bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new method based on dispersive liquid–liquid microextraction for fat‐soluble vitamin determination in serum by LC–MS/MS
Authors: Li Jufang , Chen Congyan , Sun Xingchao , Hu Zhineng , Wu Chaochao , Gao Qiang , Ying Guoqing 
Published: May 2023

AbstractA green and inexpensive pretreatment known as dispersive liquid–liquid microextraction (DLLME) was developed in this assay coupled with the LC–MS/MS method for routine analysis of fat soluble vitamins (FSVs). The technique was performed with methanol as the dispersive solvent and dichloromethane as the extraction solvent. The extraction phase containing FSVs was evaporated to dryness and reconstituted in a mixture of acetonitrile and water. The influence variables concerning the DLLME procedure were optimized. After that, the method was investigated for its applicability in LC–MS/MS analysis. As a result, the parameters were settled for the optimal conditions during the DLLME process. A cheap and lipid‐free substance was found as an alternative to serum to eliminate the matrix effect while preparing the calibrators. The method validation indicated that it was suitable for determining FSVs in serum. Moreover, this method was applied successfully to determine serum samples, which was consistent with the literature. In summary, the DLLME method developed in this report was reliable and more cost‐effective than the traditional LC–MS/MS method, and could be applied in the future.
Identifying hormones and other perioperative risk factors for postoperative delirium after endoscope‐assisted transsphenoidal pituitary adenoma resection: A retrospective, matched cohort study
Authors: Liu Jin , Qian Jinyu , Wang Xia , Lin Jie , Yang Sunyan , Hu Rong , Xian Jishu , Feng Hua , Chen Yujie , Tan Binbin 
Published: May 2023

AbstractObjectiveAs a complex and acute brain dysfunction, if postoperative delirium (POD) occurs in the postoperative period, it will lead to a prolonged length of stay in the critical care unit, with increased hospitalization costs and higher mortality. A few case reports inspired us to pay close attention to pituitary tumor‐associated delirium. We hypothesized that the changes in hormone levels after pituitary tumor resection might be associated with POD occurrence.MethodsRetrospective analysis was performed on data from a single‐center cohort study conducted at Southwest Hospital between January 2018 and May 2022. A total of 360 patients with pituitary tumors who underwent endoscope‐assisted transsphenoidal pituitary tumor resection were divided into two groups at a 1:3 ratio, with 36 patients in the POD group and 108 patients in the non‐POD group matched by propensity score, age, sex, and tumor size. Basic characteristics, pituitary adenoma features, endocrine levels and other biochemical indicators, and Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU) for postoperative delirium were documented for further analysis.ResultsLower insulin‐like growth factor‐1 (IGF‐1, p = .024) and corticotropin‐releasing hormone (CRH, p = .005) levels were closely associated with postoperative delirium and with high levels of blood glucose (GLU, p = .023) after surgery. Subsequent analysis indicated that serum potassium (OR: 0.311, 95% CI 0.103–0.935), sodium (OR: 0.991, 95% CI 0.983–1.000), CRH (OR: 0.964, 95% CI 0.936–0.994), and GLU (OR: 1.654, 95% CI 1.137–2.406) levels in the perioperative period were independent risk factors for delirium.ConclusionsOur study indicated that lower serum CRH, potassium, sodium, and GLU levels may be associated with the occurrence of POD after endoscopic‐assisted transsphenoidal surgery. These data provide preliminary evidence for the management of POD in pituitary adenoma patients after surgery. Further studies are needed to identify pharmacological and nonpharmacological multicomponent treatment strategies.
Polymorphic nanobody crystals as long‐acting intravitreal therapy for wet age‐related macular degeneration
Authors: Zhu Shuqian , Fan Shilong , Tang Tianxin , Huang Jinliang , Zhou Heng , Huang Chengnan , Chen Youxin , Qian Feng 
Published: May 2023

