bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementation with Berry Juice and Vitamin E Ameliorates Blood Cholesterol Level and Alters Gut Microbiota Composition
Authors: Chen Bangwei , Li Yaxin , Li Zhiming , Hu Xiaojie , Zhen Hefu , Chen Hongyun , Nie Chao , Hou Yong , Jin Xin , Xiao Liang , Li Tao
Published: May 2023

Scope

Antioxidants, including vitamin E (VE) and grape seed extract, as anti-aging supplementation have been widely used to improve human health. However, the role of gut microbiota in dietary antioxidant supplementation is debatable. This study aimed to assess the longitudinal impact of dietary supplementation with antioxidant compounds on body health and the gut microbiota.

Methods and results

One hundred and twenty healthy individuals were randomly divided into a placebo group (amylodextrin) and three experimental groups ingesting different supplement (VE, grape seed extract, or mixed berry juice). Blood and fecal samples were collected during three intervention phases. We found that VE and mixed berry juice ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances ofLachnospirasp. andFaecalibacteriumspp. increased in the VE and berry juice groups. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species.

Conclusion

Juice and VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids.
Mechanical Dispersion Discriminates between Arrhythmic and Non-Arrhythmic Sudden Death: From the POST SCD Study
Authors: Tastet Lionel , Ramakrishna Satvik , Lim Lisa J. , Bibby Dwight , Olgin Jeffrey E. , Connolly Andrew J. , Moffatt Ellen , Tseng Zian H. , Delling Francesca N.
Published: May 2023

Background

Global longitudinal strain (GLS) and mechanical dispersion (MD) by speckle-tracking echocardiography can predict sudden cardiac death (SCD) beyond left ventricular ejection fraction (LVEF) alone. However, prior studies have presumed cardiac cause from EMS records or death certificates rather than gold-standard autopsies.

Objectives

We sought to investigate whether abnormal GLS and MD, reflective of underlying myocardial fibrosis, are associated with autopsy-defined sudden arrhythmic death (SAD) in a comprehensive postmortem study.

Methods

We identified and autopsied all World Health Organization-defined (presumed) SCDs ages 18-90 via active surveillance of out of hospital deaths in the ongoing San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study to refine presumed SCDs to true cardiac causes. We retrieved all available pre-mortem echocardiograms and assessed LVEF, LV-GLS, and MD. The extent of LV myocardial fibrosis was assessed and quantified histologically.

Results

Of 652 autopsied subjects, 65 (10%) had echocardiograms available for primary review, obtained at a mean 1.5 years before SCD. Of these, 37 (56%) were SADs and 29 (44%) were non-SADs; fibrosis was quantified in 38 (58%). SADs were predominantly male, but had similar age, race, baseline comorbidities, and LVEF compared to non-SADs (all p>0.05). SADs had significantly reduced LV-GLS (median: –11.4% versus –18.5%, p=0.008) and increased MD (median: 14.8 ms versus 9.4 ms, p=0.006) compared to non-SADs. MD was associated with total LV fibrosis by linear regression in SADs (r=0.58, p=0.002).

Conclusion

In this countywide postmortem study of all sudden deaths, autopsy-confirmed arrhythmic deaths had significantly lower LV-GLS and increased MD than non-arrhythmic sudden deaths. Increased MD correlated with higher histologic levels of LV fibrosis in SADs. These findings suggest that increased MD, which is a surrogate for the extent of myocardial fibrosis, may improve risk stratification and specification for SAD beyond LVEF.

PERSPECTIVES

Competency in medical knowledge

Mechanical dispersion derived from speckle tracking echocardiography provides better discrimination between autopsy-defined arrhythmic vs non-arrhythmic sudden death than LVEF or LV-GLS. Histological ventricular fibrosis correlates with increased mechanical dispersion in SAD.

Translational outlook

Speckle tracking echocardiography parameters, in particular mechanical dispersion, may be considered as a non-invasive surrogate marker for myocardial fibrosis and risk stratification in SCD.
How suitable are clinical vignettes for the evaluation of symptom checker apps? A test theoretical perspective
Authors: Kopka Marvin , Feufel Markus A. , Berner Eta S. , Schmieding Malte L.
Published: May 2023

Objective

To evaluate the ability of case vignettes to assess the performance of symptom checker applications and to suggest refinements of the methods of case vignette-based audit studies.

Methods

We re-analyzed the publicly available data of two prominent case vignette-based symptom checker audit studies by calculating common metrics of test theory. Furthermore, we developed a new metric, the Capability Comparison Score (CCS), which controls for different degrees of item difficulty of the set of cases each symptom checker evaluated. We then scrutinized whether applying test theory and the CCS alter the performance ranking of the investigated symptom checkers.

Results

In both studies most symptom checkers changed their rank order of triage capability when adjusting for item difficulty with the CCS. The previously reported triage accuracies commonly overestimated the capability of symptom checkers because they do not account for the fact that symptom checkers tend to selectively appraise easier cases. Many case vignettes in both studies showed insufficient (very low and even negative) values of item-total correlation.

