bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of autistic-like behaviors in adult rats prenatally exposed to valproic acid through early suppression of orexin receptor
Authors: Piri Fatemeh , Salmani Mahmoud Elahdadi , Sepehri Hamid
Published: November 2023

Introduction:

Autism spectrum disorder (ASD) is a disabling psychiatric disease characterized by impairments in communication and social skills. The pathophysiology of autism is complex and not fully known. Considering the incidence of sleep disorders in individuals with ASD and the important role of orexin in sleep, it is possible to hypothesize that an alteration of the orexinergic system could be implicated in the pathogenesis of autism symptoms. The present study was conducted to investigate the effect of suvorexant [dual orexin receptor antagonists (DORAs)] on autism-like behavior in prenatally valproic acid (VPA)-exposed rats].

Methods:

Wistar female rats were administered VPA [600 mg/kg, intraperitoneally (i.p.)] or normal saline (10 ml/kg, i.p.; vehicle control) on gestational day 12.5. Thirty-two male offspring were divided into four groups: Control, VPA, Suvorexant+VPA, and VPA+Risperidone. The pups were given suvorexant [20 ml/kg, by mouth/orally (p.o.)] or risperidone (1 ml/kg, p.o.) daily from postnatal day (PND) (40–54). The offspring were tested for repetitive behaviors and cognitive ability with a Y-maze task on PND 55, and social interaction was assessed by play behavior in the open field on PND 56. And anxiety with using the three-chamber social assay on PND 56.

Results:

In the Y-maze apparatus, spontaneous alteration significantly decreased in the prenatal VPA-treated rats compared to control rats showing autistic-like behavior, and 2-week suvorexant increased the alternation, indicating the beneficial effect of suvorexant. Prenatal treatment with VPA, impaired play behavior (sniffing, grooming, and darting), and increased anxiety-related behavior. Suvorexant treatment attenuated the problems in male offspring’s social behavior.

Conclusion:

Our results showed that suvorexant improved ASD-associated behaviors in the VPA-treated rats, and the orexinergic system may be associated with the pathogenesis of autism symptoms.
Maxillary Sinus Floor Augmentation With Allograft Alone Compared With Alternate Grafting Materials: A Systematic Review and Meta-Analysis
Authors: Guruprasad Meghana , Kulloli Anita , Mehta Vini , Fiorillo Luca , Cicciu Marco
Published: November 2023

A meta-analysis of scientific literature was conducted to ascertain the superiority between allografts and other regenerative grafts for maxillary sinus floor augmentation (MSFA). Review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and registered in PROSPERO-CRD42023392766. Electronic databases like PubMed, Google scholar and Ebsco Host were searched from 2000 to December 2022 for studies reporting MSFA using allografts or other regenerative grafts. Quality assessment of included studies was evaluated using the Cochrane risk of bias (ROB)-2 tool for randomized controlled trials through its domains. Risk of bias summary graph and ROB summary applicability concern were plotted using RevMan software version 5.3. The standardized mean difference was used as a summary statistic measure with random effect model and P value <0.05 as statistically significant. Four studies fulfilled the eligibility criteria and were included in qualitative synthesis, of which all 4 studies were suitable for meta-analysis. Pooled estimate through standardized mean difference signifies that new bone formation was more or less similar for both graft materials, whereas regenerative grafts showed more residual bone grafts (P>0.05). Publication bias through funnel plot showed symmetric distribution with the absence of systematic heterogeneity. Both allografts and other regenerative grafts are equally effective in the MSFA in terms of new bone formation, whereras regenerative grafts showed more residual bone grafts. Furthermore, randomized controlled trials are required to establish evidence in outcomes involving sinus floor augmentation and different graft materials.
QuantiFERON-CMV as a Predictor of CMV Events During Preemptive Therapy in CMV-seropositive Kidney Transplant Recipients
Authors: Reusing José O. , Agena Fabiana , Kotton Camille N. , Campana Gustavo , Pierrotti Ligia Camera , David-Neto Elias
Published: November 2023

Background.

Prevention of cytomegalovirus (CMV) infection after kidney transplantation is costly and burdensome.

Methods.

Given its promising utility in risk stratification, we evaluated the use of QuantiFERON-CMV (QFCMV) and additional clinical variables in this prospective cohort study to predict the first clinically significant CMV infection (CS-CMV, ranging from asymptomatic viremia requiring treatment to CMV disease) in the first posttransplant year. A cost-effectiveness analysis for guided prevention was done.

Results.

One hundred adult kidney transplant recipients, CMV IgG+, were given basiliximab induction and maintained on steroid/mycophenolate/tacrolimus with weekly CMV monitoring. Thirty-nine patients developed CS-CMV infection (viral syndrome, n = 1; end-organ disease, n = 9; and asymptomatic viremia, n = 29). A nonreactive or indeterminate QFCMV result using the standard threshold around day 30 (but not before transplant) was associated with CS-CMV rates of 50% and 75%, respectively. A higher QFCMV threshold for reactivity (>1.0 IU interferon-γ/mL) outperformed the manufacturer’s standard (>0.2 IU interferon-γ/mL) in predicting protection but still allowed a 16% incidence of CS-CMV. The combination of recipient age and type of donor, along with posttransplant QFCMV resulted in a prediction model that increased the negative predictive value from 84% (QFCMV alone) to 93%. QFCMV-guided preemptive therapy was of lower cost than preemptive therapy alone (P < 0.001, probabilistic sensitivity analysis) and was cost-effective (incremental net monetary benefit of 210 USD) assuming willingness-to-pay of 2000 USD to avoid 1 CMV disease.

