bluuebunny/crossref_metadata_2025 huggingface dataset:
A protocol to differentiate the chondrogenic ATDC5 cell‐line for the collection of chondrocyte‐derived extracellular vesicles
Authors: Marchan‐Alvarez Jose G. , Teeuwen Loes , Mamand Doste R. , Gabrielsson Susanne , Blomgren Klas , Wiklander Oscar P. B. , Newton Phillip T.
Published: September 2024

Skeletal growth and fracture healing rely on the mineralization of cartilage in a process called endochondral ossification. Chondrocytes firstly synthesize and then modify cartilage by the release of a wide range of particles into their extracellular space. Extracellular vesicles (EVs) are one type of such particles, but their roles in endochondral ossification are yet to be fully understood. It remains a challenge to obtain representative populations of chondrocyte‐derived EVs, owing to difficulties both in preserving the function of primary chondrocytes in culture and in applying the serum‐free conditions required for EV production. Here, we used the ATDC5 cell‐line to recover chondrocyte‐derived EVs from early‐ and late‐differentiation stages, representing chondrocytes before and during cartilage mineralization. After screening different culture conditions, our data indicate that a serum‐free Opti‐MEM‐based culture medium preserves chondrocyte identity and function, matrix mineralization and cell viability. We subsequently scaled‐up production and isolated EVs from conditioned medium by size‐exclusion chromatography. The obtained chondrocyte‐derived EVs had typical ultrastructure and expression of classical EV markers, at quantities suitable for downstream experiments. Importantly, chondrocyte‐derived EVs from late‐differentiation stages had elevated levels of alkaline phosphatase activity. Hence, we established a method to obtain functional chondrocyte‐derived EVs before and during cartilage mineralization that may aid the further understanding of their roles in endochondral bone growth and fracture healing.
Supernumerary Chromosomes Enhance Karyotypic Diversification of Narrow‐Headed Voles of the Subgenus Stenocranius (Rodentia, Mammalia)
Authors: Pavlova Svetlana V. , Romanenko Svetlana A. , Matveevsky Sergey N. , Kuksin Aleksander N. , Dvoyashov Ivan A. , Kovalskaya Yulia M. , Proskuryakova Anastasiya A. , Serdyukova Natalia A. , Petrova Tatyana V.
Published: September 2024

The subgenus Stenocranius contains two cryptic species: Lasiopodomys gregalis (subdivided into three allopatrically distributed and genetically well‐isolated lineages A, B, and C) and Lasiopodomys raddei. To identify karyotype characteristics of this poorly studied cryptic species complex, we used comparative cytogenetic analysis of 138 individuals from 41 localities in South Siberia and Mongolia. A detailed description of the L. raddei karyotype and of the L. gregalis lineage С karyotype is presented for the first time. The A chromosome complement of all examined narrow‐headed voles consisted of 2n = 36 and a fundamental number of autosomal arms (FNa) of 50. Between species, patterns of differential staining were similar, though additional C‐heterochromatic blocks were found in L. gregalis lineages; Ag‐positive nucleolar organizers and ribosomal DNA (rDNA) clusters are located on eight and nine acrocentric pairs, respectively. No B chromosomes (Bs) were found in the Early Pleistocene relic L. raddei, while one to five small heterochromatic acrocentric Bs were detected in all L. gregalis lineages; the number and frequency of Bs varied considerably within lineages, but no intraindividual variation was observed. In both species, telomeric repeats were visualized at termini of all chromosomes, including Bs. The number and localization of rDNA clusters on Bs varied among B‐carriers. Immunodetection of several meiotic proteins indicated that meio‐Bs are transcriptionally inactive and have a pattern of meiotic behavior similar to that of sex chromosomes (some homology of Bs to sex chromosomes is supposed). The nature, mechanisms of inheritance and stability of Bs in L. gregalis require further investigation.
Intra‐ and extracellular real‐time analysis of perfused fibroblasts using an NMR bioreactor: A pilot study
Authors: Urzì Christian , Meyer Christoph , Mathis Déborah , Vermathen Peter , Nuoffer Jean‐Marc
Published: September 2024

Introduction

Metabolomic discrimination of different mitochondrial defects is challenging. We describe an NMR‐based bioreactor allowing real‐time intra‐ and extracellular metabolic investigation of perfused fibroblasts.

Objectives

The objective of this study is (I) determining whether metabolic investigations of perfused fibroblasts overall and separated for intra‐ and extracellular contributions by real‐time NMR allows for discrimination of different representative mitochondrial defects in a feasibility study and (II) gaining insight into physiological consequences of mitochondrial dysfunction in basal condition and during glycolysis inhibition.

Methods

Overall, intra‐ and extracellular metabolomes of malate dehydrogenase 2 (MDH2), pyruvate dehydrogenase (PDH), complex I (CI) deficient fibroblasts, and control fibroblasts were investigated under standard culture conditions and under glycolysis inhibition. In addition to “overall” metabolite quantification, intra‐ and extracellular metabolic contributions were separated based on diffusion rate differences.