AbstractWet age‐related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti‐vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter‐injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti‐VEGF nanobody, we obtained a series of anti‐VEGF nanobodies with identical protein structures and VEGF binding affinities, while drastically different crystallization propensities and crystal lattice structures. Among these nanobody crystals, the P212121 lattice appeared to be denser and released protein slower than the P1 lattice, while nanobody crystals embedding zinc coordination further slowed the protein release rate. The polymorphic protein crystals could be a potentially breakthrough strategy for chronic intravitreal administration of anti‐VEGF proteins.
Label‐free atherosclerosis diagnosis through a blood drop of apolipoprotein E knockout mouse model using surface‐enhanced Raman spectroscopy validated by machine learning algorithm
Authors: Lee Sanghwa , Jue Miyeon , Cho Minju , Lee Kwanhee , Paulson Bjorn , Jo Hanjoong , Song Joon Seon , Kang Soo‐Jin , Kim Jun Ki 
Published: May 2023

AbstractThe direct preventative detection of flow‐induced atherosclerosis remains a significant challenge, impeding the development of early treatments and prevention measures. This study proposes a method for diagnosing atherosclerosis in the carotid artery using nanometer biomarker measurements through surface‐enhanced Raman spectroscopy (SERS) from single‐drop blood samples. Atherosclerotic acceleration is induced in apolipoprotein E knockout mice which underwent a partial carotid ligation and were fed a high‐fat diet to rapidly induce disturbed flow‐induced atherosclerosis in the left common carotid artery while using the unligated, contralateral right carotid artery as control. The progressive atherosclerosis development of the left carotid artery was verified by micro‐magnetic resonance imaging (micro‐MRI) and histology in comparison to the right carotid artery. Single‐drop blood samples are deposited on chips of gold‐coated ZnO nanorods grown on silicon wafers that filter the nanometer markers and provide strong SERS signals. A diagnostic classifier was established based on principal component analysis (PCA), which separates the resultant spectra into the atherosclerotic and control groups. Scoring based on the principal components enabled the classification of samples into control, mild, and severe atherosclerotic disease. The PCA‐based analysis was validated against an independent test sample and compared against the PCA‐PLS‐DA machine learning algorithm which is known for applicability to Raman diagnosis. The accuracy of the PCA modification‐based diagnostic criteria was 94.5%, and that of the machine learning algorithm 97.5%. Using a mouse model, this study demonstrates that diagnosing and classifying the severity of atherosclerosis is possible using a single blood drop, SERS technology, and machine learning algorithm, indicating the detectability of biomarkers and vascular factors in the blood which correlate with the early stages of atherosclerosis development.
Soluble CD80 oral delivery by recombinant Lactococcus suppresses tumor growth by enhancing antitumor immunity
Authors: Lin Ziqing , Tang Yanqing , Chen Zerong , Li Simin , Xu Xueyan , Hou Xufeng , Chen Zhenhui , Wen Junjie , Zeng Weisen , Meng Xiaojing , Fan Hongying 
Published: May 2023

AbstractCD80 is an important co‐stimulatory molecule that participates in the immune response. Soluble CD80 can induce T cell activation and overcome PDL1‐mediated immune suppression. In this study, we aimed to construct recombinant Lactococcus lactis for oral delivery of the soluble CD80 (hsCD80) protein or the fusion protein containing the cholera toxin B subunit (CTB) and hsCD80 (CTB‐hsCD80) under the control of the nisin‐inducible expression system. The recombinant L. lactis expressed and secreted hsCD80 or CTB‐hsCD80 fusion proteins after induction by nisin in vitro and in the enteric cavity. Additionally, the CTB‐hsCD80 fusion protein showed uptake by intestinal epithelial cells, was cleaved by the furin protease, and was released as free hsCD80 protein into the blood circulation. Orally administered hsCD80 and CTB‐hsCD80 containing L. lactis increased the proportion of activated T cells in the spleen and intestinal epithelium, inhibited tumor growth, and prolonged the survival of tumor‐bearing mice. The hsCD80‐containing L. lactis showed greater therapeutic effects on primary colonic adenoma in APCmin/− mice and completely suppressed tumor growth. Further, recombinant CTB‐hsCD80 in L. lactis was more efficient than hsCD80‐containing bacteria in inhibiting the growth of xenografted colon cancer and melanoma cells. hsCD80 engineered probiotics may serve as a promising new approach for antitumor immunotherapy, especially for colorectal cancer.
Biomimetic in situ tracheal microvascularization for segmental tracheal reconstruction in one‐step
Authors: Sun Fei , Shen Zhiming , Zhang Boyou , Lu Yi , Shan Yibo , Wu Qiang , Yuan Lei , Zhu Jianwei , Pan Shu , Wang Zhihao , Wu Cong , Zhang Guozhong , Yang Wenlong , Xu Xiangyu , Shi Hongcan 
Published: May 2023

