bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation of Dissolved Organic Matter Chemistry in the Runoff From Slopes Covered With Biocrusts Under Rainfall: Insights From the Linkages Between the Optical and Molecular Composition Analyses
Authors: Chen Guo , Wang Hao , Zhang Qing‐wei , Geng Ren , Wang Jian , Yi Yuan‐bi , Li Ming , He Ding
Published: October 2024

Variation of dissolved organic matter (DOM) largely affects the regional and even global carbon cycle. Both optical techniques and ultra‐high‐resolution mass spectrometry have their advantages and disadvantages, and the combination of them can better track DOM cycles. However, the relationship between the optical and molecular characteristics of DOM in the runoff from slopes covered with biocrusts are still unclear. Therefore, optical techniques and Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR MS) were combined to explore the DOM composition in the runoff from different runoff plots (i.e., bare runoff plot [BP], cyanobacterial crusts covered runoff plot [CP], mixed crusts covered runoff plot [MIP], moss crusts covered runoff plot [MOP]) under different rainfall intensities in the current study. The findings stated that the runoff from BP and CP exhibited a higher proportion of terrestrial DOM under heavy rainfall intensity (HRI), whereas DOM in the runoff from MIP and MOP were primarily controlled by microbial sources. The DOM unique molecules in the runoff from CP were more recalcitrant under HRI than those under light rainfall intensity (LRI), and these differences decreased with the increased with the succession stage of biocrusts. The results of aromaticity characterized by optical method and FT‐ICR MS were generally consistent. Meanwhile, Spearman correlation analysis also indicated that the optical parameters can be utilized for the estimation of molecular characteristics and labile in the runoff from slopes covered with biocrusts after the necessary calibration of the correction between the optical and molecular parameters.
Effective elasto‐(visco)plastic coefficients of a bi‐phasic composite material with scale‐dependent size effects
Authors: Giammarini Alessandro , Ramírez‐Torres Ariel , Grillo Alfio
Published: October 2024

We employ the theory of asymptotic homogenization (AH) to study the elasto‐plastic behavior of a composite medium comprising two solid phases, separated by a sharp interface and characterized by mechanical properties, such as elastic coefficients and “initial yield stresses” (i.e., a threshold stress above which remodeling is triggered), that may differ up to several orders of magnitude. We speak of “plastic” behavior because we have in mind a material behavior that, to a certain extent, resembles plasticity, although, for biological systems, it embraces a much wider class of inelastic phenomena. In particular, we are interested in studying the influence of gradient effects in the remodeling variable on the homogenized mechanical properties of the composite. The jump of the mechanical properties from one phase to the other makes the composite highly heterogeneous and calls for the determination of effective properties, that is, properties that are associated with a homogenized “version” of the original composite, and that are obtained through a suitable averaging procedure. The determination of the effective properties results convenient, in particular, when it comes to the multiscale description of inelastic processes, such as remodeling in soft or hard tissues, like bones. To accomplish this task with the aid of AH, we assume that the length scale over which the heterogeneities manifest themselves is several orders of magnitude smaller than the characteristic length scale of the composite as a whole. We identify both a fine‐scale problem and a coarse‐scale problem, each of which characterizes the elasto‐plastic dynamics of the composite at the corresponding scale, and we discuss how they are reciprocally coupled through a transfer of information from one scale to the other. In particular, we highlight how the coarse‐scale plastic distortions influence the fine‐scale problem. Moreover, in the limit of negligible hysteresis effects, we individuate two viscoplastic effective coefficients that encode the information of the two‐scale nature of the composite medium in the upscaled equations. Finally, to deal with a case study tractable semi‐analytically, we consider a multilayered composite material with an initial yield stress that is constant in each phase. Such investigation is meant to contribute to the constitution of a robust framework for devising the effective properties of hierarchical biological media.
Gain enhancement of compact CPW‐Fed ultra‐wideband antenna using an FSS reflector
Authors: Hammache Boualem , Messaoudene Idris , Belazzoug Massinissa , Titouni Salem , Messai Abderraouf , Denidni Tayeb A.
Published: October 2024