Conclusions

A test theoretic perspective helps identify previously unreported limitations to the validity of case vignette-based symptom checker assessments and provides guidance on how to improve the quality of case vignettes and metrics for appraising their quality. A more elaborate metric, which accounts for item difficulty of vignettes an app did (not) evaluate, might prove more meaningful than accuracy alone for competitive assessment of symptom checkers. Our approach contributes to standardizing the methods to appraise symptom checker capability to yield more generalizable results.
Artificial intelligence-based histopathology image analysis identifies a novel subset of endometrial cancers with distinct genomic features and unfavourable outcome
Authors: Darbandsari Amirali , Farahani Hossein , Wiens Matthew , Cochrane Dawn , Asadi Maryam , Mirabadi Ali Khajegili , Jamieson Amy , Farnell David , Ahmadvand Pouya , Douglas Maxwell , Leung Samuel , Abolmaesumi Purang , Jones Steven JM , Talhouk Aline , Kommoss Stefan , Gilks C Blake , Huntsman David G. , Singh Naveena , McAlpine Jessica N. , Bashashati Ali
Published: May 2023

Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employed artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identified a novel sub-group of NSMP EC patients that had markedly inferior progression-free and disease-specific survival (termed ‘p53abn-like NSMP’), in a discovery cohort of 368 patients and an independent validation cohort of 290 patients from another center. Shallow whole genome sequencing revealed a higher burden of copy number abnormalities in the ‘p53abn-like NSMP’ group compared to NSMP, suggesting that this new group is biologically distinct compared to other NSMP ECs. Our work demonstrates the power of AI to detect prognostically different and otherwise unrecognizable subsets of EC where conventional and standard molecular or pathologic criteria fall short, refining image-based tumor classification.
Combined metagenomic- and culture-based approaches to investigate bacterial strain-level associations with medication-controlled mild-moderate atopic dermatitis
Authors: Lane Starr Nicole M , Al-Rayyan Numan , Smith Jennifer M , Sandstrom Shelby , Swaney Mary Hannah , Salamzade Rauf , Steidl Olivia , Kalan Lindsay R , Singh Anne Marie
Published: May 2023

Background

The skin microbiome is disrupted in atopic dermatitis (AD). Existing research focuses on moderate-severe, unmedicated disease.

Objective

Investigate metagenomic- and culture-based bacterial strain-level differences in mild, medicated AD, and the effects these have on human keratinocytes (HK).

Methods

Skin swabs from anterior forearms were collected from 20 pediatric participants; 11 participants with AD sampled at lesional and nonlesional sites and 9 age- and sex-matched controls). Participants had primarily mild-moderate AD and maintained medication use. Samples were processed for microbial metagenomic sequencing and bacterial isolation. Isolates identified asS. aureuswere tested for enterotoxin production. HK cultures were treated with cell free conditioned media from representativeStaphylococcusspecies to measure barrier effects.

Results

Metagenomic sequencing identified significant differences in microbiome composition between AD and control groups. Differences were seen at the species- and strain-levels forStaphylococci, withS. aureusonly found in AD participants and differences inS. epidermidisstrains between control and AD swabs. These strains showed differences in toxin gene presence, which was confirmedin vitroforS. aureusenterotoxins. The strain from the most severe AD participant produced enterotoxin B levels >100-fold higher than the other strains (p<0.001). Strains also displayed differential effects on HK metabolism and barrier function.

Conclusions

Strain level differences in toxin genes fromStaphylococcusstrains may explain varying effects on HK, withS. aureusandnon-aureusstrains negatively impacting viability and barrier function. These differences are likely important in AD pathogenesis.

KEY MESSAGES

Staphylococcal strain effects, more so than species effects, impact keratinocyte barrier function and metabolism, suggesting that strain level differences, and not species-level, may be critical in AD pathogenesis.

The microbiome from mild, medicated atopic dermatitis patients harborStaphylococcusstrains with detrimental effects on skin barrier, and may not only be mediated byS. aureus.

CAPSULE SUMMARY

Patients with mild atopic dermatitis controlled by medication may still harbor strains ofStaphylococcus spp.that carry toxins that negatively impact skin barrier function.
PYCR1 Levels Track with Premature and Chronological Skin Aging
Authors: Sotiropoulou Kortessa , Yumlu Saniye , Hirano Tomoko , Maier Michael , Loh Abigail , Ong Peh Fern , Yim Onn Siong , Liu Chunping , Vial Emmanuel , Altunoğlu Umut , Nampoothiri Sheela , de Silva Deepthi , Fischer-Zirnsak Björn , Kayserili Hülya , Lai Poh San , Dreesen Oliver , Kabashima Kenji , Kornak Uwe , Escande-Beillard Nathalie , Reversade Bruno
Published: May 2023

