bluuebunny/crossref_metadata_2025 huggingface dataset:
General population screening for type 1 diabetes using islet autoantibodies at the preschool vaccination visit: a proof-of-concept study (the T1Early study)
Authors: Scudder Claire , Townson Julia , Gillespie Kathleen M , Bowen-Morris Jane , Evans Philip , Jones Sarah , Thomas Nicholas P B , Stanford Jane , Fox Robin , Todd John A , Greenfield Sheila , Dayan Colin M , Besser Rachel E J
Published: November 2023

Objective

Type 1 diabetes (T1D) screening programmes testing islet autoantibodies (IAbs) in childhood can reduce life-threatening diabetic ketoacidosis. General population screening is required to detect the majority of children with T1D, since in >85% there is no family history. Age 3-5 has been proposed as an optimal age for a single screen approach.

Design

Capillary samples were collected from children attending their pre-school vaccination and analysed for IAbs to insulin, glutamic acid decarboxylase, islet antigen-2, and zinc transporter 8, using Radiobinding/Luciferase Immunoprecipitation Systems assays. Acceptability was assessed using semi-structured interviews and open-ended postcard questionnaires with parents.

Setting

Two primary care practices in Oxfordshire, UK.

Main outcome measures

The ability to collect capillary blood to test IAbs in children at the routine pre-school vaccination (3.5-4 years).

Results

Of 134 parents invited, 66 (49%) were recruited (median age 3.5y (IQR 3. 4-3.6), 26(39.4%) male); 63 provided a sample (97% successfully). Parents (n=15 interviews, n=29 postcards) were uniformly positive about screening aligned to vaccination and stated they would have been less likely to take part had screening been a separate visit. Themes identified included preparedness for T1D, and the long-term benefit outweighing short-term upset. The perceived volume of the capillary sample was a potential concern and needs optimising.

Conclusions

Capillary IAb testing is a possible method to screen children for T1D. Aligning collection to the pre-school vaccination visit can be convenient for families and allows a universal approach without the need for an additional visit.

KEY MESSAGES

What is already known on this topic?

Screening children for type 1 diabetes by measuring islet autoantibodies (IAbs) may reduce life-threatening diabetic ketoacidosis. The optimal age for screening children at a single timepoint has been proposed as age 3-5. Routine immunisations are given at a similar age.

What does this study add?

Aligning IAb testing with the pre-school vaccination visit (age 3.5-4y) is feasible and acceptable. Potential barriers and facilitators of this approach are explored.

How this study might affect research, practice or policy?

The routine vaccination programme is a potential opportunity to screen children for future type 1 diabetes, offering improved engagement and potentially reducing the costs associated with a screening programme; all of which need exploration in a large and definitive study.
Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction
Authors: McCracken Celeste , Szabo Liliana , Abdulelah Zaid A. , Vago Hajnalka , Nichols Thomas E. , Petersen Steffen E. , Neubauer Stefan , Raisi-Estabragh Zahra
Published: November 2023

Background

The utility of ventricular asymmetry as an imaging biomarker for cardiovascular risk has not been assessed in population cohorts.

Objectives

This study presents a comprehensive assessment of the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases.

Methods

Cardiovascular magnetic resonance (CMR) imaging metrics derived from automated image analysis were examined, along with clinical outcomes ascertained through linked health records. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV, RV) end-diastolic volumes. The normal range for ventricular symmetry was defined in a healthy subset without cardiorespiratory disease. Participants with values outside the 5th-95thpercentiles of the healthy distribution were classed as either LV dominant (LV/RV > 112%) or RV dominant (LV/RV < 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures.

Results

The analysis includes 44,796 participants (average age 64.1±7.7 years; 51.9% women). Ventricular asymmetry, in either direction, was associated with older age and adverse cardiovascular remodeling. LV-dominance was linked to an array of pre-existing vascular risk factors and cardiovascular diseases, and a two-fold increased risk of incident heart failure, non-ischemic cardiomyopathies, and left-sided valvular disorders. RV dominance was associated with an elevated risk of all-cause mortality.

Conclusions

Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics.

Condensed abstract

Healthy hearts have a predictable symmetry. Asymmetry produced when one, e.g. the left ventricular (LV) volume outweighs the right, or vice versa, could be an important indicator of underlying disorders, and powerful risk indicator for future disease. In this study of 44,796 UK Biobank participants, we show that LV dominance associates significantly with clinical risk factors, existing heart disease, and a two-fold increased risk for future heart failure, non-ischemic cardiomyopathies, and left-sided valvular disorders. RV dominance was associated with an increased risk of all-cause mortality. Ventricular asymmetry is easily calculated from conventional imaging metrics and could be a highly useful addition to the clinician’s toolkit.

Central illustration:

Ventricular volume asymmetry associates with adverse outcomes
Rational Empiric Antibiotic Escalation Applied to Specific Patient Groups
Authors: Bamber Ranjeet , Sullivan Brian , Gorman Léo , Lee Winnie WY , Avison Matthew B , Dowsey Andrew W , Williams Philip
Published: November 2023

Background

Clinicians commonly escalate empiric antibiotic therapy due to poor clinical progress, without microbiology guidance. When escalating, they should take account of how resistance to an initial antibiotic affects the probability of resistance to subsequent options. The term Escalation Antibiogram (EA) has been coined to describe this concept. One difficulty when applying the EA concept to clinical practice is understanding the uncertainty in results and how this changes for specific patient subgroups.