In this paper, an enhancement gain of compact CPW‐Fed antenna using a single layer frequency selective surfaces (FSSs) reflector for ultra‐wideband (UWB) applications is presented. A hexagonal CPW‐Fed antenna with a size of 30 × 30 mm2 is realized to provide a UWB bandwidth operation. In this study, a novel design of an FSS unit cell with reduction and a small size of 8 × 8 mm2 is proposed. It allows one to achieve a UWB band‐stop response between 3 and 11.5 GHz. The FSS reflector has 7 × 7 units with a total size of 56 × 56 mm2. This reflector is placed below the antenna at a distance of 20 mm. The main objective of this contribution is to improve the gain level of the antenna, where the proposed antenna achieves an improvement of realized gain of 6.2 dBi with increasing from 2.2 to 8.4 dBi. The antenna became more directive after the integration of the FSS reflector with a directional radiation pattern. The numerical and experimental results are in good concordance with the simulated one. This study is performed in terms of voltage standing wave ratio, radiation pattern, realized gain, and radiation efficiency.
Determination of the pKa Value of a Brønsted Acid by 19F NMR Spectroscopy
Authors: Griffiths Emily F. , Dixon Jay A. , Caffyn Andrew J. M. , Langley Stuart K. , Maciá Beatriz , Caprio Vittorio , Mewis Ryan E.
Published: October 2024

Brønsted acids, such as phosphoric acids derived from chiral 1,1′‐bi‐2‐naphthol (BINOL), are important catalysts in the formation of carbon–carbon and carbon–heteroatom bonds, for example. The catalytic activity of these Brønsted acids is strongly linked to their acidity, and as such, the evaluation of compounds to determine pKa values provides insight into their catalytic activity. Herein, a 19F{1H} NMR methodology is detailed to determine the pKa of a fluorinated binaphthyl‐derived phosphinic acid, rac‐1, in acetonitrile and in the presence of a fluorinated sulfonamide reference compound (2–4). The approach was tested initially using 2 and 3, with the ΔpKa (0.08) in strong agreement with previously reported values (6.6 for 2 and 6.68/6.73 for 3). Sigmoidal curves of normalised chemical shift change (Δδ) against equivalents of the base phosphazene P1‐tBu added overlapped for 2 and 3, but in the case of rac‐1 and either 2, 3 or 4, there was significant separation. A variety of different approaches for determining the ΔpKa were compared. Values of pKa determined when the normalised Δδ was 90% were optimal for 2 and 3, whereas a normalised Δδ of 75% was optimal for 4, resulting in the pKa of rac‐1 being determined to be 8.47–8.71.
Speedy Component Resolution Using Spatially Encoded Diffusion NMR Data
Authors: Lorandel Benjamin , Rocha Hugo , Cazimajou Oksana , Mishra Rituraj , Bernard Aurélie , Bowyer Paul , Nilsson Mathias , Dumez Jean‐Nicolas
Published: October 2024

Diffusion‐ordered NMR spectroscopy (DOSY) is a powerful tool to analyse mixtures. Spatially encoded (SPEN) DOSY enables recording a full DOSY dataset in just one scan by performing spatial parallelisation of the gradient dimension. The simplest and most widely used approach to processing DOSY data is to fit each peak in the spectrum with a single or multiple exponential decay. However, when there is peak overlap, and/or when the diffusion decays of the contributing components are too similar, this method has limitations. Multivariate analysis of DOSY data, which is an attractive alternative, consists of decomposing the experimental data, into compound‐specific diffusion decays and 1D NMR spectra. Multivariate analysis has been very successfully used for conventional DOSY data, but its use for SPEN DOSY data has only recently been reported. Here, we present a comparison, for SPEN DOSY data, of two widely used algorithms, SCORE and OUTSCORE, that aim at unmixing the spectra of overlapped species through a least square fit or a cross‐talk minimisation, respectively. Data processing was performed with the General NMR Analysis Toolbox (GNAT), with custom‐written code elements that now expands the capabilities, and makes it possible to import and process SPEN DOSY data. This comparison is demonstrated on three different two‐component mixtures, each with different characteristics in terms of signal overlap, diffusion coefficient similarity, and component concentration.
Color‐map recommendation for MR relaxometry maps
Authors: Fuderer Miha , Wichtmann Barbara , Crameri Fabio , de Souza Nandita M. , Baeßler Bettina , Gulani Vikas , Wang Meiyun , Poot Dirk , de Boer Ruud , Cashmore Matt , Keenan Kathryn E. , Ma Dan , Pirkl Carolin , Sollmann Nico , Weingärtner Sebastian , Mandija Stefano , Golay Xavier
Published: October 2024