De Barsy syndrome is a recessive progeroid disease classified under the group of cutis laxa syndromes. The disease is attributed to loss-of-function mutations inPYCR1orALDH18A1, leading to premature skin aging. Here we report fivePYCR1pathogenic alleles and a mouse knockout model of the disease. Through these investigations, we have confirmed the key role of PYCR1 in preventing dermal thinning and other connective tissue abnormalities. However, it remains unknown whether endogenous PYCR1 levels undergo changes during normal aging. To address this query, we examined its levels in cultured human cutaneous fibroblasts subjected to induced or replicative senescence. In both instances, PYCR1 levels dropped and correlated with the loss of proliferative capacity. Furthermore, we validated the relevance of these findingsin vivo, by comparing young and chronologically aged human skin, and found that the levels of PYCR1 in the dermis, but not the epidermis, significantly decreased with age. Our results confirm that the loss of PYCR1 is a driver of human skin aging and that its levels in healthy individuals can serve as a biomarker for connective tissues undergoing normal chronological aging.
Comparison of the urinary proteome in depressed patients before and after modified electroconvulsive therapy
Authors: Tang Shuxuan , Guo Tong , Sha Sha , Wei Jing , Liu Yuqing , Yang Jian , Wang Gang , Gao Youhe
Published: May 2023

Modified electroconvulsive therapy (MECT) is an effective treatment for mood and psychiatric disorders and provides rapid and significant improvements in severe symptoms of several mental health conditions. We attempted to compare the urinary proteome of each depressive patient before and after electroconvulsive therapy. The common biological processes enriched by differential proteins through GO analysis with most patients mainly included cell adhesion (9/9 patients), immune response (7/9), axon guidance (7/9), and oxidation stress (7/9). Moreover, the common biological pathways identified by Ingenuity Pathway Analysis software showed that acute phase response signaling (7/9 patients), NRF2-mediated oxidative stress response (7/9), synaptogenesis signaling pathway (5/9), and ephrin B signaling (5/9) were all upregulated among each patient and were involved in promoting synaptic plasticity and neuroplasticity. Common biological processes and pathways in urine were reported to be related to the mechanism of MECT in the treatment of mental illnesses. In addition, the common differential proteins CSPG4, CBG, APP, NCAM1, and ARSA were suspected to be related to memory loss, memory damage, and memory formation, which might be the effects of MECT.
Patient-specific alterations in blood plasma cfRNA profiles enable accurate classification of cancer patients and controls
Authors: Morlion Annelien , Decruyenaere Philippe , Schoofs Kathleen , Anckaert Jasper , Nuytens Justine , Vanden Eynde Eveline , Verniers Kimberly , Everaert Celine , Offner Fritz , Van Dorpe Jo , Thas Olivier , Vandesompele Jo , Mestdagh Pieter
Published: May 2023

Circulating nucleic acids in blood plasma form an attractive resource to study human health and disease. Here, we applied mRNA capture sequencing of blood plasma cell-free RNA from 266 cancer patients and cancer-free controls (discovery n = 208, 25 cancer types; replication n = 58, 3 types). We observed cancer type-specific as well as pan-cancer alterations in cell-free transcriptomes compared to controls. Differentially abundant RNAs were heterogenous among patients and among cohorts, hampering identification of robust cancer biomarkers. Therefore, we developed a novel method that compares each individual cancer patient to a reference control population to identify so-called biomarker tail genes. The number of biomarker tail genes in a sample enables distinguishing an individual cancer patient from controls. The potential of this novel approach was confirmed in additional cohorts of 65 plasma donors (2 lymphoma types) and 24 urine donors (bladder cancer). Together, our findings demonstrate heterogeneity in cell-free RNA alterations among cancer patients and propose that case-specific alterations can be exploited for classification purposes.
Food & You: A Digital Cohort on Personalized Nutrition
Authors: Héritier Harris , Allémann Chloé , Balakiriev Oleksandr , Boulanger Victor , Carroll Sean F. , Froidevaux Noé , Hugon Germain , Jaquet Yannis , Kebaili Djilani , Riccardi Sandra , Rousseau-Leupin Geneviève , Salathé Rahel M. , Salzmann Talia , Singh Rohan , Symul Laura , Ugurlu-Baud Elif , Verteuil Peter de , Salathé Marcel
Published: May 2023

Nutrition is a key contributor to health. Recently, several studies have identified associations between factors such as microbiota composition and health-related responses to dietary intake, raising the potential of personalized nutritional recommendations. To further our understanding of personalized nutrition, detailed individual data must be collected from participants in their day-to-day lives. However, this is challenging in conventional studies that require clinical measurements and site visits. So-called digital or remote cohorts allowin situdata collection on a daily basis through mobile applications, online services, and wearable sensors, but they raise questions about study retention and data quality. “Food & You” is a personalized nutrition study implemented as a fully digital cohort in which participants track food intake, physical activity, gut microbiota, glycemia, and other data for two to four weeks. Here, we describe the study protocol, report on study completion rates, and describe the collected data, focusing on assessing their quality and reliability. Overall, the study collected data from over 1000 participants, including high-resolution data of nutritional intake of more than 46 million kcal collected from 315,126 dishes over 23,335 participant days, 1,470,030 blood glucose measurements, 49,110 survey responses, and 1,024 stool samples for gut microbiota analysis. Retention was high, with over 60% of the enrolled participants completing the study. Various data quality assessment efforts suggest the captured high-resolution nutritional data accurately reflect individual diet patterns, paving the way for digital cohorts as a typical study design for personalized nutrition.
Health care provider and client experiences of counselling on depot medroxyprogesterone acetate subcutaneous (DMPA-SC) for self-injection in Malawi
Authors: Erlank Chelsey Porter , Ali Gracious , Birhanu Frehiwot , Stanley Melinda , Chirwa Jessie Salamba , Kachale Fannie , Gunda Andrews
Published: May 2023

