bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of local anesthesia on ciliary dyskinesia diagnosis by digital high‐speed videomicroscopy
Authors: Benchimol Lionel , Bricmont Noemie , Bonhiver Romane , Hans Grégory A. , Lefebvre Philippe , Kempeneers Celine , Poirrier Anne‐Lise 
Published: October 2024

AbstractSummaryThis prospective study investigates the impact of local anesthesia on ciliary function in nasal epithelium. The primary objective was to assess whether lidocaine 2% and naphazoline 0.5% nasal spray alter ciliary beat frequency and pattern in subjects undergoing nasal brushing, aiming to enhance primary ciliary dyskinesia (PCD) diagnosis.HypothesisIt was hypothesized that local anesthesia administration would not significantly affect ciliary function in nasal epithelium.Study DesignA prospective, simple‐blind randomized study was conducted between 2020 and 2023. The study employed digital high‐speed videomicroscopy to analyze ciliary beat frequency and pattern.Patient/Subject SelectionA cohort of 38 participants was recruited, consisting of 25 healthy volunteers and 13 referred individuals (including seven diagnosed with PCD). Selection criteria ensured the absence of chronic respiratory diseases, recent respiratory tract infections, or regular use of nasal medications.MethodologyParticipants underwent nasal brushing with administration of lidocaine and naphazoline nasal spray in one nostril and saline in the contralateral nostril. Ciliary beat frequency and pattern were measured using digital high‐speed video microscopy.ResultsNasal spray administration did not significantly alter ciliary beat frequency or pattern compared to saline (p = 0.841 and p = 0.125, respectively). Subgroup analysis revealed consistent results across healthy volunteers, referred patients, and PCD patients.ConclusionLocal anesthesia with lidocaine and naphazoline spray did not affect ciliary function outcomes. These findings support the safe use of these agents in clinical practice for PCD diagnostic procedures. Further research with larger cohorts is warranted for validation.
Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone‐sensitive prostate cancer: A multicenter study
Authors: Yanagisawa Takafumi , Fukuokaya Wataru , Hatakeyama Shingo , Narita Shintaro , Muramoto Katsuki , Katsumi Kouta , Takahashi Hidetsugu , Urabe Fumihiko , Mori Keiichiro , Tashiro Kojiro , Iwatani Kosuke , Shimomura Tatsuya , Habuchi Tomonori , Kimura Takahiro 
Published: October 2024

AbstractPurposeWe aimed to assess the differential efficacy and safety of androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, and apalutamide, in patients with metastatic hormone‐sensitive prostate cancer (mHSPC) in a real‐world practice setting.MethodsWe retrospectively reviewed the records of consequent 668 patients with mHSPC treated with ARPI plus androgen deprivation therapy between September 2015 and December 2023. Based on the LATITUDE criteria, the comparison among abiraterone, enzalutamide, and apalutamide was exclusively conducted in high‐risk patients. Prostate‐specific antigen (PSA) responses such as the achievement of 95% and 99% PSA decline, overall survival (OS), cancer‐specific survival (CSS), time to castration‐resistant prostate cancer (CRPC), and the incidence of adverse events (AEs) were compared. All two‐group comparisons relied on propensity score matching (PSM) to minimize the effect on possible confounders.ResultsIn total, 297 patients with high‐risk mHSPC treated with abiraterone, 127 with enzalutamide, and 142 with apalutamide were compared. There were no differences in time to CRPC (p = 0.13), OS (p = 0.7), and CSS (p = 0.5) among the three ARPIs. No differences were observed in the achievement rates for 95% PSA decline at 3 months among the three ARPIs, while abiraterone was significantly better in 99% PSA decline achievement compared to apalutamide (72% vs. 57%, p = 0.003). The aforementioned oncologic outcomes were sustained even when performing PSM analyzes. Although skin rash for APA (34%) was the highest incidence of AEs, there were no differences in the rates of severe AEs across the three ARPIs. Enzalutamide resulted in the lowest treatment discontinuation rates (10%) other than disease progression compared to the other regimens.ConclusionsAbiraterone, enzalutamide, and apalutamide have comparable oncologic outcomes in terms of OS, CSS, and time to CRPC in patients with high‐risk mHSPC. Our data on differential treatment discontinuation rates, PSA response, and AE profiles can help guide clinical decision‐making.
Beauveria bassiana associated with a novel biomimetic hydrogel to control Aedes albopictus through lure and kill ovitraps
Authors: Friuli Marco , Lia Riccardo Paolo , Nitti Paola , Lamanna Leonardo , Otranto Domenico , Pombi Marco , Demitri Christian , Cafarchia Claudia 
Published: October 2024