Conclusions.

Guided CMV prevention by the prediction model with QFCMV is cost-effective and would spare from CMV surveillance in 42% of patients with low risk for CS-CMV.
Coiled-coil-mediated dimerization of Atg16 is required for binding to the PROPPIN Atg21
Authors: Bueno-Arribas Miranda , Cruz-Cuevas Celia , Navas María-Angeles , Escalante Ricardo , Vincent Olivier
Published: November 2023

PROPPINs/WIPIs are β-propeller proteins that bind phosphoinositides and contribute to the recruitment of protein complexes involved in membrane remodelling processes such as autophagosome formation and endosomal trafficking. Yeast Atg21 and mammalian WIPI2 interact with Atg16/ATG16L1 to mediate recruitment of the lipidation machinery to the autophagosomal membrane. Here, we used the reverse double two-hybrid method (RD2H) to identify residues in Atg21 and Atg16 critical for protein–protein binding. Although our results are generally consistent with the crystal structure of the Atg21-Atg16 complex reported previously, they also reveal that dimerization of the Atg16 coiled-coil domain is required for Atg21 binding. Furthermore, most of the residues identified in Atg21 are conserved in WIPI2 and we showed that these residues also mediate ATG16L1 binding. Strikingly, these residues occupy the same position in the β-propeller structure as residues in PROPPINs/WIPIs Hsv2 and WIPI4 that mediate Atg2/ATG2A binding, supporting the idea that these proteins use different amino acids at the same position to interact with different autophagic proteins. Finally, our findings demonstrate the effectiveness of the RD2H system to identify critical residues for protein–protein interactions and the utility of this method to generate combinatory mutants with a complete loss of binding capacity.
Null regions: a unified conceptual framework for statistical inference
Authors: Smiley Adam H. , Glazier Jessica J. , Shoda Yuichi
Published: November 2023

Ruling out the possibility that there is absolutely no effect or association between variables may be a good first step, but it is rarely the ultimate goal of science. Yet that is the only inference provided by traditional null hypothesis significance testing (NHST), which has been a mainstay of many scientific fields. Reliance on NHST also makes it difficult to define what it means to replicate a finding, and leads to an uncomfortable quandary in which increasing precision in data reduces researchers' ability to perform theory falsification. To solve these problems, in recent years several alternatives to traditional NHST have been proposed. However, each new test is described using its own terminology and practiced in different fields. We describe a simple, unified framework for conceptualizing all these tests so that it is not necessary to learn them separately. Moreover, the framework allows researchers to conduct any of these tests by asking just one question: is the confidence interval entirely outside the
null region(s)
? This framework may also help researchers choose the test(s) that best answers their research question when simply ruling out ‘no effect at all’ is not enough.
Global warming intensifies the interference competition by a poleward-expanding invader on a native dragonfly species
Authors: Nagano Koki , Hiraiwa Masayoshi K. , Ishiwaka Naoto , Seko Yugo , Hashimoto Koya , Uchida Taizo , Sánchez-Bayo Francisco , Hayasaka Daisuke
Published: November 2023

Rapid climate warming has boosted biological invasions and the distribution or expansion polewards of many species: this can cause serious impacts on local ecosystems within the invaded areas. Subsequently, native species may be exposed to threats of both interspecific competition with invaders and temperature rises. However, effects of warming on interspecific interactions, especially competition between invader and native species remains unclear. To better understand the combined threats of biological invasions and warming, the effect of temperature on competitive interactions between two dragonfly species, the expanding
Trithemis aurora
from Southeast Asia and the Japanese native
Orthetrum albistylum speciosum
were assessed based on their foraging capacity. Although the stand-alone effect of temperature on foraging intake of the native dragonfly was not apparent, its intake significantly decreased with increasing temperatures when the invader
T. aurora
was present. Such reductions in foraging might lead to displacement of the native species through competition for food resources. This suggests that impacts of invader species against native species are expected to be more severe when interspecific competition is exacerbated by temperature rises.
Sublethal doses of insecticide reduce thermal tolerance of a stingless bee and are not avoided in a resource choice test
Authors: Farnan Holly , Yeeles Peter , Lach Lori
Published: November 2023