Since the introduction of depot medroxyprogesterone acetate (DMPA-SC) in 2018, Malawi has achieved national coverage of trained providers in the public sector and steady increases in uptake of DMPA-SC. However, the rate of clients opting to self-inject DMPA-SC has remained lower than early acceptability studies suggested. Providers play an instrumental role in building client confidence to self-inject through counselling. This cross-sectional qualitative study explored the perspectives of providers and injectable clients on the integration of self-injection into contraceptive counselling, to identify best practices and gaps. The study was conducted at public sector sites in three districts (Nkhotakota, Mzimba South, Zomba) in Malawi. In-depth interviews were conducted with provider-administered injectable clients, self-injecting clients, and DMPA-SC trained providers. All providers interviewed reported successfully integrating self-injection into their approach. During health education sessions, providers tended to focus mainly on benefits of self-injection to spark interest in the method, and then follow that up with more in-depth information in individual counselling. Due to time pressures, a minority of providers reported replacing individual counselling with small-group counselling and limited their use of peer testimonials, visualizations, and demonstrations. Most providers skipped client practice on inanimate objects, feeling this was either not necessary or not appropriate given stock or resource constraints. Current self-injecting clients showed the best recall for self-injection steps and tended to report having received comprehensive, supportive counselling including aspects such as peer testimonials, visualizations, and demonstrations to build confidence. Injectable clients who had declined self-injection tended to demonstrate less detailed recall of key self-injection messages and report receiving incomplete information, and lack of peer testimonials, visualization, or demonstrations. Comprehensive counselling and training from supportive providers, including best practices identified in this study, are vital to improving client confidence to self-inject. Providers should be supported to overcome time- and resource-pressures to invest in these best practices.
Protein unfolding thermodynamics predict multicomponent phase behavior
Authors: Rana Neha , Kodirov Rukhillo , Shakya Anisha , King John T.
Published: May 2023

An increasing number of proteins are known to undergo liquid-liquid phase separation (LLPS), with or without nucleic acids or partner proteins, forming dense liquid-like phases termed biomolecular condensates. This physical phenomenon has been implicated in the existence of cellular membraneless organelles as well as in the formation of pathological protein aggregates in several human diseases. While common structural features of proteins with a propensity to undergo LLPS have been well documented, currently there is no thermodynamic framework capable of predicting the phase behavior of native proteins. Here, we show that two fundamental thermodynamic properties associated with the unfolding of a native protein, change in heat capacity (ΔCunfold) and change in Gibbs free energy (ΔGunfold), are sufficient to predict the formation of multicomponent biomolecular condensates. We find that proteins with smallΔCunfoldandΔGunfoldvalues, which indicate a native state that is thermodynamically similar to the fully unfolded state, promote LLPS. In contrast, proteins with largeΔCunfoldandΔGunfoldvalues promote aggregation. We also demonstrate that the stability of the liquid-like condensate can be predicted from the proximity of a protein’s thermodynamic variable values to the phase boundary. This work elucidates a deep connection between single-protein thermodynamics and multicomponent phase behavior, and provides an avenue for predicting pathological droplet-aggregate transition.

Significance Statement

Biomolecular phase transitions, such as LLPS of proteins and nucleic acids, is emerging as an important concept in understanding the link between dysregulation of membraneless compartmentalization in cells and several human diseases. Currently, analysis of structural features such as intrinsic disorder and charged residue content is the “rule-of-thumb” to predict a protein’s propensity to undergo LLPS. There are several instances where this qualitative approach fails, potentially due to not accounting for a protein’s native structure. We demonstrate an empirical correlation between the unfolding thermodynamics of native proteins and their phase behavior, which enables a quantitative prediction of multicomponent LLPS. This novel approach, based on single-protein thermodynamics, has the potential to quantitatively predict pathological phase transitions of proteins in degenerative human diseases.
Convergent evolution of noxious heat sensing by TRPA5, a novel class of heat sensor inRhodnius prolixus
Authors: Liénard Marjorie A. , Baez-Nieto David , Tsai Cheng-Chia , Valencia-Montoya Wendy A. , Werin Balder , Johanson Urban , Lassance Jean-Marc , Pan Jen Q. , Yu Nanfang , Pierce Naomi E.
Published: May 2023

