bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods of species pool determination as predictors of survival in seeding and transplanting experiments
Authors: Janíková Eva , Lepš Jan
Published: May 2023

Community composition is limited by a species' ability to reach, establish and survive on a site. Establishment and survival are constrained by both abiotic conditions and biotic interactions that operate together on local scales. They decide which species from the pool will form the community. For this reason, it is very important to clearly define the species pool, against which the community composition is compared.

The effect of biotic and abiotic factors can be assessed experimentally, and the species pool by using estimation methods based on broad‐scale observational data. We compared success of five species pool estimation methods in predicting establishment and survival in a seed/transplant addition experiment.

In four different locations, we added resident and non‐resident species to plots with and without competition and tested the ability of the species to thrive in both competition‐free gaps (constrained mainly by abiotic conditions) and in intact vegetation (complete community filter). In these treatments, we studied the seedling recruitment and survival, and the establishment and survival of pregrown transplants. The ability of species pool assessment methods to predict species performance in individual treatments was compared. The comparison of results from individual treatments indicates the importance of individual components of the community filter.

Species pool assessment methods, based on species co‐occurrence patterns (Beals index, favourability and unconstrained ordination), were the best predictors of species performance in the intact vegetation, but were less successful in the competition‐free environment. Methods based on co‐occurrence patterns were the most effective for predicting seedling establishment, while seed germination alone and transplant survival were poorly predictable.

The biotic filter was the principal factor defining our community composition, especially for the process of seedling establishment. The roles of biotic and abiotic filters are very difficult to distinguish without an experimental approach and the ratio of their importance changes during plant ontogenesis.

Read the free Plain Language Summary for this article on the Journal blog.
Disconnection between plant–microbial nutrient limitation across forest biomes
Authors: Liu Ji , Fang Linchuan , Qiu Tianyi , Bing Haijian , Cui Yongxing , Sardans Jordi , Du Enzai , Chen Ji , Tan Wenfeng , Delgado‐Baquerizo Manuel , Zhou Guiyao , Cui Qingliang , Penuelas Josep
Published: May 2023

Nitrogen (N) and phosphorus (P) are essential elements limiting plant–microbial growth in forest ecosystems. However, whether the pattern of plant–microbe nutrient limitation is consistent across forest biomes and the associated potential mechanisms remain largely unclear, limiting us to better understand the biogeochemical processes under future climate change.

Here, we investigated patterns of plant–microbial N/P limitation in forests across a wide environmental gradient and biomes in China to explore the divergence of plant–microbial N/P limitation and the driving mechanisms.

We revealed that 42.6% of the N/P limitation between plant–microbial communities was disconnected. Patterns in plant–microbial N/P limitations were consistent only for 17.7% of N and 39.7% of P. Geospatially, the inconsistency was more evident at mid‐latitudes, where plants were mainly N limited and microbes were mainly P limited. Furthermore, our findings were consistent with the ecological stoichiometry of plants and microbes themselves and their requirements. Whereas plant N and P limitation was more strongly responsive to meteorological conditions and atmospheric deposition, that of microbes was more strongly responsive to soil chemistry, which exacerbated the plant–microbe N and P limitation divergence.

Our work identified an important disconnection between plant and microbial N/P limitation, which should be incorporated into future Earth System Model to better predict forest biomes–climate change feedback.

Read the free Plain Language Summary for this article on the Journal blog.
Precipitation regime changes alter allometry and plasticity of meristem allocation in annual herbaceous plants in a semiarid sandy grassland, northern China
Authors: Sun Shanshan , Liu Xinping , Medina‐Roldán Eduardo , He Yuhui , Lv Peng , Xu Yuanzhi
Published: May 2023

The three principal fates of axillary meristem in flowering plants are growth (G), reproduction (R), and inactivity (I). The allocation relationships between each meristem and plant size in annual herbaceous plants tend to change with altered precipitation (P) patterns in arid and semiarid grasslands. Here, we examined the allometry and plasticity of meristem allocation in three dominant annual herbaceous plants: Setaria viridis, Corispermum macrocarpum, and Bassia dasyphylla in a semiarid sandy grassland in northern China. We determined the range of plant sizes for each of the three species in the following treatments: ambient environment (Amb), P increased by 30% (P[+]) and by 60% (P[++]), P decreased by 30% (P[−]) and by 60% (P[− −]), drought for 46 days from May 1st to June 15th (D1) and from July 1st to August 15th (D2). We found that meristem allocation to branching intensity increased while allocation to apical dominance decreased with increasing plant size under decreased precipitation and seasonal drought. Decreased precipitation and seasonal drought caused the slope of allometry of meristem allocation in the three species to be significantly different from 1. Plasticity of meristem allocation to G, R, and I in S. viridis tended to be significantly greater in August under P(+) and P(++) while in C. macrocarpum tended to be greater in July under P(−), P(− −), D1, and D2. Our findings are important components of an adaptive strategy in annual herbaceous plants throughout the development stage, which will contribute to predict their developmental dynamics in the semiarid sandy grassland under future climate change.
Alternatives to Paying Child Benefit to the Rich: Means‐Testing or Higher Tax?
Authors: Rees Ray , Thoresen Thor O. , Vattø Trine E.
Published: May 2023

