bluuebunny/crossref_metadata_2025 huggingface dataset:
Unequal genetic redundancy among the rice transcription factors OsMADS2 and OsMADS4 reveals distinct roles in floret organ development
Authors: ZamZam Mohamed , Singh Sharad , Peesapati Raghavaram , Prakash Sandhan , Simonini Sara , Grossniklaus Ueli , Vijayraghavan Usha
Published: August 2023

Functional diversification of transcription factors and of their downstream targets contributes to the emergence of new organ morphologies. To better understand the molecular mechanisms underlying floral organ specification in rice, we investigated the function ofOsMADS2andOsMADS4, the ricePISTILLATA(PI) paralogs controlling lodicule and stamen formation. The morphological characterization ofosmads2null mutants generated by CRISPR/Cas9 reiterated OsMADS2’s nonredundant role in lodicule development. Furthermore, it uncovered unreported roles in controlling flowering time, floral meristem size, floral organ number, cell wall metabolism, and sterile lemma development. Although downregulation ofOsMADS4did not affect floral organ development, doubly perturbedosmads2d8/d8osmads4kdflorets exhibited more severe abnormalities than theosmads2single mutant. Doubly perturbed inflorescences also exhibited defective rachis extension and parthenocarpy. Remarkably, ubiquitous overexpression ofOsMADS4inosmads2rescued the different abnormalities of theosmads2mutant but resulted in defective anther development and reduced seed set, phenotypes also observed whenArabidopsis PIwas overexpressed in wild-type rice. These findings suggest that increased ubiquitousPIactivity is detrimental to anther development. To uncover genes whose (in)direct regulation may contribute to these phenotypes, we combined the genome-wide identification of OsMADS2 binding regions (ChIP-Seq) with transcriptome profiling (RNA-Seq). These analysis uncovered several OsMADS2 target genes that are implicated in lodicule and stamen development and in controlling floral organ number,e.g.,PECTIN METHYLESTERASE 24(PME24),GLYCOSIDE HYDROLASE 9B16(GH9B16),TAPETUM DEGENERATION RETARDATION(TDR),SPOROCYTELESS(SPL),FLORAL ORGAN NUMBER 1(FON1),YUCCA3 andYUCCA7. Altogether, our results provide insights on the underlying molecular mechanisms of ricePIparalogs in floral organ specification, thereby expanding our understanding of their function as well as their conservation and diversification.
DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A/YTHDF1
Authors: Zhang Yuwei , Zhao Jieyu , Chen Xiaona , Lyu Kaixin , Ding Yiliang , Sun Hao , Kwok Chun-Kit , Wang Huating
Published: August 2023

RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box helicase 36 (DHX36) is known to bind and unwind RNA G-quadruplex (rG4) structure but the transcriptome-wide RNA structure remodeling induced by DHX36 binding and the impact on RNA fate remain poorly understood. Here, we investigate the RNA structurome alteration induced by DHX36 depletion. Our findings reveal that DHX36 binding induces structure remodeling not only at the localized binding sites but also on the entire mRNA transcript most pronounced in3’UTR regions. DHX36 binding increase structural accessibility at 3’UTRs which is correlated with decreased post-transcriptional mRNA abundance. Further analyses and experiments uncover that DHX36 binding sites are enriched for N6-methyladenosine (m6A) modification and YTHDF1 binding; and DHX36 induced structural change may facilitate YTHDF1 binding to m6A sites leading to RNA degradation. Altogether, our findings uncover the structural remodeling effect of DHX36 binding and its impact on RNA abundance through regulating m6A dependent YTHDF1 binding.
Somrit: The Somatic Retrotransposon Insertion Toolkit
Authors: D’Costa Alister V. , Simpson Jared T.
Published: August 2023

Mobile elements, such as retrotransposons, have the ability to express and re-insert themselves into the genome, with over half the human genome being made up of mobile element sequence. Somatic mobile element insertions (MEIs) have been shown to cause disease, including some cancers. Accurate identification of where novel retrotransposon insertion events occur in the genome is crucial to understand the functional consequence of an insertion event. In this paper we describe somrit, a modular toolkit for detecting somatic MEIs from long reads aligned to a reference genome. We identify the initial read-to-reference mapping step as a potential source of error when the insertion is similar to a nearby repeat in the reference genome and develop a consensus-realignment procedure to resolve this. We show how somrit improves the sensitivity of detection for rare somatic retrotransposon insertion events compared to existing tools, and how the local realignment procedure can reduce false positive translocation calls caused by mis-mapped reads bearing MEIs. Somrit is openly available at:https://github.com/adcosta17/somrit
Predicting Protein-Ligand Binding Structure Using E(n) Equivariant Graph Neural Networks
Authors: Dhakal Ashwin , Gyawali Rajan , Cheng Jianlin
Published: August 2023

