bluuebunny/crossref_metadata_2025 huggingface dataset:
Accounting for R&D: Evidence and Implications*
Authors: Canace Thomas G. , Jackson Scott B. , Ma Tao , Zimbelman Aaron
Published: April 2022

Accounting rules require that certain R&D expenditures be capitalized, but academic research often states that all R&D expenditures must be immediately expensed. An accurate understanding of actual R&D accounting practices is critical because that understanding influences research questions and design choices. To examine the competing R&D accounting perspectives, we survey 184 experienced financial officers. Our survey reveals that R&D capitalization is common and extensive in practice. Over 90% of respondents indicate that their firm capitalizes at least some R&D expenditures, and our evidence shows that about 22% of annual R&D expenditures are capitalized. When facing an earnings shortfall, respondents indicate that firms are often willing to cut R&D expense. However, respondents also indicate an unwillingness to cut types of R&D expenses that cause long‐term harm—for example, laying off scientists or delaying the execution of trials—and they often redirect the freed‐up R&D resources to R&D expenditures that are capitalized. Using archival data, we also corroborate our survey finding about the pervasiveness of capitalized R&D, and we demonstrate its empirical implications. Our study helps to align the characterization of R&D accounting rules in the academic literature with the authoritative professional literature and provides a more nuanced understanding of firms’ R&D response to an earnings shortfall.
Relational Epistemology and Amazonian Land‐based Education: Learning the Ideas of Intra‐dependency in the Central Purus River
Authors: Virtanen Pirjo Kristiina
Published: April 2022

This article discusses relational land‐based education in the Brazilian Amazon and the idea of intra‐dependency. The data produced with the Apurinã presents the intra‐relational spaces of knowing created between different beings, human and other‐than‐human, which contrast with the notion of individual learners. Apurinã co‐existence in learning also sheds light on the emotional dimension of Amazonian relational epistemology, while its inclusion of human–environment relations can contribute to taking seriously the practice of care toward other‐than‐human beings.
Dutch spirits, East Indians, and Hindu deities in Guyana: Contests over land
Authors: Mello Marcelo Moura
Published: April 2022

In modern‐day Guyana (formerly British Guiana) residents of the coastal region of the country are susceptible to other‐than‐human powers: the spirits of Dutch colonizers, who claim ownership over the land, especially in areas where sugar plantations once operated. Regarded as the “masters of the land,” or “boundary masters,” Dutch spirits demand offerings and the recognition of land rights from their human co‐habitants. Through a description of rituals towards the land performed by members of a heterodox Hindu sect, the worship of the goddess Kali, this article addresses territorial sovereignty through the lens of lived and embodied practices of co‐habitation between East Indians and Dutch spirits, giving special attention to the processes of establishing proprietary rights over the land through such acts as planting trees.
miR‐3184‐3p enriched in cerebrospinal fluid exosomes contributes to progression of glioma and promotes M2‐like macrophage polarization
Authors: Xu Hao , Li Ming , Pan Ziwen , Zhang Zongpu , Gao Zijie , Zhao Rongrong , Li Boyan , Qi Yanhua , Qiu Wei , Guo Qindong , Zhang Shouji , Fan Yang , Zhao Shulin , Wang Shaobo , Guo Xing , Deng Lin , Xue Hao , Li Gang
Published: April 2022

Liquid biopsy is a novel strategy for tumour diagnosis. The contents of cerebrospinal fluid (CSF) exosomes could reflect glioma status, hence sampling exosomes from CSF is a means of liquid biopsy for glioma. However, few studies have focused on the function of microRNAs in CSF exosomes. In this study, we found that miR‐3184‐3p was enriched in CSF exosomes in glioma patients and was downregulated after tumour resection. We found that miR‐3184 facilitates glioma progression in two ways. On the one hand, miR‐3184 directly promotes proliferation, migration, and invasion while inhibiting apoptosis in glioma. On the other hand, miR‐3184 in glioma‐derived exosomes polarizes macrophages to an M2‐like phenotype, which further aggravates tumour progression. Overall, the current findings uncovered a new mechanism and highlighted the significant role of miR‐3184 in glioma progression. Furthermore, exosomal miR‐3184 could be a considerable factor with potential applications in glioma diagnosis and treatment in the future.
The Evolution of Chunks in Sequence Learning
Authors: Tosatto Laure , Fagot Joël , Nemeth Dezso , Rey Arnaud
Published: April 2022

Chunking mechanisms are central to several cognitive processes and notably to the acquisition of visuo‐motor sequences. Individuals segment sequences into chunks of items to perform visuo‐motor tasks more fluidly, rapidly, and accurately. However, the exact dynamics of chunking processes in the case of extended practice remain unclear. Using an operant conditioning device, 18 Guinea baboons (Papio papio) produced a fixed sequence of nine movements during 1000 trials by pointing to a moving target on a touch screen. Response times analyses revealed a specific chunking pattern of the sequence for each baboon. More importantly, we found that these patterns evolved during the course of the experiment, with chunks becoming progressively fewer and longer. We identified two chunk reorganization mechanisms: the recombination of preexisting chunks and the concatenation of two distinct chunks into a single one. These results provide new evidence on chunking mechanisms in sequence learning and challenge current models of associative and statistical learning.
Face‐Processing Differences Present in Grapheme‐Color Synesthetes
Authors: Mannix Thea , Sørensen Thomas Alrik
Published: April 2022

Grapheme‐color synesthesia is a heterogeneous neurological phenomenon whereby the experience of a grapheme automatically and involuntarily elicits an experience of color. While the majority of synesthesia research has focused on inducer‐specific influences of synesthetic associations, more recent efforts have examined potential broader differences. Based on spontaneous reports from synesthetes detailing problems with face recognition, in conjunction with the geographical proximity of neurological regions relevant to both synesthesia and face processing, we sought to examine whether synesthetes demonstrated atypical face‐processing abilities.