Results and Discussion

Overall metabolites: Chemometric analysis of the entire metabolome revealed good separation between control, PDH and MDH2, while CI was less well separated. However, mixed intra‐ and extracellular changes complicated interpretation of the cellular metabolism. Intra‐ and extracellular metabolites: Compartment specific chemometrics revealed possibly augmenting metabolomic separation between control and deficient cell lines under basal and inhibition condition. All mitochondrial defects exhibited upregulation of glycolytic metabolism compared to controls. Inhibition of glycolysis resulted in perturbations of other metabolic pathways such as glutaminolysis, alanine, arginine, glutamate, and proline metabolism. MDH2 showed upregulation of alanine and glutamate metabolism, while the CI defect revealed lower intracellular arginine and downregulation of glutamate and arginine‐dependent proline synthesis.

Conclusion

Discrimination of intra‐ and extracellular metabolic contributions helps understanding the underlying mechanisms of mitochondrial disorders, uncovers potential metabolic biomarkers, and unravels metabolic pathway‐specific adaptations in response to metabolic perturbations.
Implications for extreme midlatitude weather events of secondary flow associated with polar jets
Authors: Ren Diandong , Leslie Lance M.
Published: September 2024

In the Earth's general circulation, polar jets act as baroclinic pumps of angular momentum and heat. Reanalysis datasets indicate that shear changes near jets induce upward displacements of the jet cores, suggesting a weakening thermodynamic pumping over the last 50 years. From secondary flow theory, a well‐established principle in fluid dynamics, an increased frequency of heatwaves and persistent winter storms is expected. The ageostrophic wind shear between 700 and 50 hPa indicates the strength of this secondary circulation. The weakening tendency during the reanalysis period also exists in multimodel simulations under the RCP8.5 emissions scenario for the 21st century. The reduction between the periods 2005–2025 and 2081–2100 reaches 18%, 5.3% and 19%, respectively, for the North America, Mid‐Europe and East Asia sectors of the Northern Hemisphere polar jet. Within this background, cold‐surge events are the result of synergic co‐working of several factors. The occurrence trend for transitional season winter extreme events also is examined. The winter extremes seemingly have larger temperature drops. However, in a warming climate, they emerge more rapidly from extreme cold states. The storm tracks, especially over North America, have equatorward extensions, indicating that winter storms can reach lower latitudes. Due to the temperature‐dependence of air viscosity, secondary flows decrease more slowly than the main zonal flow. This imposes an important adjustment to the traditional polar amplification effects on midlatitude winter extremes. During a warmer winter (the primary manifestation of a warmer climate), spatially uniform positive trends in cold extreme events are not expected. There are, however, regions experiencing more winter extremes. These regions show consistent patterns in both the reanalysis period and the remainder of the 21st century.
Disorders of gut–brain interaction are common diagnoses among infants and toddlers in gastroenterology practices in Latin America
Authors: Velasco‐Benítez Carlos A. , Alvarez‐Baumgartner Maura , Ortiz‐Rivera Claudia J. , Velasco‐Suárez Daniela A. , Reynoso Zarzosa Fátima A. , Espriu Ramírez Mariana X. , Macías‐Flores Jorge A. , Zablah Córdova Roberto A. , Chanis Águila Ricardo A. , Mejía Castro Milton D. , Suazo Yunuen Rivera , Balda Amber N. , Saps Miguel
Published: September 2024

Objectives

To assess the relative frequency and associated factors of disorders of gut–brain interaction (DGBIs) in outpatient gastrointestinal (GI) clinics in young children of Latin America.

Methods

Cross‐sectional study in 10 pediatric GI outpatient clinics (private and public) in five countries of Latin America (El Salvador, México, Colombia, Panamá, and Nicaragua). Parents of patients 1 month 4 years of age from outpatient clinics complete/d a diagnostic questionnaire for DGBIs per Rome IV criteria (QPGS‐IV, Spanish version). We conducted descriptive analysis, two‐sample t‐tests and chi‐square tests, univariate analyses, and logistic regression to evaluate risk factors.

Results

We collected data from 783 children. In total, 34.5% had a DGBI. Overall, functional constipation (FC) was the most common diagnosis (23.4%) in children of all ages (infants, 16.1%, 1–4‐years‐old, 32.7%). In infants, the second most common DGBI was regurgitation (6.6%) and in 1–4‐years‐old and cyclic vomiting syndrome (4.1%). The diagnosis of a DGBI was significantly associated with a family history of DGBIs (odds ratio [OR] 2.97, 95% confidence interval [CI] 1.61–5.57, p = 0.0001). Patients who identified as black (OR 2.25, 95% CI 1.28–3.92, p = 0.0021) or mixed race (OR 1.76, 95% CI 1.25–2.48, p = 0.0006) were also significantly associated with a higher likelihood of DGBIs.