Insecticides and climate change are among the multiple stressors that bees face, but little is known about their synergistic effects, especially for non-
Apis
bee species. In laboratory experiments, we tested whether the stingless bee
Tetragonula hockingsi
avoids insecticide in sucrose solutions and how
T. hockingsi
responds to insecticide and heat stress combined. We found that
T. hockingsi
neither preferred nor avoided sucrose solutions with either low (2.5 × 10
−4
ng µl
−1
imidacloprid or 1.0 × 10
−4
ng µl
−1
fipronil) or high (2.5 × 10
−3
ng µl
−1
imidacloprid or 1.0 × 10
−3
ng µl
−1
fipronil) insecticide concentrations when offered alongside sucrose without insecticide. In our combined stress experiment, the smallest dose of imidacloprid (7.5 × 10
−4
ng) did not significantly affect thermal tolerance (CT
max
). However, CT
max
significantly reduced by 0.8°C (±0.16 SE) and by 0.5°C (±0.16 SE) when bees were fed as little as 7.5 × 10
−3
ng of imidacloprid or 3.0 × 10
−4
ng of fipronil, respectively, and as much as 1.5°C (±0.16 SE) and 1.2°C (±0.16 SE) when bees were fed 7.5 × 10
−2
ng of imidacloprid or 3.0 × 10
−2
ng of fipronil, respectively. Predictions of temperature increase, and increased insecticide use in the tropics suggest that
T. hockingsi
will be at increased risk of the effects of both stressors in the future.
A new approach to derive productivity of tropical forests using radar remote sensing measurements
Authors: Henniger Hans , Huth Andreas , Bohn Friedrich J.
Published: November 2023

Deriving gross & net primary productivity (GPP & NPP) and carbon turnover time of forests from remote sensing remains challenging. This study presents a novel approach to estimate forest productivity by combining radar remote sensing measurements, machine learning and an individual-based forest model. In this study, we analyse the role of different spatial resolutions on predictions in the context of the Radar BIOMASS mission (by ESA). In our analysis, we use the forest gap model FORMIND in combination with a boosted regression tree (BRT) to explore how spatial biomass distributions can be used to predict GPP, NPP and carbon turnover time (
τ
) at different resolutions. We simulate different spatial biomass resolutions (4 ha, 1 ha and 0.04 ha) in combination with different vertical resolutions (20, 10 and 2 m). Additionally, we analysed the robustness of this approach and applied it to disturbed and mature forests. Disturbed forests have a strong influence on the predictions which leads to high correlations (
R
2
> 0.8) at the spatial scale of 4 ha and 1 ha. Increased vertical resolution leads generally to better predictions for productivity (GPP & NPP). Increasing spatial resolution leads to better predictions for mature forests and lower correlations for disturbed forests. Our results emphasize the value of the forthcoming BIOMASS satellite mission and highlight the potential of deriving estimates for forest productivity from information on forest structure. If applied to more and larger areas, the approach might ultimately contribute to a better understanding of forest ecosystems.
Proof of Straughan’s claim on Payne–Song’s and modified Guyer–Krumhansl’s equations
Authors: Mariano Paolo Maria
Published: November 2023

We prove a claim by Brian Straughan who conjectured that Payne–Song’s and modified Guyer–Krumhansl’s equations can be justified in (and derived from) the general model-building framework for the mechanics of complex bodies, so they emerge from the modelling of microstructural effects. The proof is based on taking into account micro-to-macro spatial scaling and a decomposition of the heat flux into a standard Fourier-type component and one measuring microstructural event with associated and balanced actions.
Some remarks on the solution of the cell growth equation
Authors: Mirotin Adolf R.
Published: November 2023

A process of growth and division of cells is modelled by an initial boundary value problem that involves a first-order linear functional partial differential equation, the so-called sell growth equation. The analytical solution to this problem was given in the paper Zaidi
et al.
(Zaidi
et al
. 2015 Solutions to an advanced functional partial differential equation of the pantograph type (
Proc. R. Soc. A
471
, 20140947 (
doi:10.1098/rspa.2014.0947
)). In this note, we simplify the arguments given in the paper mentioned above by using the theory of operator semigroups. This theory enables us to prove the existence and uniqueness of the solution and to express this solution in terms of Dyson–Phillips series. The asymptotics of the solution is also discussed from the point of view of the theory of operator semigroups.
Hybrid cyber-attack compensation of sustainable microgrid using active disturbance rejection control strategy
Authors: Sharma Komal , Yadav Anil Kumar , Sharma Bharat Bhushan
Published: November 2023

A modified active disturbance rejection control (ADRC) strategy for the frequency regulation of sustainable microgrid against hybrid cyber-attacks is proposed in this paper. The proposed technique mitigates the effect of attacks which in turn regulates the frequency of microgrid. The sustainable microgrid consists of solar and wind as renewable energy sources, energy storage systems (ESSs) like battery ESS and flywheel ESS, and controllable sources of energy like fuel cell and diesel generator. The cyber-attacks such as false data injection, denial-of-service and time delay attack are considered for designing the proposed ADRC technique. The robustness of the microgrid system with the proposed controller is investigated by varying generation and load, stochastic nature of attacks, parametric uncertainties and generation rate constraint and governor dead band nonlinearities. Further, the stability analysis of the microgrid with proposed ADRC is investigated under the aforementioned cyber-attacks using the small gain theorem.
Incorporating environmental heterogeneity and observation effort to predict host distribution and viral spillover from a bat reservoir
Authors: Ribeiro Rita , Matthiopoulos Jason , Lindgren Finn , Tello Carlos , Zariquiey Carlos M. , Valderrama William , Rocke Tonie E. , Streicker Daniel G.
Published: November 2023