Purpose

To harmonize the use of color for MR relaxometry maps and therefore recommend the use of specific color‐maps for representing , , and maps and their inverses.

Methods

Perceptually linearized color‐maps were chosen to have similar color settings as those proposed by Griswold et al. in 2018. A Delphi process, polling the opinion of a panel of 81 experts, was used to generate consensus on the suitability of these maps.

Results

Consensus was reached on the suitability of the logarithm‐processed Lipari color‐map for and the logarithm‐processed Navia color‐map for and . There was consensus on color bars being mandatory and on the use of a specific value indicating “invalidity.” There was no consensus on whether the ranges should be fixed per anatomy.

Conclusion

The authors recommend the use of the logarithm‐processed Lipari color‐map for displaying quantitative maps and maps; likewise, the authors recommend the logarithm‐processed Navia color‐map for displaying , , , and maps.

This work originated with the Quantitative MR Study Group of the International Society of Magnetic Resonance in Medicine (ISMRM); it has the approval of the Publication Committee and of the Board of the ISMRM.
Highly efficient image navigator based 3D whole‐heart cardiac MRA at 0.55T
Authors: Castillo‐Passi Carlos , Kunze Karl P. , Crabb Michael G. , Munoz Camila , Fotaki Anastasia , Neji Radhouene , Irarrazaval Pablo , Prieto Claudia , Botnar René M.
Published: October 2024

Purpose

To develop and evaluate a highly efficient free‐breathing and contrast‐agent‐free three‐dimensional (3D) whole‐heart Cardiac Magnetic Resonance Angiography (CMRA) sequence at 0.55T.

Methods

Free‐breathing whole‐heart CMRA has been previously proposed at 1.5 and 3T. Direct application of this sequence to 0.55T is not possible due to changes in the magnetic properties of the tissues. To enable free‐breathing CMRA at 0.55T, pulse sequence design and acquisition parameters of a previously proposed whole‐heart CMRA framework are optimized via Bloch simulations. Image navigators (iNAVs) are used to enable nonrigid respiratory motion‐correction and 100% respiratory scan efficiency. Patch‐based low‐rank denoising is employed to accelerate the scan and account for the reduced signal‐to‐noise ratio at 0.55T. The proposed approach was evaluated on 11 healthy subjects. Image quality was assessed by a clinical expert (1: poor to 5: excellent) for all intrapericardiac structures. Quantitative evaluation was performed by assessing the vessel sharpness of the proximal right coronary artery (RCA).

Results

Optimization resulted in an imaging flip angle of , fat saturation flip angle of , and six k‐space lines for iNAV encoding. The relevant cardiac structures and main coronary arteries were visible in all subjects, with excellent image quality (mean ) and minimal artifacts (mean ), with RCA vessel sharpness () comparable to previous studies at 1.5T.

Conclusion

The proposed approach enables 3D whole‐heart CMRA at 0.55T in a 6‐min scan (), providing excellent image quality, minimal artifacts, and comparable vessel sharpness to previous 1.5T studies. Future work will include the evaluation of the proposed approach in patients with cardiovascular disease.
MR electrical properties mapping using vision transformers and canny edge detectors
Authors: Giannakopoulos Ilias I. , Carluccio Giuseppe , Keerthivasan Mahesh B. , Koerzdoerfer Gregor , Lakshmanan Karthik , De Moura Hector L. , Cruz Serrallés José E. , Lattanzi Riccardo
Published: October 2024

Purpose

We developed a 3D vision transformer‐based neural network to reconstruct electrical properties (EP) from magnetic resonance measurements.

