bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic analysis of selection bias in a natural experiment: Investigating in-utero famine effects on elevated body mass index in the Dutch Hunger Winter Families Study
Authors: Zhou Jiayi , Indik Claire E. , Kuipers Thomas B. , Li Chihua , Nivard Michel G. , Ryan Calen P. , Tucker-Drob Elliot M. , Taeubert M. Jazmin , Wang Shuang , Wang Tian , Conley Dalton , Heijmans Bastiaan T. , Lumey LH , Belsky Daniel W.
Published: October 2023

Natural-experiment designs that compare survivors of in-utero famine exposure to unaffected controls suggest that in-utero undernutrition predisposes to development of obesity. However, birth rates drop dramatically during famines. Selection bias could arise if factors that contribute to obesity also protect fertility and/or fetal survival under famine conditions. We investigated this hypothesis using genetic analysis of a famine-exposed birth cohort. We genotyped participants in the Dutch Hunger Winter Families Study (DHWFS, N=950; 45% male), of whom 51% were exposed to the 1944-1945 Dutch Famine during gestation and 49% were their unexposed same-sex siblings or “time controls” born before or after the famine in the same hospitals. We computed body-mass index (BMI) polygenic indices (PGIs) in DHWFS participants and compared BMI PGIs between famine-exposed and control groups. Participants with higher polygenic risk had higher BMIs (Pearson r=0.42, p<0.001). However, differences between BMI PGIs of famine-exposed participants and controls were small and not statistically different from zero across specifications (Cohen’s d=0.10, p>0.092). Our findings did not indicate selection bias, supporting the validity of the natural-experiment design within DHWFS. In summary, our study outlines a novel approach to explore the presence of selection bias in famine and other natural experiment studies.
A multi-hospital, clinician-initiated bacterial genomics program to investigate treatment failure in severeStaphylococcus aureusinfections
Authors: Giulieri Stefano G. , Leroi Marcel , Daniel Diane , Chean Roy , Bond Katherine , Walker Harry , Holmes Natasha E. , Mothobi Nomvuyo , Alexander Adrian , Jenney Adam , Beckett Carolyn , Mahony Andrew , Stevens Kerrie , Sherry Norelle L. , Howden Benjamin P.
Published: October 2023

Bacterial genomics is increasingly used for infectious diseases surveillance, outbreak control and prediction of antibiotic resistance. With expanding availability of rapid whole-genome sequencing, bacterial genomics data could become a valuable tool for clinicians managing bacterial infections, driving precision medicine strategies. Here, we present a novel clinician-driven bacterial genomics framework that applies within-patient evolutionary analysis to identify in real-time microbial genetic changes that have an impact on the outcome of severeStaphylococcus aureusinfections, a strategy that is increasingly used in cancer genomics. Our approach uses a combination of bacterial genomics and novel microbiological testing to identify and track bacterial adaptive mutations that underlie antibiotic treatment failure. We show real-life examples of the impact of our approach and propose a roadmap for the use of bacterial genomics to advance the management of severe bacterial infections.
The impact of spatial connectivity on NPIs effectiveness
Authors: Sabbatini Chiara E. , Pullano Giulia , Di Domenico Laura , Rubrichi Stefania , Bansal Shweta , Colizza Vittoria
Published: October 2023

Background

France implemented a combination of non-pharmaceutical interventions (NPIs) to manage the COVID-19 pandemic between September 2020 and June 2021. These included a lockdown in the fall 2020 – the second since the start of the pandemic – to counteract the second wave, followed by a long period of nighttime curfew, and by a third lockdown in the spring 2021 against the Alpha wave. Interventions have so far been evaluated in isolation, neglecting the spatial connectivity between regions through mobility that may impact NPI effectiveness.

Methods

Focusing on September 2020 – June 2021, we developed a regionally-based epidemic metapopulation model informed by observed mobility fluxes from daily mobile phone data and fitted the model to regional hospital admissions. The model integrated data on vaccination and variants spread. Scenarios were designed to assess the impact of the Alpha variant, characterized by increased transmissibility and risk of hospitalization, of the vaccination campaign and alternative policy decisions.

Results

The spatial model better captured the heterogeneity observed in the regional dynamics, compared to models neglecting inter-regional mobility. The third lockdown was similarly effective to the second lockdown after discounting for immunity, Alpha, and seasonality (51% vs 52% median regional reduction in the reproductive number R0, respectively). The 6pm nighttime curfew with bars and restaurants closed, implemented in January 2021, substantially reduced COVID-19 transmission. It initially led to 49% median regional reduction of R0, decreasing to 43% reduction by March 2021. In absence of vaccination, implemented interventions would have been insufficient against the Alpha wave. Counterfactual scenarios proposing a sequence of lockdowns in a stop-and-go fashion would have reduced hospitalizations and restriction days for low enough thresholds triggering and lifting restrictions.

