bluuebunny/crossref_metadata_2025 huggingface dataset:
Host-pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk
Authors: Hulse Samuel V. , Antonovics Janis , Hood Michael E. , Bruns Emily L.
Published: August 2023

Genetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host’s vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general (resistance to all pathogens) and specific (resistance to endemic pathogens only). We find that introducing coevolution into our model greatly expands the regions where general resistance can evolve, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands which conditions maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third, linkage modifying locus into our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.
The rapid decline in interaural-time-difference sensitivity for pure tones can be explained by peripheral filtering
Authors: Goupell Matthew J. , Stecker G. Christopher , Williams Brittany T. , Bilokon Anhelina , Tollin Daniel J.
Published: August 2023

Purpose

The interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. Explaining how listeners’ ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a fully compelling physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not by a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency (apical) edge of the cochlear excitation pattern produced by a pure tone.

Methods

ITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900-1500 Hz) and level (10-50 dB sensation level).

Results

Performance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern.

Conclusion

Fine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by “off-frequency” activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by having neurons sensitive to fine-structure ITD up to only about 700 Hz. A more extreme model would have only a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs.
Open datasets and code for multi-scale relations on structure, function and neuro-genetics in the human brain
Authors: Jimenez-Marin Antonio , Diez Ibai , Erramuzpe Asier , Stramaglia Sebastiano , Bonifazi Paolo , Cortes Jesus M
Published: August 2023

The human brain is an extremely complex network of structural and functional connections that operate at multiple spatial and temporal scales. Investigating the relationship between these multi-scale connections is critical to advancing our comprehension of brain function and disorders. However, accurately predicting structural connectivity from its functional counterpart remains a challenging pursuit. One of the major impediments is the lack of public repositories that integrate structural and functional networks at diverse resolutions. Addressing this issue, we provide open datasets and code enabling the examination of the correspondence between structural and functional connectivities at different scales. We present a module-level strategy that overcomes region-level approaches in understanding the structure-function correspondence. Moreover, we also provide additional resources focused on neuro-genetic associations of module-level network metrics, which present promising opportunities to further advance research in the field of network neuroscience, particularly concerning brain disorders.
memerna: Sparse RNA Folding Including Coaxial Stacking
Authors: Courtney Eliot , Datta Amitava , Mathews David H. , Ward Max
Published: August 2023

Abstract

Determining RNA secondary structure is a core problem in computational biology. Fast algorithms for predicting secondary structure are fundamental to this task. We describe a modified formulation of the Zuker-Stiegler algorithm with coaxial stacking, a stabilizing interaction in which the ends of multi-loops are stacked. In particular, optimal coaxial stacking is computed as part of the dynamic programming state, rather than inline. We introduce a new notion of sparsity, which we callreplaceability. The modified formulation along with replaceability allows sparsification to be applied to coaxial stacking as well, which increases the speed of the algorithm. We implemented this algorithm in software we callmemerna, which we show to have the fastest exact RNA folding implementation out of several popular RNA folding packages supporting coaxial stacking. We also introduce a new notation for secondary structure which includes coaxial stacking, terminal mismatches, and dangles (CTDs) information.
Genetic crosses within and between species ofCryptosporidium
Authors: Shaw Sebastian , Cohn Ian S. , Baptista Rodrigo P. , Xia Guoqin , Melillo Bruno , Agyabeng-Dadzie Fiifi , Kissinger Jessica C. , Striepen Boris
Published: August 2023

Parasites and their hosts are engaged in rapid coevolution that balances competing mechanisms of virulence, resistance, and evasion. This often leads to host specificity, but genomic reassortment between different strains can enable parasites to jump host barriers and conquer new niches. In the apicomplexan parasiteCryptosporidiumgenetic exchange has been hypothesized to play a prominent role in adaptation to humans. The sexual lifecycle of the parasite provides a potential mechanism for such exchange; however, the boundaries ofCryptosporidiumsex are currently undefined. To explore this experimentally, we established a model for genetic crosses. Drug resistance was engineered using a mutated phenylalanyl tRNA synthetase gene and marking strains with this and the previously used Neo transgene enabled selection of recombinant progeny. This is highly efficient, and genomic recombination is evident and can be continuously monitored in real time by drug resistance, flow cytometry, and PCR mapping. Using this approach multiple loci can now be modified with ease. We demonstrate that essential genes can be ablated by crossing a Cre recombinase driver strain with floxed strains. We further find that genetic crosses are also feasible between species. CrossingC. parvum,a parasite of cattle and humans, andC. tyzzeria mouse parasite resulted in progeny with a recombinant genome derived from both species that continues to vigorously replicate sexually. These experiments have important fundamental and translational implications for the evolution ofCryptosporidiumand open the door to reverse- and forward-genetic analysis of parasite biology and host specificity.