Theory and Methods

Our network uses the magnitude of the transmit magnetic field of a birdcage coil, the associated transceive phase, and a Canny edge mask that identifies the object boundaries as inputs to compute the EP maps. We trained our network on a dataset of 10 000 synthetic tissue‐mimicking phantoms and fine‐tuned it on a dataset of 11 000 realistic head models. We assessed performance in‐distribution simulated data and out‐of‐distribution head models, with and without synthetic lesions. We further evaluated our network in experiments for an inhomogeneous phantom and a volunteer.

Results

The conductivity and permittivity maps had an average peak normalized absolute error (PNAE) of 1.3% and 1.7% for the synthetic phantoms, respectively. For the realistic heads, the average PNAE for the conductivity and permittivity was 1.8% and 2.7%, respectively. The location of synthetic lesions was accurately identified, with reconstructed conductivity and permittivity values within 15% and 25% of the ground‐truth, respectively. The conductivity and permittivity for the phantom experiment yielded 2.7% and 2.1% average PNAEs with respect to probe‐measured values, respectively. The in vivo EP reconstruction truthfully preserved the subject's anatomy with average values over the entire head similar to the expected literature values.

Conclusion

We introduced a new learning‐based approach for reconstructing EP from MR measurements obtained with a birdcage coil, marking an important step towards the development of clinically‐usable in vivo EP reconstruction protocols.
Vomiting despite adherence to guidelines: Suboptimal control of vomiting in pediatric cancer patients
Authors: Ben‐Kenan Rotem Fishel , Stafford Lily K. , Temkit M'hamed , Brown Jamie , Walsh Alexandra
Published: October 2024

Objective

Vomiting is a common and distressing acute side effect of chemotherapy, negatively impacting quality of life, nutritional status, and the ability of patients to tolerate further treatment. Standardized guidelines have been developed to improve control of nausea and vomiting. We aimed to determine the benefit of adherence to clinical practice guidelines (CPGs) on complete control of acute chemotherapy‐induced vomiting in newly diagnosed pediatric patients with cancer.

Methods

An electronic dashboard of pediatric patients newly diagnosed with cancer at Phoenix Children's Hospital between August 2019 and January 2021 and receiving their first cycle of chemotherapy was utilized to monitor chemotherapy regimen, antiemetic medications, and vomiting episodes. Blocks were classified as guideline‐inconsistent, guideline‐consistent, or guideline‐consistent PLUS if additional prophylactic antiemetic medications were utilized. We identified patients with complete control of vomiting, defined as no vomiting and no additional antiemetics needed.

Results

Among 136 patients, 29% received guideline‐inconsistent care, 37% received guideline‐consistent care, and 34% received guideline‐consistent PLUS care. Overall, 48% of patients achieved complete control of vomiting. Older patients (p < 0.0001) and those receiving higher emetogenicity chemotherapy (p = 0.0003) were more likely to receive guideline‐consistent or guideline‐consistent PLUS therapy. With guideline‐consistent and ‐consistent PLUS grouped together, the diagnosis was also associated with improved adherence to CPGs (p = 0.022). Multivariate analysis showed that patients more likely to receive guideline‐consistent prophylaxis were of older age (OR 1.11, p = 0.016) and solid tumor patients (OR 5.59, p = 0.028).

Conclusions

Despite high rates of CPG adherence, complete control of vomiting remains suboptimal, which highlights the need for novel and/or risk‐adapted therapies.
Auer rod‐positive acute leukemia with predominantly lymphoid immunophenotype: Report on 11 cases and review of literature
Authors: Hrusak Ondrej , Stancikova Jitka , Vodickova Elena , Podolska Tereza , Möricke Anja , Attarbaschi Andishe , Dworzak Michael , Sestakova Zuzana , Svec Peter , Zaliova Marketa Kubricanova , Janotova Iveta , Zapletal Ondrej , Mejstrikova Ester , Stary Jan
Published: October 2024

Background

Auer rods (AuRs) are prominent intracellular structures found almost exclusively in myeloid cell malignancies, such as acute myeloid leukemia (AML), chronic and juvenile myelomonocytic leukemia and myelodysplastic syndrome. Extremely rare AuRs have been reported in patients with acute lymphoblastic leukemia (ALL) or among ambiguous lineage leukemia patients with a dominantly lymphoblastic immunophenotype.