Conclusions

Spatial connectivity induced by mobility impacted the effectiveness of interventions especially in regions with higher mobility rates. Early evening curfew with gastronomy sector closed allowed authorities to delay the third wave. Stop-and-go lockdowns could have substantially lowered both healthcare and societal burdens if implemented early enough, compared to the observed application of lockdown-curfew-lockdown, but likely at the expense of several labor sectors. These findings contribute to characterize the effectiveness of implemented strategies and improve pandemic preparedness.
The origin and maintenance of supergenes contributing to ecological adaptation in Atlantic herring
Authors: Jamsandekar Minal , Ferreira Mafalda S. , Pettersson Mats E. , Farell Edward , Davis Brian W. , Andersson Leif
Published: October 2023

Chromosomal inversions are associated with local adaptation in many species. However, questions regarding how they are formed, maintained and impact various other evolutionary processes remain elusive. Here, using a large genomic dataset of long-read and short-read sequencing, we ask these questions in one of the most abundant vertebrates on Earth, the Atlantic herring. This species has four megabase-sized inversions associated with ecological adaptation that correlate with water temperature. TheSandNinversion alleles at these four loci dominate in the southern and northern parts, respectively, of the species distribution in the North Atlantic Ocean. By determining breakpoint coordinates of the four inversions and the structural variations surrounding them, we hypothesize that these inversions are formed by ectopic recombination between duplicated sequences immediately outside of the inversions. We show that these are old inversions (>1 MY), albeit formed after the split between Atlantic herring and its sister species, the Pacific herring. They are yet to reach mutation-flux equilibrium, but the largeNeof herring combined with the common occurrence of opposite homozygotes across the species distribution has allowed effective purifying selection to prevent accumulation of genetic load and repeats within the inversions.
Feasibility of intranasal delivery of thin-film freeze-dried monoclonal antibodies
Authors: Yu Yu-Sheng , Xu Haiyue , AboulFotouh Khaled , Williams Gerallt , Suman Julie , Sahakijpijarn Sawittree , Cano Chris , Warnken Zachary N. , Wu Kevin C.-W. , Williams Robert O. , Cui Zhengrong
Published: October 2023

Monoclonal antibodies (mAbs) administered intranasally as dry powders can be potentially applied for the treatment or pre-exposure prevention of viral infections in the upper respiratory tract. However, a method to transform the mAbs from liquid to dry powders suitable for intranasal administration and a device that can spray the dry powders to the desired region of the nasal cavity are needed to fully realize the potentials of the mAbs. Herein, we report that thin-film freeze-drying can be applied to prepare aerosolizable mAb dry powders and that the dry powders can be sprayed into the posterior nasal cavity using Aptar Pharma’s Unidose (UDS) Powder Nasal Spray System. AUG-3387, a human-derived mAb that neutralizes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was used in the present study. First, we prepared AUG-3387 thin-film freeze-dried powders (i.e., TFF AUG-3387 powders) from liquid formulations containing different levels of mAbs. The TFF AUG-3387 powder with the highest solid content (i.e., TFF AUG-3387C powder) was then chosen for further characterization, including the evaluation of the plume geometry, spray pattern, and particle size distribution after the powder was sprayed using the UDS Powder device. Finally, the deposition patterns of the TFF AUG-3387C powder sprayed using the UDS Powder device were studied using 3D-printed nasal replica casts based on an adult model and a child model. It is concluded that it is feasible to intranasally deliver mAbs as dry powders by transforming the mAbs into dry powders using thin-film freeze-drying and then spray the powder using the UDS Powder device.
Optimization of a deep mutational scanning workflow to improve quantification of mutation effects on protein-protein interactions
Authors: Bendel Alexandra M. , Skendo Kristjana , Klein Dominique , Schimada Kenji , Kauneckaite-Griguole Kotryna , Diss Guillaume
Published: October 2023

Deep Mutational Scanning (DMS) assays are powerful tools to study sequence-function relationships by measuring the effects of thousands of sequence variants on protein function. During a DMS experiment, several technical artefacts might distort non-linearly the functional score obtained, potentially biasing the interpretation of the results. We therefore tested several technical parameters in the deepPCA workflow, a DMS assay for protein-protein interactions, in order to identify technical sources of non-linearities. We found that parameters common to many DMS assays such as amount of transformed DNA, timepoint of harvest and library composition can cause non-linearities in the data. Designing experiments in a way to minimize these non-linear effects will improve the quantification and interpretation of mutation effects.
A novel class of ultra-stable endospore appendages decorated with collagen-like tip fibrillae
Authors: Sleutel Mike , Zegeye Ephrem Debebe , Llarena Ann Katrin , Pradhan Brajabandhu , Fislage Marcus , O’Sullivan Kristin , Aspholm Marina , Remaut Han
Published: October 2023

Bacterial endospores are remarkable examples of biological resilience, representing a dormant and heavily fortified differentiation form capable of withstanding physical and chemical stressors detrimental to vegetative cells. In pathogenic firmicutes, spores also form an infectious particle and can take up a central role in the environmental persistence and dissemination of disease. A poorly understood aspect of spore-mediated infection is the fibrous structures or ‘endospore appendages’ (ENAs) that have been seen to decorate the spores of pathogenic Bacilli and Clostridia. New methodological approaches are opening an unprecedented window on these long enigmatic structures. Using cryoID, Alphafold modelling and genetic approaches we identify a novel class of ultra-robust ENAs formed byBacillus paranthracis. We demonstrate that L-ENA are encoded by a three-gene cluster (ena3) that contains all components for the self-assembly of ladder-like protein nanofibers of stacked heptameric rings, their anchoring to the exosporium, and their termination in a trimeric ‘ruffle’ made of a collagen-like BclA paralogue. Phylogenomic analyses shows theena3gene cluster as a mobile element with a polyphyletic distribution across pathogenic Bacilli.
The Ribosome Assembly Factor Reh1 is Released from the Polypeptide Exit Tunnel in the Pioneer Round of Translation
Authors: Musalgaonkar Sharmishtha , Yelland James , Chitale Ruta , Rao Shilpa , Ozadam Hakan , Cenik Can , Taylor David , Johnson Arlen
Published: October 2023