Significance statement

The parasiteCryptosporidiumis a leading cause of diarrheal disease. While infection is common all around the world, young children experiencing malnutrition are impacted most profoundly, and the disease is an important contributor to early childhood mortality. This study experimentally demonstrates that different strains and even species ofCryptosporidiumcan recombine their genomes through sex. The progeny of such genetic crosses shows combined features of both parents, with resistance to multiple drugs being one example. Sex thus provides a critical mechanism for the parasite to rapidly adapt to changing environments and hosts.

Genetic crosses as an experimental tool may also be harnessed in the future to discover the genes underlying differences in virulence, drug sensitivity, and immunogenicity between parasite isolates.
The Fork Protection Complex protects long replicons from DNA damage at the cost of genome instability induced by DNA topological stress
Authors: Keszthelyi Andrea , Whale Alex , Houseley Jon , Baxter Jonathan
Published: August 2023

Tof1/Timeless protects eukaryotic cells from DNA replication stress as part of the Fork Protection Complex (FPC). Tof1 supports rapid DNA replication, fork pausing, and resolution of DNA topological stress. Here, we show that disruption of FPC function through loss of either Tof1 or Mrc1 results in DNA damage in long replicons. Despite increasing DNA damage in long replicons, loss of either Tof1 or Mrc1 concurrently reduces DNA damage in regions prone to damage caused by DNA topological stress, indicating that the rapid replication promoted by the FPC fosters completing DNA replication at the cost of increased vulnerability to DNA topological stress. Supporting this we find that atof1mutation that selectively inhibits DNA topological stress resolution increases DNA damage in contexts prone to DNA topological stress. Our data indicates that the FPC balances rapid replication with recruitment of topoisomerase I to resolve the topological stress generated by increased DNA unwinding.
Poly[[aqua[μ2-1,3-bis(pyridin-4-yl)urea-κ2
N
4:N
4′]bis(μ3-5-tert-butylisophthalato-κ3
O
1:O
1′:O
3)dizinc(II)] trihydrate], a double-strand coordination polymer
Authors: Jia Jason , LaDuca Robert L.
Published: August 2023

In the title compound, {[Zn2(C12H12O4)2(C11H10N4O)(H2O)]·3H2O}
n
, monoperiodic coordination polymer double strands are held into the triperiodic crystal structure by means of N—H...O hydrogen-bonding patterns between the amide groups of the 1,3-di(pyridin-4-yl)urea ligands and unligated O atoms belonging to 5-tert-butylisophthalate ligands. One of the Zn atoms displays a tetrahedral coordination environment, while the other Zn atom adopts a five-coordinate geometry intermediate between square pyramidal and trigonal bipyramidal. Additionally, O—H...O hydrogen-bonding patterns involving the water molecules of crystallization serve as a structure-stabilizing element by aggregating the double-strand motifs.
Poly[bis[μ2-1,3-bis(pyridin-4-yl)urea-κ2
N
4:N
4′]bis(μ2-5-methylisophthalato-κ2
O
1:O
3)dizinc(II)], a parallel interpenetrated slab-like coordination polymer with {3.648}{326.728} 4,4-connected binodal topology
Authors: Jia Jason , LaDuca Robert L.
Published: August 2023

In the title compound, [Zn2(C9H6O4)2(C11H10N4O)2]
n
, diperiodic coordination polymer slabs with {3.648}{326.728} 4,4-connected binodal topology are held into a parallel interpenetrated triperiodic crystal structure by means of N—H...O hydrogen-bonding patterns.
6,8-Dichloro-3-(pyridin-2-yl)-2-[1-(pyridin-2-yl)ethyl]-1,2-dihydroquinoxaline
Authors: Malan Frederick P. , Mansour Ahmed M. , Manicum Amanda-Lee E.
Published: August 2023

The crystal structure of the racemic title compound, C20H16Cl2N4 is described, where the formation of a di-substituted 6,8-dichloro quinoxaline, containing two stereogenic centres, is confirmed.
Crop diversity, sustainable food and nutritional security among smallholder farmers in Ghana
Authors: Fremmpong Raymond Boadi , Gross Elena , Owusu Victor
Published: August 2023

Purpose

The nexus between sustainable agri-food production and food security outcomes of farm households in sub-Saharan Africa is attracting policy attention. This study analyzes the effects of crop diversity on the incidence of food scarcity, dietary diversity, and the sale and consumption of own crops.