There appears to be a general movement away from universal child benefits and towards means‐testing. In the present article we argue that instead of suppressing the labour supply of middle‐income parents by withdrawing the transfer as a function of income, one should consider the alternative of financing a generous universal child benefit by increasing taxation of income. The implications of means‐testing compared with a tax‐financed universal alternative are discussed analytically in a piecewise linear schedule and by combining information from behavioural and non‐behavioural micro‐simulation models. Our results provide support for making child benefit universal instead of means‐tested.
What taxpayers, governments and tax economists do – and what they should do
Authors: Slemrod Joel
Published: May 2023

The distinction between positive economics – describing economic programmes, situations and conditions as they exist – and normative economics – prescribing policies – has a long history. It is an especially important distinction in public economics, which by its nature concerns the actions of government. In this essay, I consider how two relatively recent developments in tax economics alter, blur or at least complicate the classic distinctions between positive and normative economics. The two developments I address are the insights generated by the study of behavioural economics and increased attention to tax evasion and tax enforcement. I organise my thoughts by addressing how three sets of actors central to public finance actually behave and should behave – taxpayers, governments and tax economists. I argue that tax economics should take seriously the substantial presence of behavioural anomalies and tax evasion, and that it has already begun to do so. I suggest some directions this effort might profitably take.
Impact of α‐tocopherol and EGCG on the oxidative stability of margarine: Exploring the possible synergistic effect mechanism
Authors: Zhang Xueyi , Pei Wenjun , Guo Yiwen , Cao Minjie , Karrar Emad , Tang Lin , Li Kangning , Chang Ming , Liu Ruijie
Published: May 2023

Margarine is a typical water‐in‐oil (W/O) emulsion fat product. Due to the presence of a water‐oil interface, the oil oxidation in the emulsion system is the interface reaction, which is much faster than that in bulk oil and shows different oxidation mechanisms. The analysis of Rancimat and electron spin resonance indicated that α‐tocopherol and EGCG show synergistic antioxidant effects in the margarine. After 20 days of accelerated oxidation storage, the antioxidant effect of the compound antioxidant (50 mg/kg α‐tocopherol + 350 mg/kg EGCG) on the margarine was significantly higher than that of the single antioxidant α‐tocopherol and EGCG. Based on the results of antioxidants partitioning, electrochemistry, fluorescence spectroscopy, and the oxidative decomposition of antioxidants, the possible mechanisms of interaction were the promotion of α‐tocopherol regeneration by EGCG, and the fact that α‐tocopherol and EGCG could act at different stages and positions of oxidation. This work will contribute to studying antioxidant interactions and can provide valuable suggestions for practical production.

Practical Application

This study aims to improve the oxidative stability of margarine by adding α‐tocopherol and epigallocatechin‐gallate (EGCG) individually and in blends. The mechanism of compound antioxidant synergistic inhibition of margarine oxidation was analyzed, providing theoretical basis and scientific basis for the research and practical application of natural antioxidant synergistic mechanism.
Developmental origins of diabetes mellitus: Environmental epigenomics and emerging patterns
Authors: Zhu Hong , Ding Guolian , Liu Xinmei , Huang Hefeng
Published: May 2023

Mounting epidemiological evidence indicates that environmental exposures in early life have roles in diabetes susceptibility in later life. Additionally, environmentally induced diabetic susceptibility could be transmitted to subsequent generations. Epigenetic modifications provide a potential association with the environmental factors and altered gene expression that might cause disease phenotypes. Here, we bring the increasing evidence that environmental exposures early in development are linked to diabetes through epigenetic modifications. This review first summarizes the epigenetic targets, including metastable epialleles and imprinting genes, by which the environmental factors can modify the epigenome. Then we review the epigenetics changes in response to environmental challenge during critical developmental windows, gametogenesis, embryogenesis, and fetal and postnatal period, with the specific example of diabetic susceptibility. Although the mechanisms are still largely unknown, especially in humans, the new research methods are now gradually available, and the animal models can provide more in‐depth study of mechanisms. These have implications for investigating the link of the phenomena to human diabetes, providing a new perspective on environmentally triggered diabetes risk.
A toolbox to explore the composition of species dynamics behind multi‐species indices
Authors: Rigal Stanislas , Knape Jonas
Published: May 2023

In the light of declining biodiversity, monitoring its fate is essential for conservation strategies. Aggregation of temporal change of different species into multi‐species indices such as geometric means makes it possible to identify species groups that are at risk as well as those that are doing well. However, aggregated indices mask the between‐species variability in the temporal trajectories, which could be of high relevance for conservation actions.

We propose a toolbox, available as an r package, to investigate compositions of species dynamics in geometric mean multi‐species indices. The toolbox is based on a dynamic factor analysis which uses species dynamics and their uncertainty to (1) identify common latent trends in those species dynamics, (2) display the variability of species dynamics and (3) extract clusters of species with similar dynamics within the species groups used for the indices.

We apply the toolbox to common breeding birds in Sweden and explore the variability in dynamics among species included in EU‐official indices for farmland and woodland species, highlighting clusters of species with related dynamics previously hidden by averaging.