Drug design is a costly and time-consuming process, often taking more than 12 years and costing up to billions of dollars. The COVID-19 pandemic has signified the urgent need for accelerated drug development. The initial stage of drug design involves the identification of ligands that exhibit a strong affinity for specific binding sites on protein targets (receptors), along with the determination of their precise binding conformation (3-dimensional (3D) structure). However, accurately determining the 3D conformation of a ligand binding with its target remains challenging due to the limited capability of exploring the huge chemical and protein structure space. To address this challenge, we propose a new E(n) Equivariant Graph Neural Network (EGNN) method for predicting the 3D binding structures of ligands and proteins. By treating proteins and ligands as graphs, the method extracts residue/atom-level node and edge features and utilizes physicochemical and geometrical properties of proteins and ligands to predict their binding structures. The results demonstrate the promising potential of EGNN for predicting ligand-protein binding poses.
Pico145 inhibits TRPC4-mediated mICATand postprandial small intestinal motility
Authors: Dryn Dariia O. , Melnyk Mariia I. , Bon Robin S. , Beech David J. , Zholos Alexander V.
Published: August 2023

Background & Aims

In intestinal smooth muscle cells, receptor-operated TRPC4 are responsible for the majority of muscarinic receptor cation current (mICAT), which initiates cholinergic excitation-contraction coupling. Our aim was to examine the effects of the TRPC4 inhibitor Pico145 on mICATand Ca2+signalling in mouse ileal myocytes, and on intestinal motility.

Methods

Ileal myocytes freshly isolated from two month-old male BALB/c mice were used for patch-clamp recordings of whole-cell currents and for intracellular Ca2+imaging using Fura-2. Functional assessment of Pico145’s effects was carried out by standardin vitrotensiometry,ex vivovideo recordings andin vivopostprandial intestinal transit measurements using carmine red.

Results

Carbachol (50 µM)-induced mICATwas strongly inhibited by Pico145 starting from 1 pM. The IC50value for the inhibitory effect of Pico145 on this current evoked by intracellularly applied GTPγS (200 µM), and thus lacking desensitisation, was found to be 3.1 pM, while carbachol-induced intracellular Ca2+rises were inhibited with IC50of 2.7 pM. In contrast, the current activated by direct TRPC4 agonist (-)-englerin A was less sensitive to the action of Pico145 that caused only ∼43% current inhibition at 100 pM. The inhibitory effect developed rather slowly and it was potentiated by membrane depolarisation. In functional assays, Pico145 produced concentration-dependent suppression of both spontaneous and carbachol-evoked intestinal smooth muscle contractions and delayed postprandial intestinal transit.

Conclusions

Pico145 is a potent GI-active small-molecule which completely inhibits mICATat picomolar concentrations and which is as effective astrpc4gene deficiency inin vivointestinal motility tests.
Insights into stereoselective ring formation in canonical strigolactone: Discovery of a dirigent domain-containing enzyme catalyzing orobanchol synthesis
Authors: Homma Masato , Wakabayashi Takatoshi , Moriwaki Yoshitaka , Shiotani Nanami , Shigeta Takumi , Isobe Kazuki , Okazawa Atsushi , Ohta Daisaku , Terada Tohru , Shimizu Kentaro , Mizutani Masaharu , Takikawa Hirosato , Sugimoto Yukihiro
Published: August 2023

Strigolactones (SLs) are plant apocarotenoids with diverse functions and structures. The widespread canonical SLs, with distinctive structural variations in their tricyclic lactone known as the ABC-ring, are classified into two types based on the C-ring configurations. The steric C-ring configuration arises during the BC-ring closure downstream of carlactonoic acid (CLA), a biosynthetic intermediate. Most plants stereoselectively produce either type of canonical SLs, e.g., tomato (Solanum lycopersicum) produces orobanchol with α-oriented C-ring. The mechanisms governing SL structural diversification are partly understood, with limited insight into the functional implications. Moreover, the precise molecular mechanism for the stereoselective BC-ring closure reaction remains unknown. Herein, we identified an enzyme called the stereoselective BC-ring-forming factor (SRF) from the dirigent protein (DIR) family, especially the DIR-f subfamily, whose biochemical function was previously unidentified, making it a pivotal enzyme in stereoselective canonical SL biosynthesis with the α-oriented C-ring. We begin by confirming the exact catalytic function of the tomato cytochrome P450 SlCYP722C, which we previously demonstrated to be involved in the orobanchol biosynthesis [Wakabayashi et al.,Sci. Adv.5, eaax9067 (2019)], to convert CLA to 18-oxocarlactonoic acid. Subsequently, we demonstrate that SRF catalyzes the stereoselective BC-ring closure reaction of 18-oxocarlactonoic acid to form orobanchol. Our approach integrates experimental and computational methods, including SRF structure prediction and molecular dynamics simulations, to propose a catalytic mechanism based on the conrotatory 4π-electrocyclic reaction for stereoselective BC-ring formation in orobanchol. The present study provides insight into the molecular basis of how plants produce SLs with specific stereochemistry in a controlled manner.
Zomato: quick commerce on the menu
Authors: Singh Jagandeep
Published: August 2023

Learning outcomes

By analyzing and discussing the case, students should be able to identify macro environmental factors that impact business decision-making; apply Michael Porter’s five forces framework; evaluate sources of synergy; understand the concept of disruptive innovation; choose sources of competitive advantage; apply the value proposition canvas; and apply tenets of Blue Ocean strategy.