A total of 16 grapheme‐color synesthetes and 16 age‐and‐gender matched controls (±3 years) completed the Cambridge Face Memory Test (CFMT; Duchaine & Nakayama, 2006) of face memory, the Vanderbilt Holistic Face Processing Task (VHPT‐F; Richler, Floyd, & Gauthier, 2014) of holistic face processing, as well as a standardized self‐report questionnaire the Faces and Emotions Questionnaire (Freeman, Palermo, & Brock, 2015). The results revealed significantly poorer performance in synesthete's ability to recognize faces in the CFMT that was driven by a reduction in upright advantage. Results also revealed a significant reduction in overall accuracy on the VHPT‐F for synesthetes, who despite this displayed a comparable holistic processing advantage compared to matched controls. Finally, synesthetes also rated themselves as significantly worse at face recognition. We suggest that this pattern may reflect differences in the development of individualized perceptual strategies.
Machine learning‐based phenotypic screening for postmitotic growth inducers uncover vitamin D3 metabolites as small molecule ribosome agonists
Authors: Jiang Zongmin , Zhang Liping , Yao Ziyue , Cao Wenhua , Ma Shilin , Chen Yu , Guang Lu , Zheng Zipeng , Li Chunwei , Yu Kang , Shyh‐Chang Ng
Published: April 2022

Objectives

To restore tissue growth without increasing the risk for cancer during aging, there is a need to identify small molecule drugs that can increase cell growth without increasing cell proliferation. While there have been numerous high‐throughput drug screens for cell proliferation, there have been few screens for post‐mitotic anabolic growth.

Materials and Methods

A machine learning (ML)‐based phenotypic screening strategy was used to discover metabolites that boost muscle growth. Western blot, qRT‐PCR and immunofluorescence staining were used to evaluate myotube hypertrophy/maturation or protein synthesis. Mass spectrometry (MS)‐based thermal proteome profiling‐temperature range (TPP‐TR) technology was used to identify the protein targets that bind the metabolites. Ribo‐MEGA size exclusion chromatography (SEC) analysis was used to verify whether the ribosome proteins bound to calcitriol.

Results

We discovered both the inactive cholecalciferol and the bioactive calcitriol are amongst the top hits that boost post‐mitotic growth. A large number of ribosomal proteins' melting curves were affected by calcitriol treatment, suggesting that calcitriol binds to the ribosome complex directly. Purified ribosomes directly bound to pure calcitriol. Moreover, we found that calcitriol could increase myosin heavy chain (MHC) protein translation and overall nascent protein synthesis in a cycloheximide‐sensitive manner, indicating that calcitriol can directly bind and enhance ribosomal activity to boost muscle growth.

Conclusion

Through the combined strategy of ML‐based phenotypic screening and MS‐based omics, we have fortuitously discovered a new class of metabolite small molecules that can directly activate ribosomes to promote post‐mitotic growth.
Dental students' knowledge of and attitudes towards prescribing medication in Western Australia
Authors: Park Joon Soo , Daniel Ben K. , Wong Pauline Y. , Abbott Paul V. , Ngo Hien C.
Published: April 2022

Introduction

Dentists can prescribe medications for prophylactic and therapeutic purposes. In Australia, dental graduates can autonomously practise within the scope of their qualifications without needing to undertake an internship post‐graduation. Although previous research has identified knowledge gaps amongst dental students in Australia on pharmacology and pharmacotherapeutic knowledge, there has been no published research that qualitatively highlights dental students' knowledge of medication prescribing in Australia. This study aimed to undertake a qualitative analysis of Western Australian dental students' attitudes towards and knowledge of medication prescribing.

Methods

This qualitative case study design employed semi‐structured interviews as means of collecting data. It utilised a purposive sampling in penultimate and final year dental students at the University of Western Australia.

Results

Twenty dental students participated in the study. Five key themes were identified in the data: current and previous education, application when delivering pharmacology and pharmacotherapeutics, teaching to ensure patient‐centred care, supervision and referral to relevant resources. Participants agreed that having previous knowledge in the area provides students with confidence regarding medication prescribing. Furthermore, students in this study valued having guidance when prescribing medications.

Conclusions

This study highlights the complexity of medication prescribing for dental students. It also highlights their experience with the current pharmacology and pharmacotherapeutics curriculum. All students interviewed valued application‐based teaching, making it specific to dentistry. If curriculum were to be redeveloped, considering their perceptions may be a valuable tool.
Climatic and biogeographical drivers of functional diversity in the flora of the Canary Islands
Authors: Hanz Dagmar M. , Cutts Vanessa , Barajas‐Barbosa Martha Paola , Algar Adam C. , Beierkuhnlein Carl , Fernández‐Palacios José‐María , Field Richard , Kreft Holger , Steinbauer Manuel J. , Weigelt Patrick , Irl Severin D. H.
Published: April 2022

Aim

Functional traits can help us to elucidate biogeographical and ecological processes driving assemblage structure. We analysed the functional diversity of plant species of different evolutionary origins across an island archipelago, along environmental gradients and across geological age, to assess functional aspects of island biogeographical theory.