The toolbox is designed to be applicable to a wide range of ecological monitoring data. By enabling a deeper exploration of the structure behind existing indices, we may refine our understanding of biodiversity change to better inform subsequent conservation policies.
Estimating process‐based model parameters from species distribution data using the evolutionary algorithm CMA‐ES
Authors: Van der Meersch Victor , Chuine Isabelle
Published: May 2023

Two main types of species distribution models are used to project species range shifts in future climatic conditions: correlative and process‐based models. Although there is some continuity between these two types of models, they are fundamentally different in their hypotheses (statistical relationships vs. mechanistic relationships) and their calibration methods (SDMs tend to be occurrence data driven while PBMs tend to be prior driven).

One of the limitations to the use of process‐based models is the difficulty to parameterize them for a large number of species compared to correlative SDMs. We investigated the feasibility of using an evolutionary algorithm (called covariance matrix adaptation evolution strategy, CMA‐ES) to calibrate process‐based models using species distribution data. This method is well established in some fields (robotics, aerodynamics, etc.), but has never been used, to our knowledge, in ecology, despite its ability to deal with very large space dimensions. Using tree species occurrence data across Europe, we adapted the CMA‐ES algorithm to find appropriate values of model parameters. We estimated simultaneously 27–77 parameters of two process‐based models simulating forest tree's ecophysiology for three species with varying range sizes and geographical distributions.

CMA‐ES provided parameter estimates leading to better prediction of species distribution than parameter estimates based on expert knowledge. Our results also revealed that some model parameters and processes were strongly dependent, and different parameter combinations could therefore lead to high model accuracy.

We conclude that CMA‐ES is an efficient state‐of‐the‐art method to calibrate process‐based models with a large number of parameters using species occurrence data. Inverse modelling using CMA‐ES is a powerful method to calibrate process‐based parameters which can hardly be measured. However, the method does not warranty that parameter estimates are correct because of several sources of bias, similarly to correlative models, and expert knowledge is required to validate results.
Rescue of neurogenesis and age‐associated cognitive decline in SAMP8 mouse: Role of transforming growth factor‐alpha
Authors: Gómez‐Oliva Ricardo , Martínez‐Ortega Sergio , Atienza‐Navarro Isabel , Domínguez‐García Samuel , Bernal‐Utrera Carlos , Geribaldi‐Doldán Noelia , Verástegui Cristina , Ezzanad Abdellah , Hernández‐Galán Rosario , Nunez‐Abades Pedro , Garcia‐Alloza Monica , Castro Carmen
Published: May 2023

Neuropathological aging is associated with memory impairment and cognitive decline, affecting several brain areas including the neurogenic niche of the dentate gyrus of the hippocampus (DG). In the healthy brain, homeostatic mechanisms regulate neurogenesis within the DG to facilitate the continuous generation of neurons from neural stem cells (NSC). Nevertheless, aging reduces the number of activated neural stem cells and diminishes the number of newly generated neurons. Strategies that promote neurogenesis in the DG may improve cognitive performance in the elderly resulting in the development of treatments to prevent the progression of neurological disorders in the aged population. Our work is aimed at discovering targeting molecules to be used in the design of pharmacological agents that prevent the neurological effects of brain aging. We study the effect of age on hippocampal neurogenesis using the SAMP8 mouse as a model of neuropathological aging. We show that in 6‐month‐old SAMP8 mice, episodic and spatial memory are impaired; concomitantly, the generation of neuroblasts and neurons is reduced and the generation of astrocytes is increased in this model. The novelty of our work resides in the fact that treatment of SAMP8 mice with a transforming growth factor‐alpha (TGFα) targeting molecule prevents the observed defects, positively regulating neurogenesis and improving cognitive performance. This compound facilitates the release of TGFα in vitro and in vivo and activates signaling pathways initiated by this growth factor. We conclude that compounds of this kind that stimulate neurogenesis may be useful to counteract the neurological effects of pathological aging.
Early psychomotor therapy in very preterm infants does not improve Bayley‐III scales at 2 years
Authors: Alberge Corine , Ehlinger Virginie , Noack Nathalie , Bolzoni Catherine , Colombié Bruno , Breinig Sophie , Dicky Odile , Delobel Malika , Arnaud Catherine
Published: May 2023

Aim

To assess the efficacy of post‐hospital psychomotor therapy in the development of very preterm infants at nine and 24 months.

Methods

We conducted a randomised controlled study at Toulouse Children's Hospital between 2008 and 2014 among preterm infants aged under 30 weeks. All infants in both groups could benefitt from physiotherapy to prevent motor disorders. The intervention group received 20 early post‐hospital psychomotor therapy sessions. The development was assessed by the Bayley Scale Infant Development at nine and 24 months.

Results

The intervention and control group contained 77 and 84 infants, respectively, with 57 infants in each group undergoing assessment at 24 months. Boys accounted for 56% of the population. Median gestational age was 28 weeks, range 25–29. The development scores at 24 months did not significantly differ between the randomisation groups. At 9 months, we observed improvements in global motricity (mean difference 0.9 point, p = 0.04) and fine motricity for the subgroup containing educationally underserved mothers (mean difference 1.6 point, p = 0.008). There was no significant difference in neuromotor functioning between the two groups.