As ectotherms, insects need a multifaceted repertoire of heat-sensitive receptors to monitor environmental temperatures and finely control behavioral thermoregulation. Here, we show thatTRPA5genes, a class of ankyrin transient receptor potential channels lost in genomes of model fruit flies or mosquitoes, are widespread across insect orders, and encode a previously uncharacterized type of heat receptors. We demonstrate that RpTRPA5B, a TRPA5 channel of the triatomine bugRhodnius prolixus(Insect: Hemiptera), primary vector of Chagas disease, forms a homo-tetrameric channel displaying a uniquely high thermosensitivity. The channel biophysical determinants include a large channel activation enthalpy change (72 kcal/mol), a high temperature coefficient (Q10= 25), and temperature-induced currents from 53 °C to 68 °C (T0.5= 58.6 °C)in vitro,similar to mammalian noxious TRPV heat receptors. Monomeric and tetrameric predictions of the ion channel architecture show reliable and conserved structural parallels with fruit fly dTRPA1, albeit depicting structural uniqueness from dTRPA, Painless and Pyrexia in the ankyrin repeat domain and the channel selectivity filter, potential modulator regions of functional characteristics of TRPs. The channel activation response, structural features and ubiquitous sensory tissue expression delineate a potential thermosensitive physiological niche close to that ofPyrexiagenes, lost during the evolution of true bugs. Overall, the finding ofTRPA5genes as a class of temperature-activated receptor illustrates the dynamic evolution of a large family of insect molecular heat detectors, with TRPs as promising multimodal sensory targets for triatomine vector control.
Fibrous finite element modeling of the optic nerve head region
Authors: Islam Mohammad R. , Ji Fengting , Bansal Manik , Hua Yi , Sigal Ian A.
Published: May 2023

The optic nerve head (ONH) region at the posterior pole of the eye is supported by a fibrous structure of collagen fiber bundles. Discerning how the fibrous structure determines the region biomechanics is crucial to understand normal physiology, and the roles of biomechanics on vision loss. The fiber bundles within the ONH structure exhibit complex three-dimensional (3D) organization and continuity across the various tissue components. Computational models of the ONH, however, usually represent collagen fibers in a homogenized fashion without accounting for their continuity across tissues, fibers interacting with each other and other synergistic effects in a fibrous structure. We present a novel fibrous finite element (FFE) model of the ONH that incorporates discrete collagen fiber bundles and their histology-based 3D organization to study ONH biomechanics as a fibrous structure. The FFE model was constructed using polarized light microscopy data of porcine ONH cryosections, representing individual fiber bundles in the sclera, dura and pia maters with beam elements and canal tissues as continuum structures. The FFE model mimics the histological in-plane orientation and width distributions of collagen bundles as well as their continuity across different tissues. Modeling the fiber bundles as linear materials, the FFE model predicts the nonlinear ONH response observed in an inflation experiment from the literature. The model also captures important microstructural mechanisms including fiber interactions and long-range strain transmission among bundles that have not been considered before. The FFE model presented here advances our understanding of the role of fibrous collagen structure in the ONH biomechanics.

Statement of Significance

The microstructure and mechanics of the optic nerve head (ONH) are central to ocular physiology. Histologically, the ONH region exhibits a complex continuous fibrous structure of collagen bundles. Understanding the role of the fibrous collagen structure on ONH biomechanics requires high-fidelity computational models previously unavailable. We present a novel computational model of the ONH that incorporates histology-based fibrous collagen structure derived from polarized light microscopy images. The model predictions agree with experiments in the literature, and provide insight into important microstructural mechanisms of fibrous tissue biomechanics, such as long-range strain transmission along fiber bundles. Our model can be used to study the microstructural basis of biomechanical damage and the effects of collagen remodeling in glaucoma.
RAmbler:de novogenome assembly of complex repetitive regions
Authors: Chakravarty Sakshar , Logsdon Glennis , Lonardi Stefano
Published: May 2023

Complex repetitive regions (also called segmental duplications) in eukaryotic genomes often contain essential functional and regulatory information. Despite remarkable algorithmic progress in genome assembly in the last twenty years, modernde novoassemblers still struggle to accurately reconstruct these highly repetitive regions. When sequenced reads will be long enough to span all repetitive regions, the problem will be solved trivially. However, even the third generation of sequencing technologies on the market cannot yet produce reads that are sufficiently long (and accurate) to span every repetitive region in large eukaryotic genomes.

In this work, we introduce a novel algorithm called RAmbler to resolve complex repetitive regions based on high-quality long reads (i.e., PacBio HiFi). We first identify repetitive regions by mapping the HiFi reads to the draft genome assembly and by detecting un-usually high mapping coverage. Then, (i) we compute thek-mers that are expected to occur only once in the genome (i.e., single copyk-mers, which we callunikmers), (ii) we barcode the HiFi reads based on the presence and the location of their unikmers, (iii) we compute an overlap graph solely based on shared barcodes, (iv) we reconstruct the sequence of the repetitive region by traversing the overlap graph.

We present an extensive set of experiments comparing the performance of RAmbler against Hifiasm, HiCANU and Verkko on synthetic HiFi reads generated over a wide range of repeat lengths, number of repeats, heterozygosity rates and depth of sequencing (over 140 data sets). Our experimental results indicate that RAmbler outperforms Hifiasm, HiCANU and Verkko on the large majority of the inputs. We also show that RAmbler can resolve several long tandem repeats inArabidopsis thalianausing real HiFi reads.