Conclusions

DGBIs are a common diagnosis in pediatric GI clinics of Latin America. Overall, FC was the most common DGBI.
How Travel Vlogs Contribute to Destination Marketing: A Comparison with DMO Promotional Videos and the Moderating Role of Destination Competitiveness
Authors: Zhou Ying , Jo WooMi , Flaherty Joan , Li Tongzhe
Published: September 2024

This two‐part study examines how travel vlogs influence tourist behaviors and, consequently, their value in destination marketing. A convenience sample of 196 North Americans who belonged to Generation Y was collected via an online experiment. The first part adopted the Attention‐Interest‐Desire‐Action (AIDA) principle as the theoretical underpinning of how travel vlogs influence Gen Y travel behaviors, contrasting them with Destination Marketing Organization (DMO) promotional videos. It was found that travel vlogs impact tourist behavior by attracting tourists' attention, delivering realistic destination information, and inspiring them. The second part examined the relationship between destination competitiveness levels and willingness to pay (WTP), and the impact of travel vlogs and DMO promotional videos on this relationship. It was shown that destination competitiveness levels exert different impacts on WTP between travel vlogs and DMO promotional videos. This study enriches the tourism destination marketing literature and suggests that DMOs tailor their strategies based on destination competitiveness.
Effects of outdoor recreation on multiple vertebrate guilds in a fragmented sagebrush‐steppe ecosystem
Authors: Aberg Madeline C. , Coates Stephanie E. , Davis Lucian J. , Wright Benjamin W. , Mervin Richard L. , Carlisle Jay D.
Published: September 2024

Outdoor recreational use is growing rapidly in the western United States, which increases the pressure on multiple‐use public lands. Balancing recreational use with conservation goals requires considering the spatial and temporal intensity of recreational use and examining its effects on multiple species within an ecosystem. In 2019–2021, we assessed the relationship between recreational intensity and the abundance of a dominant prey species (Piute ground squirrel [Urocitellus mollis]), the abundance of avian and mammalian facultative scavengers that rely on ground squirrels, and the abundance and nesting success of ground‐nesting birds at a national conservation area in southwestern Idaho, USA, where recreational shooting and off‐highway vehicle use are the primary recreational activities. Recreational intensity varied across the study site. The abundance of ground squirrels was not related to recreational intensity. The abundance of common ravens (Corvus corax) and the abundance of American badgers (Taxidea taxus), 2 common facultative scavengers, were both positively associated with recreational intensity, while the abundance of other avian facultative scavengers was not related to recreational intensity. The abundance of horned larks (Eremophila alpestris) and nesting success of long‐billed curlews (Numenius americanus), a more sensitive species, were negatively related to recreational intensity. Together, our results highlight the importance of considering variation in recreational intensity and the effect of recreation on multiple guilds within the ecosystem. An improved understanding of these relationships can be used with public land management to protect wildlife while providing opportunities for outdoor recreation.
Integrated Quad‐Color Nanoprinting and Tri‐Channel Holographic Encryption Meta‐Marks with Printable Metasurfaces
Authors: Gong Jintao , Xiong Lingxing , Zhang Fei , Pu Mingbo , Hong Minghui , Luo Xiangang
Published: September 2024

Optical metasurfaces offer innovative approaches to manipulate the amplitude, phase, frequency, and polarization of light in localized regions, thus paving the way for a viable technology that can be applied in various domains, including structural coloration, multiplexed holography, and high‐resolution displays. To address the escalating need for sophisticated encryption, a novel quadruple‐security flexible plasmonic anti‐counterfeiting platform is proposed that utilizes printable centimeter‐scale (0.6 cm) metasurfaces. These metasurfaces feature four distinct signatures: They appear as color images under ambient incoherent white light, while projecting up to three different holograms under red, green, or blue circularly polarized laser illumination. Such holographic color nanoprintings are not only easily authenticated but also difficult to imitate, offering enhanced security in anti‐counterfeiting applications. The design of these multifunctional metasurfaces, which encode information solely in the surface relief of a single polymeric material with a silver coating, allows for efficient mass production through UV nanoimprinting lithography. Given the superior performance of these multifunctional plasmonic metasurfaces, this work presents tremendous potential in various fields such as multi‐level information security, cost‐effective anti‐counterfeiting, and many others.
Effect of Corrosion Wastage on the Limit States of Monopile‐Type Offshore Wind Turbines Under Combined Wind and Rotor Blade Rotation
Authors: Sindi Abdulaziz , Kim Hyeong Jin , Chaves Igor A. , Paik Jeom Kee
Published: September 2024

In digital healthcare engineering (DHE) for aging monopile‐type offshore wind turbines, predictive health analysis is essential for robust future maintenance planning. This paper presents the development of a DHE module for the predictive health analysis of corroded monopile‐type offshore wind turbines, focusing on wind and rotor blade rotation effects. An empirical formula for predicting time‐variant corrosion wastage is derived from a statistical analysis of a decade‐long corrosion wastage database and applied to predict the corrosion depth of a 5 MW monopile‐type offshore wind turbine, serving as an illustrative example. Nonlinear finite element analyses using LS‐DYNA are performed on the corroded turbine tower under combined wind‐induced loads and rotor‐induced thrust forces. Two types of corrosion wastage, pitting, and uniform (general) corrosion, are considered. The health condition of the corroded tower is evaluated based on serviceability limit state and ultimate limit state criteria. The methodology developed in this paper will be integrated into the DHE system currently being developed by the authors for aging monopile‐type offshore wind turbines.
Catalytically active prokaryotic Argonautes employ phospholipase D family proteins to strengthen immunity against different genetic invaders
Authors: Cheng Feiyue , Wu Aici , Li Zhihua , Xu Jing , Cao Xifeng , Yu Haiying , Liu Zhenquan , Wang Rui , Han Wenyuan , Xiang Hua , Li Ming
Published: September 2024