Conclusion

The benefits of psychomotor therapy were short‐lived and did not persist post‐intervention. Our results and this organisational model encouraged us to persevere towards similar multi‐professional care.
Thrivers, survivors or exiteers: A longitudinal, interpretative phenomenological analysis of the post‐return‐to‐work journeys for workers with common mental disorders
Authors: Nielsen Karina , Yarker Jo
Published: May 2023

The research on return to work for workers with common mental disorders has primarily focused on the pre‐return journey. Relapses and recurrent sick leaves are prevalent and call for research on how we can support workers stay and thrive at work after long‐term sickness absence due to common mental disorders. In the present study, we used Longitudinal Interpretative Phenomenological Analysis to explore the experiences of returned workers' post‐return journey and the barriers and facilitators to staying and thriving at work. We conducted monthly semistructured interviews with seven returned workers over a period of 4 months. We identified three post‐return trajectories: the thrivers, the survivors and the exiteers. We identified 10 higher order themes and 13 subthemes that influenced these trajectories. At the individual level, wanting to make a valuable contribution and job crafting facilitated a sustainable return. At the group level, we identified social support as a facilitator. At the leader level, line managers making work adjustments and recognising workers as valuable were important, whereas a lack of understanding and conflicts with senior management posed as barriers. At the overarching level, the media influenced organisational values. Our findings have important implications for how organisations can facilitate a whole systems approach to support returned workers and prevent sickness absence reoccurrence and job loss.
Liberal–democratic values and philosophers' beliefs about moral expertise
Authors: Niv Yarden , Sulitzeanu‐Kenan Raanan
Published: May 2023

In recent decades, the discipline of bioethics has grown rapidly, as has the practice of ethical consultation. Interestingly, this new recognition of the relevance of moral philosophy to our daily life has been accompanied by skepticism among philosophers regarding the existence of moral expertise or the benefits of philosophical training. In his recent article in Bioethics, William R. Smith suggested that this skepticism is rooted in philosophers' belief that moral expertise is inconsistent with liberal–democratic values, when in fact they are compatible. In this paper, we provide a unique opportunity to empirically examine Smith's observation by utilizing and extending global data on philosophers' beliefs about moral expertise, involving 4087 philosophers from 96 countries. Our findings support Smith's theoretical observation and show that societal levels of support for liberal–democratic values are associated with greater skepticism about moral expertise. We suggest that these findings might be explained by the cognitive process of motivated reasoning and an invalid inference of “is” from “ought.” Consequently, the potential tension between moral expertise and liberal–democratic values is invalidly used for rejecting the existence of moral expertise, while its main and valid implication is for how moral expertise should be applied in liberal–democratic settings.
Resistance to vincristine in DLBCL by disruption of p53‐induced cell cycle arrest and apoptosis mediated by KIF18B and USP28
Authors: Rovsing Anne Bruun , Thomsen Emil Aagaard , Nielsen Ian , Skov Thomas Wisbech , Luo Yonglun , Dybkær Karen , Mikkelsen Jacob Giehm
Published: May 2023

The frontline therapy R‐CHOP for patients with diffuse large B‐cell lymphoma (DLBCL) has remained unchanged for two decades despite numerous Phase III clinical trials investigating new alternatives. Multiple large studies have uncovered genetic subtypes of DLBCL enabling a targeted approach. To further pave the way for precision oncology, we perform genome‐wide CRISPR screening to uncover the cellular response to one of the components of R‐CHOP, vincristine, in the DLBCL cell line SU‐DHL‐5. We discover important pathways and subnetworks using gene‐set enrichment analysis and protein–protein interaction networks and identify genes related to mitotic spindle organization that are essential during vincristine treatment. The inhibition of KIF18A, a mediator of chromosome alignment, using the small molecule inhibitor BTB‐1 causes complete cell death in a synergistic manner when administered together with vincristine. We also identify the genes KIF18B and USP28 of which CRISPR/Cas9‐directed knockout induces vincristine resistance across two DLBCL cell lines. Mechanistic studies show that lack of KIF18B or USP28 counteracts a vincristine‐induced p53 response suggesting that resistance to vincristine has origin in the mitotic surveillance pathway (USP28‐53BP1‐p53). Collectively, our CRISPR screening data uncover potential drug targets and mechanisms behind vincristine resistance, which may support the development of future drug regimens.
Patch testing hydroperoxides of limonene and linalool in consecutive patients—Results of the IVDK 2018–2020
Authors: Schubert Steffen , Geier Johannes , Brans Richard , Heratizadeh Annice , Kränke Birger , Schnuch Axel , Bauer Andrea , Dickel Heinrich , Buhl Timo , Vieluf Dieter , Wagner Nicola , Worm Margitta ,   for the IVDK
Published: May 2023

Background

Hydroperoxides of limonene (Lim‐OOHs) and linalool (Lin‐OOHs) are potent contact sensitizers.

Objectives

To investigate the prevalence of positive patch test (PT) reactions to Lim‐OOHs and Lin‐OOHs in consecutive patients, their demographic factors and concomitant reactions.