The code for RAmbler is available athttps://github.com/sakshar/rambler.

CCS CONCEPTS

Applied computing→Bioinformatics;Computational genomics;Molecular sequence analysis; •Theory of computation→ Graph algorithms analysis.
Exploration of an enzyme-product mapping approach for plant-derived diterpene synthases
Authors: Zhao Yalan , Liang Yupeng , Han Xiulin , Wen Mengliang
Published: May 2023

Plant-derived diterpene synthases (PdiTPSs) play a critical role in the formation of structurally and functionally diverse diterpenoids. However, the relationship between PdiTPSs and the specificity or promiscuity of their products remains unclear. To explore this correlation, the sequences of 199 functionally characterized PdiTPSs and their corresponding 3D structures were collected and manually corrected. Using this compiled annotated database, the correlations among PdiTPSs sequences, domains, structures and their corresponding products were comprehensively analyzed. However, utilizing sequence similarity network (SSN), phylogenetic trees, and structural topology features alone was insufficient for effective functional classification of PdiTPSs as these methods could not establish a clear mapping between the enzymes and products. Surprisingly, residues verified to play a function through mutagenesis experiments were located within 8Å of the substrate. Aromatic residues surrounding the substrate exhibited selectivity towards its chemical structure. Specifically, tryptophan (W) was preferentially located around the linear substrate geranylgeranyl pyrophosphate (GGPP), while phenylalanine (F) and tyrosine (Y) were preferentially located around the initial cyclized diterpene intermediate. This analysis revealed the functional space of residues surrounding the substrate of PdiTPSs, most of which have not been experimentally explored. These findings provide guidance for screening specific residues for mutation studies to change the catalytic products of PdiTPSs, allowing us to better understand the correlation between PdiTPSs and their products.
RNA tertiary structure modeling with BRiQ potential in CASP15
Authors: Chen Ke , Zhou Yaoqi , Wang Sheng , Xiong Peng
Published: May 2023

We describe the modeling method for RNA tertiary structures employed by team AIchemy_RNA2 in the 15thCritical Assessment of Protein Structure Prediction (CASP15). The method consists of the following steps. Firstly, secondary structure information was derived from various manually-verified sources. With this information, the full length RNA was fragmented into structural motifs. The structures of each motif were predicted and then assembled into the full structure. To reduce the searching conformational space, a RNA structure was organized into an optimal base folding tree. And to further improve the sampling efficiency, the energy surface was smoothed at high temperatures during the Monte Carlo sampling to make it easier to move across the energy barrier. The statistical potential energy function BRiQ was employed during Monte Carlo energy optimization.
A patient-centered view of symptoms, functional impact, and priorities in post-COVID-19 syndrome: Cross-sectional results from the Québec Action Post-COVID cohort
Authors: Mayo Nancy , Brouillette Marie-Josée , Falcone Emilia Liana , Fellows Lesley K
Published: May 2023

Background

Health services planning and mechanism-focused research would benefit from a clearer picture of symptoms, impact, and personal priorities in post-COVID-19 syndrome (PCS). This study aimed to provide estimates of the symptom, function, and quality of life (QOL) impact of PCS.

Methods

People living in Quebec, aged ≥18, were eligible for the Québec Action for/pour le Post-COVID (QAPC) study if they had symptoms lasting more than 4 weeks post-acute SARS-CoV-2 infection, with or without a positive COVID-19 test. Recruitment was through conventional and social media between September 2022-January 2023. Standardized and individualized questionnaires, in French or English, were accessed through an online portal. We report cross-sectional results from the baseline visit of the first 414 participants in this ongoing longitudinal study.

Results

Individuals spontaneously reported symptoms attributable to an average of 4.5 organ systems. Fatigue was most frequent. Effects on function and quality of life were moderate to severe, and had already persisted for a year or more in the majority. Personal intervention priorities included fatigue and post-exercise malaise, cognitive symptoms, shortness of breath, and impaired taste and smell. Women and men were similar on PCS impact, while older age was associated with lower impact.

Interpretation

Symptom clusters defined a range of severity, with fatigue a pervasive symptom at all levels of severity. Participants in this study are likely to be representative of those seeking health care for post-COVID-19 symptoms in Canada and the results can inform next steps for clinical, research, and health services planning.
Barcoding of episodic memories in the hippocampus of a food-caching bird
Authors: Chettih Selmaan N. , Mackevicius Emily L. , Hale Stephanie , Aronov Dmitriy
Published: May 2023

