bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor‐Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers
Authors: Takusagawa Shin , Treijtel Nicoline , Saito Masako , Michon Ingrid , Miyatake Daisuke , Osaki Fumio , Guro Sayuri , Fadini Tomasso , Sekino Hisakuni , Aarden‐Bakker Marlous , Kuroishi Kentaro , van Till Jan Willem Olivier , Groenendaal‐van de Meent Dorien , de Vries Michiel
Published: August 2024

ASP8302 is an orally administered positive allosteric modulator of the muscarinic M3 receptor. Two Phase 1 studies were conducted, a first‐in‐human study in Europe and a Japanese phase 1 study. Both were randomized, participant‐ and investigator‐blinded, placebo‐controlled, single and multiple ascending oral doses, parallel group, clinical studies in healthy volunteers. Both studies evaluated safety and pharmacokinetics and also included salivary secretion and pupil diameter as pharmacodynamic assessments. There were no deaths, serious adverse events, or treatment‐emergent adverse events reported leading to study discontinuation. There were no clinically relevant findings in any of the laboratory, vital signs, electrocardiogram assessments, or photosensitivity testing following multiple administration of up to 150 mg or up to 140 mg once daily for 14 days in the European first‐in‐human and Japanese Phase 1 study, respectively. The pharmacokinetics of ASP8302 were approximately linear over the dose range studied. There was no evidence of drug accumulation upon repeated dosing. In both studies, ASP8302 showed a dose‐dependent pharmacodynamic effect on saliva production at doses from 100 mg onward, which was maintained during repeated dosing. No effect was observed on pupil diameter. These data supported progression of ASP8302 into Phase 2 clinical trials for further clinical development.
In Silico Design, Chemical Synthesis, Biophysical and in Vitro Evaluation for the Identification of 1‐Ethyl‐1H‐Pyrazolo[3,4‐b]Pyridine‐Based BRD9 Binders
Authors: Colarusso Ester , Gazzillo Erica , Pierri Martina , Ruggiero Dafne , Chini Maria Giovanna , Bruno Ines , Bifulco Giuseppe , Terracciano Stefania , Lauro Gianluigi
Published: August 2024

In this work, we report the identification of novel bromodomain‐containing protein 9 (BRD9) binders through a virtual screening based on our developed 3D structure‐based pharmacophore model. The in silico workflow here described led to the identification of a promising initial hit (1) featuring the 1‐ethyl‐1H‐pyrazolo[3,4‐b]pyridine motif which represented an unexplored chemotype for the development of a new class of BRD9 ligands. The encouraging biophysical results achieved for compound 1 prompted us to explore further tailored structural modification around the C‐4 and C‐6 positions of the central core. Hence, the design and synthesis of a set of 19 derivatives (2–20) were performed to extensively investigate the chemical space of BRD9 binding site. Among them, four compounds (5, 11, 12, and 19) stood out in biophysical assays as new valuable BRD9 ligands featuring IC50 values in the low‐micromolar range. Noteworthy, a promising antiproliferative activity was detected in vitro for compound 5 on HeLa and A375 cancer cell line. The successful combination and application of in silico tools, chemical synthesis, and biological assays allowed to identify novel BRD9 binders and to expand the arsenal of promising chemical entities amenable to the recognition of this important epigenetic target.
Recycling Valuable Phenol from Polycarbonate Plastic Waste Via Direct Depolymerization and Csp2−Csp3 Bond Cleavage Under Mild Conditions
Authors: Manal Arjun K. , Rajendra Kanchan Dipika , Banerjee Arghya , Zhao Jun , Srivastava Rajendra
Published: August 2024

Upcycling plastic waste into commodity chemicals is recognized as an environmentally benign solution and beneficial for the sustained growth of humanity. Nevertheless, transition metal‐free catalysts and energy‐efficient conditions pose significant challenges due to the robust mechanical properties of plastics. Here, a strategy for selective production of phenol by upcycling polycarbonate waste via direct depolymerization and Csp2−Csp3 bond cleavage in an aqueous medium under mild conditions is reported. The commercial zeolites efficiently catalyze the depolymerization, Csp2−Csp3 bond hydrolysis, and direct Csp2−Csp3 bond scission at Cα of PC. Among all evaluated zeolites, HY (Si/Al=15) showed excellent catalytic performance, attributed to the ~75 % yield of phenol and ~15 % of acetone. The approach also employs different municipal waste PC for upcycling. Studies reveal that HY (15) exhibits high catalytic efficiency and phenol yield due to its optimum acid sites and textual properties. A scale‐up experiment demonstrated that 3.1 g of phenol was produced from 5.0 g of PC, and the mass balance was 90 %. A combination of control experiments, NMR analysis, and DFT studies proposed the reaction pathway. Our findings present a sustainable avenue for upcycling PC waste and offer a new way to produce phenol, contributing to the advancement of a circular economy.
Circulating sphingolipids in relation to cognitive decline and incident dementia: The Cardiovascular Health Study
Authors: Moseholm Kristine F. , Cronjé Héléne T. , Koch Manja , Fitzpatrick Annette L. , Lopez Oscar L. , Otto Marcia C. de Oliveira , Longstreth W. T. , Hoofnagle Andrew N. , Mukamal Kenneth J. , Lemaitre Rozenn N. , Jensen Majken K.
Published: August 2024

INTRODUCTION

Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain.