AbstractBACKGROUNDWithin the framework of sustainable and effective control methods for Aedes albopictus, two different conidial suspensions, BbCS‐1 and BbCS‐2 (respectively without and with nutrients), were used as solvents for the biopolymers water‐soluble 2‐hydroxyethylcellulose (HEC) and sodium alginate (SA). In this way, two different classes of hydrogels were prepared for each polymer (previously shown to attract tiger mosquito oviposition) to produce HEC‐based and SA‐based Bb/Gel systems with and without nutrients. The aim was to achieve a long‐lasting and cost‐effective lure‐and‐kill oviposition substrate useful for lethal ovitraps. Beauveria bassiana (Bb) survival and growth in the different Bb/Gel systems were monitored for 24 days. Following the growth assay, 24‐day‐old Bb/Gel systems were tested against Ae. albopictus eggs through a hatching test to evaluate their lethal effect.RESULTSGel systems enhance Bb's longevity (up to 24 days) more effectively than standard liquid conidial suspensions, proving that tested HEC‐ and SA‐based hydrogels are not toxic for Bb (biocompatibility) and create a microenvironment suitable to sustain prolonged fungal growth. In particular, the results indicate that gel system based on hydroxyethylcellulose is a suitable delivery substrate for supporting the activity of Bb and is simultaneously effective against Ae. albopictus eggs through a combined mechanism of mechanical effect and fungal action (CM > 90%).CONCLUSIONThe efficacy of Bb gel systems was assessed according to its properties in favouring the growth and vitality of Bb as well as in reducing the Ae. albopictus hatching eggs rate. Further studies, in semi‐field and field conditions, will be useful to evaluate the efficacy of Bb/Gel systems on adults in terms of attraction, oviposition, mortality, and potential autodissemination to propose a new tool in precision pest management. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Uncovering the interleukin‐12 pharmacokinetic desensitization mechanism and its consequences with mathematical modeling
Authors: DeBonis Jonathon , Veiseh Omid , Igoshin Oleg A. 
Published: October 2024

AbstractThe cytokine interleukin‐12 (IL‐12) is a potential immunotherapy because of its ability to induce a Th1 immune response. However, success in the clinic has been limited due to a phenomenon called IL‐12 desensitization – the trend where repeated exposure to IL‐12 leads to reduced IL‐12 concentrations (pharmacokinetics) and biological effects (pharmacodynamics). Here, we investigated IL‐12 pharmacokinetic desensitization via a modeling approach to (i) validate proposed mechanisms in literature and (ii) develop a mathematical model capable of predicting IL‐12 pharmacokinetic desensitization. Two potential causes of IL‐12 pharmacokinetic desensitization were identified: increased clearance or reduced bioavailability of IL‐12 following repeated doses. Increased IL‐12 clearance was previously proposed to occur due to the upregulation of IL‐12 receptor on T cells that causes increased receptor‐mediated clearance in the serum. However, our model with this mechanism, the accelerated‐clearance model, failed to capture trends in clinical trial data. Alternatively, our novel reduced‐bioavailability model assumed that upregulation of IL‐12 receptor on T cells in the lymphatic system leads to IL‐12 sequestration, inhibiting the transport to the blood. This model accurately fits IL‐12 pharmacokinetic data from three clinical trials, supporting its biological relevance. Using this model, we analyzed the model parameter space to illustrate that IL‐12 desensitization occurs over a robust range of parameter values and to identify the conditions required for desensitization. We next simulated local, continuous IL‐12 delivery and identified several methods to mitigate systemic IL‐12 exposure. Ultimately, our results provide quantitative validation of our proposed mechanism and allow for accurate prediction of IL‐12 pharmacokinetics over repeated doses.
Polyphyllin VI Ameliorates Pulmonary Fibrosis by Suppressing the MAPK/ERK and PI3K/AKT Signaling Pathways via Upregulating DUSP6
Authors: Xie Yuting , Gan Cailing , Liu Hongyao , Hou Yusen , Su Xingping , Xue Taixiong , Wang Doudou , Li Peilin , Yue Lin , Qiu Qiwen , Xie Yongmei , He Jun , Ye Tinghong 
Published: October 2024