Design/methodology/approach

The study uses panel data collected in 2015 and 2018 on a randomly selected sample of 2553 households from 49 villages in northern Ghana. The study employed a fixed effects modeling approach in the empirical analysis.

Findings

The study finds that crop diversity is positively associated with better dietary diversity, reduced hunger, lower food expenditure, and higher consumption of own produce. The results show positive effects of crop diversity on the total harvested output and sale of agricultural production. Whilst sales improved sustainable food and nutrition security by providing purchasing power to buy nutritional inputs in the market, consumption of own produce rather improved food availability by reducing food scarcity and malnutrition.

Practical implications

Crop diversity is one of the pathways for promoting sustainable agri-food production systems to ensure the food and nutritional security of vulnerable populations and promote biodiversity to achieve environmental goals in sub-Saharan Africa. Crop diversity reduces food expenditure and raises rural incomes through improved outputs and sales, which empowers farm households to diversify their dietary options to be able to overcome incidences of hunger and malnutrition in periods of food scarcity.

Originality/value

The present study improves the understanding of sustainable agri-food production through crop diversity and its implications on food and nutrition security outcomes. The panel data and fixed effects modelling approach address the endogeneity problem between crop diversity and household tastes and preferences.
Pricing model, engagement model and firm performance: evidence from Indian data science industry
Authors: Jhamb Deepika , Kaur Sukhpreet , Pandey Saurabh , Mittal Amit
Published: August 2023

Purpose

Data science industry is a multidisciplinary field that deals with a large amount of data and derives useful information for taking routine and strategic business decisions. The purpose of this article is to examine the relationship between pricing models, engagement models, and firm performance (FP). This study also aims at uncovering the most effective pricing model and engagement model for improving FP.

Design/methodology/approach

Indian data scientists were the respondents of the study. A total of 213 responses were carefully chosen. The data were analyzed using structural equations on Statistical Package for Social Sciences-Analysis of Moment Structures (SPSS-AMOS) version 25 software.

Findings

The findings of the study suggested the positive and significant impact of pricing models and engagement models on FP. Value-based pricing strategies have the maximum impact on FP. On the other hand, managed services have a higher influence on FP.

Originality/value

By developing a multi-faceted framework, this study is a novel contribution to the field of business strategy, especially for the data science industry.
An operationalization of antifragility in inventory management
Authors: Munoz Albert , Zhou Quan Spring
Published: August 2023

Purpose

The paper explores and characterizes antifragility in simple inventory systems exposed to demand variability, providing the initial inroads to operationalizing antifragility in the context of inventory management. Antifragility refers to the feature of a system that can benefit from uncertainty, rather than suffer from it. The paper expands the concept of inventory beyond that of risk mitigation and towards one of enabling antifragility.

Design/methodology/approach

The study employs analytical and simulation modelling of an inventory system with two classes of demand. To separate the influence of factors, a simple inventory policy with a range of fixed order quantities is modelled, allowing for the identification of antifragile regions in an experimental space.

Findings

Outputs uncover a variety of performance outcomes, ranging from settings where additional inventory yields no benefit, to areas where additional inventory results in increasing normalized profit with increasing uncertainty, demonstrating antifragility. In between these regions, increases in normalized profit are bounded, and confined to specific regions.

Research limitations/implications

This research expands academic understanding of inventory as a vehicle to achieving antifragile outcomes. Although this paper does not solve for an optimal policy as typical inventory research does, it instead characterizes the antifragile outcomes within simple inventory systems. Further research should be carried out to investigate antifragility in settings of greater complexity and design ordering policies leveraging inventory towards a gain from uncertainty.

Practical implications

Typically, inventory is used to buffer against uncertainty, and, with a given amount of inventory, the performance is expected to degrade with increasing variability. In this paper, the authors demonstrate that certain levels of additional inventory can result in antifragility and increase profitability as uncertainty increases, extending beyond traditional conceptualizations of inventory and uncertainty.