METHODS

We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini–Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia.

RESULTS

Higher plasma levels of sphingomyelin‐d18:1/16:0 (SM‐16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin‐d18:1/22:0 (SM‐22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM‐16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08–1.44]) and ceramide‐d18:1/16:0 (Cer‐16) (HR = 1.26 [95% CI: 1.10–1.45]) were associated with higher risk of incident dementia.

DISCUSSION

Several sphingolipid species appear to be involved in cognitive decline and dementia risk.

Highlights

Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.

Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.

The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.
Anti‐seasonal flooding drives substantial alterations in riparian plant diversity and niche characteristics in a unique hydro‐fluctuation zone
Authors: Liu Ye , Duan Xiaodie , Li Xiaoling , Yi Wenxiong , Chen Gong , Yang Jin , Deng Danli , Guo Xiaojuan , Yang Zhengjian , Huang Guiyun , Hu Meixiang , Ye Chen
Published: August 2024

Human‐induced disturbances such as dam construction and regulation have led to widespread alterations in hydrological processes and thus substantially influence plant characteristics in the hydro‐fluctuation zones (HFZs). To reveal utilization of limited resources and mechanisms of inter‐specific competition and species co‐existence of plant communities based on niche breadth and overlap under the different HFZs of the Three Gorges Reservoir (TGR) in China, we conducted a field investigation with 368 quadrats on the effects of hydrological alterations on plant diversity and niche characteristics. The results showed anti‐seasonal flooding precipitated the gradual disappearance of the original diverse niches, resulting in the reduction of plant species richness and functional diversity and more obvious competition among plant species with similar resource requirements. Annuals, perennials and shrubs accounted for 71.23%, 27.39% and 1.37%, respectively, suggesting that annuals and flood‐tolerant riparian herbs were favored under such novel flooding conditions. A consistent increase in species number, Shannon‐Wiener diversity index and Simpson dominance index with altitude was inconsistent with hump‐shaped diversity–disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index. This species distribution pattern might be caused by several synergetic attributes (e.g., the submergence depth, plant tolerant capacity to flooding, life form, dispersal mode and inter‐specific competition). Vegetation types shifted from xerophytes to mesophytes and eventually to hygrophytes with the increasing flooding time in the HFZs. Hydrological alterations proved to be the paramount driver of vegetation distribution in the different HFZs. The niche analysis provided the first insights on the mechanisms of resource utilization and inter‐specific competition, of which annuals could germinate quickly after soil drainage to achieve the greatest competitive advantages and occupy a larger niche space than other plants. Vegetation was still in the early stage of primary succession in the novel riparian forests. Therefore, vegetation restoration strategies should be biased towards herbaceous plants, due to annuals with better environmental adaptability, supplemented by shrubs and small trees. To establish a complete reference system for vegetation restoration, natural vegetation monitory plots in the different succession stages should be established in the different HFZs of the TGR, and their environmental conditions, community structures and inter‐specific relationships further analyzed.
Identification of metacommunities in bioregions with historical habitat networks
Authors: Harisena Nivedita Varma , Grêt‐Regamey Adrienne , Van Strien Maarten J.
Published: August 2024

Although metacommunity theory provides many useful insights for conservation planning, the transfer of this knowledge to practice is hampered due to the difficulty of identifying metacommunities in bioregions. This study aims to identify the spatial extent of metacommunities at bioregional scales using current and historical habitat data, especially because contemporary biodiversity patterns may be a result of time‐lagged responses to historical habitat configurations. Further, this estimation of the metacommunity spatial extent is based on both the habitat structure and the dispersal ability of the species. Focusing on dragonfly and damselfly (odonate) species in the eastern Swiss Plateau, the research uses wetland habitat information spanning over 110 years to create a time series of nine habitat networks between 1899 and 2010. From these networks, we identified the spatial extents of metacommunities based on the year of habitat information as well as on watershed boundaries. To identify the best metacommunity spatial extents, the study investigates whether patch pairs within a metacommunity exhibit greater similarity in species composition (i.e. lower beta‐diversity) than patch pairs between metacommunities. For the different metacommunities, we further investigated correlations between gamma diversity and metacommunity size and compare them to theoretical expectations. In both analyses we found that augmenting spatial metacommunity identification with historical geographical proximity results in stronger associations with biodiversity patterns (beta and gamma diversity) than when using only current‐day habitat or watershed information.
Species assemblages and their drivers differ between trees and lianas in a seasonal evergreen forest in Thailand
Authors: Chanthorn Wirong , Wiegand Thorsten , Nathalang Anuttara , Kanagaraj Rajapandian , Davies Stuart , Sun Zhenhua , Tripathi Nitin K. , Réjou‐Méchain Maxime , Brockelman Warren Y.
Published: August 2024