Location

Canary Islands, Spain.

Major taxa studied

Spermatophytes.

Time period

Present day.

Methods

We collected data for four traits (plant height, leaf length, flower length and fruit length) associated with resource acquisition, competitive ability, reproduction and dispersal ability of 893 endemic, non‐endemic native and alien plant species (c. 43% of the Canary Island flora) from the literature. Linking these traits to species occurrences and composition across a 500 m × 500 m grid, we calculated functional diversity for endemic, non‐endemic native and alien assemblages using multidimensional functional hypervolumes and related the resulting patterns to climatic (humidity) and island biogeographical (geographical isolation, topographic complexity and geological age) gradients.

Results

Trait space of endemic and non‐endemic native species overlapped considerably, and alien species added novel trait combinations, expanding the overall functional space of the Canary Islands. We found that functional diversity of endemic plant assemblages was highest in geographically isolated and humid grid cells. Functional diversity of non‐endemic native assemblages was highest in less isolated and humid grid cells. In contrast, functional diversity of alien assemblages was highest in arid ecosystems. Topographic complexity and geological age had only a subordinate effect on functional diversity across floristic groups.

Main conclusions

We found that endemic and non‐endemic native island species possess similar traits, whereas alien species tend to expand functional space in ecosystems where they have been introduced. The spatial distribution of the functional diversity of floristic groups is very distinct across environmental gradients, indicating that species assemblages of different evolutionary origins thrive functionally in dissimilar habitats.
Understanding the spatial polarization pattern of technology transfer network in the Guangdong–Hong Kong–Macao Greater Bay area
Authors: Cai Hechang , Feng Zhijun , Zhou Wen , Chen Jinghan , Chen Zinan
Published: April 2022

Technology transfer is a conscious knowledge transfer and diffusion, which can promote the coordinated configuration and balanced development of technological innovation elements in geographical space. From the perspective of “space of flow”, the technology transfer network is constructed. Utilizing patent technology transaction data from 2018, this study analyzes the agglomeration differentiation and spatial polarization patterns of technology transfer from network nodes, network layers, and network partition in Guangdong–Hong Kong–Macao Greater Bay Area. The conclusions are as follows: (1) The agglomeration of technology transfer is remarkable in the network, showing “two poles and two strong” as well as proximity advantages; Shenzhen and Guangzhou have become spatial poles within the network. (2) The Matthew effect is prominent and technology transfer at the spatial level is largely caused by core node interactions, while core‐edge hierarchical transmission mechanisms and geographical proximity contact characteristics are gradually developing. (3) Differences in roles between the plates are pronounced, and there is an agglomeration effect within a plate and between plates, as well as clear spillover effects.
Age of eradication and failure rates of clarithromycin‐containing triple therapy forHelicobacter pylori: A 15‐year population‐based study
Authors: Jiang Fang , Guo Chuan‐Guo , Cheung Ka Shing , Li Bofei , Law Simon Y. K. , Leung Wai K.
Published: April 2022

Background

Failure rates of clarithromycin‐containing triple therapy forH. pyloriare rising. To determine the trend of failure rates of clarithromycin‐containing triple therapy in different age groups in Hong Kong over the past 15 years.

Materials and Methods

This is a population‐based retrospective age‐period‐cohort study involving all adultH. pylori‐infected patients who had received the first course of clarithromycin‐containing triple therapy in 2003–2017. Failed eradication was identified by the need of retreatment within 2 years of eradication. Logistic regression model was used to characterize the risk of retreatment.

Results

113,526H. pylori‐infected patients were included. The overall failure rate increased from 4.83% in 2003 to 10.2% in 2016 (pfor linear trend <0.001). When stratified by age of eradication, patients 75 years or above had the lowest retreatment rate of 5.11%, which progressively increased in younger patients (60–74 years: OR 1.26, 95% CI 1.15–1.38; 45–59 years: OR 1.36, 95% CI 1.24–1.48; 18–44 years: OR 1.55, 95% CI 1.41–1.69). The results remained consistent when stratified by year of birth, and period of eradication. Other risk factors for retreatment included female (OR 1.24, 95% CI 1.18–1.30), triple therapy containing metronidazole (OR 2.30, 95% CI 2.12–2.50), and shorter duration of therapy (10 days: OR 0.88, 95% CI 0.79–0.97; 14 days: OR 0.67, 95% CI 0.58–0.77 vs 7 days).

Conclusions

While failure rates of clarithromycin‐containing triple therapy progressively increased over the past 15 years, the failure rate was particularly high among younger patients, which could undermine the potential benefits of earlyH. pylorieradication.
Forest hoverfly community collapse: Abundance and species richness drop over four decades
Authors: Barendregt Aat , Zeegers Theo , van Steenis Wouter , Jongejans Eelke
Published: April 2022

To study insect decline, an important threat to biodiversity, long‐term datasets are needed. Here we present a study of hoverfly (Diptera: Syrphidae) abundance and diversity in a Dutch forest, surrounded by other forests, and analyse the variation in insect numbers over four decades.

Between 1982 and 2021, abundance decreased by 80%. Until 1990, abundance showed a strong decrease of 10.9% per year, mainly in nationally rare species with carnivorous larvae exposed to air. From 1990, abundance stabilised, whereas from 2000, a second period of strong decline of 9.0% per year occurred, mainly in very common species.