Assembly of functional ribosomal subunits and successfully delivering them to the translating pool is a prerequisite for protein synthesis and cell growth. InS. cerevisiae,the ribosome assembly factor Reh1 binds to pre-60S subunits at a late stage during their cytoplasmic maturation. Previous work shows that the C-terminus of Reh1 inserts into the polypeptide exit tunnel (PET) of the pre-60S subunit. Unlike canonical assembly factors, which associate exclusively with pre-60S subunits, we observed that Reh1 sediments with polysomes in addition to free 60S subunits. We therefore investigated the intriguing possibility that Reh1 remains associated with 60S subunits after the release of the anti-association factor Tif6 and after subunit joining. Here, we show that Reh1-bound nascent 60S subunits associate with 40S subunits to form actively translating ribosomes. Using selective ribosome profiling, we found that Reh1-bound ribosomes populate open reading frames near start codons. Reh1-bound ribosomes are also strongly enriched for initiator tRNA, indicating they are associated with early elongation events. Using single particle cryo-electron microscopy to image cycloheximide-arrested Reh1-bound 80S ribosomes, we found that Reh1-bound 80S contain A site peptidyl tRNA, P site tRNA and eIF5A indicating that Reh1 does not dissociate from 60S until early stages of translation elongation. We propose that Reh1 is displaced by the elongating peptide chain. These results identify Reh1 as the last assembly factor released from the nascent 60S subunit during its pioneer round of translation.
Physiological concentrations of calcium interact with alginate and extracellular DNA in the matrices ofPseudomonas aeruginosabiofilms to impede phagocytosis by neutrophils
Authors: Wells Marilyn J. , Currie Hailey , Gordon Vernita D.
Published: October 2023

Biofilms are communities of interacting microbes embedded in a matrix of polymer, protein, and other materials. Biofilms develop distinct mechanical characteristics that depend on their predominant matrix components. These matrix components may be produced by microbes themselves or, for infectionsin vivo, incorporated from the host environment.Pseudomonas aeruginosais a human pathogen that forms robust biofilms that extensively tolerate antibiotics and effectively evade clearance by the immune system. Two of the important bacterial-produced polymers in the matrices ofP. aeruginosabiofilms are alginate and extracellular DNA (eDNA), both of which are anionic and therefore have the potential to interact electrostatically with cations. Many physiological sites of infection contain significant concentrations of the calcium ion (Ca2+). In this study we investigate the structural and mechanical impacts of Ca2+supplementation in alginate-dominated biofilms grownin vitroand we evaluate the impact of targeted enzyme treatments on clearance by immune cells. We use multiple particle tracking microrheology to evaluate the changes in biofilm viscoelasticity caused by treatment with alginate lyase and/or DNAse I. For biofilms grown without Ca2+, we correlate a decrease in relative elasticity with increased phagocytic success. However, we find that growth with Ca2+supplementation disrupts this correlation except in the case where both enzymes are applied. This suggests that the calcium cation may be impacting the microstructure of the biofilm in non-trivial ways. Indeed, confocal laser scanning fluorescence microscopy and scanning electron microscopy reveal unique Ca2+-dependent eDNA and alginate microstructures. Our results suggest that the presence of Ca2+drives the formation of structurally and compositionally discrete microdomains within the biofilm through electrostatic interactions with the anionic matrix components eDNA and alginate. Further, we observe that these structures serve a protective function as the dissolution of both components is required to render biofilm bacteria vulnerable to phagocytosis by neutrophils.

Abstract Figure
Heterotypic responses against nsp12/nsp13 from prior SARS-CoV-2 infection associates with lower subsequent endemic coronavirus incidence
Authors: Bean David J. , Monroe Janet , Liang Yan Mei , Borberg Ella , Senussi Yasmeen , Swank Zoe , Chalise Sujata , Walt David , Weinberg Janice , Sagar Manish
Published: October 2023

Immune responses from prior SARS-CoV-2 infection and COVID-19 vaccination do not prevent re-infections and may not protect against future novel coronaviruses (CoVs). We examined the incidence of and immune differences against human endemic CoVs (eCoV) as a proxy for response against future emerging CoVs. Assessment was among those with known SARS-CoV-2 infection, COVID-19 vaccination but no documented SARS-CoV-2 infection, or neither exposure. Retrospective cohort analyses suggest that prior SARS-CoV-2 infection, but not COVID-19 vaccination alone, protects against subsequent symptomatic eCoV infection. CD8+T cell responses to the non-structural eCoV proteins, nsp12 and nsp13, were significantly higher in individuals with previous SARS-CoV-2 infection as compared to the other groups. The three groups had similar cellular responses against the eCoV spike and nucleocapsid, and those with prior spike exposure had lower eCoV-directed neutralizing antibodies. Incorporation of non-structural viral antigens in a future pan-CoV vaccine may improve protection against future heterologous CoV infections.
Interfacial morphodynamics of proliferating microbial communities
Authors: Martínez-Calvo Alejandro , Trenado-Yuste Carolina , Lee Hyunseok , Gore Jeff , Wingreen Ned S. , Datta Sujit S.
Published: October 2023

