bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neurocognome in Childhood: Relevance of Neurocognitive Network Organization
Authors: Königs M. , Kooper C.C. , Oosterlaan J.
Published: June 2023

Neurocognitive functioning is crucial for child development, but the relevance of interplay between neurocognitive functions in childhood remains poorly understood. This explores the relevance of neurocognitive network organization in childhood by the application of network theory to neurocognitive data at the individual level. A community sample of children (N = 132), between 6 and 18 years of age (M = 11.4) performed computerized neurocognitive testing. Neurocognitive connectivity was calculated between each pair of test scores, creating individual connectivity matrices after which graph theory was applied to determine global network organization and local network organization. The relation between demographics and neurocognitive network organization was investigated with correlation analysis. The relevance for intelligence (Wechsler short forms) and behavioral problems (Strength and Difficulties Questionnaire) was assessed with multivariate regression. K-means clustering was applied to investigate the correspondence between typical neurocognitive network organizations and conventionally assessed neurocognitive performance. The results show that global as well as local neurocognitive network organization is related to age, intelligence and behavior problems. Moreover, children from neurocognitive clusters with typical configurations of global network organization also differed in terms of conventionally assessed neurocognitive performance. In conclusion, this study provides cross-sectional evidence suggesting the presence of developmental reorganization of the interplay between neurocognitive functions. Neurocognitive network organization is also related to crucial aspects of functioning in children (intelligence, behavior problems) and the level of conventionally assed neurocognitive performance. Thereby, this study shows that individual network analysis provides a complementary view on the child functioning and may hold relevance for a better understanding of child development and the influence of neuropathology on daily life functioning.
A prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomized controlled within-subject cross-over trial
Authors: Medawar Evelyn , Beyer Frauke , Thieleking Ronja , Haange Sven-Bastiaan , Rolle-Kampczyk Ulrike , Reinicke Madlen , Chakaroun Rima , von Bergen Martin , Stumvoll Michael , Villringer Arno , Witte A. Veronica
Published: June 2023

Objective

Animal studies suggest that prebiotic, plant-derived nutrients could improve homeostatic and hedonic brain functions through improvements in microbiome-gut-brain communication. However, little is known if these results are applicable to humans. Therefore, we tested the effects of high-dosed prebiotic fiber on reward-related food decision-making in a randomized controlled within-subject cross-over study and assayed potential microbial and metabolic markers.

Design

59 overweight young adults (19 females, 18-42 years, body mass index 25-30 kg/m2) underwent functional task MRI before and after 14 days of supplementary intake of 30 g/d of inulin (prebiotics) and equicaloric placebo, respectively. Short chain fatty acids (SCFA), gastrointestinal hormones, glucose/lipid and inflammatory markers were assayed in fasting blood. Gut microbiota and SCFA were measured in stool.

Results

Compared to placebo, participants showed decreased brain activation towards high-caloric wanted food stimuli in the ventral tegmental area and right orbitofrontal cortex after prebiotics (pre-registered, pFWE < 0.05). While fasting blood levels remained largely unchanged, 16S-rRNA sequencing showed significant shifts in the microbiome towards increased occurrence of, among others, SCFA-producingBifidobacteriacea, and changes in >90 predicted functional signaling pathways after prebiotic intake. Changes in brain activation correlated with changes inActinobacteriamicrobial abundance and associated activity linked with SCFA production, such as ABC transporter metabolism.

Conclusions

In this proof-of-concept study, a prebiotic intervention attenuated reward-related brain activation during food-decision making, paralleled by shifts in gut microbiota indicative of higher SCFA production.
A review of behavioural rating scales for the assessment of Attention Deficit/Hyperactivity Disorder among adults in research
Authors: Grandjean Marius , Hochman Shachar , Mukherjee Raja , Cohen Kadosh Roi
Published: June 2023

Objective

This review aims to provide researchers with a contemporary and comprehensive understanding of the current state of behavioural rating scales used in evaluating adult ADHD for research purposes. The objective is to offer guidance that enables researchers to make informed decisions when selecting the most suitable scale for their studies. Moreover, our intention was to map and compare these scales, with a specific focus on detecting feigned or invalid symptom presentation—an aspect notably overlooked in prior reviews.