Originality/value

Empirical research into designing antifragile outcomes is limited, with very few examples of increasing performance with increases in uncertainty. This article presents an initial empirical exploration of how additional inventory can result in antifragility.
CEO's self-oriented perfectionism, strategic decision comprehensiveness and firm resilience
Authors: Wang Qian , Wu Qin , Xie Luqun , Zhang Xiao
Published: August 2023

Purpose

Firm resilience is critical for firm survival and development. The purpose of this study is to investigate whether chief executive officer's (CEO) self-oriented perfectionism affects firm resilience by taking into consideration of the mediating role of strategic decision comprehensiveness and the moderating effect of competitive uncertainty.

Design/methodology/approach

This study adopts the survey method and uses two-wave survey data collected from 140 CEOs in different industries in China. The ordinary least square (OLS) regression model and path analysis are adopted to test the authors' theoretical hypotheses.

Findings

The results show that self-oriented perfectionism drives CEOs to pay attention to thoroughness and detail, which helps enhance strategic decision comprehensiveness and further facilitates firm resilience. Furthermore, the positive effect of CEO's self-oriented perfectionism on strategic decision comprehensiveness is weakened when competitive uncertainty is high.

Practical implications

To promote firm resilience, self-oriented perfectionism can be considered when hiring or promoting key decision-makers. When making strategic decisions, top managers need to search for adequate information, consider various factors and seek more alternative plans to improve strategic decision comprehensiveness to further facilitate firm resilience.

Originality/value

This study pioneers the influence of CEO's perfectionism on firm resilience and further tackles the underlying mechanism behind the influence, which contributes to extending the micro-foundation of firm resilience and enriching perfectionism literature in the strategic leadership field.
Differences in reproductive function between terminal and lateral flowers in the capitulum of Albizia julibrissin (Fabaceae) based on female fertility, ovule number, and pistil and polyad size
Authors: Mizusawa Leiko , Kato Saori , Kurosawa Takahide
Published: August 2023

The division of labor between florets responsible for reproduction and special functions occurs widely in condensed inflorescences. The capitulum of Albizia julibrissin consists of approximately 10–20 lateral flowers and usually one nectar‐secreting terminal flower; the two flower types are morphologically distinct, but the differences in reproductive function have not been revealed. To determine the differences in reproductive function between terminal and lateral flowers, we compared the ratio of terminal and lateral flowers at the flowering and young pod stages. Additionally, ovule number, stigma size, polyad size, and the ratio of flower abscission were compared between the two flower types. Significant differences were detected only in female fertility between the two flower types. At the flowering stage, 6.8% of flowers were terminal flowers, whereas at the young pod stage, all young fruits were obtained from lateral flowers. At the final stage of blooming, based on the generalized linear model analysis, the ratio of surviving terminal flowers was lower than that of the lateral flowers in a capitulum. These results suggest that the terminal flowers of A. julibrissin had female sterility or, at least, female fertility was lower than in lateral flowers. Therefore, it is necessary to reexamine some previous studies that assumed A. julibrissin to be andromonoecious with hermaphroditic terminal flowers and male lateral flowers. Further comparisons of the quality of ovules and polyads are necessary to clarify whether there is a division of labor between the terminal and lateral flowers in A. julibrissin.
Bone calcification rate as a factor of craniofacial transformations in salmonid fish: Insights from an experiment with hormonal treatment of calcium metabolism
Authors: Markevich Grigorii N. , Pavlova Nadezhda S. , Kapitanova Daria V. , Esin Evgeny V.
Published: August 2023

Adaptation to different environments can be achieved by physiological shifts throughout development. Hormonal regulators shape the physiological and morphological traits of the evolving animals making them fit for the particular ecological surroundings. We hypothesized that the artificially induced hypersynthesis of calcitonin and parathyroid hormone mutually influencing calcium metabolism could affect bone formation during early ontogeny in fish imitating the heterochrony in craniofacial ossification in natural adaptive morphs. Conducting an experiment, we found that the long‐standing treatment of salmonid juveniles with high doses of both hormones irreversibly shifts the corresponding hormone status for a period well beyond the time scale for total degradation of the injected hormone. The hormones program the ossification of the jaw suspension bones and neurocranial elements in a specific manner affecting the jaws position and pharingo‐branchial area stretching. These morphological shifts resemble the adaptive variants found in sympatric pelagic and demersal morphs of salmonids. We conclude that solitary deviations in the regulators of calcium metabolism could determine functional morphological traits via transformations in skeletal development.
Performance and field host range of the life stages of Cornops aquaticum, a biological control agent of water hyacinth
Authors: Franceschini M. Celeste , Hill Martin , Fuentes‐Rodríguez Daniela , Gervazoni Paula B. , Sabater Lara M. , Coetzee Julie A.
Published: August 2023

