bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osimertinib as Salvage Therapy in Advanced Non‐Small Cell Lung Cancer After Aumolertinib Resistance With T790M Mutation: A Case Report
Authors: Tang Yongtong , Xu Jilan , Chen Qingle , Lu Jianping , Ren Li , Lan Taihe , Liao Taihua , Chen Xiaoling , Yi Hui , Zhang Jun , Huang Jie 
Published: February 2025

ABSTRACTThe third generation of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is recommended universally as the standard treatment for non‐small cell lung cancer (NSCLC) carrying the EGFR T790M mutation. With the approval of multiple third‐generation EGFR‐TKIs, questions have arisen regarding the differences in their efficacy and how to select the most appropriate agent for individual patients. The study reports a case of an advanced NSCLC patient with multiple brain metastases. The patient initially received the pemetrexed plus carboplatin (PC) regimen for 5 months and displayed stable disease. Upon disease progression, the patient was treated with aumolertinib as second‐line treatment due to the detection of EGFR L858R and T790M mutations, but the symptoms of brain metastases deteriorated. Switching to osimertinib successfully relieved the patient's symptoms and achieved a long progression‐free survival (PFS) of nearly 2 years. Leptomeningeal metastasis was then definitively diagnosed, and the patient eventually died approximately 4 months after osimertinib resistance. This case suggests that osimertinib may be a viable option for EGFR‐mutant NSCLC patients after aumolertinib failure, especially for those with intracranial metastases.
Laparoscopic Cholecystectomy in Situs Inversus Totalis: A Case Report
Authors: Lakhey Prapti , Shrestha Milan , Sharma Rishav , Lakhey Paleswan Joshi 
Published: February 2025

ABSTRACTSitus inversus totalis is a rare condition characterized by the mirror image of the normal abdominal and thoracic viscera. Since the gallbladder is located in the left upper quadrant in this subset of patients, the diagnosis of symptomatic cholelithiasis poses a difficulty. Similarly, laparoscopic cholecystectomy in these patients is more demanding and presents technical challenges, especially for right‐handed surgeons. Herein, we report a case of a 30‐year‐old female who was a known case of situs inversus totalis and was diagnosed with symptomatic cholelithiasis and subsequently underwent laparoscopic cholecystectomy with an uneventful post‐operative period. The challenge while performing laparoscopic cholecystectomy in patients with situs inversus totalis calls for appropriate perioperative preparation and necessary modifications in the operative setup for the safe and successful operation of the patient, which is discussed in this report.
Intraoperative Fluoroscopic Verification of Satisfactory Foraminotomy in Posterior Open Decompression Surgery for Lumbar Foraminal Stenosis: A Clinical Image
Authors: Kapetanakis Stylianos , Bladowska Joanna , Tsioulas Paschalis , Tsolakidis Georgios , Siopis Christos , Gkantsinikoudis Nikolaos 
Published: February 2025

ABSTRACTLumbar spinal stenosis (LSS) represents an increasingly encountered disorder in current clinical practice, being unfavorably associated with chronic low back pain, progressive neurologic decline and disability. LSS represents the major etiology for spine surgery in elderly individuals. In the era of continuous development of novel full‐endoscopic techniques, conventional open surgery with decompression of neural elements and with or without fusion of the compromised segment continues to represent the current gold standard for surgical management of these patients. In cases with foraminal stenosis, foraminal decompression with mobilization of the exiting nerve root represents the primary aim of surgery. However, intraoperative proper identification of the extent of decompression may be problematic in specific cases with significantly altered anatomy. The aim of this clinical image is to present a rare case of a patient with symptomatic foraminal stenosis, in which the rate of satisfactory foraminal decompression was intraoperatively verified via routine C‐arm fluoroscopy. To our best knowledge, the utilization of fluoroscopy for verification of the extent of decompression in lumbar foraminal stenosis has never been reported in contemporary literature. Therefore, except for routine localization purposes, intraoperative fluoroscopy may be considered an additional measure to assess foraminal decompression in such cases.
A Multiple Linear Regression–Based Algorithm to Correct for Cosmic Rays in Raman Images
Authors: Mitsutake Hery , de Paula Eneida , Bordallo Heloisa N. , Rutledge Douglas N. 
Published: February 2025