Despite a long tradition in ecology of studying tree species assembly and its potential drivers in tropical forest communities, little information exists with respect to lianas (woody climbers), the second most abundant life form of woody plants in tropical forests. Lianas influence forest diversity and stability and provide critical resources for forest fauna. Using a unique dataset of a 30‐ha plot in Thailand, where tree and liana individuals were fully mapped, we investigated the degree to which local species assemblages of trees and lianas of different size classes (i.e., seedlings, established individuals, and large individuals) are related to local environmental conditions. We asked (1) What are the spatial patterns and environmental drivers of local tree and liana species assemblages? (2) How do such patterns and drivers differ among size classes? (3) Which species associate with these assemblages? Local assemblages of established trees showed substantial structuring by environmental variables, whereas we found only weakly structured assemblages of tree seedlings, large trees, and lianas of all size classes. Our results indicated that the biotic and abiotic drivers of local species assemblages differed strongly between tree and liana communities and across size classes. Species assemblages of trees were mainly driven by soil nutrients, leading to patchy assemblages associated with high base saturation (Alfisols) and assemblages associated with lower levels of base saturation and higher aluminum (Ultisols), whereas tree seedling assemblages were only weakly structured by riparian zones. In contrast, species assemblages of established and large lianas were primarily associated with forest canopy structure, separating low‐canopy forests from high‐canopy forests, whereas soil nutrients were the only factors associated with liana seedling assemblages. The weak environmental structuring of tree seedlings and large trees suggests that other mechanisms, such as stochastic disturbances, competition for space, or animal seed dispersal, may play an important role in structuring tree communities in this seasonal tropical forest. The weak patterns observed in liana communities across all life stages raise questions about the underlying mechanisms of liana community assembly, and further research should focus on liana niches, their dispersal mechanisms, and host tree relations.
Real‐Time Detection of Sub‐ppm Aromatic Compounds in Alcohol by Surface Plasmon Resonance Using Label‐Free Graphene
Authors: Cho Sung Hwan , Suh Jun Min , Kim Wontaek , Kim Jaehyun , Kim Yeong Jae , Lee Tae Hyung , Kim Jae Young , Sim Jaegun , Choi Seung Won , Hong Byung Hee , Kim So Young , Jang Ho Won
Published: August 2024

The increasing importance of high‐purity isopropyl alcohol (IPA) in semiconductor processing technology has led to a higher demand for technologies capable of detecting impurities in IPA. Although accurate and various impurity detection technologies have been developed, most of them have limitations in real‐time and repeatable detection of impurities. Herein, for the first time, surface plasmon resonance (SPR) sensor was developed utilizing graphene transferred Au film (Au/graphene) to detect sub‐ppm levels of 2,4‐dinitrophenol (2,4‐DNP) dissolved in IPA and this sensor demonstrates the ability to detect 2,4‐DNP in real‐time with great reversibility. The adsorption of 2,4‐DNP to graphene is found to be stronger than that for Au film because of noncovalent graphene π–π stacking interaction, and the effect of graphene is demonstrated through density function theory (DFT) calculations and enhancement in sensing performance of Au/graphene sensor. Additionally, the presence of noncovalent π–π stacking interaction between 2,4‐DNP and graphene has been demonstrated by confirming the p‐doping effect of graphene‐based solution field‐effect transistor measurements and consecutive Raman spectra analysis. This study offers experimental and theoretical insights into the adsorption kinetics of 2,4‐DNP dissolved in IPA and provides promising perspectives for real‐time sensing technology utilizing label‐free graphene to detect impurities in high‐purity cleaning agents.
Graphene‐derived microwave metamaterials and meta‐devices: Emerging applications and properties
Authors: Shao Linda , Zhu Weiren
Published: August 2024

Graphene, a two‐dimensional material renowned for its distinctive electronic band structure and remarkable physical properties, has garnered substantial attention in recent years. Its integration into metamaterials (i.e., artificially structured materials) and metamaterial‐based devices opens up exciting possibilities for manipulating electromagnetic waves with various functionalities. These metamaterials and meta‐devices, with their strong resonances, enhance interactions with incident waves, further aided by electrically tunable graphene, enabling fruitful modulation of electromagnetic waves. In this review, we present a detailed exploration of the recent advancements in graphene‐based microwave meta‐devices. We first introduce the electromagnetic properties of graphene, laying the foundation for its electromagnetic modeling and characterization. The second part introduces the fabrication and transfer methods of graphene. Next, we review the passive meta‐devices constructed with graphene, exploring how these devices leverage graphene's unique properties. We further discuss graphene‐based active meta‐devices for dynamic wave manipulations, with a focus on graphene–electrolyte–graphene sandwich structures. Lastly, the review delves into graphene‐based coding and programmable meta‐devices, highlighting their innovative applications. Each section provides a focused exploration of a specific aspect of the field, showcasing the diverse and expanding role of graphene in the microwave region. Through this comprehensive review, we aim to enrich our understanding and appreciation for the growing developments and potential of graphene in microwave technology.
Experimental study of the end effect on the mechanical behaviors of rocks under true 3D compressions
Authors: Chen Junchao , Che Zhenglu , Gao Meiben , Zhang Liang , Shen Zhonghui
Published: August 2024