Methods

A Bayesian model was developed to estimate antibiotic resistance rates in Gram-negative bloodstream infections based on phenotypic resistance data. It provides an expected value (posterior mean) with 95% credible interval to illustrate uncertainty, based on the size of the patient subgroup, and estimates probability of inferiority between two antibiotics. This model can be applied to specific patient groups where resistance rates and underlying microbiology may differ from the whole hospital population.

Results

Rates of resistance to empiric first choice and potential escalation antibiotics were calculated for the whole hospitalised population based on 10,486 individual bloodstream infections, and for a range of specific patient groups, including ICU, haematology-oncology, and paediatric patients. Differences in optimal escalation antibiotic options between specific patient groups were noted.

Conclusions

EA analysis informed by our Bayesian model is a useful tool to support empiric antibiotic switches, providing an estimate of local resistances rates, and a comparison of antibiotic options with a measure of the uncertainty in the data. We demonstrate that EAs calculated for the whole population cannot be assumed to apply to specific patient groups.
Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis
Authors: Schmidt Amand F , Davidson Michael H , Ditmarsch Marc , Kastelein John J. , Finan Chris
Published: November 2023

Elevated levels of low-density lipoprotein cholesterol (LDL-C) are linked to dementia risk, and conversely, increased plasma concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) associate with decreased dementia risk. Inhibition of cholesteryl ester transfer protein (CETP) meaningfully affects the concentrations of these blood lipids and may therefore provide an opportunity to treat dementia. Drug target Mendelian randomization (MR) was employed to anticipate the on-target effects of lower CETP concentration (µg/mL) on plasma lipids, cardiovascular disease outcomes, Lewy body dementia (LBD) as well as Parkinson’s dementia. MR analysis of lower CETP concentration recapitulated the blood lipid effects observed in clinical trials of CETP-inhibitors, as well as protective effects on CHD (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.89; 0.96), heart failure, abdominal aortic aneurysm any stroke, ischemic stroke, and small vessel stroke (0.90, 95%CI 0.85; 0.96). Consideration of dementia related traits indicated that lower CETP concentrations were associated higher total brain volume (0.04 per standard deviation, 95%CI 0.02; 0.06), lower risk of LBD (OR 0.81, 95%CI 0.74; 0.89) and Parkinson’s dementia risk (OR 0.26, 95%CI 0.14; 0.48).APOE4stratified analyses suggested the LBD effect was most pronounced inAPOE-ε4+ participants (OR 0.61 95%CI 0.51; 0.73), compared toAPOE-ε4-(OR 0.89 95%CI 0.79; 1.01); interaction p-value 5.81×10-4. Additionally, MR was employed to link plasma CETP concentration to the levels of cerebrospinal fluid and brain proteins previously implicated in neurodegenerative pathways These results suggest that inhibition of CETP may be a viable strategy to treat dementia.
Neuronal LRP4 directs the development, maturation, and cytoskeletal organization of peripheral synapses
Authors: DePew Alison T. , Bruckner Joseph J. , O’Connor-Giles Kate M. , Mosca Timothy J.
Published: November 2023

Synapse development requires multiple signaling pathways to accomplish the myriad of steps needed to ensure a successful connection. Transmembrane receptors on the cell surface are optimally positioned to facilitate communication between the synapse and the rest of the neuron and often function as synaptic organizers to synchronize downstream signaling events. One such organizer, the LDL receptor-related protein LRP4, is a cell surface receptor most well-studied postsynaptically at mammalian neuromuscular junctions. Recent work, however, has identified emerging roles for LRP4 as a presynaptic molecule, but how LRP4 acts as a presynaptic organizer, what roles LRP4 plays in organizing presynaptic biology, and the downstream mechanisms of LRP4 are not well understood. Here we show that LRP4 functions presynaptically atDrosophilaneuromuscular synapses, acting in motor neurons to instruct multiple aspects of pre- and postsynaptic development. Loss of presynaptic LRP4 results in a range of developmental defects, impairing active zone organization, synapse growth, physiological function, microtubule organization, synaptic ultrastructure, and synapse maturation. We further demonstrate that LRP4 promotes most aspects of presynaptic development via a downstream SR-protein kinase, SRPK79D. SRPK79D overexpression suppresses synaptic defects associated with loss oflrp4. These data demonstrate a function for LRP4 as a peripheral synaptic organizer acting presynaptically, highlight a downstream mechanism conserved with its CNS function, and indicate previously unappreciated roles for LRP4 in cytoskeletal organization, synapse maturation, and active zone organization, underscoring its developmental importance.
Spatially resolved proteomics of the stomatal lineage: polarity complexes for cell divisions and stomatal pores
Authors: Wallner Eva-Sophie , Mair Andrea , Handler Dominik , McWhite Claire , Xu Shou-Ling , Dolan Liam , Bergmann Dominique C.
Published: November 2023