Prokaryotic Argonautes (pAgos) provide bacteria and archaea with immunity against plasmids and viruses. Catalytically active pAgos utilize short oligonucleotides as guides to directly cleave foreign nucleic acids, while inactive pAgos lacking catalytic residues employ auxiliary effectors, such as nonspecific nucleases, to trigger abortive infection upon detection of foreign nucleic acids. Here, we report a unique group of catalytically active pAgo proteins that frequently associate with a phospholipase D (PLD) family protein. We demonstrate that this particular system employs the catalytic center of the associated PLD protein rather than that of pAgo to restrict plasmid DNA, while interestingly, its immunity against a single‐stranded DNA virus relies on the pAgo catalytic center and is enhanced by the PLD protein. We also find that this system selectively suppresses viral DNA propagation without inducing noticeable abortive infection outcomes. Moreover, the pAgo protein alone enhances gene editing, which is unexpectedly inhibited by the PLD protein. Our data highlight the ability of catalytically active pAgo proteins to employ auxiliary proteins to strengthen the targeted eradication of different genetic invaders and underline the trend of PLD nucleases to participate in host immunity.
Barrett's paradox of cooperation in the case of quasi‐linear utilities
Authors: Accinelli Elvio , Afsar Atefeh , Martins Filipe , Martins José , Oliveira Bruno M.P.M. , Oviedo Jorge , Pinto Alberto A. , Quintas Luis
Published: September 2024

This paper fits in the theory of international agreements by studying the success of stable coalitions of agents seeking the preservation of a public good. Extending Baliga and Maskin, we consider a model of
homogeneous agents with quasi‐linear utilities of the form
, where
is the aggregate contribution and the exponent
is the elasticity of the gross utility. When the value of the elasticity
increases in its natural range
, we prove the following five main results in the formation of stable coalitions: (i) the gap of cooperation, characterized as the ratio of the welfare of the grand coalition to the welfare of the competitive singleton coalition grows to infinity, which we interpret as a measure of the urge or need to save the public good; (ii) the size of stable coalitions increases from 1 up to
; (iii) the ratio of the welfare of stable coalitions to the welfare of the competitive singleton coalition grows to infinity; (iv) the ratio of the welfare of stable coalitions to the welfare of the grand coalition “decreases” (a lot), up to when the number of members of the stable coalition is approximately
and after that it “increases” (a lot); and (v) the growth of stable coalitions occurs with a much greater loss of the coalition members when compared with free‐riders. Result (v) has two major drawbacks: (a) A priori, it is difficult to “convince” agents to be members of the stable coalition and (b) together with results (i) and (iv), it explains and leads to the “pessimistic” Barrett's paradox of cooperation, even in a case not much considered in the literature: The ratio of the welfare of the stable coalitions against the welfare of the grand coalition is small, even in the extreme case where there are few (or a single) free‐riders and the gap of cooperation is large. “Optimistically,” result (iii) shows that stable coalitions do much better than the competitive singleton coalition. Furthermore, result (ii) proves that the paradox of cooperation is resolved for larger values of
so that the grand coalition is stabilized.
Understanding “local”: Prehispanic Maya mobility and diet at Pacbitun, Belize, using strontium, oxygen, sulfur, carbon, and nitrogen isotope values
Authors: Freiwald Carolyn , Rand Asta , Skaggs Sheldon , Powis Terry G.
Published: September 2024

Classic period Maya populations were mobile, and both burial patterns and dietary analyses suggest that many movers were incorporated into local communities. This paper presents a multi‐isotopic (Sr, O, S, C, and N) study of the diet and mobility of 18 Late (AD 550–800) and Terminal Classic (AD 800–900) individuals from the site of Pacbitun, Belize. Three distinct isotope systems identify where people lived at different stages of life, from the childhood origins of migrant and local Pacbitun populations to their final residences. The enamel strontium isotope ratios of the Court 3 individuals were higher than local ranges established by faunal and human bone values, suggesting elite migration, or even residential mobility within the polity. Sulfur isotope values reveal information about the local population, where all but one individual in the sample lived at the site for many years before they died. The exception was an isotopically nonlocal individual in a dedicatory deposit, as reported in other studies. Diet also informs on the receiving community and how migrants assimilated, as people with local and nonlocal isotope values ate isotopically similar foods. Individuals from elite site core contexts and those in Pacbitun's peripheral settlements both consumed C4‐enriched proteins, though there were more isotopically diverse protein sources in peripheral settlements during the Terminal Classic period. Sulfur, carbon, and nitrogen isotope data also reveal some differences in where food was acquired, including use of nonlocal fauna. Combining isotope systems that sample different body tissues also may blur the line between migrants and locals, terms that may describe the same person at different stages of life and show the need for a more nuanced discussion of ancient mobility.
Congenital Pyriform Aperture Stenosis: Not All Patients Require Open Repair
Authors: Adil Eelam , Francisco Sarah , Rahbar Reza
Published: September 2024

Objective

Evaluate the management options for congenital nasal pyriform aperture stenosis (CNPAS).

Study Design

Case series.

Setting

Tertiary referral children's hospital.

Methods

The medical records of CNPAS patients managed from January 2015 to 2023 were reviewed for medical history, management, and outcomes.