Species richness also declined strongly between 1979 and 2021: the total number of species observed in five monitoring days dropped by 44% over those 43 years. The characteristic set of dry‐forest hoverfly species disappeared over four decades.

The number of nationally rare species observed at the study site declined from 19 to 9 early on, in a period (1979–1984) that coincided with intense nitrogen input and acidification caused by agriculture in the same region. The more recent decline is likely also caused by factors from outside the forest, as forest management and conditions remained constant.

Continued influx of nutrients and pesticides at a regional level, as well as climate change are possible causes of the decline. Research is needed to quantify their relative effects.
Impact of nerve sparing in robot‐assisted radical prostatectomy on the risk of positive surgical margin and biochemical recurrence
Authors: Komori Hiroki , Blas Leandro , Shiota Masaki , Takamatsu Dai , Matsumoto Takashi , Lee Ken , Monji Keisuke , Kashiwagi Eiji , Inokuchi Junichi , Eto Masatoshi
Published: April 2022

Objectives

Nerve sparing may increase positive surgical margin rate during radical prostatectomy. Our objective was to analyze the positive surgical margin rate and location as well as its impact on biochemical recurrence according to nerve sparing procedure in robot‐assisted radical prostatectomy.

Methods

We included 814 patients treated with robot‐assisted radical prostatectomy between 2009 and 2021, and evaluated the impact of nerve sparing on positive surgical margin and biochemical recurrence using logistic regression and Cox models.

Results

Unilateral nerve sparing and bilateral nerve sparing were performed in 152 (18.6%) cases and 118 (14.5%) cases, respectively. On multivariable analysis, in addition to nerve sparing, bilateral nerve sparing, but not unilateral nerve sparing was associated with an increased risk of positive surgical margin compared with non‐nerve sparing. Positive surgical margin at any location increased the risk of biochemical recurrence. During unilateral nerve sparing, positive surgical margin in nerve sparing side, but not in non‐nerve sparing side was associated with increased risk of biochemical recurrence on multivariate analysis.

Conclusions

Taken together, surgeons need to notice an increased risk of biochemical recurrence associated with positive surgical margin when performing nerve sparing in robot‐assisted radical prostatectomy, and then need to choose the patients suitable for nerve sparing.
Factors associated with retention intention of Registered Nurses in Korean nursing homes
Authors: Min Deulle , Cho Eunhee , Kim Gwang Suk , Lee Kyung Hee , Yoon Ju Young , Kim Hyun Joo , Choi Moon Hee
Published: April 2022

Aim

To identify the factors associated with retention intention among Registered Nurses in South Korean nursing homes.

Background

Although nurses are not mandatory personnel, Korean nursing homes employ Registered Nurses.

Introduction

Determining the factors related to Registered Nurses’ retention intention is important for their job stability and ensure provision of quality care.

Methods

This mixed‐methods study employed a sequential explanatory design. A self‐reported questionnaire survey was conducted between May 1 and July 3, 2019, with 155 Registered Nurses providing direct care from 37 nursing homes. In‐depth qualitative interviews were conducted with 10 participants from August 1 to September 30, 2019. Data were analyzed using multilevel analysis for quantitative study and thematic analysis for qualitative study.

Results

The participants’ average age was 48.48 years. Personal factors related to retention intention were Registered Nurses’ role, educational level, and job satisfaction. Institutional factors were ownership, number of beds, and working environment. The qualitative study revealed five themes: “Satisfaction with meaningful relationships,” “Potential for professional growth,” “Nursing service accompanied by emotional labor,” “Poor working environments in nursing homes,” and “Unprotected nursing expertise.”

Discussion

A nursing home's work environment is related to the Registered Nurses’ retention intention. Most Registered Nurses in Korea received low wages, lacked access to career management programs, and experienced emotional labor.

Conclusion

This study highlighted the personal and institutional factors related to retention intention among Registered Nurses in South Korean nursing homes.

Implications for nursing and nursing policy

A law that designates Registered Nurses as an essential nursing home workforce is required. Further, nursing homes should increase the number of Registered Nurses to improve working conditions and thereby job satisfaction. It is also necessary to foster a working environment that facilitates professional development opportunities and job clarity.
First‐principles analysis of proton conduction mechanism in perovskite‐structured sodium tantalate
Authors: Chen Ximu , Toyoura Kazuaki , Hatada Naoyuki , Uda Tetsuya
Published: April 2022

With the aim to elucidate the proton conduction mechanism in sodium tantalite with an orthorhombic perovskite structure, o‐NaTaO3, proton sites and elementary processes of proton jumps in the crystal were explored using first‐principles calculations. In this crystal, interoctahedral hopping plays a key role in the proton conduction, contrast to cubic perovskites where protons migrate over a long range only by rotation and intraoctahedral hopping. The interoctahedral hopping results from the tilting structure of TaO6 octahedra units, which accelerates the relatively fast proton migration along b‐ and c‐axes compared to that along a‐axis. This suggests that the low symmetry of the crystal structure can be beneficial to proton conduction in some cases, although the low symmetry is generally considered to make the potential barrier of long‐range proton migration higher. Considering the trapping effect of Ti dopants as the change in the concentration of mobile protons, the calculated proton conductivity is in excellent agreement with the experimental one.
Modeling of ion exchange in glass considering large viscoelastic deformation and mechano–electrochemical coupling
Authors: Lin Chen , Wang Jianbiao , Hung Karl , Wong Evans Yi Chun , Ruan Haihui
Published: April 2022