ABSTRACTPulmonary fibrosis (PF) is a lethal disease caused by inordinate repair of damaged lungs, for which limited strategies are available. Polyphyllin VI (PPVI), extracted and isolated from Paris polyphylla Smith var. chinensis (Franch.) Hara, has been regarded as an important traditional Chinese herbal medicine for the treatment of respiratory system diseases. This study evaluated effects of PPVI on PF and its underlying mechanism. Experimental procedure For evaluating the anti‐PF effect of PPVI, we established an in vivo PF mouse model via intratracheal infusion of bleomycin (BLM) in mice and an in vitro PF model induced by TGF‐β1 in NIH/3T3, HPF and A549, respectively. Subsequently, the mechanism of PPVI effects was further explored using RNA sequencing (RNA‐Seq). The in vivo and in vitro results demonstrated that PPVI significantly inhibited inflammation, oxidative damage, and epithelial‐mesenchymal transition. Furthermore, RNA sequencing indicated that PPVI ameliorated PF by modulating inflammation and oxidative stress responses. Furthermore, dual specificity phosphatase 6 (DUSP6), was the shared and most significant differentially expressed gene associated with inflammation and oxidative stress response after PPVI treatment. Mechanistically, silencing DUSP6 can eliminate the suppressive impact on PPVI for the activation of fibroblast and the phosphorylation of ERK and AKT. Summarily, our findings revealed the potential of PPVI in mitigating PF via upregulating DUSP6 and highlighted the regulatory function of DUSP6 in the pathogenesis of PF.
Impact of high hydrostatic pressure on casein micelle‐pea protein systems and comparison with heat treatment
Authors: Serrano León Gabriela , Gravel Alexia , Perreault Véronique , Pouliot Yves , Doyen Alain 
Published: October 2024

AbstractDeveloping mixed systems with both plant‐ and animal‐based proteins is crucial to address the limitations in the techno‐functional properties of plant‐based proteins. While the impact of thermal co‐aggregation on mixed systems has been extensively studied, there is limited information on the effects of non‐thermal processes. Therefore, this study aimed to compare the effects of high hydrostatic pressure (HHP, 600 MPa–5 min) and heat (90°C for 60 min) treatments on the protein profiles in a mixed micellar casein (CN):pea protein (PPI) system, while also elucidating the interactions involved in the formation of protein aggregates. Our results showed that both HHP and heat treatments induced the formation of soluble protein aggregates through disulfide bonds. However, protein aggregation was less prominent after application of HHP. In both treatments, the aggregates primarily consisted of convicilin, vicilin, legumin and lipoxygenase. However, albumin PA2 did not contribute to HHP‐induced aggregates, and vicilin played a lesser role in their formation compared to heat‐induced aggregates. CN from the HHP‐treated CN:PPI sample did not participate in aggregate formation, as previously demonstrated after heat treatment. The presence of residual whey proteins in the CN ingredients explained the formation of CN‐whey protein aggregates after heat treatment and, to a lesser extent, after HHP treatment.
A Nonparametric Global Win Probability Approach to the Analysis and Sizing of Randomized Controlled Trials With Multiple Endpoints of Different Scales and Missing Data: Beyond O'Brien–Wei–Lachin
Authors: Zou Guangyong , Zou Lily 
Published: October 2024

ABSTRACTMultiple primary endpoints are commonly used in randomized controlled trials to assess treatment effects. When the endpoints are measured on different scales, the O'Brien rank‐sum test or the Wei–Lachin test for stochastic ordering may be used for hypothesis testing. However, the O'Brien–Wei–Lachin (OWL) approach is unable to handle missing data and adjust for baseline measurements. We present a nonparametric approach for data analysis that encompasses the OWL approach as a special case. Our approach is based on quantifying an endpoint‐specific treatment effect using the probability that a participant in the treatment group has a better score than (or a win over) a participant in the control group. The average of the endpoint‐specific win probabilities (WinPs), termed the global win probability (gWinP), is used to quantify the global treatment effect, with the null hypothesis gWinP = 0.50. Our approach involves converting the data for each endpoint to endpoint‐specific win fractions, and modeling the win fractions using multivariate linear mixed models to obtain estimates of the endpoint‐specific WinPs and the associated variance–covariance matrix. Focusing on confidence interval estimation for the gWinP, we derive sample size formulas for clinical trial design. Simulation results demonstrate that our approach performed well in terms of bias, interval coverage percentage, and assurance of achieving a pre‐specified precision for the gWinP. Illustrative code for implementing the methods using SAS PROC RANK and PROC MIXED is provided.
Selenium Adsorption on the (111), (100), (110) and (211) Surfaces of Face‐Centered‐Cubic Metals: Density Functional Calculations of the Potential Energy Surfaces
Authors: Albarracín Rivera Rolando L. , Colon‐Ruiz Yomari L. , De La Torre‐Rosa Adriana , Garcia‐Ramos Andrea I. , Garcia‐Sanchez Alondra M. , Gierbolini‐Ortiz Lianellys , Lopez‐Torres Marialejandra , Ortiz‐Rodriguez Nasya , Rivera‐Rivera Vanessa A. , Santiago‐Soler Sofia C. , Siberon‐Albertorio Jerica A. , Silva‐Burgos Juliannie N. , Torres‐Morales Coralys , Santana Juan A. 
Published: October 2024