In microbial communities, various cell types often coexist by occupying distinct spatial domains. What determines the shape of the interface between such domains—which in turn influences the interactions between cells and overall community function? Here, we address this question by developing a continuum model of a 2D spatially-structured microbial community with two distinct cell types. We find that, depending on the balance of the different cell proliferation rates and substrate friction coefficients, the interface between domains is either stable and smooth, or unstable and develops finger-like protrusions. We establish quantitative principles describing when these different interfacial behaviors arise, and find good agreement both with the results of previous experimental reports as well as new experiments performed here. Our work thus helps to provide a biophysical basis for understanding the interfacial morphodynamics of proliferating microbial communities, as well as a broader range of proliferating active systems.
Proton tautomerism and stereoisomerism in 5-[(dimethylamino)methylidene]-4-[3/4-(trifluoromethylphenyl)amino]-1,3-thiazol-2(5H)-ones: synthesis, crystal structure and spectroscopic studies
Authors: Pyrih Andrii , Łapiński Andrzej , Zięba Sylwia , Mizera Adam , Lesyk Roman , Gzella Andrzej K. , Jaskolski Mariusz
Published: October 2023

5-[(Dimethylamino)methylidene]-4-{[3-(trifluoromethyl)phenyl]amino}-1,3-thiazol-2(5H)-one and the [4-(trifluoromethyl)phenyl]amino derivative, both C13H12F3N3OS, with the trifluoromethyl group substituted at the arene ring at the meta and para positions, were synthesized to study the structural changes associated with proton tautomerism of the amidine system. The studied compounds were found to be in the amine tautomeric form in both the solid and the liquid (dimethyl sulfoxide solutions) phase. In both isomers, the [(trifluoromethyl)phenyl]amino residue assumes a synperiplanar conformation with respect to the thiazolone system, while the 5-[(dimethylamino)methylidene] residue adopts the Z configuration. Density functional theory (DFT) calculations correctly predicted that the synperiplanar arrangement is favoured in both isomers. In the crystal, the whole independent molecule of the para compound is disordered over two alternative positions, with occupancy factors of 0.926 (3) and 0.074 (3).
Risk and return in the biotech industry
Authors: Bruneo Hassan , Giacomini Emanuela , Iannotta Giuliano , Murthy Anant , Patris Julien
Published: October 2023

Purpose

Biotech companies stand as key actors in pharmaceutical innovation. The high risk and long timelines inherent with their R&D investments might hinder their access to funding, potentially stifling innovation. This study aims to explore into the appeal of biotech companies to capital market investors, whose financial backing could bolster the growth of the biotechnology sector.

Design/methodology/approach

This paper uses a dataset of 774 US publicly listed biotech firms to investigate their risk and return characteristics by comparing them to pharmaceutical firms and a sample of matched non-biotech R&D-intensive firms over the sample period 1980–2021. Tests show that the conclusions remain consistent across diverse methodological approaches.

Findings

The paper shows that biotech companies are riskier than the average firm in the market index but outperform on a risk-adjusted basis both the market and a matched group of R&D-intensive firms. This is particularly true for large capitalization biotech, which is also shown to provide a diversification benefit by reducing the downside risk in past crisis periods.

Originality/value

This paper provides insight relevant to the current debate about the overall performance of the biotech industry in terms of policy changes and their impact on small, early-stage biotech firms. While small and early-stage biotech firms are playing an increasing role in scientific innovation, this study confirms their greater vulnerability to financial risks and the importance of access to capital markets in enabling those companies to survive and evolve into larger biotech.
Precipitation predictability drives evolution of drought strategies in the common poppy, Papaver rhoeas
Authors: Springer Katja , Coquery Thibault , Holland Vera , Fitze Patrick S. , Scheepens J. F. , March‐Salas Martí
Published: October 2023

Current climate change leads to an increase in the frequency and intensity of droughts and to a decreased precipitation predictability. The few studies investigating plant evolutionary responses to contrasting predictability regimes showed that intrinsic precipitation predictability shapes plant phenotypic variation, drives evolution of phenotypic plasticity and can vary in strength and direction of selection. This suggests that the selection pressure induced by decreased precipitation predictability may lead to plants coping better with severe drought events.

To investigate whether past precipitation predictability influences plant responses to different drought conditions, we performed a common‐garden experiment applying control, short‐term and long‐term drought treatments on seedlings of Papaver rhoeas (Papaveraceae) whose progenitors experienced less versus more precipitation predictability treatments for three consecutive generations. In addition, to assess whether competition modulates plant responses, half of the plants were grown together with the widespread herbaceous plant Galium album (Rubiaceae).

In the presence of long drought episodes, plants whose progenitors experienced less predictable precipitation survived longer than those whose progenitors experienced more predictable precipitation. Furthermore, plants whose progenitors experienced less predictable precipitation had lower biomass, which is likely to reduce water loss via transpiration, and, across all drought treatments, they showed lower root investment. However, no trait differences were detected under competition, indicating that interspecific competition may limit the expression of evolutionary responses to changes induced by precipitation predictability.