Cell polarity is used to guide asymmetric divisions and create morphologically diverse cells. We find that two oppositely oriented cortical polarity domains present during the asymmetric divisions in the Arabidopsis stomatal lineage are reconfigured into polar domains marking ventral (pore-forming) and outward facing domains of maturing stomatal guard cells. Proteins that define these opposing polarity domains were used as baits in miniTurboID-based proximity labeling. Among differentially enriched proteins we find kinases, putative microtubule-interacting proteins, polar SOSEKIs with their effector ANGUSTIFOLIA, and using AI-facilitated protein structure prediction models, we identify their potential interaction interfaces. Functional and localization analysis of polarity protein OPL2 and its newly discovered partners suggest a positive interaction with mitotic microtubules and a potential role in cytokinesis. This combination of cutting-edge proteomics and structural modeling with live cell imaging provides insights into how polarity is rewired in different cell types and cell cycle stages.
Leveraging a self-cleaving peptide for tailored control in proximity labeling proteomics
Authors: Delhaye Louis , Moschonas George D. , Fijalkowska Daria , Verhee Annick , De Sutter Delphine , Van de Steene Tessa , De Meyer Margaux , Van Moortel Laura , De Bosscher Karolien , Jacobs Thomas , Eyckerman Sven
Published: November 2023

Protein-protein interactions play an important biological role in every aspect of cellular homeostasis and functioning. Proximity labeling mass spectrometry-based proteomics overcomes challenges typically associated with other methods, and has quickly become the current state-of-the-art in the field. Nevertheless, tight control of proximity labeling enzymatic activity and expression levels is crucial to accurately identify protein interactors. Here, we leverage a T2A self-cleaving peptide and a non-cleaving mutant to accommodate the protein-of-interest in the experimental and control TurboID setup. To allow easy and streamlined plasmid assembly, we built a Golden Gate modular cloning system to generate plasmids for transient expression and stable integration. To highlight our T2A Split-link design, we applied it to identify protein interactions of the glucocorticoid receptor and SARS-CoV-2 nucleocapsid and NSP7 proteins by TurboID proximity labeling. Our results demonstrate that our T2A split-link provides an opportune control that builds upon previously established control requirements in the field.

Motivation

In proximity labeling proteomics protein-protein interactions are identified byin vivobiotinylation. However, the current lack of a universally applicable negative control for differential analysis affects accurate mapping of the interactome. To bridge this gap, we conceptualized a system based on the T2A self-cleaving peptide to match expression levels between control and bait protein setups while using the same bait protein. In addition, we implemented a versatile modular cloning system to build mammalian expression vectors for, but not limited to, proximity labeling assays.
Conserved patterns of sequence diversification provide insight into the evolution of two-component systems in Enterobacteriaceae
Authors: Barretto Luke A.F. , Van Patryc-Khang T. , Fowler Casey C.
Published: November 2023

Two-component regulatory systems (TCS) are a major mechanism used by bacteria to sense and respond to their environments. Many of the same TCS are used by biologically diverse organisms with different regulatory needs, suggesting that the functions of TCS must adapt over evolution. To explore this topic, we analyzed the amino acid sequence divergence patterns of a large set of broadly conserved TCS across different branches of Enterobacteriaceae, a family of Gram-negative bacteria that includes biomedically important genera such asSalmonella,Escherichia,Klebsiella, and others. Our analysis revealed trends in how TCS sequences change across different proteins or functional domains of the TCS, and across different lineages. Based on these trends, we identified individual TCS that exhibit atypical evolutionary patterns. We observed a strong correlation for the extent of sequence variation of a given TCS across different lineages, unveiling a hierarchy TCS sequence conservation with EnvZ/OmpR as the most conserved TCS. We provide evidence that, for the most divergent of the TCS analyzed, PmrA/PmrB, different alleles were horizontally acquired by different branches of this family, and that different PmrA/PmrB sequence variants have highly divergent signal sensing domains. Collectively, this study sheds light on how TCS evolve, and serves as a compendium for how the sequences of the TCS in this family have diverged over the course of evolution.
UsingVibrio natriegensfor high-yield production of challenging expression targets and for protein deuteration
Authors: Mojica Natalia , Kersten Flore , Montserrat-Canals Mateu , Huhn G. Robb , Tislevoll Abelone M. , Cordara Gabriele , Teter Ken , Krengel Ute
Published: November 2023

Production of soluble proteins is essential for structure/function studies, however, this usually requires milligram amounts of protein, which can be difficult to obtain with traditional expression systems. Recently, the Gram-negative bacteriumVibrio natriegensappeared as a novel and alternative host platform for production of proteins in high yields. Here, we used a commercial strain derived fromV. natriegens(VmaxTMX2) to produce soluble bacterial and fungal proteins in milligram scale, which we struggled to achieve inEscherichia coli. These proteins include the cholera toxin (CT) andN-acetyl glucosamine binding protein A (GbpA) fromVibrio cholerae, the heat-labile enterotoxin (LT) fromE. coliand the fungal nematotoxin CCTX2 fromCoprinopsis cinerea. CT, GbpA and LT are secreted by the Type II secretion system in their natural hosts. When these three proteins were produced in Vmax, they were also secreted, and could be recovered from the growth media. This simplified the downstream purification procedure and resulted in considerably higher protein yields compared to production inE. coli(6– to 26-fold increase). We also tested Vmax for protein deuteration using deuterated minimal media with deuterium oxide as solvent, and achieved a 3-fold increase in yield compared to the equivalent protocol inE. coli. This is good news since isotopic labeling is expensive and often ineffective, but represents a necessary prerequisite for some structural techniques. Thus, Vmax represents a promising host for production of challenging expression targets and for protein deuteration in amounts suitable for structural biology studies.
Quantification of influenza virus mini viral RNA dynamics using Cas13
Authors: Lamb Caitlin H. , Pitré Emmanuelle M. , Elshina Elizaveta , Rigby Charlotte V. , Bisht Karishma , Oade Michael S. , Jalal Hamid , Myhrvold Cameron , Velthuis Aartjan J.W. te
Published: November 2023