Host specificity determination of weed biocontrol agents has historically relied on evidence generated through quarantine trials in the region of introduction. These trials could give ‘false positive’ results due to a maximum type I error probability, and where possible, more research under field conditions should be conducted in the region of origin. The oligophagous, semiaquatic grasshopper, Cornops aquaticum Bruner (Orthoptera: Acrididae, Tetrataeniini), was released in South Africa for the biological control of Pontederia crassipes Pellegrini and Horn (Pontederiaceae). The aim of this study was to assess how the performance and field host range of C. aquaticum varies according to its stages of development, and how this contributes to the understanding of the relationship between the fundamental (laboratory‐based) and the ecological (field‐based) host range of this grasshopper, and its implications for water hyacinth biocontrol. We conducted post‐release laboratory no‐choice trials, confining early instars (instars 1 and 2), later instars (instars 3–6), and adult females and males in mesh cages, to determine insect performance on wetland plants growing in sympatry with P. crassipes. Also, gut analysis from field‐collected C. aquaticum was done to determine the ecological host range of this insect, identifying epidermal tissue of consumed plants. In no‐choice trials, survival rates of the later instars and adult C. aquaticum were similar on Pistia stratiotes L. (Araceae), Oxycaryum cubense (Poepp. & Kunth) Lye (Cyperaceae), and P. crassipes. However, under field conditions, P. crassipes and the congeneric Pontederia azurea Sw. were the only plant contents in the guts of early instars and the most abundant species in later instars and adults. The results support the hypothesis that C. aquaticum is an oligophagous insect on the genus Pontederia, and that different life stages should be considered when conducting host‐specificity trials in externally feeding mobile herbivore species. Diet composition of field‐collected insects thus could help detect false positives in laboratory trials, being an additional and realistic approach in understanding and predicting the selection processes of the insect in the new environment. Retrospective analysis of potential agents that were rejected due to lack of host‐specificity, using the methods from this study, could add a suite of additional agents to programs where invasive weeds remain unmanaged.
Cancer in Victorian prisoners: a description of cancer diagnoses, demographics, risk factors and barriers to optimal care
Authors: Newnham Genni M. , Munton Karen , Shaw Mark , McLachlan Sue A.
Published: August 2023

Background

The Victorian prison population is growing and ageing. Little has been documented about this group's cancer incidence, presentation or treatment.

Aims

To conduct a retrospective review of Victorian prisoners with cancer, including assessment of change over 15 years and adequacy of treatment delivery.

Methods

Detailed demographic, cancer and treatment data were collected for all prisoners with malignancy treated at St Vincent's Hospital Melbourne from 2002 to 2017. Detailed analysis of adherence to Optimal Care Guidelines was undertaken for a subset. Descriptive statistics were used.

Results

We identified 200 cancers in 191 prisoners. The population was predominantly male (185 of 191, 93%), with a median age of 54 years. Rates of cigarette smoking (118 of 191, 59%), mental illness (92 of 191, 46%) and intravenous drug use (59 of 191, 29.5%) were high. Exposure‐related cancers predominated (nonmelanoma skin cancer, lung cancer and hepatoma). Most were symptomatic (154 of 191, 77%) and almost one‐third had incurable disease at diagnosis (64 of 191, 32%). The number of prisoners with cancer increased over time (2002–2006 [T1], n = 31 vs 2012–2016 [T3], n = 101), as did the median age (45 years in T1 vs 55 years in T3) and rates of mental illness (10 of 31 [32%] in T1 vs 55 of 101 [54%] in T3). Delayed treatment initiation occurred in eight of 12 (66%) assessable patients, largely because of nonattendance.

Conclusions

Victorian prisoners with cancer are at risk of poor outcomes because of late presentation, delayed treatment initiation and medical comorbidities. Tailored interventions are urgently required to improve the provision of timely, comprehensive cancer care to this vulnerable and growing population.
A novel mutation in PCD‐associated gene DNAAF3 causes male infertility due to asthenozoospermia
Authors: Wan Feng , Yu Lan , Qu Xiaowei , Xia Yanqing , Feng Ke , Zhang Lei , Zhang Na , Zhao Guihua , Zhang Cuilian , Guo Haibin
Published: August 2023

Primary ciliary dyskinesia (PCD) is a rare autosomal‐recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole‐exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD‐associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.
Family practice with fathers, social care, and capabilities
Authors: Perez‐Vaisvidovsky Nadav
Published: August 2023