In true triaxial compression tests, all three principal stresses are imposed independently. This allows for a more comprehensive analysis of the material's mechanical properties. The end effect in true triaxial compression tests is a crucial phenomenon that impacts the accuracy and reliability of the test results. In this study, a series of true triaxial compression tests is conducted to examine the influence of the end friction on the mechanical properties. The laboratory results show that the presence of the end friction could bring about an apparent increase in rock strength and also restrict the deformation in each direction showing that the stiffness (the slope of the curves) increased slightly. The rock strength could be enhanced from 24.7 to 90.7 () when the end friction is increased, which is mainly caused by the lateral interface friction. The failure mode and fracture angle of the specimen are also influenced by the end effect, showing that under high friction conditions, the failure is more ductile, and a larger fracture angle is observed. At last, in comparison with the published experimental data, the actual specific friction angle (corresponding friction coefficient is about 0.19) for the direct specimen–metal contacts in a true 3D test is numerically identified, which is empirically reasonable and higher than the tested range 0.146–0.157 obtained from double‐shear test system.
Influence of packing height on the pyrolysis products of Jimsar (China) oil shale
Authors: Wang Zeyue , Pan Luwei , Lu Hao , Dai Fangqin
Published: August 2024

The effect of particle packing height (10, 30, 50, 70 mm) on the yield and composition of oil shale pyrolysis products is investigated. The results show that the oil yield could decrease 1.0% and the noncondensable gases yield could increase 0.5% as the oil shale packing height increased from 10 to 70 mm. The main hydrocarbon gases are C1–C6 gases, and the increase of packing bed height could decrease the relative content ratio of alkanes to alkenes in hydrocarbon gases. The primary components of the derived oil are aliphatic compounds, aromatic compounds, and compounds containing heteroatoms in the carbon atoms range of C6–C28. And the hydrogen type of shale oil is mainly composed of methylene groups (about 70%) with longer alkyl chains, and CH3 in aromatics, cycloalkanes, and alkanes. The chemical composition and hydrogen type have certain regularity changes with the changing of packing height, attributing to the effect of temperature gradients between surface and center of packing bed, and the diffusing time of products through the packing bed.
An Internet of Things security‐based E parking framework for smart city application using Lora
Authors: Tripathy Shuvendra Kumar , Palai Gopinath
Published: August 2024

Finding an accessible parking spot using 5G technology can be considered as time and fuel expenses. In this manner, it might make drivers disappointed in the parking zone. This will prompt awful traffic around the parking spot and may likewise prompt a mishap. That is the reason this task proposes a Smart Parking framework that utilizes cameras which will be associated with a Raspberry Pi and it will likewise have an Android application as an interface to help book or view accessible spaces. E Parking framework for security empowerment in 5G can be characterized as the utilization of trend setting innovations for the effective activity, checking, and the board of parking inside an urban versatility technique. This task will help tackle issues referenced by permitting clients to see and select accessible space in the parking, which will keep clients from driving around. You Only Look Once (YOLO) algorithm, Adaptive Background Learning and also pre‐trained Mask‐RCNN are used for finding the nearest free parking slot. Currently, Raspberry Pi will be utilized as the connection between the Cameras and the Server, by moving information gathered from the Raspberry Pi to an online server in order to process the information and empower the Android application to get outcome. In an end, this venture will help in decreasing the measure of time a driver needs to spend around the parking just to locate an accessible spot, lessening the measure of traffic, diminishing contamination, expanding the security using 5G technologies and furthermore better monetizing the parking spot. The proposed system detects vehicles in indoor as well as outdoor parking fields accurately.
Panel treatment effects measurement: Factor or linear projection modelling?
Authors: Hsiao Cheng , Zhou Qiankun
Published: August 2024

We discuss methods of measuring the treatment effects of a unit through the use of other units in panel data by either the factor‐based (FB) approach or the linear projection (LP) approach under different sample configurations of cross‐sectional dimension
and time series dimension
. We show that the LP approach in general yields smaller mean square prediction error than the FB approach when either both
and
are large or
fixed and
or
fixed and
large. The Monte Carlo simulation and empirical example are also conducted to consider their finite sample performances.
Heterogeneous autoregressions in short T panel data models
Authors: Pesaran M. Hashem , Yang Liying
Published: August 2024

This paper considers a first‐order autoregressive (AR) panel data model with individual‐specific effects and heterogeneous AR coefficients defined on the interval
, thus allowing for some of the individual processes to have unit roots. It proposes estimators for the moments of the cross‐sectional distribution of the AR coefficients, assuming a random coefficient model for the AR coefficients without imposing any restrictions on the fixed effects. It is shown that the standard generalized method of moments estimators obtained under homogeneous slopes are biased. Small sample properties of the proposed estimators are investigated by Monte Carlo experiments and compared with a number of alternatives, both under homogeneous and heterogeneous slopes. It is found that a simple moment estimator of the mean of heterogeneous AR coefficients performs very well even for moderate sample sizes, but to reliably estimate the variance of AR coefficients, much larger samples are required. It is also required that the true value of this variance is not too close to zero. The utility of the heterogeneous approach is illustrated in the context of earnings dynamics.
Unveiling thrips morphology: A comparative analysis of microscopy‐based ultrastructural, morphological, and molecular characterization of Thrips tabaci and Thrips parvispinus in onion
Authors: Pandi Arunkumar , Malaichamy Kannan , John Samuel Kennedy , Selvaraj Dineshkumar , Kasivelu Govindaraju , Kolanthasamy Elango
Published: August 2024