Predicting the spatial occurrence of wildlife is a major challenge for ecology and management. In Latin America, limited knowledge of the number and locations of vampire bat roosts precludes informed allocation of measures intended to prevent rabies spillover to humans and livestock. We inferred the spatial distribution of vampire bat roosts while accounting for observation effort and environmental effects by fitting a log Gaussian Cox process model to the locations of 563 roosts in three regions of Peru. Our model explained 45% of the variance in the observed roost distribution and identified environmental drivers of roost establishment. When correcting for uneven observation effort, our model estimated a total of 2340 roosts, indicating that undetected roosts (76%) exceed known roosts (24%) by threefold. Predicted hotspots of undetected roosts in rabies-free areas revealed high-risk areas for future viral incursions. Using the predicted roost distribution to inform a spatial model of rabies spillover to livestock identified areas with disproportionate underreporting and indicated a higher rabies burden than previously recognized. We provide a transferrable approach to infer the distribution of a mostly unobserved bat reservoir that can inform strategies to prevent the re-emergence of an important zoonosis.
Multiple rod layers increase the speed and sensitivity of vision in nocturnal reef fishes
Authors: Fogg Lily G. , Chung Wen-Sung , Justin Marshall N. , Cortesi Fabio , de Busserolles Fanny
Published: November 2023

Most vertebrates have one layer of the dim-light active rod photoreceptors. However, multiple rod layers, known as a multibank retina, can be found in over 100 species of fish, including several deep-sea species and one family of nocturnally active reef fish, the Holocentridae. Although seemingly associated with increased photon catch, the function of multibank retinas remained unknown. We used an integrative approach, combining histology, electrophysiology and amino acid sequence analysis, applied to three species of nocturnal reef fishes, two holocentrids with a multibank retina (
Neoniphon sammara
and
Myripristis violacea
) and an apogonid with a single rod bank (
Ostorhinchus compressus
), to determine the sensory advantage of multiple rod layers. Our results showed that fish with multibank retinas have both faster vision and enhanced responses to bright- and dim-light intensities. Faster vision was indicated by higher flicker fusion frequencies during temporal resolution electroretinography as well as faster retinal release rates estimated from their rhodopsin proteins. Enhanced sensitivity was demonstrated by broadened intensity-response curves derived from luminous sensitivity electroretinography. Overall, our findings provide the first functional evidence for enhanced dim-light sensitivity using a multibank retina while also suggesting novel roles for the adaptation in enhancing bright-light sensitivity and the speed of vision.
Innovation-facilitating networks create inequality
Authors: Moser Cody , Smaldino Paul E.
Published: November 2023

Theories of innovation often balance contrasting views that either smart people create smart things or smartly constructed institutions create smart things. While population models have shown factors including population size, connectivity and agent behaviour as crucial for innovation, few have taken the individual-central approach seriously by examining the role individuals play within their groups. To explore how network structures influence not only population-level innovation but also performance among individuals, we studied an agent-based model of the Potions Task, a paradigm developed to test how structure affects a group’s ability to solve a difficult exploration task. We explore how size, connectivity and rates of information sharing in a network influence innovation and how these have an impact on the emergence of inequality in terms of agent contributions. We find, in line with prior work, that population size has a positive effect on innovation, but also find that large and small populations perform similarly
per capita
; that many small groups outperform fewer large groups; that random changes to structure have few effects on innovation in the task; and that the highest performing agents tend to occupy more central positions in the network. Moreover, we show that every network factor which improves innovation leads to a proportional increase in inequality of performance in the network, creating ‘genius effects’ among otherwise ‘dumb’ agents in both idealized and real-world networks.
BactEXTRACT: an R-Shiny app to quickly extract, plot and analyse bacterial growth and gene expression data
Authors: Dénéréaz Julien , Veening Jan-Willem
Published: November 2023

To streamline the analysis and visualization of bacterial growth and gene expression data obtained by microtiter plate readers, we developed BactEXTRACT, an intuitive, easy-to-use R-Shiny application. BactEXTRACT simplifies the transition from raw optical density, fluorescence, and luminescence measurements to publication-ready plots. This package offers a user-friendly interface that reduces the complexity involved in growth curve and gene expression analysis and is generally applicable. BactEXTRACT is available at https://veeninglab.shinyapps.io/BactEXTRACT/.
Gordonia metallireducens sp. nov., a tellurite- and selenite-resistant bacterium isolated from the sediment of an acid mine drainage stream
Authors: Grimm David , Guy Nathan , Lengyel George , Franks Jonathan , Maltman Chris
Published: November 2023