Method

We reviewed the most recent literature on behavioural rating scales for adult ADHD assessment. We evaluated the scales and compared them based on their psychometric properties and the range of symptoms that they assessed.

Results

The Conners’ Adult ADHD Rating Scales (CAARS), Mind Excessively Wandering Scale (MEWS), and Wender Utah Rating Scale (WURS) have emerged as the most accurate measures for assessing adult ADHD. Moreover, there is an increasing emphasis on the development of assessment tools, either integrated within existing scales or as independent measures, to evaluate feigning or invalid symptom presentation. In that regard, stand-alone measures have demonstrated greater effectiveness compared to embedded measures, with the ADHD Symptom Infrequency Scale (ASIS) being identified as the most accurate scale for the detection of feigning.

Conclusion

Based on this review, we provide recommendations for the behavioural rating scales with the most accurate measurement of relevant variables in research-related settings.
A non-enzymatic test for SARS-CoV-2 RNA using DNA nanoswitches
Authors: Vilcapoma Javier , Aliyeva Asmer , Hayden Andrew , Chandrasekaran Arun Richard , Zhou Lifeng , Abraham Punnoose Jibin , Yang Darren , Hansen Clinton , Shiu Simon Chi-Chin , Russell Alexis , George Kirsten St. , Wong Wesley P. , Halvorsen Ken
Published: June 2023

The emergence of a highly contagious novel coronavirus in 2019 led to an unprecedented need for large scale diagnostic testing. The associated challenges including reagent shortages, cost, deployment delays, and turnaround time have all highlighted the need for an alternative suite of low-cost tests. Here, we demonstrate a diagnostic test for SARS-CoV-2 RNA that provides direct detection of viral RNA and eliminates the need for costly enzymes. We employ DNA nanoswitches that respond to segments of the viral RNA by a change in shape that is readable by gel electrophoresis. A new multi-targeting approach samples 120 different viral regions to improve the limit of detection and provide robust detection of viral variants. We apply our approach to a cohort of clinical samples, positively identifying a subset of samples with high viral loads. Since our method directly detects multiple regions of viral RNA without amplification, it eliminates the risk of amplicon contamination and renders the method less susceptible to false positives. This new tool can benefit the COVID-19 pandemic and future emerging outbreaks, providing a third option between amplification-based RNA detection and protein antigen detection. Ultimately, we believe this tool can be adapted both for low-resource onsite testing as well as for monitoring viral loads in recovering patients.
Role of endogenous adenine in kidney failure and mortality with diabetes
Authors: Sharma Kumar , Zhang Guanshi , Hansen Jens , Bjornstad Petter , Lee Hak Joo , Menon Rajasree , Hejazi Leila , Liu Jian-Jun , Franzone Anthony , Looker Helen C. , Choi Byeong Yeob , Fernandez Roman , Venkatachalam Manjeri A. , Kugathasan Luxcia , Sridhar Vikas S. , Natarajan Loki , Zhang Jing , Sharma Varun , Kwan Brian , Waikar Sushrut , Himmelfarb Jonathan , Tuttle Katherine , Kestenbaum Bryan , Fuhrer Tobias , Feldman Harold , de Boer Ian H. , Tucci Fabio C. , Sedor John , Heerspink Hiddo Lambers , Schaub Jennifer , Otto Edgar , Hodgin Jeffrey B. , Kretzler Matthias , Anderton Christopher , Alexandrov Theodore , Cherney David , Lim Su Chi , Nelson Robert G. , Gelfond Jonathan , Iyengar Ravi ,   the Kidney Precision Medicine Project
Published: June 2023

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality, however, few mechanistic biomarkers are available for high risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from Chronic Renal Insufficiency Cohort (CRIC), Singapore Study of Macro-Angiopathy and Reactivity in Type 2 Diabetes (SMART2D), and the Pima Indian Study determined if urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in CRIC (HR 1.57, 1.18, 2.10) and SMART2D (HR 1.77, 1.00, 3.12). ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in CRIC (HR 2.36, 1.26, 4.39), SMART2D (HR 2.39, 1.08, 5.29), and Pima Indian study (HR 4.57, CI 1.37-13.34). Empagliflozin lowered UAdCR in non-macroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology and transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mammalian target of rapamycin (mTOR). Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.
No evidence for differential saccadic adaptation in children and adults with an Autism Spectrum diagnosis
Authors: Tarrit Katy , Freedman Edward G. , Francisco Ana Alves , Horsthuis Douwe J. , Molholm Sophie , Foxe John J.
Published: June 2023