The present study unveils the intricate details on the morphology of thrips through optical, field emission scanning electron microscopy (FE‐SEM) and mitochondrial cytochrome oxidase I gene‐based molecular identification tools. The variation in the morphological characters namely, antennae (seven‐segmented with forked sensorium on third, fourth segments), ctenidia (paired ctenidia were present in 5th–8th abdominal segments laterally), pronotum (two pairs of posteroangular setae) were observed in both Thrips tabaci and Thrips parvispinus, respectively. Similarly, ocelli color (brown and red colored), ocellar setae (two and three pairs of ocellar setae on the head of T. tabaci and T. parvispinus, respectively. Irregular reticulate striations on metascutum and medial striations are present in the metanotum of T. parvispinus; forewings with 6 distal setae in the first vein and 15 distal setae in the second vein in T. tabaci and forewings of T. parvispinus with complete rows of setae in the first and second vein in T. parvispinus; abdomen with median dorsal setae present in the tergite of T. tabaci and presence of 6–12 discal setae in sternites III–VI segments, absence of discal setae on sternites II and VII in T. parvispinus were observed, respectively. Further, FE‐SEM studies revealed that similar type of sensilla namely, sensilla basiconica (SBI, SBII, SBIII), sensilla chaetica (SChI, SChII), sensilla trichodea (ST), sensilla campaniformia (SCa), and sensilla cavity (SCav) were recorded in both the species and variations were observed in length of above sensilla of T. tabaci and T. parvispinus. Additionally, Bohm bristles (Bb) and microtrichia (Mt) on the antennal surface contributed to a comprehensive understanding of their ultrastructural features. The molecular characterization revealed a single ~450 bp nucleotide fragment with over 98% similarity for the confirmation of T. tabaci and T. parvispinus in concurrence with NCBI data.

Research Highlights

Microscopy‐based morphological and ultrastructural characterization of Thrips tabaci Lindeman and Thrips parvispinus Karny.
Secretory structures and histochemistry of roots, stem, and leaves of medicinal plant Fibraurea tinctoria Lour
Authors: Widuri Septina Asih , Sulistyaningsih Yohana Caecilia , Umar Abdul Halim , Ratnadewi Diah
Published: August 2024

Fibraurea tinctoria Lour. (Menispermaceae) is a medicinal plant used by many local tribes in Indonesia and other countries. This species has pharmacological potential, such as antimalaria, antibacterial, antitumor, antioxidant, anticancer, antidiabetic, anti‐inflammatory, and hepato‐protector. However, the secretory structures and sites of secondary metabolite accumulation still need to be studied. This study aimed to explore the secretory structures and reveal the accumulation sites of the main classes of secondary metabolites in the root, stem, and leaves of F. tinctoria. Histochemical analysis using various specific reagents was performed on freehand sections of the fresh organs to detect alkaloids, phenolics, terpenoids, and lipophilic compounds. Observations of secretory structures were carried out using light microscopy. The result showed that idioblast was the predominant secretory structure in the plant organs and contained all the chemical groups investigated, while laticifer accumulated alkaloids were found only in the stem. Some secondary metabolites were localized in the xylem, intercellular space, and cuticle layer. Crystals were observed in the root, stem, and leaf of this species. These results might be helpful as guide information for extracting the particular plant parts to obtain the desired secondary metabolites. It suggested that leaves are a potential alternative source of medicinal raw material of this species, in addition to the stem.

Research Highlights

The first study on secretory structures of Fibraurea tinctoria.

Secondary metabolites in F. tinctoria organs accumulate in specialized and unspecialized structures.

The idioblast is the primary secretory structure in the organs of F. tinctoria spreading over the root, stem, and leaves.
Impact of endoscopic ultrasound‐guided fine needle aspiration on positive peritoneal lavage cytology in patients with resectable pancreatic body and tail cancer
Authors: Ishii Yasutaka , Serikawa Masahiro , Uemura Kenichiro , Tatsukawa Yumiko , Nakamura Shinya , Ikemoto Juri , Miyamoto Sayaka , Arihiro Koji , Takahashi Shinya , Oka Shiro
Published: August 2024

Background/Purpose

A recent study has demonstrated that the timing of endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) significantly influences the peritoneal lavage cytology (CY) outcomes in pancreatic body‐tail cancer. The aim of this study was to clarify the impact of EUS‐FNA on CY positivity in patients with resectable pancreatic body‐tail cancer.