A polyphasic taxonomic study was carried out on strain TSed Te1T, isolated from sediment of a stream contaminated with acid drainage from a coal mine. The bacterium forms pink-pigmented colonies and has a rod–coccus growth cycle, which also includes some coryneform arrangements. This bacterium is capable of growing in the presence of up to 750 μg ml−1 tellurite and 5000 μg ml−1 selenite, reducing each to elemental form. Nearly complete 16S rRNA gene sequence analysis associated the strain with

Gordonia

, with 99.5 and 99.3 % similarity to

Gordonia namibiensis

and

Gordonia rubripertincta

, respectively. Computation of the average nucleotide identity and digital DNA–DNA hybridization comparisons with the closest phylogenetic neighbour of TSed Te1T revealed genetic differences at the species level, which were further substantiated by differences in several physiological characteristics. The dominant fatty acids were C16 : 0, C18 : 1, C16 : 1 and tuberculostearic acid. The DNA G+C content was 67.6 mol%. Major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside, while MK-9(H2) was the only menaquinone found. Mycolic acids of C56–C60 were present. Whole-cell hydrolysates contained meso-diaminopimelic acid along with arabinose and galactose as the major cell-wall sugars. On the basis of the results obtained in this study, the bacterium was assigned to the genus

Gordonia

and represents a new species with the name Gordonia metallireducens sp. nov. The type strain is TSed Te1T (=NRRL B-65678T=DSM 114093T).
Pan-Enterovirus Characterization Reveals Cryptic Circulation of Clinically Relevant Subtypes in Arizona Wastewater
Authors: Erickson Daryn E. , Simmons Kyle M. , Barrand Zachary A. , Ridenour Chase L. , Hawkinson Paige B. , Lemke Lacey , Sellner Shayne P. , Brock Breezy N. , Rivas Alexis N. , Sheridan Krystal , Lemmer Darrin , Yaglom Hayley D. , Porter W. Tanner , Belanger Monique , Torrey Rachel M. , Stills Aidan James R. , McCormack Kiley , Black Matt , Holmes Wydale , Rostain Drew , Mikus Jeremy , Sotelo Kimberly , Haq Emmen , Neupane Reshma , Weiss Joli , Johnson Jasmine , Collins Clancey , Avalle Sarah , White Chelsi , Howard Brandon J. , Maltinsky Sara A. , Whealy Ryann N. , Gordon Nathaniel B. , Sahl Jason W. , Pearson Talima , Fofanov Viacheslav Y. , Furstenau Tara , Driebe Elizabeth M. , Caporaso J. Gregory , Barber Jarrett , Terriquez Joel , Engelthaler David M. , Hepp Crystal M.
Published: November 2023

Background

Most seasonally circulating enteroviruses result in asymptomatic or mildly symptomatic infections. In rare cases, however, infection with some subtypes can result in paralysis or death. Of the 300 subtypes known, only poliovirus is reportable, limiting our understanding of the distribution of other enteroviruses that can cause clinical disease.

Objective

The overarching objectives of this study were to: 1) describe the distribution of enteroviruses in Arizona during the late summer and fall of 2022, the time of year when they are thought to be most abundant, and 2) demonstrate the utility of viral pan-assay approaches for semi-agnostic discovery that can be followed up by more targeted assays and phylogenomics.

Methods

This study utilizes pooled nasal samples collected from school-aged children and long-term care facility residents, and wastewater from multiple locations in Arizona during July–October of 2022. We used PCR to amplify and sequence a region common to all enteroviruses, followed by species-level bioinformatic characterization using the QIIME 2 platform. For Enterovirus-D68 (EV-D68), detection was carried out using RT-qPCR, followed by confirmation using near-complete whole EV-D68 genome sequencing using a newly designed tiled amplicon approach.

Results

In the late summer and early fall of 2022, multiple enterovirus species were identified in Arizona wastewater, with Coxsackievirus A6, EV-D68, and Coxsackievirus A19 composing 86% of the characterized reads sequenced. While EV-D68 was not identified in pooled human nasal samples, and the only reported acute flaccid myelitis case in Arizona did not test positive for the virus, an in-depth analysis of EV-D68 in wastewater revealed that the virus was circulating from August through mid-October. A phylogenetic analysis on this relatively limited dataset revealed just a few importations into the state, with a single clade indicating local circulation.

Significance

This study further supports the utility of wastewater-based epidemiology to identify potential public health threats. Our further investigations into EV-D68 shows how these data might help inform healthcare diagnoses for children presenting with concerning neurological symptoms.
Early-onset schizophrenia is associated with immune-related rare variants in a Chinese sample
Authors: Zhong Yuanxin , Tubbs Justin D. , Leung Perry B.M. , Zhan Na , Hui Tomy C.K. , Ho Karen K. Y. , Hung Karen S. Y. , Cheung Eric F. C. , So Hon-Cheong , Lui Simon S.Y. , Sham Pak C.
Published: November 2023

Background

Rare variants are likely to contribute to schizophrenia (SCZ), given the large discrepancy between the heritability estimated from twin and GWAS studies. Furthermore, the nature of the rare-variant contribution to SCZ may vary with the “age-at-onset” (AAO), since early-onset has been suggested as being indicative of neurodevelopment deviance.