Case overview/synopsis

The grocery retail market in India accounts for nearly 70% ($608bn) of the total retail market ($883bn). The brick-and-mortar multi-tiered distribution network for groceries encompasses a million wholesalers and distributors and 12 million retail outlets. These retail outlets serve as customer touch points where bulk of grocery shopping is done. The online grocery industry is a miniscule $5.5bn. High incomes, change in purchase behaviour, inclination towards speed and convenience on the demand side and alacrity on the supply side have paved the way for new format, quick commerce. Trends and forecasts suggest that quick commerce, a high cash burn business, will grow exponentially. Zomato has jumped onto the quick commerce bandwagon with the acquisition of loss-making Blinkit. The case analyses the quick commerce industry through the lens of Michael Porter’s five forces framework and the Blue Ocean strategy. It elaborates the profitability drivers of the industry and also examines the sources of synergy from the acquisition.

Complexity academic level

This case is suitable for a class on strategy in postgraduate-level courses. It can be used in a session on entrepreneurship and innovation.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 11: Strategy.
Inside sales managers’ utilization of cultural controls as part of a sales control portfolio to enhance overall sales performance
Authors: Conde Richard , Prybutok Victor , Thompson Kenneth , Sumlin Cameron
Published: August 2023

Purpose

The purpose of this study is to extend sales control research to inside sales. Aside from a few notable exceptions (Conde et al., 2022) much of the sales control literature has focused on a single control mechanism rather than a sales control portfolio perspective. The authors add multiple layers to Conde et al. (2022) by capturing secondary operational data and manager interviews to access sales control theory in practice.

Design/methodology/approach

With operational data from a Fortune 100 financial services company and sales manager interviews, the authors present evidence that managers apply a portfolio of controls to ensure sales agents’ overall performance.

Findings

Findings support that cultural controls have a greater influence on overall performance than a focus solely on process and outcome controls. Inside sales managers can generate better results when they focus on creating an employee-centric culture rather than controlling sales agents with formal sales controls.

Originality/value

This study extends sales control research by examining inside sales managers’ formal and informal sales controls. Historically, inside sales had sales leaders balance a myriad of sales controls grounded in strict oversight. With a few notable exceptions, the limited inside sales control research provides the opportunity to display an inside sales manager’s need to jointly focus on operational results and sales outcomes, illustrating the importance of cultural controls compared to other sales process and outcome controls. This research considerably extends sales controls research by focusing on inside sales.
Participation of women-owned SMEs in public procurement: the role of entrepreneurial orientation and knowledge management orientation
Authors: Tukamuhabwa Benjamin , Namagembe Sheila
Published: August 2023

Purpose

This study aims to examine the influence of entrepreneurial orientation and knowledge management orientation on participation of women-owned small and medium enterprises (SMEs) in public procurement. The research also aimed at examining the influence of knowledge management orientation on entrepreneurial orientation, and the mediating role of entrepreneurial orientation on the relationship between Knowledge management orientation and participation of women-owned SMEs in public procurement.

Design/methodology/approach

The study used a quantitative cross-sectional survey design. Data were collected using a drop-off pick-up method. The determined sample size for the women-owned SME firms was 123, while an effective sample size of 103 was obtained, and covariance-based structural equation modelling was used to test the research hypotheses.

Findings

Findings indicated that entrepreneurial orientation and knowledge management positively and significantly influenced both the search for tender opportunities and the number of times the firm submitted bids. Knowledge management orientation had a significant positive influence on entrepreneurial orientation, while entrepreneurial orientation partially mediated the relationship between knowledge management orientation and participation of women-owned SMEs in public procurement, thus implying that both knowledge management orientation and entrepreneurial orientation contribute to search for tender opportunities and the number of times a woman-owned SME firm submits bids.

Research limitations/implications

The study was cross-sectional and quantitative in nature, yet it involved behaviour aspects such as participation in public procurement. Further, a wholistic approach is taken when studying the SMEs disregarding the industrial characteristics to which the SME belongs.

Social implications

Almost 30% to 38% of SMEs in developing countries are owned by women. Focusing on increasing the number of women owned SMEs participating in public procurement will improve the nations’ GDP and increase the number of the citizens in the labour force due to increased employability.

Originality/value

Previous research takes a wholistic approach when examining SMEs participation in public sector procurement disregarding the impact of gender. Further, knowledge management orientation and entrepreneurial orientation in women-owned SMEs are studied for the first time in a public procurement setting.
Supporting learners with special educational needs and disabilities in the foreign languages classroom
Authors: Howard Katie B.
Published: August 2023

Due to misconceptions about the challenges of language learning, foreign languages classrooms have not always been accessible spaces for all learners. This article seeks to address the needs of students with special educational needs and/or disabilities (SEND) in the foreign languages classroom and challenge the notion that this group of students cannot or should not learn languages. Current research tends to focus on specific learning difficulties in language learning, but little research considers the language learning experiences of children with SEND more broadly. Accordingly, this article delineates the advantages of language learning for learners with SEND, drawing on emerging research that shows that second language acquisition is not only possible but positive for many learners with additional needs. It then considers some of the specific challenges that SEND learners may face in the foreign languages classroom before outlining key strategies to facilitate inclusion among this diverse group of learners.