Methods

Patients with anatomically resectable pancreatic body‐tail cancer surgically resected at Hiroshima University Hospital were enrolled, and elated clinicopathological factors, including EUS‐FNA variables and CY positivity rate, were analyzed.

Results

Of the 129 eligible patients, 16 (12%) had positive CY. The EUS‐FNA rates of the CY‐positive and CY‐negative groups were not significantly different (63% vs. 52%, p = .440). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for CY positivity (odds ratio: 5.734, p = .031). A total of 10 (14%) of the 69 patients who underwent EUS‐FNA had positive CY; however, needle specifications and the interval between EUS‐FNA and CY examination did not differ between the CY‐positive and CY‐negative groups. CY positivity rates were comparable for intervals ≤14 days and ≥15 days (17% vs. 14%, p = 1.000).

Conclusions

EUS‐FNA may not affect CY positivity in patients with resectable pancreatic body‐tail cancer, regardless of the timing.
68Ga Radiolabeling of NODASA‐Functionalized Phage Display–Derived Peptides for Prospective Assessment as Tuberculosis‐Specific PET Radiotracers
Authors: Gouws Christiaan A. , Naicker Tricia , de la Torre Beatriz G. , Albericio Fernando , Duvenhage Janie , Kruger Hendrik G. , Marjanovic‐Painter Biljana , Mdanda Sipho , Zeevaart Jan R. , Ebenhan Thomas , Govender Thavendran
Published: August 2024

This research presents the development of positron emission tomography (PET) radiotracers for detecting Mycobacterium tuberculosis (MTB) for the diagnosis and monitoring of tuberculosis. Two phage display–derived peptides with proven selective binding to MTB were identified for development into PET radiopharmaceuticals: H8 (linear peptide) and PH1 (cyclic peptide). We sought to functionalize H8/PH1 with NODASA, a bifunctional chelator that allows complexation of PET‐compatible radiometals such as gallium‐68. Herein, we report on the chelator functionalization, optimized radiosynthesis, and assessment of the radiopharmaceutical properties of [68Ga]Ga‐NODASA‐H8 and [68Ga]Ga‐NODASA‐PH1. Robust radiolabeling was achieved using the established routine method, indicating consistent production of a radiochemically pure product (RCP ≥ 99.6%). For respective [68Ga]Ga‐NODASA‐H8 and [68Ga]Ga‐NODASA‐PH1, relatively high levels of decay‐corrected radiochemical yield (91.2% ± 2.3%, 86.7% ± 4.0%) and apparent molar activity (Am, 3.9 ± 0.8 and 34.0 ± 5.3 GBq/μmol) were reliably achieved within 42 min, suitable for imaging purposes. Notably, [68Ga]Ga‐NODASA‐PH1 remained stable in blood plasma for up to 2 h, while [68Ga]Ga‐NODASA‐H8 degraded within 30 min. For both 68Ga peptides, minimal whole‐blood cell binding and plasma protein binding were observed, indicating a favorable pharmaceutical behavior. [68Ga]Ga‐NODASA‐PH1 is a promising candidate for further in vitro/in vivo evaluation as a tuberculosis‐specific infection imaging agent.
Comparison of epidemiological characteristics between hemorrhagic fever with renal syndrome patients and severe fever with thrombocytopenia syndrome patients
Authors: Wang Wen , Liu Ying , Zhang Rong , Sun Jimin , Jiang Jianmin , Wang Hongmei
Published: August 2024

Hemorrhagic fever with renal syndrome (HFRS) and severe fever with thrombocytopenia syndrome (SFTS) are both endemic in rural areas and some characteristics are similar between HFRS and SFTS, which usually lead to misdiagnosis. In this study, we summarized and compared some characteristics of HFRS and SFTS which will provide scientific information for differential diagnosis. From 2011 to 2022, a total of 4336 HFRS cases and 737 SFTS cases were reported in Zhejiang Province. Compared to SFTS, there was a higher proportion of males among HFRS cases (72.46% [3142/4336] vs. 50.88% [375/737], p = 0.000). The median age of all 4336 HFRS cases was 49 (39, 59), while the median age of SFTS cases was 66 (57, 74). In addition, the involved counties of HFRS were more than SFTS, but the number of counties affected by SFTS increased from 2011 to 2022. The majority of SFTS cases occurred in summer (from May to July), but besides summer, HFRS cases also showed a peak in winter. Finally, our results showed that the case fatality rate of SFTS was significantly higher than that of HFRS. Although there were some similarities between HFRS and SFTS, our study found several differences between them, such as gender distribution, age distribution, and seasonal distribution, which will provide scientific information for differential diagnosis of HFRS and SFTS. Further studies should be carried out to explore the mechanism of these differences.
Consumers’ purchase intention of private labels: The case of e‐retailers
Authors: Yadav Sher Singh , Kar Sanjay Kumar
Published: August 2024