Results

Fifteen patients met inclusion criteria. Six patients (40.0%) had a central mega incisor and 4 (26.7%) had holoprosencephaly. Three (20%) patients were managed with medications alone. Mean PA width was similar between patients managed medically versus those managed surgically (mean width 6.2 ± 0.15 mm vs 6.1 ± 0.38 mm). Median age at first procedure was 50 (range 8‐263) days. Seven (46.7%) underwent an initial balloon nasal dilation and 5 (33.3%) underwent an open sublabial repair. Operative time was lower in the balloon dilation group (mean 27 vs 104 minutes). Five patients had a single balloon dilation and 2 required revision procedures: 1 underwent a second balloon dilation, and 1 patient underwent a subsequent open sublabial procedure. Four patients with an initial open sublabial approach returned to the operating room for nasal balloon dilation or debridement due to nasal synechiae.

Conclusion

There has been general shift towards minimally invasive surgery. In our series, 8 (53.3%) patients were managed successfully with medical therapy or a single nasal balloon dilation procedure. Of those who underwent an open surgical repair, most (4/5) required a revision procedure due to synechiae. Given the relative success and lower operative time of balloon dilation, this option should be considered in the management algorithm for CNPAS.

Level of evidence

4.
Quantitative Spermidine Detection in Cosmetics using an Organic Transistor‐based Chemical Sensor
Authors: Sasaki Yui , Ohshiro Kohei , Kato Miyuki , Tanaka Hikaru , Yamagami Akari , Hagiya Kazutake , Minami Tsuyoshi
Published: September 2024

Spermidine is an essential biomarker related to antiaging. Although the detection of spermidine levels is in high demand in life science fields, easy‐to‐use analytical tools without sample purification have not yet been fully established. Herein, we propose an organic field‐effect transistor‐based chemical sensor for quantifying the spermidine concentration in commercial cosmetics. An extended‐gate structure was employed for organic field‐effect transistor (OFET)‐based chemical sensing in aqueous media. A coordination‐bond‐based sensing system was introduced into the OFET device to visualize the spermidine detection information through changes in the transistor characteristics. The extended‐gate‐type OFET has shown quantitative responses to spermidine, which indicates sufficient detectability (i. e., the limit of detection for spermidine: 2.3 μM) considering actual concentrations in cosmetics. The applicability of the OFET‐based chemical sensor for cosmetic analysis was validated by instrumental analysis using high‐performance liquid chromatography. The estimated recovery rates for spermidine in cosmetic ingredient products (108–111 %) suggest the feasibility of cosmetic analysis based on the OFET‐based chemical sensor.
Prognosis in elderly head and neck cancer patients without indication for treatment
Authors: Kadoya Koichi , Yagihara Kazuhiro , Katsurano Miki , Sumino Jun , Ishii Junichi , Maruta Noboru , Shibata Mari , Kim Yusoon , Ishikawa Ayataka
Published: September 2024

Aim

With an aging population, the number of older patients with head and neck malignancies is increasing. Some patients are not indicated for treatment because of their social condition or medical history. Prognostic data for patients with untreated head and neck elderly malignancies are scarce, making planning difficult. This study retrospectively examined older patients with oral malignancy who were ineligible for treatment and evaluated their prognostic factors.

Methods

Of 658 patients with oral malignancies who visited the Saitama Cancer Center, those aged >75 years who were ineligible for curative treatment (chemotherapy or palliative treatment) were included. Patients who had been treated at other hospitals or had undergone palliative treatment, including radiotherapy, were excluded. Progress since the first visit was retrospectively collected based on data from electronic medical records.

Results

Forty‐six patients were included in the study. The 12‐month survival rate was 10.6%, and the median overall survival was 6.0 months. The primary site was the maxillary gingiva (including the palate) in the largest number of patients (n = 15), and the disease stage was Stage III‐IV in the largest number of patients (n = 30). Although imaging evaluation was difficult in some patients because of their general condition, evaluating the primary site was predominantly associated with prognosis.

Conclusion

Overall, 8% of patients were deemed ineligible for treatment. The median overall survival was 6.0 months. We suggest that the evaluation of primary oral tumors may have prognostic significance.
Tuning the buckling behavior of slender, material extrusion manufactured collinear stayed polymer lattices
Authors: Ou Yating , Völlmecke Christina
Published: September 2024

A novel type of lightweight and high‐performance, collinear polymer lattice with the concept of stayed slender columns is presented, which is fabricated using extrusion–based additive manufacturing technology. The buckling and post‐buckling behavior of the stayed unit cells (UCs) and two‐dimensional lattices is investigated analytically and experimentally. The analytical study is performed with a three degree‐of‐freedom system based on the general theory of elastic stability with a Python‐based module “Pyfurc.” Uniaxial compression tests were performed on both UCs and lattices to observe the buckling behavior under applied end‐shortening. Experimental results indicate that the ultimate loads of the UCs and lattices with stays are significantly increased (approx. 4.4 times) compared to those without stays, which is achieved by adding minor weight. The study also investigated geometric imperfections in both the UCs and the lattice, and it is noteworthy that certain geometric imperfections were found to have a positive effect on the ultimate load capacity.
Changes in tropical leafing behaviour with climate change over nine decades: A case study from the Singapore Botanic Gardens
Authors: Ho Boon‐Chuan , Chia Edmund J. J. , Chong Kwek Yan , Tan Jolyn S. Y. , Tan Wan Xin , Lai Simin , Choo Thereis Y. S. , Tan Puay Yok , Er Kenneth B. H.
Published: September 2024