Methods

Between 7/2018 and 12/2020, Lim‐OOHs 0.3% pet. and Lin‐OOHs 1% pet. were patch tested in 5511 consecutive patients. We assessed PT reactivity and analysed data from patients with either positive or negative PTs to Lim‐OOHs and Lin‐OOHs.

Results

Positive PT results to Lim‐OOHs (n = 170, 3.1%) and Lin‐OOHs (n = 483, 8.8%) were frequent. Most of the positive reactions were weak (LimOOHs n = 134/LinOOHs n = 429), and even more frequently, doubtful (n = 252/n = 578) or irritant reactions (n = 81/n = 178) were documented. PT reactivity to Lim‐OOHs and Lin‐OOHs was increased in patients with irritant reactions to sodium lauryl sulphate (SLS). The proportion of leg dermatitis and concomitant positive reactions to fragrances and essential oils was increased in patients with reactivity to these hydroperoxides.

Conclusion

The observed reaction pattern suggests that both test preparations display an irritant potential with an increased risk of false positive reactions. Preparations should be chemically monitored in order to reduce irritancy. Mindful interpretation of PT results and aimed patch testing of lower concentrations is recommended.
Generation of stable integration‐free pig induced pluripotent stem cells under chemically defined culture condition
Authors: Zhu Qianqian , Wang Fengchong , Gao Dengfeng , Gao Jie , Li Guilin , Jiao Deling , Zhu Gaoxiang , Xu Kaixiang , Guo Jianxiong , Chen Tianzhi , Cao Suying , Zhi Minglei , Zhang Jinying , Wang Yingjie , Zhang Xiaowei , Zhang Danru , Yao Yixuan , Song Jian , Wei Hong‐Jiang , Han Jianyong
Published: May 2023

Genome integration‐free pig induced pluripotent stem cells (iPSCs) bring tremendous value in pre‐clinical testing of regenerative medicine, as well as conservation and exploitation of endangered or rare local pig idioplasmatic resources. However, due to a lack of appropriate culture medium, efficient induction and stable maintenance of pig iPSCs with practical value remains challenging. Here, we established an efficient induction system for exogenous gene‐independent iPSCs under chemically defined culture condition previously used for generation of stable pig pre‐gastrulation epiblast stem cells (pgEpiSCs). WNT suppression was found to play an essential role in establishment of exogenous gene‐independent iPSCs. Strikingly, stable integration‐free pig iPSCs could be established from pig somatic cells using episomal vectors in this culture condition. The iPSCs had pluripotency features and transcriptome characteristics approximating pgEpiSCs. More importantly, this induction system may be used to generate integration‐free iPSCs from elderly disabled rare local pig somatic cells and the iPSCs could be gene‐edited and used as donor cells for nuclear transfer. Our results provide novel insights into potential applications for genetic breeding of livestock species and pre‐clinical evaluation of regenerative medicine.
A leucine‐rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls
Authors: Vissers Maurits F. J. M. , Troyer Matthew D. , Thijssen Eva , Pereira Diana R. , Heuberger | Jules A. A. C. , Groeneveld Geert Jan , Huntwork‐Rodriguez Sarah
Published: May 2023

Increased leucine‐rich repeat kinase 2 (LRRK2) kinase activity is an established risk factor for Parkinson's disease (PD), and several LRRK2 kinase inhibitors are in clinical development as potential novel disease‐modifying therapeutics. This biomarker characterization study explored within‐ and between‐subject variability of multiple LRRK2 pathway biomarkers (total LRRK2 [tLRRK2], phosphorylation of the serine 935 (Ser935) residue on LRRK2 [pS935], phosphorylation of Rab10 [pRab10], and total Rab10 [tRab10]) in different biological sources (whole blood, peripheral blood mononuclear cells [PBMCs], neutrophils) as candidate human target engagement and pharmacodynamic biomarkers for implementation in phase I/II pharmacological studies of LRRK2 inhibitors. PD patients with a LRRK2 mutation (n = 6), idiopathic PD patients (n = 6), and healthy matched control subjects (n = 10) were recruited for repeated blood and cerebrospinal fluid (CSF) sampling split over 2 days. Within‐subject variability (geometric coefficient of variation [CV], %) of these biomarkers was lowest in whole blood and neutrophils (range: 12.64%–51.32%) and considerably higher in PBMCs (range: 34.81%–273.88%). Between‐subject variability displayed a similar pattern, with relatively lower variability in neutrophils (range: 61.30%–66.26%) and whole blood (range: 44.94%–123.11%), and considerably higher variability in PBMCs (range: 189.60%–415.19%). Group‐level differences were observed with elevated mean pRab10 levels in neutrophils and a reduced mean pS935/tLRRK2 ratio in PBMCs in PD LRRK2‐mutation carriers compared to healthy controls. These findings suggest that the evaluated biomarkers and assays could be used to verify pharmacological mechanisms of action and help explore the dose–response of LRRK2 inhibitors in early‐phase clinical studies. In addition, comparable α‐synuclein aggregation in CSF was observed in LRRK2‐mutation carriers compared to idiopathic PD patients.
Pleural fluid cytology of metastatic invasive stratified mucin‐producing carcinoma from the cervix: A case report
Authors: Ma Cao , Ding Fengan , Li Mingyan , Zhang Lihua
Published: May 2023