Altogether our results indicate that lower precipitation predictability mainly promotes the evolution of drought‐escape and drought‐avoidance strategies. Overall, our experiment highlights that precipitation predictability is an important evolutionary driver of plant functional responses, potentially shifting evolutionary trajectories of plants under increasing intensity of drought events.

Read the free Plain Language Summary for this article on the Journal blog.
THE(CULTURAL)WAR OF THE WORLDS: Framing Urban Redevelopment as ‘Terraforming’
Authors: Garfield‐Abrams Jennifer L. , Corcoran Thomas , Wynn Jonathan R.
Published: October 2023

External forces always shape the social construction of ‘the local’. In this article we offer a framework for understanding how external players and strategies reconfigure the social and symbolic character of local culture for new investments and new populations. We aim not only to propose a theory of urban cultural processing by nonlocals—what we call ‘urban cultural terraforming’—but to identify pressure points for local groups to make claims on or even commandeer reshaping local culture. Using two cases, casino development in a deindustrialized city and state‐designated cultural districts, we illustrate how ‘cultural terraformers’ use identifiable strategies (e.g. colonization of local sentiment, re‐creating partnerships and respatializing) to change local culture, and how groups struggle to avoid marginalization.
Microscopic anatomy of the subcommissural organ in the brain of the adult greater cane rat (Rodentia: Thryonomyidae)
Authors: Gilbert T. T. , Olopade F. E. , Ladagu A. D. , Lanipekun D. O. , Fatola O. I. , Folarin O. R. , Olopade J. O.
Published: October 2023

The subcommissural organ (SCO) is a well‐developed gland present in the brain of vertebrates. The SCO secretes glycoproteins into the circulating cerebrospinal fluid and these assemble to form Reissner's fibre. It also plays an important function in neurogenesis and axonal guidance during embryogenesis. This study delves into the microscopic anatomy of the SCO in the adult greater cane rat (GCR), shedding light on its histoarchitectural characteristics. By utilizing histological techniques and microscopic analysis, we investigated the SCO's location and cellular composition within the brain of adult GCR. Our findings showed that the SCO in this species is located ventrally to the posterior commissure (PC) and dorsally to the third ventricle. The SCO consists of specialized ependymal or nuclear cell layer and apical processes lining the third ventricle. Moreover, the SCO's proximity to the PC and the third ventricle highlights its strategic position within the brain's ventricular system. With immunohistochemical analyses, the SCO cells expressed glial fibrillary protein when immunolabelled with Glial fibrillary acid protein (GFAP) antibody, a marker for astrocytes/astrocytic‐like cells. Few microglia‐like cells were immuno‐positive for Ionized calcium‐binding adapter molecule 1 (Iba1) antibody, that are existing within the SCO. However, the SCO in the GCR showed a negative immunostaining to NeuN antibody. This study contributes to our understanding of the microscopic anatomy of the SCO in a lesser‐studied mammalian species. Further research into the SCO's functional significance especially during development in the GCR, may hold promise for more insights into neurological health and pathology.
Surgical accuracy of CAD/CAM splints using virtual surgical planning in orthognathic surgery: policy implications for healthcare in Australia
Authors: Delpachitra Seth Navinda , Bordbar Patrishia
Published: October 2023

Background

This study examines post‐surgical outcomes of maxillary position using virtual surgical planning (VSP) with computer designed and manufactured surgical splints, without the use of costly patient specific implants (PSI), in the treatment of routine nonsyndromic orthognathic patients. The cost of these personalized medical devices and their impact in the setting of cranio‐maxillofacial surgery is currently under review by The Department of Health and Aged Care in Australia.

Methods

This is a single‐centre retrospective analysis of 49 patients who underwent bimaxillary orthognathic surgery by a single surgeon at Epworth Richmond Hospital (Victoria, Australia) over a period spanning 2016 to 2020. Patients were included in the study provided their surgery was facilitated using VSP with manufacture of computer designed occlusal splints.

Results

Use of computer designed and manufactured splints were highly reliable in reproducing the virtual surgical plan, when using palatal plane, upper incisor angulation, and anterior upper facial height.

Conclusion

Use of computer designed and manufactured splints provide a method of leveraging the accuracy of VSP methods, without the additional costs associated with PSI. These findings may assist in appropriate resource allocation and case stratification in patients undergoing orthognathic surgery.
Language outcomes at 18–24 months of preterm infants from US Spanish‐ and English‐speaking homes
Authors: Feragne Megan , Tucker Richard , Mayne Julia , Vohr Betty
Published: October 2023

Aim

To evaluate the association of Spanish compared to English primary household language on preterm (PT) infants' language outcomes in the United States and to examine associations with socio‐economic factors.

Methods

This was a retrospective cohort of PT infants born <32 weeks gestation from Spanish‐speaking (n = 95) and English‐speaking homes (n = 1030) born 2005–2019. Language (primary outcome) and cognitive and motor skills (secondary outcomes) were measured using the BSID‐III at 18–24 months corrected age. Group differences were evaluated using bivariate comparisons and logistic regression analyses.

Results

Mothers reporting Spanish‐speaking homes had higher rates of public insurance and lower educational achievement. Group newborn characteristics were similar. Preterm infants from Spanish‐speaking homes had significantly lower BSID‐III language composite, cognitive composite, receptive and expressive scores compared to infants from English‐speaking homes. Logistic regression modelling identified independent negative effects of Spanish‐speaking household OR 3.26 (CI 1.89–5.62) and public insurance OR 2.31 (CI 1.71–3.12) with a protective benefit derived from breast milk OR 0.68 (CI 0.50–0.92) when adjusting for medical morbidities, socio‐economic factors and gestational age.