Procedure

We report diagnostic and follow‐up data of an international cohort of 11 children suffering from leukemias with AuRs and with significant presence of T and myeloid markers, majority of whom categorized as early T‐cell precursor (ETP, n = 7); or T‐ALL (ETP status unknown, n = 2), ALAL (acute leukemia of ambiguous lineage, n = 1), and AML reclassified from ALAL (n = 1). We described other diagnostic details and treatment types and responses. Moreover, we summarize previously published data.

Results

Among the four patients who started and remained on ALL‐type therapy, all were in the first complete remission, whereas both patients who started and remained on AML‐type therapy relapsed and died. Of the patients who followed either a combined ALL/AML protocol (Interfant 06) or who switched from one of the two types of therapy to the other, one patient died, and the remaining four were in first complete remission at the most recent follow‐up. We also searched for similar cases in the literature and found only three additional children with nonmyeloid leukemia and AuRs and 10 adults with this type of leukemia.

Conclusions

Briefly, ALL‐ or combined ALL/AML‐type therapy may be effective for treating AuR‐positive leukemia patients with a lymphoid immunophenotype.
A 19F Solvatomagnetic Comparison Method for the Determination of the α1 Scale of Solvent Hydrogen‐Bond Donation and Its Application to Deep Eutectic Solvents
Authors: Laurence Christian , Mansour Sergui , Vuluga Daniela , Legros Julien
Published: October 2024

We develop a nonsolvatochromic comparison method for the determination of the α1 scale of solvent hydrogen‐bond acidity by means of 19F NMR spectrometry. We compare the 19F chemical shifts of 4‐fluoro‐2‐methylpyridine (as a sensitive hydrogen‐bond acceptor probe) and of 4‐fluoronitrobenzene (as a chemically similar but less basic reference probe). This so‐called 19F solvatomagnetic comparison method yields the hydrogen‐bonding contribution to δ (19F)(4‐fluoro‐2‐methylpyridine) that is well correlated to α1 values obtained from the solvatochromism of Reichardt's betaine dye. Therefore, this solvatomagnetic comparison method is applied to determine the α1 values of 13 choline chloride–based deep eutectic solvents.
Radiometric calibration of UAV multispectral images under changing illumination conditions with a downwelling light sensor
Authors: Swaminathan Vaishali , Thomasson J. Alex , Hardin Robert G. , Rajan Nithya , Raman Rahul
Published: October 2024

Unmanned aerial vehicle (UAV)‐acquired multispectral images commonly suffer from radiometric inaccuracies due to changing illumination produced by intermittent cloud cover. This study addressed cloud shadow effects by integrating direct irradiance measurements from a downwelling light sensor into reflectance calculations. Two reflectance calibration methods were proposed as follows: (1) use of a single calibration reference panel for all images (Method 1) and (2) employment of a minimum distance classifier to assign color‐graded in‐field reflectance calibration targets to individual images based on their proximity in irradiance levels (Method 2). Images were acquired from 30 and 75 m flight altitudes with fixed‐exposure and auto‐exposure settings. Conventional photogrammetric calibration of UAV multispectral images inadequately addressed cloud shadows, resulting in orthomosaics with poor to moderate spatial uniformity (R2 = 0.70–0.92) and high mean absolute percentage error (MAPE = 13.52%–49.18%). The proposed calibration methods improved radiometric accuracy, yielding average R2 = 0.99 and 0.98 at 30 and 75 m images, respectively. Method 1 showed superior performance on the red‐edge and near infrared bands, and Method 2 worked best in the blue, green, and red bands. Post‐processing empirical line calibration of orthomosaics from Methods 1 and 2 reduced MAPE in reflectance estimation by at least 50% compared to conventional calibration. The clear sky reference histograms had lower Jensen–Shannon distance, higher Pearson's correlation, and improved intersection ratios with the histograms from the proposed methods, implying high similarity. Vegetation indices calculated with the proposed methods closely matched those from the reference orthomosaic, exhibiting significantly lower MAPE than conventionally calculated vegetation indices.
Stronger increase of methane emissions from coastal wetlands by non‐native Spartina alterniflora than non‐native Phragmites australis
Authors: Fuchs Andrea , Davidson Ian C. , Megonigal J. Patrick , Devaney John L. , Simkanin Christina , Noyce Genevieve L. , Lu Meng , Cott Grace M.
Published: October 2024