Objective

To examine the association of rare deleterious coding variants in early- and adult-onset SCZ in a Chinese sample.

Method

Exome sequencing was performed on DNA from 197 patients with SCZ spectrum disorder and 82 healthy controls (HC) of Chinese ancestry recruited in Hong Kong. We also gathered AAO information in the majority of SCZ samples. Patients were classified into early-onset (EOS, AAO<18) and adult-onset (AOS, AAO>18). We collapsed the rare variants to improve statistical power and examined the overall association of rare variants in SCZ versus HC, EOS versus HC, and AOS versus HC at the gene and gene-set levels by Sequence Kernel Association Test. The quantitative rare-variant association test of AAO was also conducted. We focused on variants which were predicted to have a medium or high impact on the protein-encoding process as defined by Ensembl. We applied a 100000-time permutation test to obtain empirical p-values, with significance threshold set at p < 1e-3to control family-wise error rates. Moreover, we compared the burden of targeted rare variants in significant risk genes and gene sets in cases and controls.

Results

Based on several binary-trait association tests (i.e., SCZ vs HC, EOS vs HC and AOS vs HC), we identified 7 candidate risk genes and 20 gene ontology biological processes (GOBP) terms, which exhibited higher burdens in SCZ than in controls. Based on quantitative rare-variant association tests, we found that alterations in 5 candidate risk genes and 7 GOBP pathways were significantly correlated with AAO. Based on biological and functional profiles of the candidate risk genes and gene sets, our findings suggested that, in addition to the involvement of perturbations in neural systems in SCZ in general, altered immune responses may be specifically implicated in EOS.

Conclusion

Disrupted immune responses may exacerbate abnormal perturbations during neurodevelopment and trigger the early onset of SCZ. We provided evidence of rare variants increasing SCZ risk in the Chinese population.
Public Health and Social Measures (PHSM) interventions to control COVID-19 An Overview of Systematic Reviews
Authors: Fadlallah Racha , El-Jardali Fadi , Kalach Nour , Karroum Lama Bou , Hoteit Reem , Aoun Andrew , Al-Hakim Lara , Verdugo-Paiva Francisca , Rada Gabriel , Fretheim Atle , Lewin Simon , Ludolph Ramona , Akl Elie A.
Published: November 2023

Response to the COVID-19 pandemic included a wide range of Public Health and Social Measures (PHSM). PHSM refer to a broad array of nonpharmaceutical interventions implemented by individuals, communities and governments to reduce the risk and scale of transmission of epidemic- and pandemic-prone infectious diseases. In order to inform decisions by the public, health workforce and policy-makers, there is a need to synthesize the large volume of published work on COVID-19. This study protocol describes the methodology for an overview of reviews focusing on the effectiveness and/or unintended health and socio-economic consequences of PHSM implemented during the COVID-19 pandemic. Findings can shape policy and research related to PHSM moving forward.
Exploring the possibility of collaboration for biomedical professionals and traditional healers: A Systematic Review
Authors: Ilozumba Onaedo , Koirala Suyasha , Meka Anthony , Ossai Edmund , Choudhury Sopna Mannan , Wagner Ryan , Lilford Richard
Published: November 2023

Introduction

Traditional healers play a crucial role in healthcare provision, particularly in low- and middle-income countries. Thus, there is a global interest in understanding the possibilities for collaboration between traditional healers and biomedical professionals. We believe there is the need for a comprehensive review on collaboration between traditional healers and biomedical professionals. Therefore, the aim of this review is to synthesise the literature on collaboration between traditional healer’s and biomedical professional including relevant interventions.

Methods

A systematic review was conducted, utilizing a search strategy in PubMed, Web of Science, SCOPUS, and Google Scholar. Articles addressing collaboration between traditional healers and biomedical professionals were included, with a focus on attitudes, perceptions, interventions, and collaborative models. Data extraction followed a predefined template and the D’Amour et al. framework was employed for analysis.

Results

The review identified 29 relevant articles, predominantly conducted in Africa. The majority of studies (n=22) explored attitudes and perceptions, revealing a willingness among traditional healers to collaborate, while biomedical professionals exhibited mixed feelings. Seven studies focused on interventions aimed at fostering collaboration primarily focused on improving referral systems and educational initiatives. These studies found positive outcomes. Examining collaboration through the lens of D’Amour et al.’s framework revealed that trust was a significant barrier to collaboration.

Conclusion

This review highlights a willingness to collaborate amongst of traditional healers and biomedical professionals and provides some successful examples of working across systems. It also reveals areas for attention in developing collaborative models of working.
Consistency, completeness and external validity of ethnicity recording in NHS primary care records: a cohort study in 25 million patients’ records at source using OpenSAFELY
Authors:   The OpenSAFELY Collaborative, Andrews Colm D , Mathur Rohini , Massey Jon , Park Robin , Hopcroft Lisa , Curtis Helen J , Mehrkar Amir , Bacon Seb , Hickman George , Smith Rebecca , Evans David , Ward Tom , Davy Simon , Inglesby Peter , Dillingham Iain , Maude Steven , O’Dwyer Thomas , Butler-Cole Ben , Bridges Lucy , Bates Chris , Parry John , Hester Frank , Harper Sam , Cockburn Jonathan , Goldacre Ben , MacKenna Brian , Tomlinson Laurie , Walker Alex J , Hulme William J
Published: November 2023

Background

Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data.