Episodic memory, or memory of experienced events, is a critical function of the hippocampus1–3. It is therefore important to understand how hippocampal activity represents specific events in an animal’s life. We addressed this question in chickadees – specialist food-caching birds that hide food at scattered locations and use memory to find their caches later in time4, 5. We performed high-density neural recordings in the hippocampus of chickadees as they cached and retrieved seeds in a laboratory arena. We found that each caching event was represented by a burst of firing in a unique set of hippocampal neurons. These ‘barcode-like’ patterns of activity were sparse (<10% of neurons active), uncorrelated even for immediately adjacent caches, and different even for separate caches at the same location. The barcode representing a specific caching event was transiently reactivated whenever a bird later interacted with the same cache – for example, to retrieve food. Barcodes co-occurred with conventional place cell activity6, 7, as well as location-independent responses to cached seeds. We propose that barcodes are signatures of episodic memories evoked during memory recall. These patterns assign a unique identifier to each event and may be a mechanism for rapid formation and storage of many non-interfering memories.
Wastewater surveillance suggests unreported Mpox cases in a low-prevalence area
Authors: Oghuan Jeremiah , Chavarria Carlos , Vanderwal Scout R. , Gitter Anna , Ojaruega Akpevwe Amanda , Monserrat Carlos , Bauer Cici X. , Brown Eric L. , Cregeen Sara Javornik , Deegan Jennifer , Hanson Blake M. , Tisza Michael , Ocaranza Hector I , Balliew John , Maresso Anthony W. , Rios Janelle , Boerwinkle Eric , Mena Kristina D. , Wu Fuqing
Published: May 2023

Wastewater surveillance has emerged as a valuable tool for monitoring infectious disease agents including SARS-CoV-2 and Mpox virus. However, detecting the Mpox virus in wastewater is particularly challenging due to its relatively low prevalence in the community. In this study, we detected Mpox virus in wastewater from a US-Mexico border city with a low prevalence of Mpox disease during February and March 2023 using real-time PCR assays targeting the C22L, F3L, and F8L genes. An increasing trend of viral concentration was observed 1∼2 weeks earlier than when the Mpox case was reported. Further sequencing and epidemiological analysis provided supporting evidence for unreported Mpox infections in the city. This study showcases a combined approach with multiple molecular assays for efficient detection of the Mpox virus in wastewater in a low-prevalence area. The findings emphasize the value of wastewater surveillance as a timely identification tool for infectious diseases in low-prevalence areas, and the need for heightened vigilance to control the spread of infectious diseases in such settings.
False positive glycopeptide identification via in-FAIMS fragmentation
Authors: Rangel-Angarita Valentina , Mahoney Keira E. , Kwon Catherine , Sarker Raibat , Lucas Taryn M. , Malaker Stacy A.
Published: May 2023

High-field asymmetric waveform ion mobility spectrometry (FAIMS) separates glycopeptides in the gas phase prior to mass spectrometry (MS) analysis, thus offering the potential to analyze glycopeptides without prior enrichment. Several studies have demonstrated the ability of FAIMS to enhance glycopeptide detection but have primarily focused on N-glycosylation. Here, we evaluated FAIMS for O-glycoprotein and mucin-domain glycoprotein analysis using samples of varying complexity. We demonstrated that FAIMS was useful in increasingly complex samples, as it allowed for the identification of more glycosylated species. However, during our analyses, we observed a phenomenon called “in FAIMS fragmentation” (IFF) akin to in source fragmentation but occurring during FAIMS separation. FAIMS experiments showed a 2-5-fold increase in spectral matches from IFF compared to control experiments. These results were also replicated in previously published data, indicating that this is likely a systemic occurrence when using FAIMS. Our study highlights that although there are potential benefits to using FAIMS separation, caution must be exercised in data analysis because of prevalent IFF, which may limit its applicability in the broader field of O-glycoproteomics.

Graphical abstract
A moderated mediation model of smart-device use: work–family conflict and well-being by age
Authors: Haar Jarrod , Wilkinson Simon
Published: May 2023

Purpose

Smart device use for work during family time is a growing issue of concern and is likely exacerbated by the COVID-19 pandemic. The authors test a broad range of well-being outcomes (job anxiety, job depression and insomnia) to extend the literature. Work–family conflict was included as a mediator with age as a moderator.

Design/methodology/approach

The study uses representative data from 422 New Zealand employees across a wide range of occupations, sectors, and industries from late 2020. Confirmatory factor analysis (CFA) of the data was used and moderated mediation analysis was conducted.

Findings

Overall, hypotheses were supported, with mWork positively influencing work–family and family–work conflict, and all well-being outcomes. Work–family and family–work conflict acted as mediators and age interacted with mWork leading to more conflict for older workers. Finally, moderated mediation effects were supported with age acting as a boundary condition, whereby the indirect effect of mWork on well-being outcomes increases as age increases.

Research limitations/implications

The findings highlight the danger of using mobile devices to work in family time and highlight the additional risks for older workers.

Originality/value

The mWork literature has a limited focus on well-being outcomes, and the New Zealand data provides insights from a largely underrepresented population in the literature. Further, the use of age as a moderator of mWork towards well-being outcomes provides further originality.
The effect of political connections and governance on credit ratings: substitution versus complementary view: case of Tunisian firm
Authors: Bouaine Wided , Alaya Karima , Slim Chokri
Published: May 2023

Purpose

The objective of this paper is to study the impact of political connection and governance on credit rating and whether there is a substitution or complementary relationship between them.

Design/methodology/approach

In order to achieve the objective, a succession of eight ordered probit regressions has been carried out. Moderating variables between the political connection and governance characteristics were introduced. The whole population is taken as a sample, i.e., 27 Tunisian companies that are evaluated by FITSH NORTH AFRICA agencies over a period of 10 years (2009–2018).