This work proposes a theoretical description of ion exchange in glass involving mechano–electrochemical coupling, distinct from the previous models. The generalized Maxwell viscoelastic constitutive relation and large‐deformation formulae are employed, which is indispensable for thin glass panels widely used in consumer electronics. With the theory, two‐dimensional numerical simulations based on axisymmetric and plan‐strain models are conducted. The numerical results signify lateral deformation in a double‐side ion‐exchanged glass and bending caused by single‐side or electric‐field‐assisted ion exchange. With the decrease in glass thickness, the increase in time, or applied electric potential, these deformations become more significant, leading to the relief of in‐plane stresses in the ion‐exchanged layer and the increase in stresses in other parts. This could lead to a remarkable decrease in fracture strength or cracking of an ultrathin glass panel. As the stress and diffusion are coupled, the decrease in stress in the ion‐exchanged layer leads to the increase in the depth of layer of invading ions. These numerical results clearly show the necessity to incorporate the mechano–electrochemical coupling and large deformation in modeling ion exchange, which is uninvolved in previous theoretical models. Moreover, the proposed theoretical model is directly extendable to three‐dimensional scenarios, such as curved or foldable ultrathin glass panels.
Electrochemical performance and chemical stability of proton‐conducting BaZr0.8−xCexY0.2O3−δ electrolytes
Authors: Zhou Mingyang , Liu Zhijun , Chen Meilong , Zhu Ziyi , Cao Dan , Liu Jiang
Published: April 2022

Protonic ceramic fuel cells (PCFCs) using BaZr0.8−xCexY0.2O3−δ (BZCY) as electrolyte materials have attracted widespread attention because of their high performance at reduced temperature. However, there are few systematic studies on both the performance and stability of BZCY materials. In this paper, we report our work on the electrochemical performance and chemical stability of BaZr0.8−xCexY0.2O3−δ (x = 0, 0.1, 0.3, 0.5, and 0.7) series. The results show that electronic hole conductivity decreases with increasing Ce4+ content, especially at high temperature. In addition, H2 atmosphere reduces the conductive activation energy of BZCY. On the contrary, air atmosphere causes serious electronic leakage. These effects are also reflected in the operation of PCFCs, that is, the higher the Ce4+ content, the higher the open‐circuit voltage and output power density. However, low Ce4+ content may stabilize the materials in CO2 atmosphere. At 700°C, an anode‐supported PCFC based on BaZr0.1Ce0.7Y0.2O3−δ electrolyte, using humid H2 fuel, gives a peak power density of 1.0 W cm−2. At 600°C, BaZr0.8Y0.2O3−δ and BaZr0.7Ce0.1Y0.2O3−δ show a good stability in CO2‐containing atmosphere.
Correlation between non‐insulin‐based insulin resistance indexes and the risk of prehypertension: A cross‐sectional study
Authors: Zhang Xin , Yu Chaoping , Ye Runyu , Liu Tianhu , Chen Xiaoping
Published: April 2022

The authors aimed to characterize the relationships between non‐insulin‐based insulin resistance (IR) indexes and the risk of prehypertension, and to compare their abilities to identify prehypertension. The authors recruited 3274 adults who did not have hypertension and were not taking hypoglycemic or lipid‐lowering medications. The triglyceride‐to‐high‐density lipoprotein‐cholesterol ratio (TG/HDL‐C), fasting triglyceride and glucose index (TyG), and metabolic score for IR (METS‐IR) were calculated. Bivariate Spearman's correlation analysis and multiple logistic analysis were used. The area under the receiver operating characteristic (ROC) curve was used to compare the ability of the three indexes to identify prehypertension. Systolic and diastolic blood pressure (BP) positively correlated with TG/HDL‐C (r = .272, P < .001), TyG (r = .286, P < .001), and METS‐IR (r = .340, P < .001) in the entire cohort. Multiple logistic analysis showed that the proportion of prehypertension in the third and fourth quartiles of the TG/HDL‐C (Q3 vs. Q1: odds ratio (OR) = 1.527, 95% confidence interval (CI): 1.243–1.988; Q4 vs. Q1: OR = 1.580, 95% CI: 1.231–2.028), TyG (Q3 vs. Q1: OR = 1.519, 95% CI: 1.201–1.923; Q4 vs. Q1: OR = 1.658, 95% CI: 1.312–2.614), and METS‐IR (Q3 vs. Q1: OR = 1.542, 95% CI: 1.138–2.090; Q4 vs. Q1:OR = 2.216, 95% CI: 1.474–3.331) were significantly higher than in the lowest quartiles. The areas under the curves and 95% CIs for the identification of prehypertension were .647 (.628–.667) for TG/HDL‐C, .650 (.631–.669) for TyG, and .683 (.664–.702) for METS‐IR, respectively. Thus, non‐insulin‐based IR indexes (TG/HDL‐C, TyG, and METS‐IR) are significantly associated with the risk of prehypertension. Furthermore, METS‐IR is better able to identify prehypertension than TG/HDL‐C and TyG. These non‐insulin‐based IR indexes might assist with the prevention of hypertension in primary care and areas with limited medical resources.
Punctate Administration of Ficin as a human and animal model of non‐histaminergic itch
Authors: Malewicz N.M. , Ieong H.F.‐h. , Oeck S. , Kumowski N. , Zhang Z. , Shimada S.G. , LaMotte R.H.
Published: April 2022

Background

Ficin, a cysteine protease derived from fig‐tree latex, has been reported to elicit itch and nociceptive sensations, though quantitative sensory studies are lacking. Cowhage containing the pruritic cysteine Mucunain, on the contrary, has been widely studied as activating polymodal nociceptors and eliciting a histamine‐independent itch.