Influenza A virus RNA synthesis produces full-length and aberrant RNA molecules, which include defective viral genomes (DVG) and mini viral RNAs (mvRNA). Sequencing approaches have shown that aberrant RNA species may be present during infection, and that they can vary in size, segment origin, and sequence. Moreover, a subset of aberrant RNA molecules can bind and activate host pathogen receptor retinoic acid-inducible gene I (RIG-I), leading to innate immune signaling and the expression of type I and III interferons. Understanding the kinetics and distribution of these immunostimulatory aberrant RNA sequences is important for understanding their function in IAV infection. Here, we use an amplification-free LbuCas13a-based detection method to quantify mvRNA amplification dynamics and subcellular distributions. We show that our assay can quantify the copy numbers of specific mvRNA sequences in infected tissue culture cells, ferret upper and lower respiratory tract tissue infected with two different pandemic H1N1 IAV strains, or clinical nasopharyngeal swab extracts of hospitalized patients infected with seasonal H1N1 or H3N2 strains. In addition, we find dynamic differences between immunostimulatory and non-immunostimulatory mvRNAs, as well as among mvRNAs derived from different segments, during IAV infection. Overall, our results reveal a hitherto hidden diversity in the behavior of IAV mvRNAs and suggest that individual aberrant RNAs are not produced stochastically.
A general and efficient representation of ancestral recombination graphs
Authors: Wong Yan , Ignatieva Anastasia , Koskela Jere , Gorjanc Gregor , Wohns Anthony W. , Kelleher Jerome
Published: November 2023

As a result of recombination, adjacent nucleotides can have different paths of genetic inheritance and therefore the genealogical trees for a sample of DNA sequences vary along the genome. The structure capturing the details of these intricately interwoven paths of inheritance is referred to as an ancestral recombination graph (ARG). Classical formalisms have focused on mapping coalescence and recombination events to the nodes in an ARG. This approach is out of step with modern developments, which do not represent genetic inheritance in terms of these events or explicitly infer them. We present a simple formalism that defines an ARG in terms of specific genomes and their intervals of genetic inheritance, and show how it generalises these classical treatments and encompasses the outputs of recent methods. We discuss nuances arising from this more general structure, and argue that it forms an appropriate basis for a software standard in this rapidly growing field.
Viruses contribute to microbial diversification in the rumen ecosystem and are associated with certain animal production traits
Authors: Yan Ming , Yu Zhongtang
Published: November 2023

Background

The rumen microbiome enables ruminants to digest otherwise indigestible feedstuffs, thereby facilitating the production of high-quality protein, albeit with suboptimal efficiency and producing methane. Despite extensive research delineating associations between the rumen microbiome and ruminant production traits, the functional roles of the pervasive and diverse rumen virome remain to be determined.

Results

Leveraging a recent comprehensive rumen virome database, this study analyzes virus-microbe linkages, at both species and strain levels, across 551 rumen metagenomes, elucidating patterns of microbial and viral diversity, co-occurrence, and virus-microbe interactions. Additionally, this study assesses the potential role of rumen viruses in microbial diversification by analyzing prophages found in rumen metagenome-assembled genomes. Employing CRISPR-Cas spacer-based matching and virus-microbe co-occurrence network analysis, this study suggests that rumen viruses may regulate rumen microbes at both strain and community levels via both antagonistic and mutualistic interactions. Moreover, this study establishes that the rumen virome demonstrates responsiveness to dietary shifts and associations with key animal production traits, including feed efficiency, lactation performance, weight gain, and methane emissions.

Conclusions

These findings furnish a substantive framework for subsequent investigations to decode the functional roles of the rumen virome in shaping the rumen microbiome and influencing overall animal production performance.
Structural basis for plasmid restriction by SMC JET nuclease
Authors: Roisné-Hamelin Florian , Liu Hon Wing , Taschner Michael , Li Yan , Gruber Stephan
Published: November 2023