Key points

Learners with special educational needs and/or disabilities (SEND) should not routinely be removed from the foreign languages classroom, but instead should be provided with opportunities to thrive within it. This article discusses the unique importance of foreign language learning for learners with SEND.

Research evidence suggests that learning new languages is, on the whole, possible—and perhaps hugely beneficial—for children with developmental differences and learning difficulties, but will depend on the circumstances and profile of the individual child.

The article explores some specific challenges that students with different additional needs might encounter in their foreign languages education, based on the four areas of need outlined in the SEND Code of Practice: communication and interaction; cognition and learning; social, emotional and mental health difficulties; and sensory or physical needs.

To conclude, the article presents a range of key strategies that foreign languages teachers might implement in the classroom to support learners with different special educational needs and disabilities.
Listeria monocytogenes in food businesses: From persistence strategies to intervention/prevention strategies—A review
Authors: Tuytschaever Tessa , Raes Katleen , Sampers Imca
Published: August 2023

In 2023, Listeria monocytogenes persistence remains a problem in the food business. A profound understanding of how this pathogen persists may lead to better aimed intervention/prevention strategies. The lack of a uniform definition of persistence makes the comparison between studies complex. Harborage sites offer protection against adverse environmental conditions and form the ideal habitat for the formation of biofilms, one of the major persistence strategies. A retarded growth rate, disinfectant resistance/tolerance, desiccation resistance/tolerance, and protozoan protection complete the list of persistence strategies for Listeria monocytogenes and can occur on themselves or in combination with biofilms. Based on the discussed persistence strategies, intervention strategies are proposed. By enhancing the focus on four precaution principles (cleaning and disinfection, infrastructure/hygienic design, technical maintenance, and work methodology) as mentioned in Regulation (EC) No. 852/2004, the risk of persistence can be decreased. All of the intervention strategies result in obtaining and maintaining a good general hygiene status throughout the establishment at all levels ranging from separate equipment to the entire building.
Mass spectrometry‐based approaches to assess the botanical authenticity of dietary supplements
Authors: Grazina Liliana , Mafra Isabel , Monaci Linda , Amaral Joana S.
Published: August 2023

Dietary supplements are legally considered foods despite frequently including medicinal plants as ingredients. Currently, the consumption of herbal dietary supplements, also known as plant food supplements (PFS), is increasing worldwide and some raw botanicals, highly demanded due to their popularity, extensive use, and/or well‐established pharmacological effects, have been attaining high prices in the international markets. Therefore, botanical adulteration for profit increase can occur along the whole PFS industry chain, from raw botanicals to plant extracts, until final PFS. Besides the substitution of high‐value species, unintentional mislabeling can happen in morphologically similar species. Both cases represent a health risk for consumers, prompting the development of numerous works to access botanical adulterations in PFS. Among different approaches proposed for this purpose, mass spectrometry (MS)‐based techniques have often been reported as the most promising, particularly when hyphenated with chromatographic techniques. Thus, this review aims at describing an overview of the developments in this field, focusing on the applications of MS‐based techniques to targeted and untargeted analysis to detect botanical adulterations in plant materials, extracts, and PFS.
The Global Dimension of the CAP Debate: Between a Rock and a Hard Place
Authors: Haniotis Tassos
Published: August 2023

Exuberant expectations about what EU agriculture can and should deliver in policy areas beyond its scope often contrast sharply with both farm realities and contradictions in the behaviour of individuals as citizens and consumers. This has polarised the CAP policy debate, and erroneously pushes for a choice between prioritising either climate action or food security. Recent developments, including the war in Ukraine, added to concerns about uncertain and volatile future price prospects. Food price prospects and population growth impacts are pivotal in the debate about food security as higher food costs, prospects for higher energy costs driven by the green transition and increasing income inequalities put households in both developed and the developing world at risk with respect to food affordability. Adding trends of global population growth, especially in Africa, creates a clear challenge of availability in certain products and regions. The EU's underestimated and misunderstood record of producing more with less could help EU agriculture to positively contribute to addressing both food security and climate change. However, further improving its performance requires re‐opening the debate in three priority areas where the EU must come clear on its stance and future contribution – productivity, science and trade.
Barriers and Enablers of Long‐term Land Leasing: a Case Study of Northern Ireland
Authors: Adenuga Adewale Henry , Jack Claire , McCarry Ronan , Caskie Paul
Published: August 2023