Conclusion

Public health policies and interventions in the United States should target language and cognitive outcomes of PT infants from Spanish‐speaking homes.
First dye identification analyses conducted on textiles from Old Dongola (Sudan, 17th–18th centuries CE)
Authors: Wozniak Magdalena M. , Witkowski Bartłomiej , Gierczak Tomasz , Biesaga Magdalena
Published: October 2023

The Middle Nile Valley offers exceptional environmental conditions that allow the preservation of organic materials, including textiles. This paper presents the results of the analysis of 17 samples collected from wool, cotton, and silk textiles excavated in the ancient capital of Old Dongola from layers dated to the 17th and 18th centuries CE. Chemical analysis using high performance liquid chromatography coupled with mass spectrometry (HPLC‐MS/MS) have identified both plant and animal dyes. Locally produced textiles, mostly from wool and decorated with blue, green, orange, and yellow hues, were dyed with woad (Isatis tinctoria), flavonoid plants, and madder‐type roots, which were already known and used by medieval dyers in that area. For the first time, kermes (Kermes vermilio) and lac‐dye (Kerria species) have been also identified as a dye source in samples from this group. Imported fabrics, of cotton and silk, were dyed blue with woad (I. tinctoria) but also with indigo (Indigofera tinctoria); dyer's broom (Genista tinctoria) and kermes (K. vermilio) were other dyes identified in this second group. The results of this study provide the first dye identification for textiles produced in the 17th–18th c. Sudan and contribute new data to the research on textile production and trade in post‐medieval Sudan.
Posaconazole‐ibrutinib interaction cannot be avoided by staggered dosing: How to optimize ibrutinib dose during posaconazole treatment
Authors: Olkkola Aleksi M. , Tapaninen Tuija , Tornio Aleksi , Hauta‐aho Milka , Lapatto‐Reiniluoto Outi , Neuvonen Mikko , Kiiski Johanna I. , Neuvonen Pertti J. , Niemi Mikko , Backman Janne T.
Published: October 2023

Aims

Ibrutinib is used in the treatment of certain B‐cell malignancies. Due to its CYP3A4‐mediated metabolism and highly variable pharmacokinetics, it is prone to potentially harmful drug‐drug interactions.

Methods

In a randomized, placebo‐controlled, three‐phase crossover study, we examined the effect of the CYP3A4‐inhibiting antifungal posaconazole on ibrutinib pharmacokinetics. Eleven healthy participants ingested repeated doses of 300 mg of posaconazole either in the morning or in the evening, or placebo. A single dose of ibrutinib (30, 70 or 140 mg, respectively) was administered at 9 AM, 1 or 12 h after the preceding posaconazole/placebo dose.

Results

On average, morning posaconazole increased the dose‐adjusted geometric mean area under the plasma concentration‐time curve from zero to infinity (AUC0‐∞) and peak plasma concentration (Cmax) of ibrutinib 9.5‐fold (90% confidence interval [CI] 6.3‐14.3, P < 0.001) and 8.5‐fold (90% CI 5.7‐12.8, P < 0.001), respectively, while evening posaconazole increased those 10.3‐fold (90% CI 6.7‐16.0, P < 0.001) and 8.2‐fold (90% CI 5.2‐13.2, P < 0.001), respectively. Posaconazole had no significant effect on the half‐life of ibrutinib, but substantially reduced the metabolite PCI‐45227 to ibrutinib AUC0‐∞ ratio. There were no significant differences in ibrutinib pharmacokinetics between morning and evening posaconazole phases.

Conclusions

Posaconazole increases ibrutinib exposure substantially, by about 10‐fold. This interaction cannot be avoided by dosing the drugs 12 h apart. In general, a 70‐mg daily dose of ibrutinib should not be exceeded during posaconazole treatment to avoid potentially toxic systemic ibrutinib concentrations.
“Time to be free”: Playful agency in LOVE's in‐school programme for at‐risk youth
Authors: Hausfather Nadia , Montreuil Marjorie , Ménard Jean‐Frédéric , Carnevale Franco A.
Published: October 2023

Research increasingly suggests that positive youth development programmes play an important part in preventing youth violence and promoting positive developmental trajectories. We conducted a focussed ethnography of LOVE, a social development programme aimed at supporting youth who have been exposed to violence. Building on a previous study's exploration of this programme's afterschool setting, we examined the programme's social functioning in school settings. Findings underline the role of playfulness—alongside an egalitarian/friendly approach, gentle authority/structure, strengths‐based support and a safe space to express vulnerability—to foster in youth the ability to feel free, confident/empowered, connected/empathic and positive feelings about school and life.
Repeated detection of non‐alcoholic fatty liver disease increases the incidence risk of type 2 diabetes in young adults
Authors: Kim Jin Hwa , Lyu Young Sang , Kim Mee Kyoung , Kim Sang Yong , Baek Ki‐Hyun , Song Ki‐Ho , Han Kyungdo , Kwon Hyuk‐Sang
Published: October 2023

Aim

This study aimed to investigate the effects of repeated detection of non‐alcoholic fatty liver disease (NAFLD) on the incidence risk of type 2 diabetes in young adults.