DNA loop-extruding SMC complexes play crucial roles in chromosome folding and DNA immunity. Prokaryotic SMC Wadjet (JET) complexes limit the spread of circular plasmids through DNA cleavage; yet the mechanisms for target recognition are unresolved. We show that artificial DNA circularization renders linear DNA susceptible to JET cleavage. Unlike free DNA, JET cleaves immobilized plasmid DNA at a specific site, the plasmid-anchoring point, showing that the anchor hinders DNA extrusion but not DNA cleavage implying that residual unextruded DNA is cleaved. Structures of plasmid-bound JetABC reveal two presumably stalled SMC motor units that are drastically rearranged from the resting state, together entrapping a U-shaped DNA segment, which is further converted to kinked V-shaped cleavage substrate by JetD nuclease binding. Our findings uncover mechanical bending of residual unextruded DNA as principle for non-self DNA recognition and molecular signature for plasmid cleavage. We elucidate key elements of SMC loop extrusion including motor directionality and the structure of a DNA-holding state.
Translation initiation factor eIF1.2 promotesToxoplasmastage conversion by regulating levels of key differentiation factors
Authors: Wang Fengrong , Holmes Michael J. , Hong Hea Jin , Thaprawat Pariyamon , Kannan Geetha , Huynh My-Hang , Schultz Tracey L. , Licon M. Haley , Lourido Sebastian , Dong Wenzhao , Querido Jailson Brito , Sullivan William J. , O’Leary Seán E. , Carruthers Vern B.
Published: November 2023

Abstracts

The parasiteToxoplasma gondiipersists in its hosts by converting from replicating tachyzoites to latent bradyzoites housed in tissue cysts. The molecular mechanisms that mediateT. gondiidifferentiation remain poorly understood. Through a mutagenesis screen, we identified translation initiation factor eIF1.2 as a critical factor forT. gondiidifferentiation. A F97L mutation in eIF1.2 or the genetic ablation ofeIF1.2(Δeif1.2) markedly impeded bradyzoite cyst formationin vitroandin vivo. We demonstrated, at single-molecule level, that the eIF1.2 F97L mutation impacts the scanning process of the ribosome preinitiation complex on a model mRNA. RNA sequencing and ribosome profiling experiments unveiled that Δeif1.2parasites are defective in upregulating bradyzoite induction factors BFD1 and BFD2 during stress-induced differentiation. Forced expression of BFD1 or BFD2 significantly restored differentiation in Δeif1.2parasites. Together, our findings suggest that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish chronic toxoplasmosis.
UPF1 ATPase autoinhibition and activation modulate RNA binding kinetics and NMD efficiency
Authors: Chapman Joseph H. , Youle Alice M. , Grimme Acadia L. , Neuman Keir C. , Hogg J. Robert
Published: November 2023

The RNA helicase UPF1 interacts with mRNAs, mRNA decay machinery, and the terminating ribosome to promote nonsense-mediated mRNA decay (NMD). Structural and biochemical data have revealed that UPF1 exists in an enzymatically autoinhibited “closed” state. Upon binding the NMD protein UPF2, UPF1 undergoes an extensive conformational change into a more enzymatically active “open” state, which exhibits enhanced ATPase and helicase activity. However, mechanically deficient UPF1 mutants can support efficient NMD, bringing into question the roles of UPF1 enzymatic autoinhibition and activation in NMD. Here, we identify two additional important features of the activated open state: slower nucleic acid binding kinetics and enhanced ATP-stimulated nucleic acid dissociation kinetics. Computational modeling based on empirical measurements of UPF1, UPF2, and RNA interaction kinetics predicts that the majority of UPF1-RNA binding and dissociation events in cells occur independently of UPF2 binding. We find that UPF1 mutants with either reduced or accelerated dissociation from RNA have NMD defects, whereas UPF1 mutants that are more dependent on UPF2 for catalytic activity remain active on well-established NMD targets. These findings support a model in which the kinetics of UPF1-mRNA interactions are important determinants of cellular NMD efficiency.
Effects of the Russian–Ukrainian war on the value of imports and the food trade balance in Saudi Arabia
Authors: Ghanem Adel Mohammed , Alrwis Khaled Nahar , Alaagib Sharafeldin Bakri , Aldawdahi Nageeb , Al-Nashwan Ibrahim , Ghanem Hossam
Published: November 2023

Purpose

This study aimed to measure the effects of the Russian–Ukrainian war on the value of imports and the food trade balance in Saudi Arabia.

Design/methodology/approach

Estimating the suggested model using econometric analysis for the years 1990–2021.

Findings

The amount of deficit increased in the food trade balance from 11.58 billion riyals in 1990 to 72.98 billion riyals in 2021. As for the increase in the index of food production by 10%, it leads to a decrease in the value of food imports for Saudi Arabia by 1.88%. Also, the value of the deficit in Saudi Arabia's food trade balance decreases by 5.24% as a result of a 10% rise in food exports to the country.

Originality/value

In light of the increase in the food price index to 145.8, the value of food imports and the deficit in the food trade balance exceed their counterparts in the current situation for the year 2021, at a rate of 37.1% and 44.5% for each respectively. In view of achieving huge financial surpluses as a result of the rise in oil prices, the Saudi Arabia is able to bear the high import bill and the amount of food trade balance deficit. Finally, the Russian–Ukrainian war leads to an increase in the cost of obtaining food commodities and their unavailability in the markets and thus affects the food security environment. Therefore, this study recommends the necessity of conducting more studies on the impact of the war on the food security of the Kingdom of Saudi Arabia.
Revisiting the puzzle of capital structure determinants: an empirical study based on UK firms
Authors: Rahman Md. Atiqur , Hossain Tanjila , Sen Kanon Kumar
Published: November 2023

Purpose

This study aims to measure impact of several firm-specific factors on alternative measures of leverage. The authors also aim to study impact of the subprime crisis on such associations.