In economically vulnerable situations such as the pandemic, private‐label products generate bigger appeal. The behavior of online private‐label consumers has remained understudied thus far, despite several studies suggesting that different channels lead to different consumer behaviors. This study aims to develop and test a theoretical model that elucidates the factors influencing the online purchase intention of private‐label products in a post‐pandemic scenario. We assess the role of attitude in the relationship between value consciousness, convenience, perceived quality, awareness, price consciousness, private‐label image, retailer reputation, and functional risk, in relation to purchase intention. The study is based on a sample of 318 respondents and employs variance‐based partial least squares structural equation modeling (PLS‐SEM) for data analysis using Smart PLS 3. This study is one of the first to delve into post‐pandemic research on online private‐label products during an economic downturn. This study explores the purchase intention toward online private‐label products by drawing on the theory of planned behavior, attribution theory, and cue utilization theory. Our results reveal that retailer reputation influences private‐label image, which affects purchase intention. Additionally, perceived quality, private‐label image, and attitude positively influence the purchase intention of private‐label products. Retailer reputation also affects private‐label image and value consciousness. Furthermore, convenience has a positive effect on attitudes toward the online purchase of private labels. Interestingly, price consciousness did not affect the purchase intention of online private labels. These findings have significant implications for private‐label online retailers and policymakers. This article extends the current private‐label theory and holds promise for future application in an omnichannel private‐label context.
Premodulator microbiome alterations associated with postmodulator growth outcomes in pediatric cystic fibrosis: Can we predict outcomes?
Authors: Sanville Julie , O'Toole George A. , Madan Juliette , Coker Modupe
Published: August 2024

Objectives

The gut microbiota plays an important role in childhood growth. Our longitudinal cohort includes children with cystic fibrosis (CwCF) treated with highly effective modulator therapy. We aimed to elucidate early premodulator microbial signatures associated with postmodulator weight for CwCF later in childhood.

Methods

Stool samples were collected from CwCF at 13 days to 60 months. Metagenomic sequencing determined differentially abundant taxa. Children with body mass index or weight for length Z‐scores within 1 standard deviation of the mean (SD) were considered normal weight, those >1 SD were classified as risk of overweight while children <1 SD were considered undernourished, although no CwCF met this latter criterion here. Multivariate regression models were applied to identify significant associations between metadata and microbial taxonomic relative abundances.

Results

One hundred and eighty‐nine stool samples were analyzed from 39 CwCF. We identified statistically significant differences in early microbiome patterns among those at risk of being overweight compared to those who were normal weight when adjusted for age, sex, CF mutation, and early feeding method. Early microbiome was a stronger driver of growth status than current modulator use. Among those at risk of overweight, several taxa that were consistently in lower abundance included Eggerthella lentha, Ruminococcus, Bacteroides, with increase in abundance of Bacteroides stercoris.

Conclusions

The early microbiome strongly predicts growth in the setting of modulator use for CwCF and we identify microbiome signatures associated with risk of being overweight. We highlight the possibility for interventions or early alternations to nutritional guidance for prevention of comorbid complications.
Does Technological Innovativeness Influence Users' Experiences With Virtual Reality Tourism?
Authors: Sousa Nuno , Jorge Filipa , Teixeira Mário Sérgio , Losada Nieves , Alén Elisa , Guttentag Daniel
Published: August 2024

Immersive experiences offered by virtual reality (VR) have the power to impact tourists' decision‐making and on‐site experiences. However, prior research has focused on explaining VR's acceptance by tourists as a function of technological capacity, rather than user characteristics, such as innovativeness. This research intends to fill the existing knowledge gap regarding the role of technological innovativeness on VR experiences. To do so, this study examines whether individuals' technological innovativeness influences their perceptions of a VR tourism experience and, in turn, their intention to recommend the experience. The study provides a VR experience to 405 tourists at a winery. The results reveal that the tourists' technological innovativeness influences their perception of enjoyment, experience quality, and satisfaction. These findings suggest that, when developing or distributing VR content, the technological innovativeness of the audience is important to consider. The findings have theoretical and practical value, with direct implications for tourism professionals and policymakers.
Photoangiolytic Lasers for Treatment of Benign Laryngeal Lesions: A Systematic Review and Meta‐Analysis
Authors: Bhat Akash M. , Marrero‐Gonzalez Alejandro R. , Nguyen Shaun A. , Scharner Megan , Meenan Kirsten , Sataloff Robert T.
Published: August 2024

Objectives

To compare the efficacy of the 445‐nm blue laser to the 585‐nm pulsed dye laser (PDL) and 532‐nm potassium‐titanyl‐phosphate (KTP) laser in the treatment of benign laryngeal lesions.

Data Sources

Cochrane Library, PubMed, Scopus, and CINAHL.

Review Methods

Following PRISMA guidelines, databases were searched from inception through January 29, 2024, for studies reporting the use of photoangiolytic lasers for treatment of benign laryngeal lesions, including the 585‐nm PDL, 532‐nm KTP laser, and 445‐nm blue laser. Outcome measures included lesion resolution (%), mean differences (Δ) in Voice Handicap Index (VHI‐10), and summed dysphonia grade, roughness, and breathiness (GRB) scale.