The aim of this article is to offer a novel theoretical perspective on family practitioners' engagement with fathers, through the lens of theories of social care and capabilities. The paper shows how research on low engagement of fathers in family‐ and child‐related social interventions has advanced along three main axes: (a) giving voice to fathers, (b) analyzing workers' perceptions, and (c) what works analysis of father‐oriented programs. I point to several problems in existing research: the absence of a unifying theoretical framework and the lack of sufficient attention to issues of relationality and agency. Theories of care and the capabilities approach are offered as a framework. Applying these theoretical frameworks to existing research on father engagement raises new questions and directions for further studies, mainly in two directions: first, relationality and the configurations of relations and power within families and within welfare systems, and second, the effect of agency on father engagement.
Thrombotic microangiopathy associated with anticancer and immune system targeting drugs: New insights from real‐world data using the WHO pharmacovigilance database
Authors: Largeau Bérenger , Thoreau Benjamin , Grangé Steven , Jonville‐Béra Annie‐Pierre , Halimi Jean‐Michel
Published: August 2023

Background

The worldwide development of immune system targeting/anticancer drugs has revolutionized immuno‐oncology, but their implication in thrombotic microangiopathy syndromes (TMA) is increasingly suspected. Using real‐world data, the aim of this study was to identify drugs associated with TMA reporting and to describe the evolution of TMA reporting over time with a focus on these drugs.

Methods

A global disproportionality study was performed using the individual case safety reports (ICSRs) extracted from the World Health Organization (WHO) pharmacovigilance database (VigiBase) from its inception (1968) to April 30, 2022.

Results

Of the 31,251,040 ICSRs, 6946 cases of suspected drug‐induced TMA were included from 55 countries. The outcome was fatal in 18.2% of cases. A total of 72 immune system targeting/anticancer drugs were associated with significant overreporting, including 17 drugs with a potential new safety concern for TMA. Although the rate of TMA reporting per million of ICSRs has remained fairly stable, an absolute increase in reported cases of suspected drug‐induced TMA has been observed over the last decade. The pattern of drugs reported in TMA has evolved with a substantial increase in the proportion of cases involving immune system‐targeting drugs/anticancer drugs from 47.3% (205/433) in the period 1992–2001 to 80.7% (3819/4730) in the period 2012–2021.

Conclusion

Several recently marketed immune system targeting/anticancer drugs have been identified as potential new drugs associated with TMA, which will require confirmatory studies. The number of drugs associated with TMA reporting markedly increased within the past 10 years, primarily due to innovative anticancer drugs.
Parasite manipulation of host phenotypes inferred from transcriptional analyses in a trematode‐amphipod system
Authors: Rand David M. , Nunez Joaquin C. B. , Williams Shawn , Rong Stephen , Burley John T. , Neil Kimberly B. , Spierer Adam N. , McKerrow Wilson , Johnson David S. , Raynes Yevgeniy , Fayton Thomas J. , Skvir Nicholas , Ferranti David A. , Zeff Maya Greenhill , Lyons Amanda , Okami Naima , Morgan David M. , Kinney Kealohanuiopuna , Brown Bianca R. P. , Giblin Anne E. , Cardon Zoe G.
Published: August 2023

Manipulation of host phenotypes by parasites is hypothesized to be an adaptive strategy enhancing parasite transmission across hosts and generations. Characterizing the molecular mechanisms of manipulation is important to advance our understanding of host–parasite coevolution. The trematode (Levinseniella byrdi) is known to alter the colour and behaviour of its amphipod host (Orchestia grillus) presumably increasing predation of amphipods which enhances trematode transmission through its life cycle. We sampled 24 infected and 24 uninfected amphipods from a salt marsh in Massachusetts to perform differential gene expression analysis. In addition, we constructed novel genomic tools forO. grillusincluding a de novo genome and transcriptome. We discovered that trematode infection results in upregulation of amphipod transcripts associated with pigmentation and detection of external stimuli, and downregulation of multiple amphipod transcripts implicated in invertebrate immune responses, such as vacuolar ATPase genes. We hypothesize that suppression of immune genes and the altered expression of genes associated with coloration and behaviour may allow the trematode to persist in the amphipod and engage in further biochemical manipulation that promotes transmission. The genomic tools and transcriptomic analyses reported provide new opportunities to discover how parasites alter diverse pathways underlying host phenotypic changes in natural populations.
Clinical characteristics and severity of diabetic ketoacidosis: A cross‐sectional study from a tertiary hospital in Ghana
Authors: Atiase Yacoba , Yorke Ernest , Akpalu Josephine , Reynolds Margaret , Annan Ofoliquaye Allotey , Aryee Robert , Hayfron‐Benjamin Charles , Yawson Alfred
Published: August 2023

Objectives

Diabetic ketoacidosis (DKA) is a common, severe and often fatal complication of diabetes. This study aimed to investigate the clinical characteristics and precipitants of DKA, as well as factors associated with DKA severity in Ghanaian patients.