This study analyses the cytomorphological findings from a female patient with malignant pleural effusion resulting from invasive stratified mucin‐producing carcinoma (ISMC) metastasis. The clinical symptoms, immunocytochemical staining and differential diagnosis of ISMC are summarised.
Effect of obesity on venous blood flow in the lower limbs
Authors: Langan Ewan A. , Wienandt Malte , Bayer Andreas , Ellebrecht Lena , Kahle Birgit
Published: May 2023

Background and objectives

Although obesity is a recognized risk factor for the development of lower limb venous disease, less attention has been paid to objectively measuring the effect of centripetal obesity on blood flow in the lower limbs.

Patients and methods

The diameter of lower limb veins and venous blood flow were measured in 44 patients (65.6 ± 12.5 years, 25 females, 19 males) with centripetal obesity and chronic venous disease.

Results

The mean diameter of both common femoral veins (CFV) increased significantly in the semi‐supine position following elevation of the panniculus (right: ∆0.73 ± 1.21 mm; p ≤ 0.001, left: ∆1.16 ± 1.42 mm; p ≤ 0.001). Moreover, there was a significant increase in venous flow volume in the left CFV (∆62.96 ± 117.85 ml/min; p  =  0.001). Similarly, there was an increase in the diameter of left great saphenous vein (∆0.24 ± 0.41 mm; p  =  0.002), measured at the mid‐thigh, when the patient lifted their abdominal panniculus. Finally, the grade of obesity correlated with the extent of the venous disease.

Conclusions

These data provide preliminary evidence that centripetal obesity results in both structural and hemodynamic changes in the lower limb veins, even in the absence of classical reflux.
A geometrical perspective on development
Authors: Raju Archishman , Siggia Eric D.
Published: May 2023

Cell fate decisions emerge as a consequence of a complex set of gene regulatory networks. Models of these networks are known to have more parameters than data can determine. Recent work, inspired by Waddington's metaphor of a landscape, has instead tried to understand the geometry of gene regulatory networks. Here, we describe recent results on the appropriate mathematical framework for constructing these landscapes. This allows the construction of minimally parameterized models consistent with cell behavior. We review existing examples where geometrical models have been used to fit experimental data on cell fate and describe how spatial interactions between cells can be understood geometrically.
Sources of Inaccuracy in Boron Isotope Measurement Using LA‐MC‐ICP‐MS
Authors: Fietzke Jan , Anagnostou Eleni
Published: May 2023

Laser ablation multi‐collector‐inductively coupled plasma‐mass spectrometry (LA‐MC‐ICP‐MS) has become a valuable tool for the in situ measurement of the boron isotope composition of geological samples at high (tens to hundreds of μm) spatial resolution. That said, this application suffers from significant analytical challenges. We focus in this study on the underlying processes of two of the main causes for inaccuracies using this technique. We provide empirical evidence that not only Ca ions (Sadekov et al. 2019, Standish et al. 2019, Evans et al. 2021) but also Ar ions, that are reflected within the flight tube of the mass spectrometer, are the source for previously reported issues with spectral baselines. We also address the impact of plasma conditions on the instrumental mass fractionation as a source for matrix‐ and mass‐load‐related analytical biases. Comparing experimental data with the results of a dedicated release and diffusion model (RDM) we estimate that a close to complete (~ 97%) release of boron from the sample aerosol is needed to allow for consistently accurate LA boron isotope measurement results without the need for corrections.
Medical students and residents appreciate ebooks’ convenience, but prefer the print book reading experience
Authors: Watson Erin M.
Published: May 2023

Background

Increasingly, libraries buy medical monographs as ebooks, but that may not be what medical students and residents want. Some studies have shown that they prefer print books for some types of reading. On the other hand, for participants in distributed medical programs, ebooks are more accessible.

Objectives

To determine whether medical students and residents at an institution with a distributed medical education program prefer medical ebooks or print books.

Methods

In February 2019, 844 medical students and residents were invited to complete an online questionnaire on their format preferences.

Results

Two hundred thirty‐two students and residents responded. Most preferred electronic format for reading a few pages, but print for entire books. Respondents preferred ebooks because they were immediately available, searchable and could be used on the go, and print books because they strained users' eyes less, facilitated absorption of the text and could be held in users’ hands. The location of respondents and year of study had little effect on responses.

Discussion

Libraries should consider buying quick reference and large, heavy textbooks as ebooks and pocket‐sized or shorter, single‐topic titles, in print format.