Design/methodology/approach

The authors utilized an unbalanced panel data of 973 firm-year observations on 47 UK listed non-financial firms for the years 1990–2019. Book-based and market-based long-term and total leverage measures have been used as explained variables. The explanatory variables are profitability, size, two measures of growth, asset tangibility, non-debt tax shields, firm age and product uniqueness. Fixed effect and random effect models with clustered robust standard errors have been utilized for data analysis. To find the effect of subprime crisis, original dataset was split to create pre-crisis and post-crisis datasets.

Findings

The authors find that profitability significantly reduces leverage while firms having more tangible assets use significantly more debt in capital structure. Firm size and non-debt tax shield have statistically insignificant positive impact on leverage. Having more unique products reduces use of external debt, albeit insignificantly. Growth, when measured as market-to-book ratio, has inconsistent impact, whereas capital expenditure insignificantly reduces leverage. Age is found to be an insignificant predictor of leverage. After the subprime crisis, firms started relying more on internal fund instead of external debt, more particularly short-term debt. Having more collateral is gradually becoming more important for availing external debt.

Research limitations/implications

Data limitations restrict generalization of the findings.

Originality/value

This is one of the pioneering attempts to show how subprime crisis altered the theoretical domain of capital structure research in the UK.
The importance of warehouses in logistics outsourcing: benchmarking the perspectives of 3PL providers and shippers
Authors: Baglio Martina , Colicchia Claudia , Creazza Alessandro , Dallari Fabrizio
Published: November 2023

Purpose

An ever-increasing number of companies outsource logistics activities to third-party logistics (3PL) providers to beat the competition. From the buyer's (shippers') perspective, selecting the right 3PL provider is crucial, and from the 3PL provider's perspective, it is imperative to be attractive and to retain clients. To this aim, a potential lever can be physical assets, such as warehouses, which the literature has traditionally neglected. The objective is to benchmark the importance of warehouses for 3PL providers to attract/retain clients and for shippers to select the right 3PL provider.

Design/methodology/approach

The authors performed an empirical investigation through interviews on dyads (3PL providers/shippers) and utilized the Best-Worst Method (BWM) to rank the criteria used in the 3PL buying process and allow the warehouse's role to emerge.

Findings

Results show that the 3PL buying process consists of four phases and three evaluation steps. The selection criteria are classified into three groups: order qualifiers, order winners and retention factors. The warehouse has different levels of importance throughout the process. It appears that it can indirectly enhance the attractiveness and retention capability of 3PL providers through other selection criteria.

Originality/value

By combining the resource-based view and the customer value theory, this research extends the theory on logistics outsourcing by studying the phases of the 3PL buying process and scrutinizing the criteria used in different evaluation steps. The research adds a double perspective of analysis (3PL providers and shippers), which is missing in the literature, and focuses on the importance of warehouses.
Advertising fee as a new supply chain coordination approach between hotels and online travel agencies
Authors: Chen Chi-Jen
Published: November 2023

Purpose

Channel coordination has become an essential part of researching hotel supply chain management practices. This paper develops an improved channel coordination approach to coordinate the profit distribution between hotels and online travel agencies (OTAs) achieved through an introduction of advertising fees. This direction further improves the decentralization of cooperation and achieves Pareto improvement to achieve mutual profitability.

Design/methodology/approach

The methodology used in this study involves Stackelberg game theory employed for the decision-making and analysis of both the hotel and OTA. The OTA, acting as the leader, offers a hotel a contract specifying the commission rate that the hotel will pay to the respective OTA. The hotel, acting as a follower, sets a self-interested room rate as a given response. A deterministic, price-sensitive linear demand function is utilized to derive possible analytical solutions once centralized, noncooperative decentralization and cooperative decentralized channel occurs.

Findings

Results show that a new channel coordination approach is possible, namely via advertising fees. Prior to channel coordination, the OTA tends to set a higher commission rate, and the hotel sets a higher room rate in response under noncooperative decentralization. As such, this results in a lower channel-wide profit for all. One way to reduce channel-wide profit loss is to use a method of cooperative decentralization, which can, and will result in optimal profit as centralization takes place. However, the lack of incentives makes cooperative decentralization unfeasible. Further improvement is possible by using advertising fees based on a cooperative decentralization agreement, which can reach Pareto improvement.

Practical implications

This paper helps the OTA industry and hotel owners cooperate by way of smoother coordination. This study provides practitioners with two important practical implications. The first one is that the coordination between the hotel industry and OTA through cooperative decentralization allows for the achievement of higher profitability than that of noncooperative decentralization. The second one is that this paper solves the outstanding problem of insufficient incentives characteristic of cooperative decentralization by means of an advertising fee as a new supply chain coordination approach.