Methods

We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in >25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census.

Results

78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%).

Conclusions

Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.
Evaluating and mitigating unfairness in multimodal remote mental health assessments
Authors: Jiang Zifan , Seyedi Salman , Griner Emily , Abbasi Ahmed , Rad Ali Bahrami , Kwon Hyeokhyen , Cotes Robert O. , Clifford Gari D.
Published: November 2023

Research on automated mental health assessment tools has been growing in recent years, often aiming to address the subjectivity and bias that existed in the current clinical practice of the psychiatric evaluation process. Despite the substantial health and economic ramifications, the potential unfairness of those automated tools was understudied and required more attention.

In this work, we systematically evaluated the fairness level in a multimodal remote mental health dataset and an assessment system, where we compared the fairness level in race, gender, education level, and age.Demographic parity ratio (DPR)andequalized odds ratio (EOR)of classifiers using different modalities were compared, along with the F1 scores in different demographic groups. Post-training classifier threshold optimization was employed to mitigate the unfairness.

No statistically significant unfairness was found in the composition of the dataset. Varying degrees of unfairness were identified among modalities, with no single modality consistently demonstrating better fairness across all demographic variables. Post-training mitigation effectively improved both DPR and EOR metrics at the expense of a decrease in F1 scores.

Addressing and mitigating unfairness in these automated tools are essential steps in fostering trust among clinicians, gaining deeper insights into their use cases, and facilitating their appropriate utilization.

Author summary

In this work, we systematically explored and discussed the unfairness reporting and mitigation of automated mental health assessment tools. These tools are becoming increasingly important in mental health practice, especially with the rise of telehealth services and large language model applications. However, they often carry inherent biases. Without proper assessment and mitigation, they potentially lead to unfair treatment of certain demographic groups and significant harm. Proper unfairness reporting and mitigation of these tools is the first step to building trust among clinicians and patients and ensuring appropriate application.

Using our previously developed multimodal mental health assessment system, we evaluated the unfairness level of using various types of features of the subjects for mental health assessment, including facial expressions, acoustic features of the voice, emotions expressed through language, general language representations generated by large language models, and cardiovascular patterns detected from the face. We analyzed the system’s fairness across different demographics: race, gender, education level, and age. We found no single modality consistently fair across all demographics. While unfairness mitigation methods improved the fairness level, we found a trade-off between the performance and the fairness level, calling for broader moral discussion and investigation on the topic.
Generating synthetic data in digital pathology through diffusion models: a multifaceted approach to evaluation
Authors: Pozzi Matteo , Noei Shahryar , Robbi Erich , Cima Luca , Moroni Monica , Munari Enrico , Torresani Evelin , Jurman Giuseppe
Published: November 2023

Synthetic data has recently risen as a new precious item in the computational pathologist’s toolbox, supporting several tasks such as helping with data scarcity or augmenting training set in deep learning. Nonetheless, the use of such novel resources requires a carefully planned construction and evaluation, to avoid pitfalls such as the generation of clinically meaningless artifacts.

As the major outcome described in the current manuscript, a novel full stack pipeline is introduced for the generation and evaluation of synthetic pathology data powered by a diffusion model. The workflow features, as characterizing elements, a new multifaceted evaluation strategy with an embedded explainability procedure effectively tackling two critical aspects of the use of synthetic data in health-related domains.

An ensemble-like strategy is adopted for the evaluation of the produced data, with the threefold aim of assessing the similarity of real and synthetic data through a set of well-established metrics, evaluating the practical usability of the generated images in deep learning models complemented by explainable AI methods, and validating their histopathological realism through a dedicated questionnaire answered by three professional pathologists.

The pipeline is demonstrated on the public GTEx dataset of 650 WSIs, including five different tissues, conditioning the training step of the underlying diffusion model. An equal number of tiles from each of these five tissues are then generated. Finally, the reliability of the generated data is assessed using the proposed evaluation pipeline, with encouraging results. We show that each of these evaluation steps are necessary as they provide complementary information on the generated data’s quality.