Long‐term land leasing offers a viable alternative to land ownership in relation to increasing efficiency of agricultural production, economies of scale, and delivering environmental improvements in terms of land management. However, with no significant tenanted sector in Northern Ireland, access to land via long‐term land leasing is limited. This study analysed the barriers and enablers of long‐term land leasing. To achieve our objective, we employed a mixed methods approach. The results show that the main barriers to long‐term land leasing were environmental concern (around how the land will be managed), inheritance tax implications and the potential effect of long‐term land leasing on future succession plans of the farm business. We also found that as much as 70 per cent of the farmers surveyed believe the inclusion of a ‘break clause’ and the introduction of income tax incentives will encourage the adoption of long‐term land leasing, while 61 per cent of the farmers stated that the environmental management of the land will encourage long‐term land leasing. The study concluded that any model designed to encourage long‐term land leasing in Northern Ireland should include clauses which cover the environmental management of the land and break clauses. Income tax incentives for landowners could also be considered.
Dietitian‐led micronutrient management in a public bariatric surgery outpatient clinic
Authors: Lewis Carrie‐Anne , Hiatt Joanne , de Jersey Susan , Osland Emma J. , Hickman Ingrid J.
Published: August 2023

Aims

This study aimed to explore the multidisciplinary team attitudes and knowledge of bariatric surgery micronutrient management (pre‐ and postoperative care) and to evaluate the implementation of an extended‐scope of practice dietitian‐led model of care for micronutrient monitoring and management.

Methods

A mixed method study design included quantitative evaluation of micronutrient testing practices and deficiency rates. Qualitative reflexive thematic analysis was used to interpret multidisciplinary experience with micronutrient monitoring in a traditional and dietitian‐led model of care. In addition, deductive analysis used normalisation process theory mapping of multidisciplinary experience with the implementation of the dietitian‐led model of care.

Results

In the traditional model, a lack of quality evidence to guide micronutrient management, and a tension in trust between surgeons and patients related to adherence to micronutrient prescriptions were described as challenges in current practice. The dietitian‐led model was seen to overcome some of these challenges, increasing collaborative, and coordinated, consistent and personalised patient care that led to increased testing for and detection of micronutrient deficiencies. Barriers to sustainability of the dietitian‐led model included a lack of workforce succession planning, and no clearly defined delegation for some aspects of care.

Conclusion

An extended scope dietitian‐led model of care for micronutrient management after bariatric surgery improves clinical care. Challenges such as succession planning must be considered in design of extended scope services.
Multiresponse optimization of the extrusion process for ready‐to‐eat snacks from pineapple byproducts and maize flour
Authors: Vivar‐Vera María A. , Navarro‐Cortez Ricardo O. , Hernández‐Santos Betsabé , Ramírez‐Rivera Emmanuel J. , Torruco‐Uco Juan G. , Ramírez‐Figueroa Enrique , Amador‐Mendoza Adolfo , Cruz‐Cabrera Irma , Rodríguez‐Miranda Jesús
Published: August 2023

This research aimed to optimize the processing conditions to obtain ready‐to‐eat extruded snacks with a high fiber content from mixtures of pineapple byproduct powder (PBP) and nixtamalized maize flour (PBP‐NMF) or maize flour (PBP‐MF). The effects of barrel temperature, feed moisture content, and PBP were evaluated. The increase in barrel temperature has a negative effect on the bulk density, the water absorption index, and the texture in both mixtures (PBP‐MF and PBP‐NMF) and increases the expansion index and the water solubility index in the mixture with MF. The increase in the feed moisture content increased the bulk density and water absorption index in both mixtures and the texture in the mixtures with MF. The increasing PBP decreases the expansion index and increases the water solubility index in both mixtures. The increase in PBP in the mixtures with MF decreases the water absorption index, texture, and bulk density. From the optimization, four products were obtained, two for the NMF mixture and two for the MF mixtures. The optimal formulations can be considered a good source of total fiber (12.46−12.78 g/100 g) and protein (8.27−8.85 g/100 g) with good acceptance by consumers.

Practical Application

Pineapple byproducts in combination with nixtamalized and nonnixtamalized maize flour are viable raw materials for the development of ready‐to‐eat extruded snacks with a high content of dietary fiber and good acceptance by consumers. Due to their characteristic nutritional properties, the consumption of this ready‐to‐eat snack could present potential benefits for human health.
idopNetwork: A network tool to dissect spatial community ecology
Authors: Dong Ang , Wu Shuang , Che Jincan , Wang Yu , Wu Rongling
Published: August 2023

Network models have been used as a tool to characterize internal workings of complex systems. The amount of topological and functional information extracted from a network depend on the method of network inference and the type of network data.

An interdisciplinary computational model has been proposed to reconstruct informative, dynamic, omnidirectional and personalized networks (idopNetwork) from any data domains including static data.

We implement idopNetwork as an R‐based cartographic tool to characterize spatially varying interspecies interaction networks using the abundance data of multiple species from different geographical locations. This tool provides a unified framework for integrating power curve fitting based on allometrical scaling law, functional clustering, LASSO‐based variable selection, quasi‐dynamic ordinary differential equation solving, species abundance decomposition and network visualization. It coalesces all species from different spaces into location‐specific networks.

