initially planned timeframe. From this point of view, this study is an important case and may contribute to worldwide tunneling literature.
Examining compulsive exercise as a risk factor for eating disorder symptoms in first‐year college students using a latent change score modeling approach
Authors: Palermo Madeline , Rancourt Diana 
Published: April 2024

AbstractObjectiveResearch suggests that both compulsive exercise and eating disordered behaviors increase during college. Despite strong cross‐sectional associations between compulsive exercise and eating disorders, it is unknown if compulsive exercise is a variable risk factor for eating disorders or simply a correlate. It was hypothesized that increases in compulsive exercise would significantly and prospectively predict increases in overall number of eating disorder symptoms over the study period.MethodA total of 265 first year college students who did not meet criteria for a full or subthreshold eating disorder diagnosis at Time 1 (age M = 18.15; SD = 0.42; 122 female [46%] at Time 1) completed reports of compulsive exercise and eating disorder symptoms via online questionnaires at four timepoints over the 9‐month 2021–2022 academic year (76% retention rate). Hypotheses were tested using a bivariate latent change score model.ResultsHypotheses were not supported. Change in compulsive exercise did not predict change in number of eating disorder symptoms. Change in number of eating disorder symptoms also did not predict change in compulsive exercise.ConclusionsCompulsive exercise did not emerge as a variable risk factor for the development of eating disorder symptoms among first year college students. The relationship between these behaviors should be investigated at different developmental timepoints, such as early adolescence, and potential third variables that may explain the observed co‐occurrence should be explored.Public significanceThis study investigated whether increases in compulsive exercise predicted increases in number of eating disorder symptoms among first year college students. Compulsive exercise did not significantly predict number of eating disorder symptoms. Additional research is warranted to clarify the relationship between compulsive exercise and eating disorder symptoms.