Objectives

We tested whether ficin in heat‐inactivated cowhage spicules would elicit itch and nociceptive sensations in humans, and analogous behaviours in mice, which are similar to those evoked by native cowhage, and whether these behaviours in mice were dose‐dependent when ficin was injected intradermally.

Methods

Human volunteers rated the magnitude of itch and nociceptive sensations evoked by either native cowhage spicules or heat‐inactivated spicules soaked in 1, 10 or 100 mg/mL ficin (0.03, 0.3 and 3 ng of ficin in spicule tip), applied to forearm. In mice, itch‐like scratching and nociceptive‐like wiping were recorded in response to either native cowhage, to heat‐inactivated spicules that were either inactive or contained 100 mg/mL ficin, or to intradermal injections of 1.25, 2.5 or 5 μg/ 5 μL, each treatment applied to the cheek.

Results

The dose of 100 mg/mL ficin in spicules evoked comparable magnitudes of itch, nociceptive sensations and areas of cutaneous dysesthesia as native cowhage in humans and comparable itch‐like scratching and pain‐like wiping behaviours in mice. But to elicit similar behaviours when injected intradermally in mice a greater amount of ficin (1.25 μg) was required.

Conclusion

Spicule delivery or intradermal injection of ficin elicits behaviours in mice that model itch and nociceptive sensations in humans, suggesting that ficin may be useful in translating mechanistic research on the neural mechanisms of pruritic and nociceptive effects of cysteine proteases between the two species.
A metabotropic glutamate receptor 3 (mGlu3R) isoform playing neurodegenerative roles in astrocytes is prematurely up‐regulated in an Alzheimerʼs model
Authors: Turati Juan , Rudi Julieta , Beauquis Juan , Carniglia Lila , López Couselo Federico , Saba Julieta , Caruso Carla , Saravia Flavia , Lasaga Mercedes , Durand Daniela
Published: April 2022

Subtype 3 metabotropic glutamate receptor (mGlu3R) displays a broad range of neuroprotective effects. We previously demonstrated that mGlu3R activation in astrocytes protects hippocampal neurons from Aβ neurotoxicity through stimulation of both neurotrophin release and Aβ uptake. Alternative‐spliced variants of mGlu3R were found in human brains. The most prevalent variant, mGlu3Δ4, lacks exon 4 encoding the transmembrane domain and can inhibit ligand binding to mGlu3R. To date, neither its role in neurodegenerative disorders nor its endogenous expression in CNS cells has been addressed. The present paper describes for the first time an association between altered hippocampal expression of mGlu3Δ4 and Alzheimer's disease (AD) in the preclinical murine model PDAPP‐J20, as well as a deleterious effect of mGlu3Δ4 in astrocytes. As assessed by western blot, hippocampal mGlu3R levels progressively decreased with age in PDAPP‐J20 mice. On the contrary, mGlu3Δ4 levels were drastically increased with aging in nontransgenic mice, but prematurely over‐expressed in 5‐month‐old PDAPP‐J20‐derived hippocampi, prior to massive senile plaque deposition. Also, we found that mGlu3Δ4 co‐precipitated with mGlu3R mainly in 5‐month‐old PDAPP‐J20 mice. We further showed by western blot that primary cultured astrocytes and neurons expressed mGlu3Δ4, whose levels were reduced by Aβ, thereby discouraging a causal effect of Aβ on mGlu3Δ4 induction. However, heterologous expression of mGlu3Δ4 in astrocytes induced cell death, inhibited mGlu3R expression, and prevented mGlu3R‐dependent Aβ glial uptake. Indeed, mGlu3Δ4 promoted neurodegeneration in neuron–glia co‐cultures. These results provide evidence of an inhibitory role of mGlu3Δ4 in mGlu3R‐mediated glial neuroprotective pathways, which may lie behind AD onset.

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Real‐world efficacy of lutetium peptide receptor radionuclide therapy in patients with neuroendocrine tumours
Authors: Almeamar Hussein , Cullen Lisa , Murphy David J. , Crowley Rachel K. , Toumpanakis Christos , Welin Staffan , O'Shea Donal , O'Toole Dermot
Published: April 2022