We demonstrate the utility of this tool by analysing different organs that are spatially interconnected via microbiomes within the host using two datasets from the gut microbiota and plant microbiota. Given that biodiversity and organization vary biogeographically at different scales, idopNetwork will find its widespread application to modelling and estimating interspecific interactions with differing functions across space.
Exogenous growth regulators amplify the morpho‐physiology, root architecture and dry‐matter accumulation in seed potato
Authors: Singh Amanpreet , Aulakh Charanjit Singh , Chawla Neena , Khepar Varinder
Published: August 2023

Enhancing the productivity of seed potato production systems by improving the size of the tubers is a primary concern. Punjab, a state located in the northwest region of India, meets 60% of the country's seed requirements. In order to optimize the morpho‐physiological aspects, root structure, and overall yield of seed‐sized tubers, research trials were carried out at Punjab Agricultural University, Ludhiana over two consecutive years. The trial consisted of 11 different treatments and was conducted using a randomized complete block design with three replications. The application of Gibberellic acid at a concentration of 200 ppm, at 45 and 60 days after sowing (DAS), resulted in significantly higher yields of seed‐sized tubers measuring <4.5 cm. This treatment also exhibited superior root architecture parameters and accumulation of dry matter, outperforming all other growth regulation treatments. Compared to the untreated control group, the Gibberellic acid application led to a remarkable increase of 45.9% and 39.8% in seed‐sized tuber yields. Furthermore, it significantly boosted the protein, starch, antioxidant (total phenols), sugar (total and reducing), and mineral content (nitrogen, phosphorus, and potassium) in the tubers, surpassing the effects of all other growth regulation treatments. These results suggested that the exogenous use of gibberellic acid (200 ppm) at 45 and 60 DAS substantially improved the physiology, root architecture, and yield of seed‐sized tubers.
Oral immunotherapy in alpha‐gal red meat allergy: Could specific IgE be a potential biomarker in monitoring management?
Authors: Ünal D. , Eyice‐Karabacak D. , Kutlu A. , Demir S. , Tüzer C. , Arslan A. F. , Işık S. R. , Gelincik A.
Published: August 2023

Background

Oral immunotherapy (OIT) is a promising treatment for food allergies. Our aim was to establish the long‐term safety and efficacy of a novel red meat (RM) OIT in galactose‐alpha‐1,3‐galactose (alpha‐gal) allergy in adults.

Methods

Out of 20 patients with confirmed RM allergy, five (41.66%) underwent an early OIT, seven (58.33%) underwent a delayed protocol and eight patients who were not desensitized formed the patient control group. 15 and 27 day RM OIT for early‐onset and delayed‐onset alpha‐gal allergy were administered, respectively. Desensitized patients were recommended to continue eating at least 100 g RM every day for 6 months and every other day in the following 6 months. After a year, the consumption was recommended 2/3 times in a week. Patients were followed up with skin tests with commercial beef and lamb extracts, fresh raw/cooked beef and lamb and cetuximab and also with serum alpha‐gal specific Immunoglobulin‐E (sIgE) in the first and fifth years.

Results

All patients who underwent OIT became tolerant to RM. During the 5 year follow‐up, the median alpha‐gal sIgE concentration gradually decreased in nine patients who consumed RM uneventfully while remained unchanged in the control group (p = .016). In two patients, rare tick bites acted as inducers of hypersensitivity reactions with concomitant elevation of alpha‐gal sIgE concentrations whereas one patient with low follow‐up alpha‐gal sIgE concentrations consumed RM uneventfully after frequent tick bites.

Conclusions

Our study showed the long‐term safety and efficacy of alpha‐gal OIT. Additionally, alpha‐gal sIgE seems to be a potential biomarker to monitor OIT.
Dupilumab‐induced eosinophilia in patients with diffuse type 2 chronic rhinosinusitis
Authors: Ryser Fabio S. , Yalamanoglu Ayla , Valaperti Alan , Brühlmann Catrin , Mauthe Tina , Traidl Stephan , Soyka Michael B. , Steiner Urs C.
Published: August 2023

Background

Dupilumab, a monoclonal anti‐IL‐4Rα antibody, is approved for several type 2 mediated inflammatory diseases like asthma, atopic dermatitis, and diffuse type 2 chronic rhinosinusitis (CRS). Clinical studies had reported a transient increase in blood eosinophils during dupilumab therapy.

This study aimed to assess the impact of elevated blood eosinophils on clinical outcome and to investigate the cause of high blood eosinophil levels under dupilumab therapy.

Methods

Patients suffering from diffuse type 2 CRS treated with dupilumab were examined on days 0, 28, 90, and 180 after therapy start. Sino‐Nasal‐Outcome‐Test Score (SNOT‐22), Total Nasal Polyp Score (TNPS), and blood samples were collected. Cytokine measurements and proteomics analysis were conducted. Flow cytometry analysis measured receptor expression on eosinophils.