Originality/value

This paper offers both the problem and solution regarding the lack of incentives that hamper cooperative decentralization without the use of advertising fees. This paper is unique in that it derives analytical solutions regarding commissions levied in a typical hotel supply chain under noncooperative decentralization.
Identifying and ranking critical success factors for digital court
Authors: Farzaneh Kondori Narges , Rouhani Saeed
Published: November 2023

Purpose

In the digital age, courts need to be able to provide their services faster, more efficiently and less costly. Disruptive technologies like artificial intelligence can transform courtroom services in completely new ways. This study aims to investigate and rank the critical success factors of digital courts.

Design/methodology/approach

The literature of digital court and the factors influencing its success have been reviewed and a framework consisting of 26 factors in seven categories was designed. These factors have been ranked using the fuzzy TOPSIS method.

Findings

The results show that the factor of Accessibility to the system had the absolute best precedence, followed by the factors of User satisfaction and Information security. The factor of Political convergence of the government and the judicial system had the lowest priority.

Originality/value

This research guides current movements towards employing transformational technologies, tackling modern challenges and providing new opportunities to enhance the digital journey of the court ecosystem actors.
Leverage and regulatory capital ratios in Japan
Authors: Abbas Faisal , Ali Shoaib
Published: November 2023

Purpose

This study aims to understand how quickly Japanese banks readjust their capital ratios (leverage, regulatory capital, tier-I capital and common equity) following an economic shock.

Design/methodology/approach

This study uses a two-step system GMM framework to test the study's hypotheses using the annual data of Japanese commercial and cooperative banks ranging from 2005 to 2020.

Findings

The findings show that banks adjust their leverage ratio faster than regulatory capital, tier-I capital and common equity ratios. In addition to that, the results reveal that the speed of capital adjustment is higher for commercial banks than for cooperative banks, suggesting higher economic costs and implications for commercial banks. Furthermore, it is worth noting that well-capitalised (under-capitalised) banks tend to prioritise the adjustments to common equity (leverage) before considering the adjustments to leverage (common equity). According to the results, high-liquid (low-liquid) banks alter their regulatory capital and tier-I capital ratios (leverage) more quickly (more slowly) than low-liquid (high-liquid) banks.

Practical implications

The findings suggest that when formulating and implementing new banking regulations, particularly in assessing and adjusting specific capital requirements under Pillar II of Basel III, management (including bankers, regulators and policymakers) should consider the heterogeneity observed in the rate of capital adjustment across various bank characteristics. Additionally, bank managers should also consider the speed of adjustment when determining optimal half-life and target capital structures.

Originality/value

To the author's knowledge, this study represents a pioneering investigation into the rate of adjustment of capital ratios (leverage, regulatory, tier-I and common equity) within Japan's banking sector. The study employs a comprehensive dataset encompassing both commercial and cooperative banks to facilitate this analysis. A notable contribution to the existing body of literature, this study offers a detailed analysis and emphasises the varying degrees of adjustment in capital ratios. The study also highlights the heterogeneous nature of the adjustment rate in these ratios by categorising the data into well-capitalised, under-capitalised, highly liquid and low-liquid banks.
Development of the internal family systems model: Honoring contributions from family systems therapies
Authors: Brenner Elizabeth G. , Schwartz Richard C. , Becker Carol
Published: November 2023

We describe Richard Schwartz's development of the Internal Family Systems model (IFS) from his position as a Structural/Strategic family therapist. Four decades ago, Schwartz struggled to help clients who exhibited serious risk of harm to self and others. Through a process of inquiry, he began to work with the positive intentions behind his most challenging clients' harmful thoughts and behaviors. He applied foundational ideas from family systems thinking to patterns of internal experiences. As he experimented with ways of applying these ideas, he created an approach to healing. We summarize the IFS model delineating ways a range of family systems theory and practice inform its development and contribute to its best practice. Our purposes are to inform IFS practitioners who are not trained in foundational family systems models as well as to acknowledge the significant contributions family therapy theories made in the development and best practice of the IFS model.
The economic hierarchy, linkage, and directions between the three northeastern provinces of China and Russian Far East
Authors: Xu Shuang , Chu Nanchen , Wu Xiangli
Published: November 2023

The economic hierarchy index, economic linkage model, and economic membership model are used to study the economic hierarchy, linkage, and direction of Northeast China and Russian Far East from 2005 to 2020, using the three northeastern provinces of China and 11 Far East federal subjects of Russia as the research objects. The findings are as follows: (1) There is a major polarization effect between developed affluent economic regions and stagnant isolated backward regions in the economic rankings in the 11 Russian Far East federal subjects from 2005 to 2020. (2) The three northeastern provinces of China have more economic linkages with their near Russian neighbors— the east‐oriented Primorsky Territory, the north‐oriented Amur Region, and the north‐oriented Khabarovsk Territory, than with their farther neighbors— the Chukotka Autonomous Area, Magadan Region, and Kamchatka Territory. (3) From 2005 to 2020, the Primorsky Territory has been serving as the focal point of economic linkages between Russian Far East and Northeast China, showing the expanding outward pattern resembling the concentric circles.
Impact of post‐progression survival in second‐line treatment with molecular target agents for unresectable hepatocellular carcinoma
Authors: Tajiri Kazuto , Muraishi Nozomu , Murayama Aiko , Hayashi Yuka , Yasuda Ichiro
Published: November 2023

Aim

Sequential therapies are essential to extend overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). Several second‐line treatments with molecular target agents have shown survival benefits. However, the significance of post‐progression survival (PPS) in extending OS in patients with HCC given such treatments remains uncertain.