Findings

The outcomes are mixed. They show that the political connection does not always influence credit rating; the size and board independence always improves credit rating; the duality between the functions affects credit rating; whereas the majorities’ proportion does not influence credit rating; and a substitution between the political connection and the governance characteristics is validated.

Research limitations/implications

Like any other research, our results are factors of our measures and variable choice and depends heavily on the how these variables were conceived. Also, although our number of observations responds to the statistical result generalization requirements, our sample remains relatively narrow with 27 companies only.

Practical implications

In practice, the research will allow investors to have a better vision upon the future of their investments based on whether to develop their governance system or promote political networking. It will also prompt lenders to look beyond ratings and consider factors such as political connections to make a rational judgment on their future placements.

Social implications

This study leads us to find various solutions: the establishment of credit agencies that take into consideration all the data of all the operators taken as a whole (bank, leasing company, and factoring). It encourages the reorganization of the Tunisian banking sector through mergers for example.

Originality/value

This study is a pioneer in the credit rating field in Tunisia, where the source of debt financing is the most used by all enterprises across all sectors. This study extends the literature of political connection effectiveness, independent directors, board size, in improving corporate performance and credit rating.
An analysis of comment letters on a new, stand-alone standard for audits of less complex entities’ financial statements
Authors: Haapamäki Elina Elisabet , Mäki Juha
Published: May 2023

Purpose

The objective of this paper is to extend the debate on audit quality in the less complex entity (LCE) context by analyzing comment letters submitted to the International Auditing and Assurance Standards Board (IAASB). The IAASB has drafted a new, stand-alone standard for audits of LCEs’ financial statements.

Design/methodology/approach

The Gioia method is utilized to conduct the qualitative analysis. This enables the material to shine and provide a comprehensive picture of the important aspects of the comment letters about the International Standard on Auditing (ISA) for LCEs. A content analysis of the 145 comment letters is conducted to identify the extent of the support for and the arguments against the new, stand-alone draft standard for audits of LCEs’ financial statements. In addition, this study considers how the comment letters describe the respondents’ views on audit quality in relation to the new standard. Finally, the tone of the comment letters and audit quality arguments is investigated.

Findings

The findings provide a useful framework of the most frequently used arguments supporting and opposing the ISA for LCEs. Within the themes identified, a wide variety of issues and concerns are discussed. The results reveal that the arguments in the comment letters are contradictory. For instance, when discussing audit quality, those interest groups that perceived many positive opportunities in the adoption of the ISA for LCEs thought that the audit quality would increase. Conversely, those interest groups that were skeptical about the success of the ISA for LCEs argued that the audit quality could be compromised by the general prejudice that the ISA for LCEs might be perceived as a lower-quality audit with fewer procedures.

Originality/value

This paper is, to the best of the authors’ knowledge, the first to examine the content of comment letters in the context of a new, stand-alone standard for audits of LCEs. The international audience can utilize the results in the context of the widely discussed issue of reducing LCEs’ auditing obligations. This study aims to contribute to the two streams of accounting literature concerning audit quality and political lobbying.
Attitude, repurchase intention and brand loyalty toward halal cosmetics
Authors: Hussain Khalil , Fayyaz Muhammad Shahzeb , Shamim Amjad , Abbasi Amir Zaib , Malik Sana Jawed , Abid Muhammad Farrukh
Published: May 2023

Purpose

This study aims to investigate consumer brand loyalty toward halal cosmetics using the theory of planned behavior through repurchase intention, which is primarily relying on the consumer’s attitude toward halal cosmetics. Important predictors such as trust on halal cosmetics, quality of halal cosmetics and religious beliefs of millennial Muslim female consumers shape consumer attitude.

Design/methodology/approach

The present study used the quantitative research design and deductive approach to collect the data from 275 halal cosmetics users in Pakistan by using a judgmental sampling approach.

Findings

Findings of the study provide useful insights for both theory and practice. The results support product quality, religious belief and trust on halal cosmetics as predictors of consumer’s attitude toward halal cosmetics that further develop consumers’ repurchase intention, which in turn enhances their overall brand loyalty. Besides, the findings also show that consumer repurchase intention has a mediating effect between consumer attitude toward halal cosmetics and consumer brand loyalty.

Practical implications

The current study helps in advancing practitioners’ understanding of female consumers’ brand loyalty in the halal cosmetics context. This study is considered to be greatly helpful for managers to gain knowledge about how repurchase intention and brand loyalty of millennial Muslim female consumers can be developed in the halal cosmetics segment, especially in the case of Pakistan.

Originality/value

Brand loyalty has been investigated by previous studies through different predictors and antecedents. This study contributes to the literature of brand loyalty by empirically examining and validating the different antecedents of consumer attitude that are accountable for creating consumer brand loyalty in the domain of halal cosmetics within the Pakistani cultural context. The current study also enhances the previous scholarly understanding on halal cosmetics by investigating the mediating role of consumer repurchase intention of halal cosmetics that further extends the discussion for both theory and practice.