Materials and Methods

In this nationwide population‐based observational study using data from the Korean National Health Insurance Service, approximately 1 125 015 young adults aged 20‐39 years who underwent health screening four times between 2009 and 2013 were included. NAFLD was defined as a fatty liver index (FLI) of ≥60. Repeated detection of NAFLD scores was defined as the number of times the participants met the criteria for NAFLD (0‐4). To account for the degree of repeated detection of NAFLD, weighted repeated NAFLD scores were scaled as a sum by assigning points (0 points for FLI <30, 1 point for 30 ≤ FLI < 60, and 2 points for FLI ≥60) ranging from 0 to 8 points.

Results

The multivariable‐adjusted hazard ratios of type 2 diabetes associated with repeated detection of NAFLD scores of 1, 2, 3 and 4 were 2.74 (95% confidence interval 2.57‐2.921), 3.45 (3.221‐3.694), 4.588 (4.303‐4.892) and 6.126 (5.77‐6.504), respectively. The incidence risk of type 2 diabetes increased significantly with repeated detection of the NAFLD score. In the analysis of the weighted repeated NAFLD score, the hazard ratios for the incidence of type 2 diabetes showed a significant continuous positive linear association with increasing scores.

Conclusions

Repeated detection of NAFLD influenced the incidence risk of type 2 diabetes in young adults, and a higher degree of repeated detection of NAFLD was independently associated with the risk of type 2 diabetes in young adults.
Associations of cataract, cataract surgery with dementia risk: A systematic review and meta‐analysis of 448,140 participants
Authors: Liu Xin , Guan Zeyu , Liang Shucheng , Feng Shenghui , Zhou Yue
Published: October 2023

Background

Cataract is the leading cause of blindness around the world. Previous investigations have assessed the relationship between cataract, cataract surgery and dementia risk, but their results remain controversial. Herein, we conducted a meta‐analysis to evaluate the associations between cataract, cataract surgery and the risk of dementia.

Methods

We systemically screened the literature from three electronic databases PubMed, EMBASE and CENTRAL until April 2023. The data were collected by two independent researchers. The hazard ratios (HRs) or odds ratios (ORs) from eligible studies with 95% confidence intervals (CIs) were adjusted into the risk ratios (RRs), which were pooled using the random‐effects model.

Results

A total of nine studies with 448,140 participants reported the associations between cataract or cataract surgery and the risk of dementia were included in this meta‐analysis. The outcomes of our pooled analysis indicated that cataract was associated with an increased risk of all‐cause dementia (RR = 1.24, 95% CI, 1.14–1.35, p < .00001), Alzheimer's disease (RR = 1.22, 95% CI, 1.10–1.35, p = .0002) and vascular dementia (RR = 1.29, 95% CI, 1.01–1.66, p = .04). Cataract surgery is associated with a reduction of the dementia risk (RR = 0.74, 95% CI, 0.67–0.81, p < .00001).

Conclusions

Current evidence from the existing studies supports that cataract is associated with an increased risk of dementia, and cataract surgery may be instrumental in reducing the risk of dementia in patients with cataract.
Connected headwaters: Indelible field evidence of dispersal by a diverse caddisfly assemblage up stream valleys to dry catchment boundaries
Authors: Lancaster Jill , Downes Barbara J. , Finn Debra S. , St Clair Rosalind M.
Published: October 2023

1. Integral to many ecological models is the notion that dispersal connects populations and communities in disparate locations. For stream insects, however, there is very little empirical information about which species and what proportion of the species in a community are likely to disperse, in what direction and how far they travel, and whether dispersal is successful in connecting populations and communities. This study examines whether species of caddisfly can disperse between catchments and potentially connect communities.

2. We used a novel sampling design comprising five pairs of streams. Each stream in a pair flowed from the same boundary, but in opposite directions and into isolated catchments. We surveyed abundances of adult caddisflies on the catchment boundary (boundary species) where there was no water (Up location), and on two locations per stream (Middle, Down locations) where there was permanently flowing water (resident species). If caddisflies fly along the topographic features of stream valleys, then we expected to find adults on the ridge between catchments and, if dispersal is successful, stream communities in adjacent catchments should have similar species composition.

3. Over 130 species of caddisfly (from 18 families) were collected. Approximately half of them occurred on at least one catchment boundary, and Up locations averaged almost 20 species. Boundary species included both the smallest‐ and largest‐bodied taxa and they were a near perfect subset of species in resident assemblages. However, boundary species were not simply the most common in resident assemblages. There was no evidence of sex‐biased dispersal. Unsurprisingly, assemblage composition varied across the landscape, within and among catchments. However, resident assemblages within stream pairs were significantly more similar to one another than unpaired streams in either the same or in different catchments.

4. Our results suggest that a surprisingly diverse set of caddisflies disperse up to catchment boundaries and potentially connect streams on either side of catchment divides. Nevertheless, many other caddisfly species were never recorded at Up sites and hence may never or only rarely reach catchment boundaries.