Conclusions

Libraries have a responsibility to make both print and ebooks available to their users.
Clinical applications of gene therapy for rare diseases: A review
Authors: Papaioannou Ioannis , Owen James S. , Yáñez‐Muñoz Rafael J.
Published: May 2023

Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non‐viral strategies. The use of adeno‐associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR‐T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase‐severe combined immunodeficiency (ADA‐SCID) and β‐thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice‐switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases.
Molten salt synthesis and antioxidation property of SiC‐coated mesocarbon microbeads
Authors: Xie Wenqi , Zhang Xiaoyu , Zhang Biao , Lin Huaizhi , He Kai , Shi Zhongqi
Published: May 2023

Mesocarbon microbead (MCMB) is a prospective candidate as the raw material for nuclear graphite. However, the poor resistance to high‐temperature oxidation limits its application. Herein, a dense SiC coating was prepared by molten salt synthesis on the surface of MCMB to improve its antioxidation performance. The effect of molten salt synthesis reaction time on the phase composition, microstructure, and antioxidation performance of the SiC‐coated MCMB particles was investigated. A theoretical model was established to explain the SiC coating growth rule well, in conformity with the carbon vacancy diffusion mechanism in SiC coating. The SiC coating synthesized for 7 h with the thickness of .385 µm remarkably promoted the high‐temperature antioxidation property of MCMB. The kinetics analysis indicated that the SiC coating obstructed the oxygen diffusion effectively during the oxidation process. The as‐fabricated SiC‐coated MCMBs with good oxidation resistance show great promise for application in nuclear industry and other antioxidative fields.
PARENTAL KNOWLEDGE AND EXPERIENCES AFTER SURGERY FOR CHRONIC OTITIS MEDIA
Authors: Marais J , Armstrong MWJ
Published: May 2023

SUMMARY Sixty‐four parents completed questionnaires pertaining to their knowledge, attitudes and experiences both before and two months after their children underwent adenoidectomy and grommet insertion. Although a positive image of and high satisfaction with both procedure and inpatient stay were demonstrated, many parents failed to appreciate the existence, nature and frequency of possible complications. Parents should be given quite explicit descriptions of the most common postoperative problems.
PAIN CONTROL AFTER HYSTERECTOMY: AN OBSERVER‐BLIND, RANDOMISED TRIAL OF LORNOXICAM VERSUS TRAMADOL
Authors: Ilias W , Jansen M
Published: May 2023

SUMMARY This 24‐hour, randomised, double‐blind, placebo‐controlled study compared the efficacy and tolerability of intravenous injections of lornoxicam 4mg and 8mg with tramadol 50mg in 78 female patients aged 20‐65 years with moderate to intolerable postoperative pain following mainly hysterectomy. Patients who received lornoxicam 8mg had a significantly (p<0.05) longer time to first remedication than placebo recipients and tended to have a greater reduction in pain intensity and a longer time to withdrawal due to ‘non‐response’ than tramadol and placebo patients. Lornoxicam was well tolerated at both doses and was associated with a lower incidence of adverse events than tramadol. Thus, intravenous lornoxicam at a dose of 8mg is superior to placebo and at least as effective as intravenous tramadol 50mg in relieving moderate to intolerable post‐hysterectomy pain. Furthermore, lornoxicam seems to possess a more favourable tolerability profile than tramadol.
COMPARATIVE EFFECTS OF CALCIPOTRIOL OINTMENT (50μg/g) AND 5% COAL TAR/2% ALLANTOIN/0.5% HYDROCORTISONE CREAM IN TREATING PLAQUE PSORIASIS
Authors: Pinheiro N
Published: May 2023

The comparative efficacy, tolerability and acceptability of calcipotriol ointment (50μg/g) and 5% coal tar/2% allantoin/0.5% hydrocortisone cream were determined in 122 patients with chronic plaque psoriasis affecting at least 100 cm2 of skin. Both preparations were applied twice daily for up to 8 weeks. At the end of treatment, investigators considered calcipotriol significantly more effective in the proportion of patients ‘cleared’ or ‘markedly improved’ (calcipotriol 72.3%,coal tar/allantoin/hydrocortisone 49.1%: p<0.02). Calcipotriol was also superior in reducing the total sign score (p=0.002), and individual scores for scaliness (p<0.0001) and thickness (p=0.001). The proportion of patients with less than 100 cm2 of affected skin at the end of treatment was significantly greater in the calcipotriol group (p<0.05). Patients considered calcipotriol significantly more effective overall (p<0.02) and in reducing flakiness/scaliness of skin (p=0.001). Adverse events, most of which were application related and mild to moderate, were recorded in 15 (23.1%) patients using calcipotriol and in 10 (17.5%) patients using coal tar/allantoin/hydrocortisone (n.s.), and contributed to treatment withdrawal in one (1.5%) and three (5.3%) patients, respectively. (Br J Clin Pract 1997; 51(1): 16‐19)
FRUSEMIDE‐INDUCED BULLOUS PEMPHIGOID
Authors: Panayiotou BN , Prasad MVR , Zaman MN
Published: May 2023

SUMMARY Bullous pemphigoid is a rare complication of frusemide therapy. We present two patients in whom the link between frusemide and this condition was not recognised early, and continued frusemide therapy resulted in prolonged leg blistering and ulceration. On withdrawing the drug, all lesions in both patients resolved completely. Although uncommon, this frusemide reaction needs to be borne in mind as it can add to the morbidity of elderly patients with heart failure.
VITAMIN B6 RESPONSIVE SIDEROBLASTIC ANAEMIA IN A PATIENT WITH TUBERCULOSIS
Authors: Demiroglu H , Dündar S
Published: May 2023