ABSTRACTRaman imaging is a powerful technique for simultaneously obtaining chemical and spatial information on diverse materials. One of the most common detectors used on Raman equipment is the charge coupled detector (CCD) due its high sensitivity. However, CCDs are also sensitive to cosmic rays, that generate very narrow and intense signals: cosmic ray spikes. Since these peaks can be very intense and numerous, it is important to eliminate them before any data analysis. Some methods to do this use comparison of neighboring pixels to identify spikes, but when using the line‐scanning acquisition mode, it is common that these spikes appear in two or more pixels close together. Thus, in this work, a new algorithm has been developed to correct for cosmic ray spikes in Raman images, based on multiple linear regression (MLR). This algorithm takes less than 1 min in images with more than 70,000 spectra and removes all spikes, even those at low intensity.
Multimodal Stacked Modeling for Simultaneous Detection of Nutrient Concentrations With Turbidity Correction
Authors: Nini Meryem , Nohair Mohamed 
Published: February 2025

ABSTRACTIn this paper, an innovative method for the simultaneous determination of nitrite, nitrate, and COD in water in the presence of turbidity as a source of noise in spectroscopic data has been investigated. UV–Vis absorption spectrometry and advanced machine learning are proposed to develop a stacking model, a sophisticated modeling approach that combines several basic models (PLS, Lasso, and Ridge regression) and a meta‐regressor (Random Forest regressor) to improve prediction accuracy by incorporating baseline correction and principal component analysis (PCA) to mitigate the effects of turbidity on spectroscopic data. After applying these corrections, a significant improvement was observed: The root mean square error (RMSE) and the mean absolute error (MAE) were significantly reduced, and the correlation coefficient (R2) between predicted and actual values of nitrite, nitrate, COD, and turbidity was greater than 0.96, for all compounds in the test data set, that demonstrate the ability of the proposed stacking model to accurately predict nutrient concentrations simultaneously, even in complex environments; the proposed model may provide a valuable alternative to wet chemical methods. Due to its high accuracy and fast response, the proposed model can be used as an algorithm for the construction of nutrient sensors. This paper highlights the importance of integrating advanced modeling and data correction techniques to improve the robustness and accuracy of predictive models in environmental chemistry, thus providing valuable information for environmental monitoring and management.
A Conjugated Porous Organic Polymer as a Metal‐Free Bifunctional Electrocatalyst for Enhanced Water Splitting
Authors: Chakraborty Argha , Roy Saraswati , Hassan Afshana , Porwal Pragti , Sarkar Sayantan , Ahmad Dar Manzoor , Roy Sounak , Mukhopadhyay Suman 
Published: February 2025

AbstractA conjugated porous organic polymer (SMCOP‐4) with imine linkage and triazine functional moiety was rationally designed and synthesized by an imine condensation reaction. The π‐conjugated network of SMCOP‐4 facilitates electron mobility, enhancing electrochemical activity. Metal‐free electrocatalyst SMCOP‐4 shows superior performance for HER and OER with a low overpotential of 139 mV and 295 mV, respectively, at 10 mA cm−2 current density and with small Tafel slopes in alkaline electrolytes. Along with the low overpotential values, the electrocatalyst is highly stable at electrochemical conditions. Further, density functional theory calculations were carried out to identify the most active sites in catalyzing the HER and OER on the SMCOP‐4 catalyst.
Bioinspired Total Synthesis and Structural Reidentification of Alstrostines
Authors: Hiruma Daiki , Yoshidome Akiho , Rakumitsu Kenta , Kitajima Mariko , Hitora Yuki , Tsukamoto Sachiko , Schinnerl Johann , Brecker Lothar , Ishikawa Hayato 
Published: February 2025