Results

A total of 45 studies were included for meta‐analysis, consisting of 348 patients treated with PDL, 550 patients with KTP laser, and 338 patients with blue laser. Treatment with blue laser resulted in the greatest lesion resolution (94.0%; 95% confidence interval [CI]: 90.2%–96.7%), followed by KTP laser (90.4%; 95% CI: 84.1%–95.2%), and PDL (86.9%; 95% CI: 62.9%–99.2%). VHI‐10 improved significantly in patients following treatment with blue laser (Δ13.3; 95% CI: 10.7–16.0; p < 0.0001), KTP laser (Δ10.3; 95% CI: 7.4–13.3; p < 0.0001), and PDL (Δ7.4; 95% CI: 4.8–10.1; p < 0.0001). GRB improved significantly in patients following treatment with blue laser (Δ4.1; 95% CI: 2.9–5.2; p < 0.0001), KTP laser (Δ3.0; 95% CI: 2.0–4.0; p < 0.0001), and PDL (Δ2.5; 95% CI: 0.8–4.2; p = 0.005).

Conclusions

Photoangiolytic lasers are effective in treating benign laryngeal lesions. Blue lasers are promising for laryngeal laser surgery. Laryngoscope, 134:4847–4857, 2024
Genetic Analysis of Melanoma Types Using Japanese Genomic Database
Authors: Matsumoto Hayato , Nagano Hiromi , Kyutoku Takayuki , Yamashita Masaru
Published: August 2024

Objectives

The purpose of this study is to compare genetic mutations, tumor mutation burden (TMB), and the effects of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in head and neck mucosal melanoma (HNMUM) with those in skin melanoma (SKM) and ocular melanoma (OM).

Methods

Data were analyzed for 72 consecutive patients with HNMUM, including 366 with SKM and 31 with OM, registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C‐CAT) between June 2019 and October 2023. Genetic alterations and TMB were determined by FoundationOne CDx next‐generation sequencing.

Results

The top 10 mutations in HNMUM were RAD21 (47.2%), NBN (45.8%), MYC (40.3%), LYN (31.9%), NRAS (29.1%), IRF4 (23.6%), DAXX (22.2%), KIT (22.2%), NOTCH3 (20.8%), and DDR1 (19.4%), with 16.6 ± 0.8 (mean ± SEM) mutations/individual. In SKM, BRAF (p = 0.04) mutation was associated with a significantly better prognosis. The TMB values were 5.7 ± 2.1 (mean ± SEM) in HNMUM, 4.1 ± 0.2 in SKM, and 3.4 ± 0.9 in OM, with no significant differences among the three groups. The median survival time for patients with distant metastases was 803 (95% confidence interval: 539‐NA) days for HNMUM, 1413 (831–2172) days for SKM, and 1138 (438‐NA) days for OM.

Conclusions

The top 10 mutations in HNMUM are closer to those in OM than those in SKM. There was no significant difference in TMB values or survival rates with regard to the therapeutic effect of ICIs among the diseases, which suggests that current treatment of HNMUM with ICIs is appropriate.

Level of Evidence

3 Laryngoscope, 2024
Severe Acute Motor Exacerbations (SAME) across Metabolic, Developmental and Genetic Disorders
Authors: Couto Blas , Galosi Serena , Steel Dora , Kurian Manju A. , Friedman Jennifer , Gorodetsky Carolina , Lang Anthony E.
Published: August 2024

Acute presentation of severe motor disorders is a diagnostic and management challenge. We define severe acute motor exacerbations (SAME) as acute/subacute motor symptoms that persist for hours‐to‐days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing/dysphagia). Phenomenology includes dystonia, choreoathetosis, combined movement disorders, weakness, and hemiplegic attacks. SAME can develop in diverse diseases and can be preceded by triggers or catabolic states. Recent descriptions of SAME in complex neurodevelopmental and epileptic encephalopathies have broadened appreciation of this presentation beyond inborn errors of metabolism. A high degree of clinical suspicion is required to identify appropriately targeted investigations and management. We conducted a comprehensive literature analysis of etiologies. Reported triggers are described and classified as per pathophysiological mechanism. A video of six cases displaying multiple SAME with diverse outcomes is provided. We identified 50 different conditions that manifest SAME, some associated with developmental regression. Etiologies include disorders of metabolism: energy substrate, amino acids, complex molecules, vitamins/cofactors, minerals, and neurotransmitters/synaptic vesicle cycling. Non‐metabolic neurodegenerative and genetic disorders that present with movement disorders and epilepsy can additionally manifest SAME. A limited number of triggers are grouped here, together with an approach to investigations and general management strategies. Several neurogenetic and neurometabolic disorders manifest SAME. Identifying triggers can help in certain cases narrow the differential diagnosis and guide the expeditious application of targeted therapies to minimize adverse developmental and neurological consequences. This process may inform pathogenesis and eventually improve our understanding of the mechanisms that lead to the development of SAME. © 2024 International Parkinson and Movement Disorder Society.
Functional Movement Disorder as a Prodromal Symptom of Parkinson's Disease—Clinical and Pathophysiological Insights
Authors: Matar Elie , Tinazzi Michele , Edwards Mark J. , Bhatia Kailash P.
Published: August 2024

Functional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow‐up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.