Methods

Cross‐sectional study of the medical records of all 70 adult patients >18 years managed for DKA in the adult emergency room of Korle‐Bu Teaching Hospital in Ghana from March 2019 to July 2019. DKA diagnosis was based on hyperglycaemia >11.0 mmol/L, ketonuria (more than 2+) plus acidaemia of (pH < 7.3) or bicarbonate (HCO3−) <15.0 mmol/L. However, when serum bicarbonate and pH were not available, clinical signs of acidosis, for example, Kussmaul breathing aided in the diagnosis. DKA severity was assessed based on the Joint British Diabetes Societies (JBDS) guidelines of factors suggestive of severe DKA. Multivariable logistic regression was used to determine the factors associated with DKA severity. Odds ratio and 95% confidence interval for factors associated with DKA severity were determined.

Results

The mean (±standard deviation) age, diabetes duration and blood sugar at admission were 44.06 (±16.23) years, 7.19 (±6.04) years and 26.37 (±6.70) mmol/L, respectively. Females comprised 51.4% of the study population. The most common presenting symptoms were generalised weakness (30.0%) and fever (14.3%). The major precipitants were infection (70.0%) and non‐compliance (22.9%). Overall, 71.4% of participants had features suggestive of severe DKA. In a multivariable regression model, Type 2 diabetes was associated with over fourfold decreased odds of severe DKA (OR 0.23, 95% CI [0.07–0.76], p = 0.016). Patient education on prevention of DKA was documented for only 18.6% of patients before being discharged.

Conclusion

In this study, more than 70% of the study participants had features suggestive of severe DKA, with infection being the most common precipitant of DKA. 51.4% of patients had Type 2 diabetes which was associated with a statistically lower risk of severe DKA. Female sex tended to be positively associated with DKA severity. In a setting where the venous/arterial pH and bicarbonate levels may be inaccessible and/or unaffordable, using clinical features as found in the JBDS guidelines may help categorise patients and escalate care when needed. Indeed it may be useful to validate the use of the JBDS criteria for use in such settings.
Randomizing spectral cues used to resolve front-back reversals in sound-source localization
Authors: Yost William A.
Published: August 2023

Front-back reversals (FBRs) in sound-source localization tasks due to cone-of-confusion errors on the azimuth plane occur with some regularity, and their occurrence is listener-dependent. There are fewer FBRs for wideband, high-frequency sounds than for low-frequency sounds presumably because the sources of low-frequency sounds are localized on the basis of interaural differences (interaural time and level differences), which can lead to ambiguous responses. Spectral cues can aid in determining sound-source locations for wideband, high-frequency sounds, and such spectral cues do not lead to ambiguous responses. However, to what extent spectral features might aid sound-source localization is still not known. This paper explores conditions in which the spectral profile of two-octave wide noise bands, whose sources were localized on the azimuth plane, were randomly varied. The experiment demonstrated that such spectral profile randomization increased FBRs for high-frequency noise bands, presumably because whatever spectral features are used for sound-source localization were no longer as useful for resolving FBRs, and listeners relied on interaural differences for sound-source localization, which led to response ambiguities. Additionally, head rotation decreased FBRs in all cases, even when FBRs increased due to spectral profile randomization. In all cases, the occurrence of FBRs was listener-dependent.
Adseverin, an actin-binding protein, modulates hypertrophic chondrocyte differentiation and osteoarthritis progression
Authors: Chan Byron , Glogauer Michael , Wang Yongqiang , Wrana Jeffrey , Chan Kin , Beier Frank , Bali Supinder , Hinz Boris , Parreno Justin , Ashraf Sajjad , Kandel Rita
Published: August 2023