Societal Impact Statement

The invasive species S. alterniflora and P. australis are fast growing coastal wetland plants sequestering large amounts of carbon in the soil and protect coastlines against erosion and storm surges. In this global analysis, we found that Spartina and Phragmites increase methane but not nitrous oxide emissions, with Phragmites having a lesser effect. The impact of the invasive species on emissions differed greatly among different types of native plant groups, providing valuable information to managers and policymakers during coastal wetland planning and restoration efforts. Further, our estimated net emissions per wetland plant group facilitate regional and national blue carbon estimates.

Globally, Spartina alterniflora and Phragmites australis are among the most pervasive invasive plants in coastal wetland ecosystems. Both species sequester large amounts of atmospheric carbon dioxide (CO2) and biogenic carbon in soils but also support production and emission of methane (CH4). In this study, we investigated the magnitude of their net greenhouse gas (GHG) release from invaded and non‐invaded habitats.

We conducted a meta‐analysis of GHG fluxes associated with these two species and related soil carbon content and plant biomass in invaded coastal wetlands.

Our results show that both invasive species increase CH4 fluxes compared to uninvaded coastal wetlands, but they do not significantly affect CO2 and N2O fluxes. The magnitude of emissions from Spartina and Phragmites differs among native habitats. GHG fluxes, soil carbon and plant biomass of Spartina‐invaded habitats were highest compared to uninvaded mudflats and succulent forb‐dominated wetlands, while being lower compared to uninvaded mangroves (except for CH4).

This meta‐analysis highlights the important role of individual plant traits as drivers of change by invasive species on plant‐mediated carbon cycles.
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

This 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.

Hypothesis

It was hypothesized that local anesthesia administration would not significantly affect ciliary function in nasal epithelium.

Study Design

A 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 Selection

A 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.

Methodology

Participants 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.

Results

Nasal 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.

Conclusion

Local 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

Purpose

We 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.

Methods

We 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.

Results

In 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.

Conclusions

Abiraterone, 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

BACKGROUND

Within 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.

RESULTS

Gel 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%).

CONCLUSION

The 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

The 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

Pulmonary 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

Developing 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

Multiple 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

In 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

Herein 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

Two 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

The 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

Dithieno[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

Efficient 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.
Poly(4‐Vinylpyridine)‐Based Cubosomes: Synthesis, Assembly, and Loading Capabilities
Authors: Schumacher Marcel , Tänzer Nadine , Braun Marius G. , Trömer Manuel , Quintieri Giada , Goel Mahima , Heidelmann Markus , Gröschel André H.
Published: October 2024

Polymer cubosomes (PCs) are 3D porous microparticles with high surface area that have great potential for applications that require a large interfacial area including catalysis, drug delivery, and energy storage. Most reported PCs are based on chemically inert block copolymers (BCPs) with limited intrinsic functionality, which is why they have been mainly used as templating material. Herein, the synthesis, self‐assembly, and loading of poly(4‐vinylpyridine) (P4VP)‐based PCs are reported. The pyridinic moieties are located inside the PC wall and are well‐known functional groups for coordination, cross‐linking, and pH response, which is demonstrated on platinum coordination and pH‐dependent dye release.