Alstrostine A and isoalstrostine A are monoterpenoid indole alkaloid glycosides with unique structures found in the plant families Apocynaceae and Rubiaceae. With molecular weights exceeding 900, nine chiral centers (excluding sugar rings), and complex fused‐ring structures, the structural elucidation of these molecules using spectral analysis is highly challenging. Therefore, their structural identification through total synthesis is important in both natural product chemistry and synthetic organic chemistry. In this study, we successfully accomplished the first asymmetric total syntheses of these alkaloids in 18 or 19 steps. A key synthetic feature was a two‐ or three‐component coupling reaction between secologanin and a pyrrolidinoindoline moiety based on our proposed biosynthetic pathway. This approach enabled the synthesis of all isomers of the pyrrolidinoindoline ring, which constitutes the upper fragment of the alstrostines, and allowed us to revise the stereochemistry of alstrostine A. Additionally, a compound previously isolated as alstrostine A from Palicourea luxurians (Rubiaceae) was successfully reidentified and renamed as epialstrostine A.
Photoinduced Radical Luminescence of Diazapyrene Derivatives upon Complexation with Cucurbit[n]uril Hosts
Authors: Wang Chunmei , Xia Zengyan , Han Xie , Zhao Zhiyong , Liu Simin 
Published: February 2025

Molecular design with an electron donor‐acceptor (D‐A) structure and host‐guest complexation are effective strategies for stabilizing radicals. Herein, we report the design and synthesis of cationic diazapyrene derivatives featuring a D‐A structure, as well as the influence of host‐guest complexation on their photoinduced organic radical photophysical properties. Compared to the methylated diazapyrene 1, the other three derivatives 2‐4, containing triphenylamine, coumarin, and naphthalene units as D groups, respectively, are more favorable for the generation of radicals. Binding studies reveal that cucurbit[8]uril (CB[8]) forms 1:1 inclusion complexes with derivatives 2‐4, while CB[10] forms a 2:2 inclusion complex with 2 and supramolecular polymers with 3 and 4. The radical luminescence of derivatives 1‐4 in aqueous solution is significantly promoted upon complexation with CB[8] or CB[10]. Additionally, the emission color of 3 shifts from cyan to yellow‐green upon light irradiation in the presence of CB[8].
External Phosphate Binding Triggered Formation of Coordination Bridged Dimer of Macrocyclic Trinuclear Complex
Authors: Zhao Jiachen , Varzhel Nadiia , Hokimoto Yuya , Nakamura Takashi 
Published: February 2025

Macrocyclic complexes with spatially‐arranged coordination sites have the potential to create unique supramolecular systems that combine the precise switching of self‐assembled structures with the coordinative recognition of specific molecules. We now report a macrocyclic trinuclear Zn complex that undergoes a unique dimerization by molecular binding from the outside. The multinuclear complex was synthesized from a trispap ligand, a designed macrocyclic trimer of an N,N,O‐type tridentate chelating unit pap. This macrocyclic ligand is capable of fixing the metal centers and retaining their exchangeable coordination sites. The macrocyclic trimer reacts with zinc acetate to form the trinuclear complex, in which the coordination sites of the three zinc atoms are aligned perpendicular to the macrocyclic plane and capped with the acetates. Subsequently, phosphate anion, PO43–, coordinates from one side of the macrocycle in a tripodal manner. This phosphate binding produced an electrically‐neutral complex moiety with available coordination sites on the other side of the macrocycle which leads to the formation of the coordination‐bridged dimer.
Exploring Naproxen Cocrystals Through Solid‐State Vibrational Circular Dichroism
Authors: Sklenář Adam , Zehnacker‐Rentien Anne , Kaminský Jakub , Rohlíček Jan , Bouř Petr 
Published: February 2025

ABSTRACTVibrational circular dichroism (VCD) spectroscopy appears as a useful method for characterizing optically active substances in the solid state. This is particularly important for active pharmaceutical ingredients. However, measurement and interpretation of the spectra bring about many difficulties. To assess the experimental and computational methodologies, we explore an anti‐inflammatory drug, naproxen. Infrared (IR) and VCD spectra of the pure compound and its cocrystals with alanine and proline were recorded, and the data were interpreted by quantum chemical simulations based on a cluster model and density functional theory. Although unpolarized IR spectroscopy can already distinguish pure ingredients from cocrystals or a mixture, the VCD technique is much more sensitive. For example, the naproxen carboxyl group strongly interacts with the zwitterionic alanine in the cocrystal via two strong hydrogen bonds, which results in a rather rigid structure crystallizing in the chiral P212121 Sohncke group and its VCD is relatively strong. In contrast, the d‐proline and (S)‐naproxen cocrystal (P21 group) involves a single hydrogen bond between the subunits, which together with a limited motion of the proline ring gives a weaker signal. Solid‐state VCD spectroscopy thus appears useful for exploring composite crystal structures and interactions within them, including studies of pharmaceutical compounds.
The impact of repeated drug desensitisation on quality of life in drug hypersensitivity
Authors: Gorgulu Akin Begum , Kepil Ozdemir Secil , Doganay Erdogan Beyza , Gelincik Asli , Goksel Ozlem , Dursun Adile Berna , Isık Sacide Rana , Demir Semra , Akten Hatice Serpil , Bavbek Sevim 
Published: February 2025