SUMMARY A 39‐year‐old woman was admitted with fatigue, weight loss and fever. Nothing, except skin pallor could be found on physical examination. Her haemoglobin (Hb) was 6.3 g/dl. The blood picture showed dimorphic red cell changes and there were dyserythropoiesis and ring sideroblasts in the bone marrow. After detailed investigations, she was diagnosed with tuberculosis, and anaemia was assigned to chronic disease. With anti‐tuberculosis therapy (including isoniazid), her Hb and bone marrow findings returned to normal. After cessation of therapy, Hb fell to 8.9 g/dl. Bone marrow examination again showed dyserythropoietic morphologic abnormalities and ring sideroblasts. No reason could be identified to explain the recurrence of anaemia. When we realised that preparations of isoniazid included vitamin B6 to prevent the development of sideroblastic anaemia, we challenged with pyridoxin 200 mg daily. Her Hb rose to 14.6 g/dl. We suggest that in any cases with sideroblastic anaemia, if no cause can be identified, or anaemia persists or recurs despite therapy, pyridoxine therapy should be instituted.
BILATERAL URETERIC OBSTRUCTION SECONDARY TO THE PROLONGED USE OF TIAPROFENIC ACID
Authors: Crew JP , Donat R , Roskell D , Fellows GJ
Published: May 2023

SUMMARY There is increasing awareness that the long‐term use of the non‐steroidal anti‐inflammatory agent tiaprofenic acid (Surgam) is associated with a severe form of cystitis. The condition is usually reversible with complete resolution of symptoms on stopping the drug. We present a case of tiaprofenic acid‐induced cystitis resulting in bilateral hydronephrosis suggesting ureteric obstruction. The previous reported cases are reviewed and the risks of delay in withdrawal of the drug and of permanent ureteric damage are discussed.
CAUSES AND CLINICAL OUTCOME OF ACUTE UPPER GASTROINTESTINAL BLEEDING: A PROSPECTIVE ANALYSIS OF 1534 CASES
Authors: Thomopoulos K , Katsakoulis E , Vagianos C , Mimidis K , Margaritis V , Nikolopoulou V
Published: May 2023

SUMMARY Despite considerable improvement in the diagnostic and therapeutic approach to patients with acute upper gastrointestinal (GI) bleeding, several studies suggest there has been no overall change in mortality. The aim of this study was to evaluate prospectively the effect of early emergency diagnostic and therapeutic endoscopy and medico‐surgical collaboration in the clinical outcome of 1534 patients with acute upper GI bleeding treated in our hospital over the past five years. Emergency endoscopy and injection haemostasis were performed within 24 hours of admission, or immediately after resuscitation, in patients with massive bleeding; patients were then treated with close co‐operation between surgeons and gastroenterologists. We observed an increase in the incidence of peptic ulcer (67%) with a simultaneous decrease in the incidence of gastroduodenitis (13.5%) as a cause of bleeding compared with the previous decade. In peptic ulcer bleeding, emergency surgical haemostasis was required in 92 patients (8.9%), while none of the patients with erosive gastroduodenitis required surgical intervention. Overall mortality was 2.9%, and in peptic ulcer bleeding patients 2.1% with a postsurgical mortality of 8.7%. Peptic ulcer remains the main cause of upper GI bleeding. Improved clinical outcome and low mortality can be achieved with early diagnostic and therapeutic endoscopy and medico‐surgical collaboration.
BONE AND COLLAGEN MARKERS IN PAEDIATRIC PRACTICE
Authors: Crofton PM , Kelnar CJH
Published: May 2023

SUMMARY Biochemical markers of bone and collagen turnover have been found to be a valuable adjunct to measurements of bone mineral density in post‐menopausal women in whom they appear to be independent predictors of osteoporosis and fracture risk. In children, they have been less extensively studied but have begun to find a similar complementary role in a number of disorders affecting bone turnover and growth. Although they may give helpful information in their reflection of recent bone turnover and growth in various disorders, their principal value appears to be in giving an early and sensitive indication of response to treatment, before changes in either height velocity or bone mineral density can be accurately determined. This review discusses the use and limitations of these markers in children, the clinical conditions in which they have been studied and their potential value in monitoring either beneficial or adverse effects of treatment on bone turnover and growth.
LYMPHOMA ARISING FROM HASHIMOTO'S THYROIDITIS: AN UNUSUAL CAUSE OF ACUTE STRIDOR
Authors: Arullendran P , Pflfjderer AG
Published: May 2023

SUMMARY We report an unusual presentation of non‐Hodgkin's lymphoma of the thyroid which mimicked an acute infective thyroiditis and was associated with acute stridor and dysphagia. The mode of presentation and diagnosis of thyroid lymphoma are discussed and the value of early fine needle aspiration emphasised.
MASSIVE SCROTAL HAEMATOMA: A COMPLICATION OF PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY
Authors: Shah J , Middleton S , Derodra J
Published: May 2023

Scrotal haematoma is an unusual complication following percutaneous transluminal angioplasty. It carries significant morbidity and causes extreme discomfort to the patient. We describe the case of a 75‐year‐old diabetic man who developed this complication. Recommendations are made for investigation and management of this problem, which is so infrequently encountered in clinical practice.