AbstractIn this study, we expand the computational investigation of selenium, which has previously been limited to metals such as Cu, Fe, Pd, Au, and Pt. Utilizing density functional theory calculations, we explore the adsorption and diffusion of selenium at a low‐coverage regime of 0.25 ML on a broader range of metal surfaces, including Ni, Cu, Rh, Pd, Ag, Ir, Pt, and Au. Our results reveal that selenium exhibits a distinct preference for three‐fold or four‐fold high‐coordination sites on most studied surfaces. We further analyze the minimum energy diffusion pathways, demonstrating that the energy barrier for selenium's surface diffusion varies significantly based on the orientation and nature of the metal surfaces. Specifically, on (100) surfaces, selenium exhibits the highest diffusion energy, ranging from 0.60 eV in Au(100) to 1.12 eV in Pd(100). The diffusion behavior on (110) and (211) surfaces is also elaborated, emphasizing the unique trends observed compared to previously studied elements like sulfur. Importantly, this study is a new reference for future computational analyses, filling existing gaps by providing comprehensive data on selenium adsorption on various face‐centered cubic metal surfaces not previously reported.
Thioesterification and Hydrothiolation of α, β‐Unsaturated Esters with Aliphatic Thiols under Mild Conditions
Authors: Shi Yijun , Yan Guoli , Yin Shuo , Cao Han , Bie Fusheng , Xiong Jie 
Published: October 2024

AbstractHerein the one‐pot thioesterification and hydrothiolation of α, β‐unsaturated esters with aliphatic thiols was reported at room temperature. The mechanism was indirectly revealed which α, β‐unsaturated thioester was the intermediate. The advantages of this method included transition‐metal‐free, mild conditions, broad substrate scope and good functional group tolerance. On the other hand, the hydrothiolation of α, β‐unsaturated aliphatic esters at room temperature was also developed.
Synthesis of New Fluorinated Tubastatin A Derivatives Based on Cyclopentane/Cyclohexane with Good Anti‐tumor Activity in Vitro
Authors: Mo Xiangdong , Liu Yinbo , Mo Xiaofeng , Luo Huaxin , Irfan Majeed , Deng Rong , Zhu Xiaofeng , Wang Hui , Zeng Zhuo 
Published: October 2024

AbstractTwo series of novel fluorinated Tubastatin A derivatives based on cyclopentane or cyclohexane substitution were first time synthesized by 5 steps at high yield. The influence of the cycloalkanes substituted N‐methylpiperidine and/or fluorinated group on the cap group of Tubastatin A for the in vitro anti‐tumor activity of seven different tumor cell lines (human hepatoma cells Bel7402 and HepG2, human nasopharyngeal carcinoma cells CNE2 and SUNE1, human breast cancer cells MDA‐MB‐231 and MCF‐7, and human pancreatic cancer cells SW1990) was investigated. Compared with Tubastatin A, these novel derivatives with fluorinated groups on the benzene ring of the cap group enhance activity, and modification of the N‐methylpiperidine to cycloalkanes of the cap group improves solubility. The most promising compound trifluoromethyl and cyclohexane substituted derivative, N‐hydroxy‐4‐((6‐(trifluoromethyl)‐1,2,3,4‐tetrahydro‐9H‐carbazol‐9‐yl)methyl) benza‐mide (6 h), had a wide range of anti‐tumor cell range, the IC50 value for human pancreatic cancer cell line SW1990 was 1.17 μM. Hence, fluorinated groups and cyclohexane result in a wide range of anti‐tumor cell range and good anti‐cancer activity.
Identification of Potent CHK2 Inhibitors‐Modulators for Therapeutic Application in Cancer: A Machine Learning Integrated Fragment‐Based Drug Design Approach
Authors: Sudhir Kolpe Mahima , Sardarsinh Suryawanshi Vikramsinh , Eldesoky Gaber E. , Hossain Dilnawaz , Chunarkar Patil Pritee , Bhowmick Shovonlal 
Published: October 2024