5. These outcomes suggest, firstly, that some caddisflies are capable of trans‐catchment dispersal but it is incorrect to assume that all caddisflies are good dispersers, as is often stated in the literature. Secondly, caddisfly assemblages in headwater streams may be less isolated than is often considered and the dendritic structure of stream networks may be less important for their distribution patterns than the proximity of tributaries in neighbouring catchments, in many landscapes. Trans‐catchment dispersal could ensure community connectivity and facilitate recovery after catchment‐wide extinctions.
Inequalities in undergraduate participation and performance in Irish higher education
Authors: Borooah Vani , Knox Colin
Published: October 2023

This paper focuses on two aspects of gender inequality in Irish higher education: inequality in participation by gender and inequality of performance by gender, institution and subject. We use a rich set of data from the Higher Education Authority of Ireland which detail inter alia enrolment in institutions of higher education—Universities and Institutes of Technology—and record the class of degree received by graduating students, by subject and gender. The first aspect was the participation of women. Although more women enrolled as full‐time undergraduates in universities than did men, the reverse was the case in the Institutes of Technology. This had much to do with the subject structure of universities vis‐à‐vis the Institutes of Technology in tandem with the subject preferences of women and men. The second issue was inequality in performance. A major conclusion of this paper is thatafterenrolment there was little difference between the success rates of women and men in receiving first‐class degrees in the different subjects but there was considerable difference between the institutions.
X‐ray computed tomography of deep‐sea clay as tools to detect rare earth elements and yttrium enrichment
Authors: Usui Yoichi , Yasukawa Kazutaka , Iijima Koichi , Machiyama Hideaki , Ichiyama Yuji , Tanaka Erika , Fujinaga Koichiro
Published: October 2023

Pelagic clay that contains rare‐earth elements and yttrium (REY) at over 2000 ppm (termed “highly REY‐rich mud”) has been reported from a few areas in the western North Pacific Ocean through focused geochemical analyses. Those REY are carried by biogenic calcium phosphate, suggesting that the formation of highly REY‐rich mud involves enhanced biological productivity. However, detecting REY enrichment in sediment is time‐consuming, and the global significance of the formation of REY‐rich mud is still under debate. Here we perform x‐ray computed tomography (CT) analyses on cores recovered around Minamitorishima Island and demonstrate the positive correlation with highly REY‐rich mud and high CT numbers of the sediment. The variation of the CT number matches the wet bulk density. Further quantitative analyses using direct measurements of density and geochemistry suggest that a grain density increase and a porosity decrease due to the REY‐carrying biogenic apatite are essential to explain the high CT numbers in the REY‐enriched layer. While the chemical composition itself is of minor importance to elevate the CT numbers, our results suggest that x‐ray CT can be a proxy for highly REY‐rich mud.
Evaluation of a Model of Colour Vision by Magnitude Scalings: Discussion of Collected Results
Authors: Hunt R. W. G. , Luo M. R.
Published: October 2023

Coefficients of variation that show the degree to which the Hunt model of colour vision is successful in predicting the LUTCRI appearance data are gathered together in this article for a very wide range of viewing conditions. The model now consistently predicts these data as closely as the results of a single observer. agree with the average results of a group of six observers. The nature of the adjustments that have had to be made to the model to achieve this result are described. and their implications are discussed.
Suicide Prediction Revisited
Authors: Pokorny Alex D.
Published: October 2023

Data from a 1983 prospective study of suicide in a cohort of 4800 psychiatric inpatients were reanalyzed using logistic regression, which is more appropriate for a binary outcome. The results were the same as in the previous study: too few of the subsequent suicides were identified and there were too many false positives to make this procedure useful. Several additional “artificial” logistic regression analyses were done: one series randomly removed increasing numbers of nonsuicide cases to increase the base rates; another series added an increasingly powerful hypothetical “test.” Both of these maneuvers helped, but fell well short of perfection.
Suicide Causation: Pies, Paths, and Pointless Polemics
Authors: O'Carroll Patrick
Published: October 2023

Most people readily agree that suicide is caused by a complex web of many different factors. However, for many people the concept of a single event resulting from the combined effect of a constellation of different factors (multiple causation) is imperfectly understood. Unfortunately, a naive understanding of multiple causation can lead to needless arguments about what “really” causes suicide, and pointless debate about the “right” point for preventive intervention. In this paper, I review several simple conceptual models of multiple causation as they relate to suicide prevention. I suggest that a more explicit understanding of the nature of multiple causation has the potential to obviate some of these misguided arguments and to facilitate cooperative prevention efforts among person who choose to apply their energies at different points in the causal chain of suicide.
Suicide as Social Logic
Authors: Kral Michael J.
Published: October 2023

Although suicide is not viewed as a mental disorder per se, it is viewed by many if not most clinicians, researchers, and lay people as a real or natural symptom of depression. It is at least most typically seen as the unfortunate, severe, yet logical end result of a chain of negative self‐appraisals, negative events, and hopelessness. Extending an approach articulated by the early French sociologist Gabriel Tarde, in this paper I argue that suicide is merely an idea, albeit a very bad one, having more in common with societal beliefs and norms regarding such things as divorce, abortion, sex, politics, consumer behavior, and fashion. I make a sharp contrast between perturbation and lethality, concepts central to Edwin S. Shneidman's theory of suicide. Evidence supportive of suicide as an idea is discussed based on what we are learning from the study of history and culture, and about contagion/cluster phenomena, media/communication, and choice of method. It is suggested that certain individuals are more vulnerable to incorporate the idea and act of suicide into their concepts of self, based on the same principles by which ideas are spread throughout society. Just as suicide impacts on society, so does society impact on suicide.