Lutetium peptide receptor radio nuclide therapy (Lu‐PRRT) is an effective treatment for progressive, metastatic, somatostatin‐receptor‐positive, well‐differentiated neuroendocrine tumours (WD‐NETs). Here, we report a single centre experience of real‐world efficacy, long‐term side effects, and challenges of this treatment. This was a retrospective analysis. All patients linked with our centre who had Lu‐PRRT were included. Clinicopathological data were analysed using descriptive statistics, Kaplan–Meier, and Cox regression. A total of 45 patients had Lu‐PRRT, of those 30 (67%) were males, and 13 (29%) were more than 65 years old. The primary site was small intestine in 30 (67%) patients, pancreas in seven (16%) patients, and lung in three (7%) patients. The tumor was grade 1 in 15 (35%) patients, grade 2 in 22 (48%) patients, and grade 3 in six (13%) patients. A total of 41 (91%) patients had liver metastasis, and 20 (44%) patients had carcinoid syndrome. Lu‐PRRT was the second‐line therapy in all patients. Krenning's score was 4 in 36 (80%) patients and 3 in nine (20%) patients. The median waiting time to start Lu‐PRRT therapy was 87 days. The median follow‐up was 41 months. A total of 23 (51%) patients had a partial response, 18 (40%) patients had stable disease, and four (9%) patients had progression. None of the patients had a complete response. The median progression‐free survival (PFS) was 38 months (95% CI: 25.8–50.1). The median overall survival (OS) was not reached. Nine patients died during follow‐up (death from any cause). Prior treatment with targeted therapies or high dose somatostatin analogues were negative predictors of Lu‐PRRT outcome (p‐values of < .001 and < .045, respectively). There were two serious haematological toxicities, one patient developed acute myeloid leukaemia (AML), and the other developed chronic myeloid leukaemia (CML). Lu‐PRRT is an effective second‐line treatment for metastatic WD‐NETs. The effect of targeted therapies on Lu‐PRRT outcome was significant and needs to be clarified in further studies.
Effect of antiepileptic drugs on serum biochemical marker levels of first and second trimester screening tests
Authors: Besimoglu Berhan , Öcal Fatma Doğa , Sinaci Selcan , Atalay Ayşegül , Tanaçan Atakan , Şahin Dilek
Published: April 2022

Objectives

Our aim in this study was to evaluate the effect of antiepileptic drugs on biochemical components of screening tests.

Materials and Methods

This longitudinal case–control study was performed at Ankara City Hospital, Ankara, Turkey, from June 2020 to January 2021. The case group included epileptic singleton pregnant women which were using antiepileptic drugs, between 18 and 44 years of age. The control group included healthy pregnant women between 18 and 44 years old who did not use any drugs. Maternal medical, obstetric, and gynecological history were recorded. The antiepileptic agents that are used in our study were; lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, valproic acid, and clonazepam. For the aneuploidy screening program conducted in our laboratory, the biochemical markers that are analyzed include; free b‐hCG and PAPP‐A in the first trimester, as well as AFP, HCG, and unconjugated estriol (uE3) in the second trimester. MoM values of these markers were compared between the case and control groups.

Results

Fifty‐three pregnant women with epilepsy using antiepileptic drugs were compared with 106 healthy pregnant women. The levels of serum‐free b‐hCG, and PAPP‐A were similar between the case and control groups (p = 0.653, p = 0.351). For the second‐trimester screening biochemical markers, the maternal serum uE3 and AFP levels expressed as MoM were significantly higher in the epileptic group than in the control patients (p = 0.015 and p = 0.001).

Conclusion

Serum marker levels of second‐trimester screening tests may be affected by antiepileptic drugs, which may lead to misinterpretation of the risk level. Antiepileptic drug usage should be considered when evaluating screening test results.
A coherent biogeographical framework for Old World Neogene and Pleistocene mammals
Authors: Gibert Corentin , Zacaï Axelle , Fluteau Frédéric , Ramstein Gilles , Chavasseau Olivier , Thiery Ghislain , Souron Antoine , Banks William , Guy Franck , Barboni Doris , Sepulchre Pierre , Blondel Cécile , Merceron Gildas , Otero Olga
Published: April 2022

In order to understand mammalian evolution and compute a wide range of biodiversity indices, we commonly use the ‘bioregion’, a spatial division adapted to ecological and evolutionary constraints. While commonly conducted by neontologists, the establishment of bioregions in palaeontology is generally a secondary analysis, shaped on subjective time scales and areas specific to the investigated questions and groups. This heterogeneity, coupled with the scale‐dependency of biodiversity indices, prevents the clear identification of macroecological and macroevolutionary trends for large taxonomic groups like extinct mammals. Here we tackle this issue by providing a coherent framework for Neogene and Pleistocene mammals of the Old World following two steps: (1) a temporal scale adapted to mammalian evolutionary history (i.e. evolutionary fauna) is defined by poly‐cohort analysis; (2) bioregions are then computed for each evolutionary fauna by clustering, ordination and intermediate approaches at multiples spatial scales (i.e. continental to regional) for Eurasia and Africa. Additionally, providing a coherent framework for a wide range of mammalian datasets, our results show: (1) the synchronous emergence and fall of five mammalian evolutionary faunas identified at chronological scales varying from the epoch to the geological stage; (2) a transition from a longitudinal to a latitudinal biogeographical structuring between the Miocene and Pliocene, especially in Europe; (3) the long‐term affinity of southern Asian with African faunas, in sharp contrast with the modern Palaearctic bioregion extension; and (4) the establishment of a vast Mediterranean bioregion from fragmented areas in the Late Miocene to its full extent in the Pleistocene.
The benefits of specialized knowledge in polycentric governance
Authors: Vantaggiato Francesca Pia , Lubell Mark
Published: April 2022