AbstractThe CHK2 protein regulates the cell division cycle and responds to DNA damage. Additionally, it facilitates the repair of DNA damage and maintains the integrity of its biological processes. Dysregulation of the CHK2 protein is associated with a predisposition to harmful diseases. The current research protocol was designed to identify novel hit molecules as CHK2 inhibitors and disrupt the normal biological function of the CHK2 protein via a fragment‐based drug discovery approach. The protocol involved generating fragments using the MacFrag tool, followed by a chemical similarity search utilizing RDKit to identify fragment molecules analogous to previously established CHK2 inhibitor scaffolds. The bioactive molecules were constructed using the Fragmenstein tool, followed by molecular docking simulations to investigate their binding affinity. In addition, pharmacokinetic properties were analyzed, and a molecular dynamics simulation study was conducted to assess the stability of selected compounds with CHK2 protein. Finally, five novel compounds were identified as excellent CHK2 inhibitors through the FBDD and show good binding interactions at active sites of CHK2 with beneficial ADMET properties. This research work presents novel CHK2 inhibitor molecules that have the potential to be utilized in drug discovery, serving as key leads for future advancements in healthcare industries and sectors.
Efficient Synthesis of Dithieno[3,2‐B:2’,3’‐d]Thiophenes Derivatives with Promising Optoelectronic Properties Via a One‐Pot, Two‐Step Method with Elemental Sulfur
Authors: Zhang Peng , Li Shiju , Li Zongmiao , Yuan Bowei , Liu Fanming , Zhou Shaodong 
Published: October 2024

AbstractDithieno[3,2‐b:2’,3’‐d]thiophene (DTT) derivative contains three annulated thiophene rings, which have attracted great attention in the field of materials due to its planar and conjugated molecular, structural rigidity, and increased solubility. Herein, the one‐step modular construction of a series of structurally well‐defined 2,6‐disubstituted dithieno[3,2‐b:2’,3’‐d]thiophenes (2,6‐DTT) involves Pd/Cu(I)‐catalyzed Sonogashira coupling and LiNH2‐mediated ring‐closing reaction with element sulfur was reported. The method allows the selective and straightforward introduction of different aryl substitution into DTT without otherwise tedious separation and purification processes. The preliminary study of the thermal and photophysical properties demonstrated that the introduction of substituent in phenyl has great impact for the parent molecule, which enable this protocol to synthesis high‐performance 2,6‐DTT through the different alkynes.
Efficient CuOAc/DMAP/DEAD‐Catalyzed Aerobic Oxidative Synthesis of Quinazolines
Authors: Ji Yue , Dang Ze‐Lin , Niu Meng‐Long , Gao Qiang , Liu Xuemei 
Published: October 2024

AbstractEfficient approaches toward the synthesis of quinazolines and dihydroisoquinolines have been developed through copper‐catalyzed aerobic oxidative dehydrogenation of N‐heterocycles. The dehydrogenation was achieved through copper‐catalyzed aerobic oxidative dehydrogenation and azodicarboxylate esters‐mediated dehydrogenation of amines. Azodicarboxylate esters could be regenerated from copper‐catalyzed dehydrogenation of corresponding hydrazodicarboxylate esters, which made this catalytic dehydrogenation process more efficient and reactive.
Study on Transformation of Glassy and Crystalline Inclusions in Cord Steel during Heat Treatment at 1100 °C
Authors: Lei Xubo , Li Jianli , Zeng Qiang , Yu Yue , Zhu Hangyu 
Published: October 2024

To clarify the transformation of the glassy and crystalline inclusions in cord steel during heat treatment, four groups of MnO–SiO2–Al2O3 systems with different MgO contents are designed to obtain samples with both glassy and crystalline inclusions by slow‐cooling, and then the samples are isothermal held at 1100 °C for 120 min. The results of X‐ray diffraction and scanning electron microscope and energy dispersive spectrometer indicate that after isothermal holding, the MgMnSiO4 crystalline phase transforms into MgAl2O4 and MnSiO3 phases in 5 wt% MgO system, while partial MgMnSiO4 phase transforms into MgSiO3 phase in 10 wt% MgO system. Besides, the MgMnSiO4 crystalline phase transforms into MgSiO3 and Mg2SiO4 phases in 15 wt% MgO system, while the Mg2SiO4 crystalline phase partially transforms into MgSiO3 phase in 20 wt% MgO system. Combined with the calculation results of FactSage 8.1, it shows that the higher the MgO content in the system, the stronger the crystallization ability and the easier the formation of the crystalline phase. During the isothermal holding process, the elements in inclusions continuously diffuse and migrate, so that the glassy phase transforms into crystalline phase, while the crystalline phase grows further and the internal glassy phase disappear, accompanied by the transformation of the crystal type.