Societal Impact Statement

Long‐term phenology data is crucial to elucidate the effects of climate change on plants, but such efforts are lacking in the tropics. Historical records at the Singapore Botanic Gardens and ongoing phenological monitoring have allowed us to study leafing behaviour and its association with changing rainfall patterns over nine decades in equatorial Singapore. We found that the leafing behaviour of trees in our tropical site changed between 1927 and 2022. This study was made possible by assiduous past and present record‐keeping, and demonstrates the potential of botanical gardens as sentinels of environmental change, which is especially important in the tropics.

Understanding tropical phenology and the potential impacts of a changing climate requires long‐term monitoring but such efforts are rare in the tropics. We took advantage of the availability of historical phenological and weather records at the Singapore Botanic Gardens and ongoing phenological monitoring to ask whether leafing behaviour has changed over an exceptionally long period of about nine decades, and whether these changes are associated with changing rainfall patterns in supposedly aseasonal Singapore.

Records of leaf flush intervals from 1927 to 1939 in the Singapore Botanic Gardens were compared against leaf flush intervals calculated from present‐day phenological monitoring conducted since 2016. Daily rainfall was modelled as a predictor of present‐day leaf flushing events using moving‐window analyses.

Leaf flush intervals have shortened considerably for most of the species that were monitored in the two periods. Mean daily rainfall over a window of 1 to 4 months before was negatively associated with probability of leaf flushing for five species and positively associated with four out of a total of 23 species analysed. Long‐term rainfall records from 1929 to 2022 show that February has become drier and May has become wetter since the 1960s.

The results consistently support that more distinctive dry and wet periods today compared to nine decades ago have resulted in more frequent leaf flushing, which may have implications for plant‐herbivore interactions, nutrient cycling and consequently plant health and ecosystem resilience. We also demonstrate the potential and importance of supporting long‐term research in botanical gardens in the tropics.
Population pharmacokinetic modeling of vedolizumab for graft‐versus‐host disease prophylaxis in adults with allogeneic hematopoietic stem cell transplant
Authors: Waterhouse Timothy , Baron Kyle , Eure Westley , Chen Chunlin , Dirks Nathanael L. , Jansson Johan , Akbari Mona , Mehrotra Shailly
Published: September 2024

We aimed to characterize the population pharmacokinetics (PK) of vedolizumab for acute graft‐versus‐host disease prophylaxis in adults undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) and assess potential clinically relevant covariates. Dosing, patient characteristics, and PK from a phase 1b, open‐label, dose‐finding study of vedolizumab 75 mg initial dose escalated to 300 mg and a phase 3 study of vedolizumab 300 mg in patients receiving allo‐HSCT were analyzed using a two‐compartment population PK model with linear elimination. Covariates included age, race, weight, sex, albumin, lymphocyte count, GvHD type, and concomitant medications. Weight, albumin, and lymphocyte count were time‐varying covariates. Model selection was driven by goodness‐of‐fit criteria, precision of parameter estimates, and visual predictive checks. In 193 patients undergoing allo‐HSCT, vedolizumab PK were well described by a two‐compartment, linear PK model. Using reference covariate values, final parameter estimates (95% confidence intervals [CI]) were: clearance, 0.148 (0.136, 0.162) L/day; central volume of distribution, 3.12 (3.03, 3.21) L; intercompartmental clearance, 0.500 (0.408, 0.612) L/day; and peripheral volume of distribution, 3.95 (3.52, 4.44) L. Weight and albumin were the most important predictors of vedolizumab PK, with clearance decreasing by ≈20% for low body weight/high albumin and increasing by ≈30% for high body weight/low albumin. There was an inverse relationship between vedolizumab clearance and age, but no detectable effect for lymphocyte count or GvHD type. Post hoc analyses did not detect any relationship between vedolizumab PK and concomitant medications. In summary, the covariates studied did not have a clinically meaningful effect on the PK of vedolizumab.
Design and synthesis of some novel structurally diverse thiochroman derivatives as fungicides against phytopathogenic fungi
Authors: Liu Wenjing , Li Yong , Liang Jun , Li Yi , Zhu Gaofeng , Wang Jianta , Chen Wenzhang , Tang Lei , Fan Lingling
Published: September 2024

BACKGROUND

Plant diseases infected by pathogenic fungi have a devastating effect on global agricultural and food industry yields. The development of novel, environmentally friendly, and efficient fungicides is an important technique for preventing and combatting phytopathogenic fungi.