AbstractBackgroundMeasurement of disease‐specific quality of life (QOL) is crucial in evaluating the effects of disease and response to treatment. Patients' efforts to avoid the responsible medication can have a negative impact on the QOL of patients with drug hypersensitivity reactions (DHRs). The Drug Hypersensitivity QOL Questionnaire (DrHy‐Q) is the only specific tool measuring disease specific QOL in patients with DHRs.ObjectiveTo evaluate the effect of repeated drug desensitisation on disease‐specific QOL using the Turkish version of DrHy‐Q in a prospective multicentre study.MethodsPatients scheduled to undergo repeated desensitisations with the same drug were included in the study. Baseline DrHy‐Q scores were recorded for each patient prior to the commencement of the desensitisation procedure. DrHy‐Q scores were then calculated following each desensitisation procedure.ResultsThe study included 111 patients with two or more desensitisations (age mean ± SD, years: 53.87 ± 11.36, F/M:94/17). The drugs most implicated in DHRs were chemotherapeutics (91 of 111 patients, 82%) followed by biologicals (16 of 111 patients, 14.4%). Before the desensitisation process, the median (min–max) pre‐DrHy‐Q score was 39 (16–74). The median (min–max) DrHy‐Q scores after the first three desensitisation were 35 (19–69), 34 (15–68) and 35 (15–64), respectively. There was a statistically significant improvement in DrHy‐Q scores after the first three desensitisation in comparison with baseline.ConclusionThe health‐related disease‐specific QOL of patients with hypersensitivity to drugs significantly improved after the first three, but not after subsequent drug desensitisations, as compared to baseline.
Advances in Lipid Nanoparticle‐Based Disease Treatment
Authors: Zhou Yujie , Ge Qiqi , Wang Xin , Wang Yuhui , Sun Qianqian , Wang Jianhao , Yang Tie , Wang Cheng 
Published: February 2025

AbstractLipid nanoparticles (LNPs) have emerged as a transformative platform for the targeted delivery of therapeutic agents, revolutionizing treatment paradigms across a spectrum of diseases. Since the inception of liposomes in the 1960s, lipid‐based nanotechnology has evolved to address limitations such as poor bioavailability, off‐target effects, and instability, thereby enhancing the efficacy and safety of drug administration. This review highlights the latest advancements in LNPs technology, focusing on their application in cancer therapy, gene therapy, infectious disease management, glaucoma, and other clinical areas. Recent studies underscore the potential of LNPs to deliver messenger RNA (mRNA) and small interfering RNA (siRNA) for precise genetic intervention, exemplified by breakthroughs in RNA interference and CRISPR‐Cas9 genome editing. Additionally, LNPs have been successfully employed to ameliorate conditions, demonstrating their versatility in addressing both acute and chronic disorders. However, challenges persist concerning large‐scale manufacturing, long‐term stability, and comprehensive safety evaluations. Future research must focus on optimizing formulations, exploring synergistic combinations with existing therapies, and expanding the scope of treatable diseases. The integration of LNPs into personalized medicine and the exploration of applications in other diseases represent promising avenues for further investigation. LNPs are poised to play an increasingly central role in the development of next‐generation therapeutics.
First‐order Sobolev spaces, self‐similar energies and energy measures on the Sierpiński carpet
Authors: Murugan Mathav , Shimizu Ryosuke 
Published: February 2025