Policy forums bring individual actors together to deliberate on specific policy issues. The literature found that actors' perceptions of forum performance depend on both their individual characteristics (goals, expertise, resources) and forum processes (trust, learning, beliefs). However, we do not know how different combinations of actors, embodying different types of knowledge or expertise, relate to forum performance. We distinguish between policy and institutional specialization. Forum participants can be policy specialists, who are experts on the policy issue, and/or institutional specialists, who are expert of the policy process in the governance system. The former excel at problem definition and facilitation; the latter enable inclusivity. We surmise that higher proportions of specialized actors positively affect the group's perceptions of forum performance in terms of both process and outcomes, particularly in high conflict forums. We test this claim using survey data on 55 policy forums working on adaptation to sea level rise in the San Francisco Bay Area, collected in summer 2018. The empirical findings lend support to our hypothesis as concerns policy specialists but not as concerns institutional specialists. Further research should devote more effort to study how actor composition affects forum performance.
Semen characteristics of ganders kept as genetic resources conservation programme
Authors: Łukaszewicz Ewa , Jerysz Anna , Kowalczyk Artur
Published: April 2022

The creation of genetic reserves of domesticated animal species and breeds almost become a necessity in the recent years, but there is a question what is the value of semen of males kept ex situ in vivo as gene conservation flocks. Presented studies assessed the response to semen collection by dorso‐abdominal massage and the quantitative and qualitative semen characteristics of six goose breeds (Pomorska, Garbonosa, Kuban, Landes, Roman and Slovakia) covered by the genetic resources’ protection programme. Fourteen semen collection attempts were performed per male. In each breed there were ganders with low and high sensitivity to massage. The most positive reactions were stated in Pomorska ganders (67.9%) and the least in Kuban breed (52.60%). Individual male evaluation showed that only in three breeds (Pomorska, Garbonosa and Kuban) there were individuals showing 100% susceptibility to semen collection, in some breeds only one to four positive reactions (ending with ejaculation) were noted. Results obtained indicated breed and male effect on analysed semen traits, with the exception of sperm motility. The highest number of live normal sperm (44.2% on average), sperm concentration (530 × 106 ml−1), the highest Semen Quality Factor (92.9) and sperm motility (50.30%) were found in semen of Kuban ganders, while the lowest values of these traits (28.7%; 230 × 106 ml−1; 11.4 respectively) in Slovakia ganders. The lowest sperm motility (38.3%) was observed in ganders of Roman breed, but comparing to the other breeds existing differences were not significant. Significant differences in sperm morphology between individual ganders were also observed.
Non-Participation in Smartphone Data Collection Using Research Apps
Authors: Keusch Florian , Bähr Sebastian , Haas Georg-Christoph , Kreuter Frauke , Trappmann Mark , Eckman Stephanie
Published: April 2022

Research apps allow to administer survey questions and passively collect smartphone data, thus providing rich information on individual and social behaviours. Agreeing to this novel form of data collection requires multiple consent steps, and little is known about the effect of non-participation. We invited 4,293 Android smartphone owners from the German Panel Study Labour Market and Social Security (PASS) to download the IAB-SMART app. The app collected data over six months through (a) short in-app surveys and (b) five passive mobile data collection functions. The rich information on PASS members from previous survey waves allows us to compare participants and non-participants in the IAB-SMART study at the individual stages of the participation process and across the different types of data collected. We find that 14.5 percent of the invited smartphone users installed the app, between 12.2 and 13.4 percent provided the different types of passively collected data, and 10.8 percent provided all types of data at least once. Likelihood to participate was smaller among women, decreased with age and increased with educational attainment, German citizenship, and PASS tenure. We find non-participation bias in substantive variables, including overestimation of social media usage and social network size and underestimation of non-working status.
Testing for a Change in Mean after Changepoint Detection
Authors: Jewell Sean , Fearnhead Paul , Witten Daniela
Published: April 2022

While many methods are available to detect structural changes in a time series, few procedures are available to quantify the uncertainty of these estimates post-detection. In this work, we fill this gap by proposing a new framework to test the null hypothesis that there is no change in mean around an estimated changepoint. We further show that it is possible to efficiently carry out this framework in the case of changepoints estimated by binary segmentation and its variants, ℓ0 segmentation, or the fused lasso. Our setup allows us to condition on much less information than existing approaches, which yields higher powered tests. We apply our proposals in a simulation study and on a dataset of chromosomal guanine-cytosine content. These approaches are freely available in the R package ChangepointInference at https://jewellsean.github.io/changepoint-inference/.
Optimal and Maximin Procedures for Multiple Testing Problems
Authors: Rosset Saharon , Heller Ruth , Painsky Amichai , Aharoni Ehud
Published: April 2022

Multiple testing problems (MTPs) are a staple of modern statistical analysis. The fundamental objective of MTPs is to reject as many false null hypotheses as possible (that is, maximize some notion of power), subject to controlling an overall measure of false discovery, like family-wise error rate (FWER) or false discovery rate (FDR). In this paper we provide generalizations to MTPs of the optimal Neyman-Pearson test for a single hypothesis. We show that for simple hypotheses, for both FWER and FDR and relevant notions of power, finding the optimal multiple testing procedure can be formulated as infinite dimensional binary programs and can in principle be solved for any number of hypotheses. We also characterize maximin rules for complex alternatives, and demonstrate that such rules can be found in practice, leading to improved practical procedures compared to existing alternatives that guarantee strong error control on the entire parameter space. We demonstrate the usefulness of these novel rules for identifying which studies contain signal in numerical experiments as well as in application to clinical trials with multiple studies. In various settings, the increase in power from using optimal and maximin procedures can range from 15% to more than 100%.