Results

Sixty‐eighty patients were included. Baseline eosinophilia ≥0.3G/L was observed in 63.2% of patients, and in 30.9% of patients, eosinophils increased by ≥0.5G/L under dupilumab. Subjects with eosinophilia ≥0.3G/L at baseline had the best SNOT‐22 mean change compared to no eosinophilia. Eosinophil elevation during dupilumab therapy had no impact on clinical scores. The eosinophil adhesion molecule VCAM‐1 decreased significantly during therapy in all patients. The chemokine receptor CXCR4 was significantly down‐ and IL‐4 upregulated in subjects with eosinophil increase.

Conclusion

Our findings suggest that increased eosinophils in type 2 CRS are associated with a good clinical response to dupilumab. Patients with elevated IL‐4 at baseline developed dupilumab‐induced transient eosinophilia. We identified the downregulation of VCAM‐1 and surface markers CD49d and CXCR4 on eosinophils as possible explanations of dupilumab‐induced eosinophilia.
Assembling Under the Westway: The Emergence of Social Infrastructure in North Kensington, London
Authors: Sendra Pablo , Belson Toby Laurent , Picardi Marco Thomas
Published: August 2023

This paper explores the generative capacity of activist movements defending their community assets from commodification or closure to produce new forms of social infrastructure. We explore this through the case study of activism along the Westway, a motorway in West London. The area has a strong tradition of community activism, particularly in the 1960s and the 2010s. Through a Participatory Action Research approach, we elaborate a historical account of the formation of social infrastructure under the Westway and surrounding spaces. In doing so, we develop a framework—processes, alliances, and capacities—to understand how communities and activist groups contesting the loss of community spaces can generate new forms of social infrastructure—both physical spaces such as play spaces or cultural venues, and social and caring relationships such as friendships or support networks. These informal spaces and alliances can shed light on how to build alternative, bottom‐up forms of social infrastructure.
Nordic survey showed wide variation in discharge practices for very preterm infants
Authors: Arwehed Sofia , Axelin Anna , Björklund Lars J. , Thernström Blomqvist Ylva , Heiring Christian , Jonsson Baldvin , Klingenberg Claus , Metsäranta Marjo , Ågren Johan , Lehtonen Liisa
Published: August 2023

Aim

We aimed to describe clinical practices and criteria for discharge of very preterm infants in Nordic neonatal units.

Methods

Medical directors of all 89 level‐2 and level‐3 units in Denmark, Finland, Iceland, Norway and Sweden were invited by e‐mail to complete a web‐based multiple‐choice survey with the option to make additional free‐text comments.

Results

We received responses from 83/89 units (93%). In all responding units, discharge readiness was based mainly on clinical assessment with varying criteria. In addition, 36% used formal tests of cardiorespiratory stability and 59% used criteria related to infant weight or growth. For discharge with feeding tube, parental ability to speak the national language or English was mandatory in 45% of units, with large variation among countries. Post‐discharge home visits and video‐consultations were provided by 59% and 51%, respectively. In 54% of units, parental preparation for discharge were not initiated until the last two weeks of hospital stay.

Conclusion

Discharge readiness was based mainly on clinical assessment, with criteria varying among units despite similar population characteristics and care structures. This variation indicates a lack of evidence base and may unnecessarily delay discharge; further studies of this matter are needed. Earlier parental preparation and use of interpreters might facilitate earlier discharge.
Temporal variations of vaccine hesitancy amid the COVID‐19 outbreaks in Hong Kong
Authors: Leung Cyrus Lap Kwan , Li Kin Kit , In Wei Wan , Tam Wilson , McNeil Edward B. , Tang Arthur , Wong Samuel Yeung Shan , Kwok Kin On
Published: August 2023

To inform the dynamic adjustments of vaccination campaigns, this study examined the transitions among vaccine hesitancy profiles over the COVID‐19 pandemic progression and their predictors and outcomes. The transition patterns among hesitancy profiles over three periods were identified using a latent transition analysis with individuals from a longitudinal cohort study since the emergence of COVID‐19 in Hong Kong. Four profiles (i.e., skeptics, apathetics, fence‐sitters, and believers) emerged consistently over time. From Period 1 (third and fourth pandemic waves) to Period 2 (dormant period, vaccine rollout), 14.17% of believers became fence‐sitters (ambivalization), and 12.11% of fence‐sitters became apathetics (apathetization). From Period 2 to Period 3 (omicron surge and vaccine mandates), 20.21% of believers became fence‐sitters. Lower trust in government predicted a transition to skepticism, whereas higher trust predicted the opposite. Staying as believers was associated with decreased hygienic and social distancing behavior. The stable hesitancy profiles amid the rapid vaccine uptake suggest that structural factors rather than personal agency may drive the surge. Ambivalization and apathetization may signal disengagement in preventive behaviors. Trust in the government is crucial in the pandemic response. Public health interventions may improve compliance with guidelines and prevent skepticism and apathy.
Autonomy and control in the (home) office: Finance professionals' attitudes toward working from home in Canada as a result of COVID‐19 lockdowns
Authors: Cockayne Daniel , Treleaven Christina
Published: August 2023