RESULTS

Herein, 99 thiochroman‐based derivatives containing hydroxyl, sulfoxide, sulfone, carbonyl, double bond, amino, imine, oxime, oxime ester, and amide moieties were synthesized. The antifungal activities of the target compounds against ten typical phytopathogenic fungi were also investigated. The bioassay results illustrated that most of the target compounds exhibited moderate to excellent antifungal effects against the tested fungi in vitro. Among these, thiochroman‐oxime derivatives (12a–12m) exerted a promising inhibition effect, especially against Fusarium solani, Fusarium graminearum, Valsa mali, and Botrytis cinerea strains. Furthermore, the compounds 12f and 12g markedly suppressed the spore germination germ and tube growth. At the same time, they exerted excellent protective effects against potatoes infected by F. solani, making them superior to commercial fungicides Hymexazol and Chlorothalonil. Notably, the compounds 12d and 12f also showed excellent protective effects against cherry tomatoes infected by B. cinerea. Further mechanistic studies revealed that compound 12f exerted an antifungal effect by overtly altering the mycelium structure and remarkably increasing cell membrane permeability. Fortunately, the excellent bioactive compounds showed good safety against human hepatic cell lines (WRL‐68). The preliminary structure–activity relationship analysis revealed that the introduction of hydroxyl or oxime fragments at the thiopyran ring might be significantly beneficial to antifungal activity.

CONCLUSION

This study provides thiochroman compounds that can be used in the development of novel botanical fungicides for the management of phytopathogenic fungi. © 2024 Society of Chemical Industry.
CLVSim: A comprehensive framework for crewed lunar vehicle simulation—Modeling and applications
Authors: Lan Qingning , Ding Liang , Yang Huaiguang , Richter Lutz , Wang Zhengyin , Gao Haibo , Deng Zongquan
Published: September 2024

Crewed lunar vehicles (CLVs) significantly enhance astronauts’ exploration range and efficiency on the moon, paving the way for more comprehensive scientific research. Utilizing computer simulations offers an effective alternative to conducting experiments in low‐gravity conditions if backed up by appropriate model validation. This study introduces a detailed simulation framework CLVSim (Crewed Lunar Vehicle Simulation), including subsystems of smoothed particle hydrodynamics (SPH) soft terrain, suspensions, motors, wheels, fenders, and driver. A high‐fidelity instance of CLVSim was modeled and benchmarked based on the Lunar Roving Vehicle (LRV) from the “Apollo” program. Each subsystem was independently modeled and benchmarked based on the information from the Apollo handbook. These subsystems were then integrated to benchmark the overall operation of the CLV with experiment in a simulated lunar environment, with a mean relative error of 8.6%. The mean relative error between simulation and experiment for all subsystems and overall CLV test was less than 10%. Further applications of CLVSim were investigated. For instance, two fender designs were investigated to evaluate their effectiveness in mitigating dust emission from wheels. The vehicles’ performances were examined with four different configurations: a standard CLV on flat terrain, and CLVs with two types of suspension stiffness and torque coordination strategy driveline on rugged terrain. Comparing the maneuverability of CLVs with passive and differential drive to those with stiffer suspensions, there were approximately 9% and 7% savings in steering, respectively. The high fidelity and potential for advanced research of the simulation framework were demonstrated in areas like CLV mechanism design, dust prevention and control strategy design.
Multi‐Objective Route Outlining and Collision Avoidance of Multiple Humanoid Robots in a Cluttered Environment
Authors: Kashyap Abhishek Kumar , Parhi Dayal R.
Published: September 2024

In robotics, navigating a humanoid robot through a cluttered environment is challenging. The present study aims to enhance the footstep and determine optimal paths regarding the robot's route length. The objective function for navigation of multiple humanoid robots is presented to optimize the route length and travel time. A hybrid technique using a probabilistic roadmap (PRM) and firefly algorithm (FA) is presented for humanoid robot navigation in a cluttered environment with static and dynamic obstacles. Sensory information, such as barrier range in the left, right, and front directions, is fed into the PRM framework that allows the humanoid robot to walk steadily with an initial steering angle. It finds the shortest path using the Bellman–Ford algorithm. The FA technique is used for efficient guidance and footstep modification in a cluttered environment to find a smooth and optimized path. To avoid static obstacles, the suggested hybrid technique provides optimum steering angles and ensures the minimum route length by taking the output of PRM as its input. A 3D simulator and a real‐world environment have been used for simulation and experiment in a cluttered environment utilizing the developed model and standalone methods. The humanoid robot achieves the target in all scenarios, but the FA‐tuned PRM technique is advantageous to this purpose, as shown by the convergence curve, route length, and travel duration. Multiple humanoid robot navigation has an additional self‐collision issue, which is eliminated by employing a dining philosopher controller as the base technique. In addition, the proposed controller is evaluated in contrast to the existing technique. The developed strategy ensures effectiveness and efficacy depending on these findings.
Going to the archives: Combining palaeoecological and contemporary data to support river restoration appraisals
Authors: White J. C. , Seddon E. , Hill M. J. , Mathers K. L. , Bridger M. , Hannah D. M. , Wood P. J.
Published: September 2024