AbstractFor any , we construct ‐energies and the corresponding ‐energy measures on the Sierpiński carpet. A salient feature of our Sobolev space is the self‐similarity of energy. An important motivation for the construction of self‐similar energy and energy measures is to determine whether or not the Ahlfors regular conformal dimension is attained on the Sierpiński carpet. If the Ahlfors regular conformal dimension is attained, we show that any optimal Ahlfors regular measure attaining the Ahlfors regular conformal dimension must necessarily be a bounded perturbation of the ‐energy measure of some function in our Sobolev space, where is the Ahlfors regular conformal dimension. Under the attainment of the Ahlfors regular conformal dimension, the ‐Newtonian Sobolev space corresponding to any optimal Ahlfors regular metric and measure is shown to coincide with our Sobolev space with comparable norms, where is the Ahlfors regular conformal dimension.
Enhancing Reproducibility in Chemotaxis Assays for Caenorhabditis elegans
Authors: Cesar Leona , Morud Julia 
Published: February 2025

AbstractThe ability of Caenorhabditis elegans (C. elegans) to navigate complex environments is essential for their survival. This natural behavior is commonly used in chemotaxis assays, which are important tools for studying the function of sensory neurons and neural circuits. Chemotaxis has been essential for discovering fundamental functions in neuronal signaling during the past decades. However, a lack of thoroughly optimized and standardized procedures can lead to variable results that can be difficult to interpret. To improve reproducibility, we optimized several aspects of chemotaxis protocols by testing different odorant concentrations, numbers of worms, and assay durations, as well as the preparation of chemotaxis plates and the washing procedures of worms. The usage of a 2‐choice or a 4‐choice assay was also evaluated. Our new protocol improves the clarity of results and simplifies worm counting. The protocol optimization is condensed into a 5‐day step‐by‐step protocol that increases the reproducibility of chemotaxis in C. elegans. Compared to previously published chemotaxis protocols, the revised method reduces day‐to‐day variability using an improved and standardized assay design that ensures clear and reliable results. Several key components in the assay preparation and during the assay have been evaluated based on previous protocols, such as odor concentration, worm density, and assay length. By considering multiple factors that influence the worm's behavior, our optimized protocol enhances the reproducibility of chemotaxis assays in C. elegans, making them more reliable and accessible for studying phenotypes related to olfaction and neural circuit behavior. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol: Optimized Chemotaxis Assay for C. elegans
Redefining Cell Culture Using a 3D Flipwell Co‐culture System: A Mimetic for Gut Architecture and Dynamics In Vitro
Authors: Beamer Maria A. , Furuta Saori 
Published: February 2025

AbstractGut mucosae are composed of stratified layers of microbes, a selectively permeable mucus, an epithelial lining, and connective tissue homing immune cells. Studying cellular and chemical interactions between the gut mucosal components has been limited without a good model system. We have engineered a three‐dimensional (3D) multi‐cellular co‐culture system we coined “3D Flipwell system” using cell culture inserts stacked against each other. This system allows an assessment of the impact of a gut mucosal environmental change on interactions between gut bacteria, epithelia, and immune cells. As such, this system can be utilized in examining the effects of exogenous stimuli, such as dietary nutrients, bacterial infection, and drugs, on the gut mucosa that could predetermine how these stimuli might influence the rest of body. Here, we describe the methods of construction and application of the new 3D Flipwell system we utilized previously in assessing the crosstalk between the gut mucosa and macrophage polarization. We demonstrate the physiological responses of different components of the co‐cultures to Sepiapterin (SEP), the precursor of the nitric oxide synthase cofactor tetrahydrobiopterin (BH4). We reported previously that SEP induces a pro‐immunogenic shift of macrophages having acquired an immune suppressive phenotype. We also showed that SEP induces a defense mechanism of commensal gut bacteria. The protocol describing the assembly and use of the 3D Flipwell co‐culture system herein would grant its utility in evaluating the concurrent effects of pharmacologic and microbiologic stimuli on gut mucosal components. © 2025 The Author(s). Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: 3D Flipwell construction, assembly, and collagen coatingBasic Protocol 2: Flipwell cell seeding and cell cultureBasic Protocol 3: Addition of bacterial culture to the Flipwell systemBasic Protocol 4: Flipwell disassembly for scanning electron microscopy (SEM) studiesBasic Protocol 5: Immunofluorescence antibody staining for confocal microscopy