In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this correlates with actin cytoskeleton alterations suggesting that it regulates gene expression essential for proper phenotype. This study reports that OA is associated with the loss of adseverin, an actin capping and severing protein. Adseverin deletion (Adseverin
−/−
) in mice compromised articular chondrocyte function, by reducing F-actin and aggrecan expression and increasing apoptosis, Indian hedgehog, Runx2, MMP13, and collagen type X expression, and cell proliferation. This led to stiffer cartilage and decreased hyaline and increased calcified cartilage thickness. Together, these changes predisposed the articular cartilage to enhanced OA severity in Adseverin
−/−
mice who underwent surgical induction of OA. Adseverin
−/−
chondrocyte RNA sequencing and in vitro studies together suggests that adseverin modulates cell viability and prevents mineralization. Thus, adseverin maintains articular chondrocyte phenotype and cartilage tissue homeostasis by preventing progression to hypertrophic differentiation in vivo. Adseverin may be chondroprotective and a potential therapeutic target.
The causal mutation leading to sweetness in modern white lupin cultivars
Authors: Mancinotti Davide , Czepiel Katarzyna , Taylor Jemma L. , Golshadi Galehshahi Hajar , Møller Lillian A. , Jensen Mikkel K. , Motawia Mohammed Saddik , Hufnagel Bárbara , Soriano Alexandre , Yeheyis Likawent , Kjaerulff Louise , Péret Benjamin , Staerk Dan , Wendt Toni , Nelson Matthew N. , Kroc Magdalena , Geu-Flores Fernando
Published: August 2023

Lupins are high-protein crops that are rapidly gaining interest as hardy alternatives to soybean; however, they accumulate antinutritional alkaloids of the quinolizidine type (QAs). Lupin domestication was enabled by the discovery of genetic loci conferring low QA levels (sweetness), but the precise identity of the underlying genes remains uncertain. We show that
pauper
, the most common sweet locus in white lupin, encodes an acetyltransferase (AT) unexpectedly involved in the early QA pathway. In
pauper
plants, a single-nucleotide polymorphism (SNP) strongly impairs AT activity, causing pathway blockage. We corroborate our hypothesis by replicating the
pauper
chemotype in narrow-leafed lupin via mutagenesis. Our work adds a new dimension to QA biosynthesis and establishes the identity of a lupin sweet gene for the first time, thus facilitating lupin breeding and enabling domestication of other QA-containing legumes.
Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination
Authors: Welch Stephen R. , Spengler Jessica R. , Genzer Sarah C. , Coleman-McCray JoAnn D. , Harmon Jessica R. , Sorvillo Teresa E. , Scholte Florine E. M. , Rodriguez Sergio E. , O’Neal T. Justin , Ritter Jana M. , Ficarra Georgia , Davies Katherine A. , Kainulainen Markus H. , Karaaslan Elif , Bergeron Éric , Goldsmith Cynthia S. , Lo Michael K. , Nichol Stuart T. , Montgomery Joel M. , Spiropoulou Christina F.
Published: August 2023

Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease.
Predictors of positive patient-reported outcomes from ‘Early Intervention in Psychosis’: a national cross-sectional study
Authors: Williams Ryan , Morris Aimee , Gupta Veenu , Penington Ed , Cullen Alexis E , Quirk Alan , French Paul , Lennox Belinda , Bottle Alex , Crawford Mike J
Published: August 2023

Background

The components of care delivered by Early Intervention in Psychosis (EIP) services vary, but the impact on patient experience is unknown.

Objective

To investigate associations between components of care provided by EIP services in England and patient-reported outcomes.

Methods

2374 patients from EIP services in England were surveyed during the National Clinical Audit of Psychosis. Participants were asked about the care they received, and completed the ‘Patient Global Impressions’ Scale (rating whether their mental health had improved), and ‘Friends and Family Test’ (rating whether they would recommend their service). Information about service structure was obtained from service providers. We analysed associations between outcomes and components of care using multilevel regression.

Findings

The majority of participants were likely to recommend the treatment they had received (89.8%), and felt that their mental health had improved (89.0%). Participants from services where care coordinators had larger case loads were less likely to recommend their care. Participants were more likely to recommend their care if they had been offered cognitive behavioural therapy for psychosis, family therapy or targeted interventions for carers. Participants were more likely to report that their mental health had improved if they had been offered cognitive behavioural therapy for psychosis or targeted interventions for carers.

Conclusions

Specific components of EIP care were associated with improved patient reported outcomes. Psychosocial interventions and carer support may be particularly important in optimising outcomes for patients.

Clinical implications

These findings emphasise the need for small case load sizes and comprehensive packages of treatment in EIP services.