River restoration practices are being increasingly implemented to help offset the global degradation of freshwater ecosystems. The ecological success of such projects is typically determined via post‐project appraisals comparing restored conditions against specified baselines (e.g., pre‐project and/or non‐restored data), but such approaches can overlook broader ecosystem recovery patterns. Using freshwater macroinvertebrate communities, this study examined ecological responses to river restoration that are seldom assessed: (i) sub‐annual temporal trajectories and (ii) palaeoecological versus contemporary community comparisons. Palaeoecological samples contained assemblages that existed prior to major anthropogenic pressures, which were collected from a sinuous palaeochannel that was restored and reconnected during the study; after which contemporary macroinvertebrate samples were collected. The restored channel initially supported an impoverished community, but taxonomic richness and densities were comparable to non‐restored conditions after 13‐months. The freshwater shrimp (Gammarus pulex) and non‐native New Zealand mud snail (Potamopyrgus antipodarum) proliferated 7‐months post‐restoration, and follow‐up biomonitoring highlighted their dominance prevailed 5‐years later. Such evidence indicates how ecosystem dynamics in the aftermath of restoration can shape longer‐term recovery. Palaeoecological communities exhibited higher biodiversity and conservation values compared with contemporary samples. This highlights that escalating anthropogenic pressures since the mid‐20th Century degraded macroinvertebrate communities, notably constraining marginal‐dwelling and lentic specialists. With palaeochannel reconnections being widely applied worldwide, this study demonstrates the value in collecting palaeoecological data before restoration works to provide valuable baseline information. As the global anthropogenic footprint increasingly degrades suitable “reference” river environments, palaeoecological data can better characterize biodiversity losses and potentially provide target conditions informing effective restoration activities.
Approximate maximum likelihood estimation in cure models using aggregated data, with application to HPV vaccine completion
Authors: Rice John D. , Kempe Allison
Published: September 2024

Research into vaccine hesitancy is a critical component of the public health enterprise, as rates of communicable diseases preventable by routine childhood immunization have been increasing in recent years. It is therefore important to estimate proportions of “never‐vaccinators” in various subgroups of the population in order to successfully target interventions to improve childhood vaccination rates. However, due to privacy issues, it may be difficult to obtain individual patient data (IPD) needed to perform the appropriate time‐to‐event analyses: state‐level immunization information services may only be willing to share aggregated data with researchers. We propose statistical methodology for the analysis of aggregated survival data that can accommodate a cured fraction based on a polynomial approximation of the mixture cure model log‐likelihood function relying only on summary statistics. We study the performance of the method through simulation studies and apply it to a real‐world data set from a study examining reminder/recall approaches to improve human papillomavirus (HPV) vaccination uptake. The proposed methods may be generalized for use when there is interest in fitting complex likelihood‐based models but IPD is unavailable due to data privacy or other concerns.
Performance of mixed effects models and generalized estimating equations for continuous outcomes in partially clustered trials including both independent and paired data
Authors: Lange Kylie M. , Sullivan Thomas R. , Kasza Jessica , Yelland Lisa N.
Published: September 2024

Many clinical trials involve partially clustered data, where some observations belong to a cluster and others can be considered independent. For example, neonatal trials may include infants from single or multiple births. Sample size and analysis methods for these trials have received limited attention. A simulation study was conducted to (1) assess whether existing power formulas based on generalized estimating equations (GEEs) provide an adequate approximation to the power achieved by mixed effects models, and (2) compare the performance of mixed models vs GEEs in estimating the effect of treatment on a continuous outcome. We considered clusters that exist prior to randomization with a maximum cluster size of 2, three methods of randomizing the clustered observations, and simulated datasets with uninformative cluster size and the sample size required to achieve 80% power according to GEE‐based formulas with an independence or exchangeable working correlation structure. The empirical power of the mixed model approach was close to the nominal level when sample size was calculated using the exchangeable GEE formula, but was often too high when the sample size was based on the independence GEE formula. The independence GEE always converged and performed well in all scenarios. Performance of the exchangeable GEE and mixed model was also acceptable under cluster randomization, though under‐coverage and inflated type I error rates could occur with other methods of randomization. Analysis of partially clustered trials using GEEs with an independence working correlation structure may be preferred to avoid the limitations of mixed models and exchangeable GEEs.
A Causal Mediation Approach to Account for Interaction of Treatment and Intercurrent Events: Using Hypothetical Strategy
Authors: Wu Kunpeng , Zhang Xiangliang , Zheng Meng , Zhang Jianghui , Chen Wen
Published: September 2024

Hypothetical strategy is a common strategy for handling intercurrent events (IEs). No current guideline or study considers treatment–IE interaction to target the estimand in any one IE‐handling strategy. Based on the hypothetical strategy, we aimed to (1) assess the performance of three estimators with different considerations for the treatment–IE interaction in a simulation and (2) compare the estimation of these estimators in a real trial. Simulation data were generalized based on realistic clinical trials of Alzheimer's disease. The estimand of interest was the effect of treatment with no IE occurring under the hypothetical strategy. Three estimators, namely, G‐estimation with and without interaction and IE‐ignored estimation, were compared in scenarios where the treatment–IE interaction effect was set as −50% to 50% of the main effect. Bias was the key performance measure. The real case was derived from a randomized trial of methadone maintenance treatment. Only G‐estimation with interaction exhibited unbiased estimations regardless of the existence, direction or magnitude of the treatment–IE interaction in those scenarios. Neglecting the interaction and ignoring the IE would introduce a bias as large as 0.093 and 0.241 (true value, −1.561) if the interaction effect existed. In the real case, compared with G‐estimation with interaction, G‐estimation without interaction and IE‐ignored estimation increased the estimand of interest by 33.55% and 34.36%, respectively. This study highlights the importance of considering treatment–IE interaction in the estimand framework. In practice, it would be better to include the interaction in the estimator by default.