AbstractFormation of functional and perfusable vascular network is critical to ensure the long‐term survival and functionality of the engineered tissue tracheae after transplantation. However, the greatest challenge in tracheal‐replacement therapy is the promotion of tissue regeneration by rapid graft vascularization. Traditional prevascularization methods for tracheal grafts typically utilize omentum or muscle flap wrapping, which requires a second operation; vascularized segment tracheal orthotopic transplantation in one step remains difficult. This study proposes a method to construct a tissue‐engineered tracheal graft, which directly forms the microvascular network after orthotopic transplantation in vivo. The focus of this study was the preparation of a hybrid tracheal graft that is non‐immunogenic, has good biomechanical properties, supports cell proliferation, and quickly vascularizes. The results showed that vacuum‐assisted decellularized trachea‐polycaprolactone hybrid scaffold could match most of the above requirements as closely as possible. Furthermore, endothelial progenitor cells (EPCs) were extracted and used as vascularized seed cells and seeded on the surfaces of hybrid grafts before and during the tracheal orthotopic transplantation. The results showed that the microvascularized tracheal grafts formed maintained the survival of the recipient, showing a satisfactory therapeutic outcome. This is the first study to utilize EPCs for microvascular construction of long‐segment trachea in one‐step; the approach represents a promising method for microvascular tracheal reconstruction.
Digital therapeutics in the clinic
Authors: Phan Philana , Mitragotri Samir , Zhao Zongmin 
Published: May 2023

AbstractDigital therapeutics are emerging as a new form of therapeutic interventions. Unlike conventional therapeutics, digital therapeutics deliver interventions directly to patients using an evidence‐based, clinically evaluated software to treat, manage, or prevent diseases. Digital therapeutics manifest in diverse forms such as web‐based applications, mobile applications on smart devices, virtual reality, and video games. As its own product category for FDA approval, digital therapeutics can function as stand‐alone treatments or in combination with conventional therapeutics to improve adherence and/or efficacy. Here, we review the clinical landscape of digital therapeutics. We summarize FDA‐approved products and their clinical use, overview >300 ongoing clinical trials, and discuss challenges for their clinical translation and strategies to overcome the same.
Correlation between KRAS mutation subtypes and prognosis in Chinese advanced non‐squamous non‐small cell lung cancer patients
Authors: Liu Feiwen , Wang Fang , He Jianbo , Zhou Shaozhang , Luo Min 
Published: May 2023