Methods

Through a systematic review of the literature in the PubMed database, this study investigated the correlation between PPS and OS and that between progression‐free survival (PFS) and OS in patients with HCC given second‐line treatments.

Results

In total, 3935 patients who had received second‐line treatment with regorafenib, ramucirumab, or cabozantinib, which are approved molecular target agents, were identified. In the patients treated with regorafenib, PPS showed a strong correlation with OS (R2 = 0.729, R = 0.854, p < 0.001) whereas PFS showed a weak correlation (R2 = 0.218, R = 0.467, p = 0.021). In the patients treated with ramucirumab, PPS showed a strong correlation with OS (R2 = 0.800, R = 0.894, p = 0.016) whereas PFS showed a negligible correlation (R2 = 0.020, R = 0.140, p = 0.791). In the patients treated with cabozantinib, PPS showed a strong correlation with OS (R2 = 0.856, R = 0.925, p = 0.003) as did PFS (R2 = 0.946, R = 0.973, p < 0.001).

Conclusions

PPS plays a more significant role than PFS in extending OS in patients given second‐line treatment for unresectable HCC. Sequential therapies after disease progression in second‐line treatment are essential to acquire good OS. Maintenance of hepatic reserve function and the patient's general condition is essential during systemic treatments for unresectable HCC.
Slurry infiltration and sintering cycle‐dependent mechanical properties of 3D oxide/oxide ceramic matrix composites
Authors: Sun Xun , Tian Zhenghao , Jiang Ru , Liu Haitao
Published: November 2023

In this study, oxide/oxide ceramic matrix composites reinforced with three‐dimensional fiber preform were fabricated by a slurry infiltration and sintering (SIS) process. The influence of the SIS cycle on microstructures and mechanical properties of the 3D oxide/oxide composite was investigated. Results showed that the porous matrix was densified due to the SIS effect. The elastic modulus of the weak matrix and interfacial shear strength increased with the increasing SIS cycle. This led to an obvious improvement in flexural strength and interlaminar shear strength of the composite. The fracture toughness and work of fracture of the composite slightly decreased. A good balance between fracture strength and damage tolerance was achieved on the sixth SIS fabricated oxide/oxide composite, which had a high flexural strength of 295.1 ± 14.9 MPa, a high interlaminar shear strength of 18.2 ± .5 MPa, and a high fracture 11.5 ± .8 MPa m1/2. The SIS process is a promising way to fabricate the 3D oxide/oxide composite.
Responses of the rat foetus to maternal injections of adrenaline and vasopressin
Authors: CHERNOFF N. , GRABOWSKI C. T.
Published: November 2023

Injection of 0·5–2·0 units of vasopressin or 25–100 μg of adrenaline into the peritoneal cavity of pregnant rats produced a transient slowing of the foetal heart. The bradycardia could be induced in foetuses after 15–21 days of gestation. Foetal heart rates dropped from normal values of 140–180 beats/min, often to less than 20 beats/minute. The period of bradycardia was dose dependent and ranged from 30 to 65 minutes.

Maternal injection of the hormones produced a fall in foetal blood pressure from an average of 54, often to less than 20 mm of water, in 17‐day foetuses. Direct injection of the hormones into the pericardial sac of the foetuses had the opposite effect and pressures rose an average of 15 mm of water 1 min after the injection.

During the period of bradycardia, the potassium concentrations in foetal serum rose from an average value of 8·9 mequiv/1. to an average of 17·3 mequiv/litre. Concentrations of serum sodium fell from 126·2 to 121·4 mequiv/l. during the bradycardia. No changes were detected in the concentrations of either calcium or chloride. Foetal Po2 levels fell from 25 to 15, Pco2 rose from 61 to 89 or more, and pH fell from 7·19 to 6·86 during the bradycardia.

Maternal death and uterine clamping caused foetal bradycardia and a rise in foetal serum potassium to an average of 20·2 mequiv/litre.

It is concluded that interruption of normal uterine blood flow by vasoconstruction (adrenaline or vasopressin) or direct blockage (uterine clamping) results in a transient hypoxia, bradycardia, and serum ion changes in foetuses.
Role of adrenergic neurone blockade in the hypotensive action of propranolol
Authors: ELIASH SARAH , WEINSTOCK MARTA
Published: November 2023

Propranolol, in doses of 25–100 μg/kg, blocks contractions of the nictitating membrane to nerve stimulation but not to injected noradrenaline.

This adrenergic neurone blocking action of propranolol is antagonized by amphetamine.

It is also reversed by raising the dose of propranolol to amounts exceeding 0·5 mg/kg.

Still larger amounts potentiate the responses of the nictitating membrane to both submaximal stimulation of the cervical sympathetic nerve and to injected noradrenaline.

The (+) isomer of propranolol produced adrenergic nerve blockade and some degree of hypotension without blocking cardiac β‐adrenoceptors.

The relevance of adrenergic neurone blockade to the hypotensive effect of propranolol is discussed.