This paper explores the shift to working from home among finance professionals in Canada as a result of the COVID‐19 pandemic. We present the results of a survey that invited quantitative and qualitative responses about attitudes toward working from home, the overlap between paid and unpaid (i.e., childcare and other caregiving) work in the home, changing relationships with employers, and preferences regarding the organisation and location of work. We argue that enforced working from home signalled a shift in outlook among finance professionals that, beyond stated preferences to work from home, shows both that many are seeking more autonomy and control over their working lives and a distinct ambivalence about working from home. This is significant in sectors like finance where overwork is common and in‐office dynamics are seen, especially by managers and employers, as particularly important in relation to mentorship, advancement, and promotion, often within rigid masculinist hierarchies. Thus, an eventual return to ‘normal’, i.e., full‐time office‐based work, may be especially appealing in this sector. This paper contributes to the expanding literature on working from home resulting from COVID‐19 lockdowns in white‐collar professions within and outside of geography, with a focus on the literatures on work, workplaces, and social reproduction in economic and financial geography.
A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase‐based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia
Authors: Yin Qiufen , Cheng Zeneng , Yang Minghua , Wang Shengfeng , Xie Feifan
Published: August 2023

Aims

Methotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT‐based hepatotoxicity remains unclear. This study aimed to develop a semimechanistic PK/pharmacodynamic (PD) model to characterize the MTX‐induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukaemia.

Methods

A retrospective study was conducted on paediatric patients who received high‐dose (3–5 g/m2) MTX treatment. MTX concentrations were assessed at 24‐h intervals until the concentration dropped below 0.1 μmol/L. ALT concentrations were measured both before and after MTX administration. A population PK model was initially developed, which was later connected to a semimechanistic hepatotoxicity model.

Results

The PK model was developed using 354 MTX concentrations obtained from 51 patients, while the PD model was constructed using 379 ALT concentrations collected from 48 patients. The optimal PK model for MTX consisted of a 2‐compartment structure, where body surface area served as a covariate for clearance and central volume of distribution. An indirect response model coupled to a liver injury signal transduction model was developed to describe the dynamics of ALT after MTX administration. The drug effect was adequately described by a linear model, exhibiting considerable interoccasion variability for each treatment session. No significant covariates were identified to have an impact on the PD parameters.

Conclusion

A semimechanistic model was developed to describe ALT‐based hepatotoxicity of MTX, and it has the potential to serve as a valuable tool for characterizing drug‐induced hepatotoxicity.
Oncological outcomes after attempted nerve‐sparing radical prostatectomy (NSRP) in patients with high‐risk prostate cancer are comparable to standard non‐NSRP: a longitudinal long‐term propensity‐matched single‐centre study
Authors: Furrer Marc A. , Sathianathen Niranjan , Gahl Brigitta , Corcoran Niall M. , Soliman Christopher , Rodriguez Calero Jose Antonio , Ineichen Gallus B. , Gahl Miriam , Kiss Bernhard , Thalmann George N.
Published: August 2023

Objective

To assess the long‐term safety of nerve‐sparing radical prostatectomy (NSRP) in men with high‐risk prostate cancer (PCa) by comparing survival outcomes, disease recurrence, the need for additional therapy, and perioperative outcomes of patients undergoing NSRP to those having non‐NSRP.

Patients and methods

We included consecutive patients at a single, academic centre who underwent open RP for high‐risk PCa, defined as preoperative prostate‐specific antigen level of > 20 ng/mL and/or postoperative International Society of Urological Pathology Grade Group 4 or 5 (i.e., Gleason score ≥ 8) and/or ≥pT3 and/or pN1 assessing the RP and lymph node specimen. We calculated a propensity score and used inverse probability of treatment weighting to match baseline characteristics of patients with high‐risk PCa who underwent NSRP vs non‐NSRP. We analysed oncological outcome as time‐to‐event and calculated hazard ratios (HRs).

Results

A total of 726 patients were included in this analysis of which 84% (n = 609) underwent NSRP. There was no evidence for the positive surgical margin rate being different between the NSRP and non‐NSRP groups (47% vs 49%, P = 0.64). Likewise, there was no evidence for the need for postoperative radiotherapy being different in men who underwent NSRP from those who underwent non‐NSRP (HR 0.78, 95% confidence interval [CI] 0.53–1.15). NSRP did not impact the risk of any recurrence (HR 0.99, 95% CI 0.73–1.34, P = 0.09) and there was no evidence for survival being different in men who underwent NSRP to those who underwent non‐NSRP (HR 0.65, 95% CI 0.39–1.08). There was also no evidence for the cancer‐specific survival (HR 0.56, 95% CI 0.29–1.11) or progression‐free survival (HR 0.99, 95% CI 0.73–1.34) being different between the groups.

Conclusion

In patients with high‐risk PCa, NSRP can be attempted without compromising long‐term oncological outcomes provided a comprehensive assessment of objective (e.g., T Stage) and subjective (e.g., intraoperative appraisal of tissue planes) criteria are conducted.