AbstractPurposeThe relationship between mutant KRAS and the risk of disease progression and death in advanced non‐squamous non‐small cell lung cancer (NSCLC) is still controversial among current studies, and the effects of distinct KRAS mutations on prognosis may be different. This study aimed to further investigate the association between them.Patients and MethodsOf the 184 patients eventually included in the study, 108 had KRAS wild type (WT) and 76 had KRAS mutant type (MT). Kaplan–Meier curves were plotted to describe the survival for patients among groups, while log‐rank tests were conducted to evaluate the survival differences. The univariate and multivariate Cox regression were performed to identify predictors, and subgroup analysis was used to verify the interaction effect.ResultsSimilar efficacy of first‐line therapy was observed for KRAS MT and WT patients (p = 0.830). The association between KRAS mutation and progression‐free survival (PFS) was not significant in univariate analysis (hazard ratio [HR] = 0.94; 95% CI, 0.66–1.35), and no KRAS mutation subtype significantly affected PFS. However, KRAS mutation and KRAS non‐G12C were associated with increased risk of death compared to KRAS WT in univariate and multivariate analysis. Univariate and multivariate analysis also confirmed that chemotherapy combined with antiangiogenesis or immunotherapy in the KRAS mutation group was associated with decreased risk of disease progression. However, the overall survival (OS) among KRAS mutant patients received different first‐line treatments did not significantly differ.ConclusionKRAS mutations and their subtypes are not independent negative predictors of PFS, while KRAS mutation and KRAS non‐G12C were independent prognostic factors for OS. Chemotherapy combined with antiangiogenesis or immunotherapy conferred decreased risk of disease progression to KRAS mutation patients compared to single chemotherapy.
A case series and literature review on 98 pediatric patients of germ cell tumor developing growing teratoma syndrome
Authors: Hsieh Ming‐Yun , Chen Hsin‐Hung , Lee Chih‐Ying , Hung Giun‐Yi , Chang Tsung‐Yen , Chen Shih‐Hsiang , Lai Jin‐Yao , Jaing Tang‐Her , Cheng Chao‐Neng , Chen Jiann‐Shiuh , Tsai Hsin‐Lin , Yu Ting‐Yen , Hou Ming‐Hsin , Ho Cheng‐Yin , Yen Hsiu‐Ju 
Published: May 2023

AbstractIntroductionMalignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited.MethodsWe retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS.ResultsThe sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety‐five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event‐free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5‐year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001).ConclusionFor patients with high‐risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.
Antiproliferative and Apoptotic Effects of pH‐Responsive Veratric Acid‐Loaded Polydopamine Nanoparticles in Human Triple Negative Breast Cancer Cells
Authors: Harini Ganesh , Shree Ganesh S. , Anushikaa Ramprasad , Bharathi Ramanathan , Aravind Sankaranarayanan , Vatsala Kumari , Shanmugavadivu Abinaya , Selvamurugan Nagarajan 
Published: May 2023

AbstractVeratric acid (VA) is plant‐derived phenolic acid known for its therapeutic potential, but its anticancer effect on highly invasive triple‐negative breast cancer (TNBC) is yet to be evaluated. Polydopamine nanoparticles (nPDAs) were chosen as the drug carrier to overcome VA's hydrophobic nature and ensure a sustained release of VA. We prepared pH‐sensitive nano‐formulations of VA‐loaded nPDAs and subjected them to physicochemical characterization and in vitro drug release studies, followed by cell viability and apoptotic assays on TNBC cells (MDA‐MB‐231 cells). The SEM and zeta analysis revealed spherical nPDAs were uniform size distribution and good colloidal stability. In vitro drug release from VA‐nPDAs was sustained, prolonged and pH‐sensitive, which could benefit tumor cell targeting. MTT and cell viability assays showed that VA‐nPDAs (IC50=17.6 μM) are more antiproliferative towards MDA‐MB‐231 cells than free VA (IC50=437.89 μM). The induction of early and late apoptosis by VA‐nPDAs in the cancer cells was identified using annexin V and dead cell assay. Thus, the pH response and sustained release of VA from nPDAs showed the potential to enter the cell, inhibit cell proliferation, and induce apoptosis in human breast cancer cells, indicating the anticancer potential of VA.
Unimolecular Reactivity of [Cu(R)(CF3)3]−Complexes (R=Organyl): Stepwise versus Concerted Mechanism in Copper‐Mediated Trifluoromethylation
Authors: Zimmer Bastian , Auth Thomas , Koszinowski Konrad 
Published: May 2023