Overall, all the aforementioned features characterize the proposed workflow as a fully-fledged solution for generative AI in digital pathology representing a potentially useful tool for the digital pathology community in their transition towards digitalization and data-driven modeling.
Three components of glucose dynamics – value, variability, and autocorrelation – are independently associated with coronary plaque vulnerability
Authors: Sugimoto Hikaru , Hironaka Ken-ichi , Yamada Tomoko , Otowa-Suematsu Natsu , Hirota Yushi , Otake Hiromasa , Hirata Ken-Ichi , Sakaguchi Kazuhiko , Ogawa Wataru , Kuroda Shinya
Published: November 2023

Impaired glucose homeostasis leads to numerous complications, with coronary artery disease (CAD) being a major contributor to healthcare costs worldwide. Given the limited efficacy of current CAD screening methods, we investigated the association between glucose dynamics and a predictor of coronary events measured by virtual histology-intravascular ultrasound (%NC), with the aim of predicting CAD using easy-to-measure indices. We found that continuous glucose monitoring (CGM)-derived indices, particularly average daily risk ratio (ADRR) and AC_Var, exhibited stronger predictive capabilities for %NC compared to commonly used indices such as fasting blood glucose (FBG), hemoglobin A1C (HbA1c), and plasma glucose level at 120 min during oral glucose tolerance tests (PG120). Factor analysis identified three distinct components underlying glucose dynamics – value, variability, and autocorrelation – each independently associated with %NC. ADRR was influenced by the first two components and AC_Var by the third. FBG, HbA1c, and PG120 were influenced only by the value component, making them insufficient for %NC prediction. Our results were validated using data sets from Japan (n=64), America (n=53), and China (n=100). CGM-derived indices reflecting the three components of glucose dynamics can serve as more effective screening tools for CAD risk assessment, complementing or possibly replacing traditional diabetes diagnostic methods.
Using the Public Health and Social Measures Severity Index for analysing government responses to COVID-19 in the WHO European Region
Authors: Wippel Christoph , Owen Lisa , Cocciolone Dominic , Sane Jussi , Addo Jennifer , Gapp Christian , Latta Aimee , Lindmark Sandra , Schmidt Tanja
Published: November 2023

Public health and social measures (PHSM), such as adaptions to the operation of schools, businesses and workplaces, international travel measures and restrictions on gatherings and people’s movements, as well as individual preventive measures such as physical distancing, have been a vital set of tools utilized by many countries to mitigate the spread of SARS-CoV-2 virus throughout the COVID-19 pandemic. In January 2020, the WHO Regional Office for Europe started to systematically monitor, collect and categorize data on response measures taken by its Member States. In order to visualize and analyse the collected data, WHO developed a methodology for quantifying the response measures into an index, capturing the severity of these policy measures in terms of six key indicators. The aim of this article is to describe the methodology underlying the index, including data collection, categorization and calculation, in order to provide researchers and policy-makers with a better understanding of its application. Furthermore, it provides an overview and examples of possible applications of the index, as well as serve as a reference for subsequent research on the effectiveness of PHSM, including empirical studies and models that can help to guide health policies, their timing and severity.
Visceral Adiposity and Subclinical Left Ventricular Remodeling
Authors: Luu Judy , Gebhard Catherine , Friedrich Matthias G. , Desai Dipika , Schulze Karleen M , de Souza Russell , Al-Khazraji Baraa K. , Awadalla Philipp , Lettre Guillaume , Ho Vikki , Dummer Trevor , Hicks Jason , Piche Marie-Eve , Poirier Paul , Teo Koon K. , Yusuf Salim , Tardif Jean-Claude , Vena Jennifer , Lee Douglas S. , Marcotte Francois , Larose Eric , Smith Eric E. , Anand Sonia S.
Published: November 2023

Introduction

Visceral adiposity is emerging as a key driver of cardio-metabolic risk factors and cardiovascular disease (CVD), but its relationship with cardiac structure and function is not well characterized across sexes. Using the Canadian Alliance for Healthy Heart and Minds (CAHHM), a large population-based cohort study, we sought to determine the association of visceral adipose tissue (VAT) on subclinical left ventricular (LV) remodeling in males and females.

Methods

As part of the CAHHM study, 6522 participants free of clinical CVD (mean age: 57.4 [8.8 SD] years; 3,671 females, 56%) underwent magnetic resonance imaging (MRI) in which LV parameters and VAT volume were measured. Information about demographic factors, CV risk factors, and anthropometric measurements were obtained. Subclinical cardiac remodelling was defined as altered LV concentricity, represented by increased LV mass-to-volume ratio (LVMV).

Results

Males had a higher VAT volume (80.8 mL; 95% CI: 74.6 t 86.9) compared to females (64.7 mL; 95% CI: 58.5 to 70.8), adjusted for age and height. Among both males and females, VAT was significantly associated with subclinical cardiac remodeling (increased LVMV), independent of other CV risk factors. In multiple regression models adjusted for cardiovascular risk factors, age, and height, every 1 sex-specific standard deviation increase in VAT corresponded to an increase of 0.037 g/mL in LVMV (95% CI: 0.032 to 0.041; p<0.001), which was consistent across both sexes. Notably, a 1 standard deviation increase in VAT is associated with a LVMV that is 20 times higher than what is observed with natural aging alone (0.0020 g/mL rise in LVMV (95% CI 0.0016 to 0.0025), and 1.5 times higher than the impact of an integrated measure of CV risk factors (0.024 g/mL; 95% CI: 0.020 to 0.028).

Conclusion

VAT significantly influences subclinical cardiac remodeling in both males and females, independent of other cardiovascular risk factors and age. Further research to understand the pathways by which VAT contributes to accelerated cardiac aging is needed.