AbstractThe cuprate complexes [Cu(R)(CF3)3]−(R=organyl) offer an efficient synthetic access to valuable trifluoromethylation products RCF3. Here, electrospray‐ionization mass spectrometry is used to analyze the formation of these intermediates in solution and probe their fragmentation pathways in the gas phase. Furthermore, the potential energy surfaces of these systems are explored by quantum chemical calculations. Upon collisional activation, the [Cu(R)(CF3)3]−complexes (R=Me, Et, Bu,sBu, allyl) afford the product ions [Cu(CF3)3]⋅−and [Cu(CF3)2]−. The former obviously results from an R⋅ loss, whereas the latter originates either from the stepwise release of R⋅ and CF3⋅ radicals or a concerted reductive elimination of RCF3. The gas‐phase fragmentation experiments as well as the quantum chemical calculations indicate that the preference for the stepwise reaction toward [Cu(CF3)2]−increases with the stability of the formed organyl radical R⋅. This finding suggests that the recombination of R⋅ and CF3⋅ radicals may possibly contribute to the formation of RCF3from [Cu(R)(CF3)3]−in synthetic applications. In contrast, the [Cu(R)(CF3)3]−complexes (R=aryl) only yield [Cu(CF3)2]−when subjected to collision‐induced dissociation. These species exclusively undergo a concerted reductive elimination because the competing stepwise pathway is disfavored by the low stability of aryl radicals.
Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues
Authors: García‐Marquina Guillermo , Núñez‐Franco Reyes , Grajales‐Hernández Daniel , Jiménez‐Osés Gonzalo , López‐Gallego Fernando 
Published: May 2023

AbstractThis study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p‐nitrophenyl esters have emerged as alternate substrates for LovD9‐catalyzed acylation. While vinyl esters can reach product yields as high as the ones obtained by α‐dimethyl butyryl‐S‐methyl‐3‐mercaptopropionate (DMB‐SMMP), the thioester for which LovD9 was evolved, p‐nitrophenyl esters display a reactivity even higher than DMB‐SMMP for the first acylation step yet the acylation product yield is lower. The reaction mechanisms were elucidated through quantum mechanics (QM) calculations.
Linguistic Framing of Artificial Intelligence: What Language to Use When Talking about Artificial Intelligence
Authors: Lammers Svenja , Lasch Alexander 
Published: May 2023

AbstractA psycholinguistic study was conducted to assess the level of trust in different fictional products with varying framing. It was found that the product type has the greatest influence on the level of acceptance, while the expert or layperson status of the participants has the least influence. The second most relevant influencing factor is framing. The level of trust is estimated higher by all groups when a product description using the frame SUPPORTING rather than the frames DECIDING or CONTROL is presented.
Interleaved boost converter open switch fault detection and reconfiguration using harmonic selection calculation
Authors: Badaoui Yacine , Gouichiche Abdelmadjid , Safa Ahmed , Messlem Youcef , Chibani Abdelilah , Chedjara Zakaria 
Published: May 2023

SummaryIn this paper, a new technique for open‐circuit switch fault (OCF) detection and reconfiguration of an interleaved boost converter (IBC) is proposed. Harmonic selection calculation (HSC) is elaborated from the frequency domain analysis using the Fourier transformer of the input current. The symmetric phase shifting of the inductor currents has induced some characteristics in the input current that make the HSC an interesting tool for the fault detection process of an OCF. The HSC consists of selecting the adequate harmonic for detecting and isolating an OCF with a thresholding strategy. The proposed approach can handle different operation modes such as CCM, DCM, load change, and parameter change. Besides the short‐time detection (less than one cycle), this technique is based on the measurement of the only used inductor currents, which means that it does not require any additional hardware. The effectiveness of the proposed HSC technique is verified by simulation and experimental tests for three interleaved boost converters under different situations, such as load change, conduction mode change, and OCF mode. The obtained results show the validity of the proposed technique.