Background

Altered patterns of eye-movements during scene exploration, and atypical gaze preferences in social settings, have long been noted as features of the Autism phenotype. While these are typically attributed to differences in social engagement and interests (e.g., preferences for inanimate objects over face stimuli), there are also reports of differential saccade measures to non-social stimuli, raising the possibility that fundamental differences in visuo-sensorimotor processing may be at play. Here, we tested the plasticity of the eye-movement system using a classic saccade-adaptation paradigm to assess whether individuals with ASD make typical adjustments to their eye-movements in response to experimentally introduced errors. Saccade adaptation can be measured in infants as young as 10 months, raising the possibility that such measures could be useful as early neuromarkers of ASD risk.

Methods

Saccade amplitudes were measured while children and adults with ASD (N=41) and age-matched typically developing (TD) individuals (N=68) made rapid eye-movements to peripherally presented targets. During adaptation trials, the target was relocated from 20-degrees to 15-degrees from fixation once a saccade to the original target location was initiated, a manipulation that leads to systematic reduction in saccade amplitudes in typical observers.

Results

Neither children nor adults with ASD showed any differences relative to TD peers in their abilities to appropriately adapt saccades in the face of persistently introduced errors.

Conclusions

Of the three studies to date of saccade adaptation in ASD, none have shown frank deficits in saccade adaptation. Unlike prior studies, we found no evidence for a slower adaptation rate during the early adaptation phase, and no of evidence greater variance of saccade amplitudes in ASD. In post-hoc analysis, there was evidence for larger primary saccades to non-adapted targets, a finding requiring replication in future work.
Potential role of fructose on human colon DNA methylation in racial disparities observed for colorectal cancer risk
Authors: Devall Matthew A. , Eaton Stephen , Hu Gaizun , Sun Xiangqing , Jakum Ethan , Venkatesh Samyukta , Powell Steven M. , Yoshida Cynthia , Weisenberger Daniel J. , Cooper Gregory S. , Willis Joseph , Ebrahim Seham , Zoellner Jamie , Casey Graham , Li Li
Published: June 2023

Background and aims

An increasing body of observational studies has linked fructose intake to colorectal cancer (CRC). African Americans (AAs) are significantly more likely than European Americans to consume greater quantities of fructose and to develop right-side colon cancer. Yet, a mechanistic link between these two associations remains poorly defined. We aimed to identify differentially methylated regions (DMRs) associated with dietary fructose consumption measures obtained from food frequency questionnaires in a cohort of normal colon biopsies derived from AA men and women (n=79)

Methods

DNA methylation data from this study was obtained using the Illumina Infinium MethylationEPIC kit and is housed under accession GSE151732. DMR analysis was carried out usingDMRcatein right and matched left colon, separately. Secondary analysis of CRC tumors was carried out using data derived from TCGA-COAD, GSE101764 and GSE193535. Differential expression analysis was carried out on CRC tumors from TCGA-COAD usingDESeq2.

Results

We identified 4,263 right-side fructose-DMRs. In contrast, only 24 DMRs survived multiple testing corrections (FDR<0.05) in matched, left colon. To identify targets by which dietary fructose drives CRC risk, we overlaid these findings with data from three CRC tumor datasets. Remarkably, almost 50% of right-side fructose-DMRs overlapped regions associated with CRC in at least one of three datasets.TNXBandCDX2ranked among the most significant fructose risk DMRs in right and left colon respectively that also displayed altered gene expression in CRC tumors.

Conclusions

Our mechanistic data support the notion that fructose has a greater CRC-related effect in right than left AA colon, alluding to a potential role for fructose in contributing to racial disparities in CRC.
An Early Adverse Drug Event Detection Approach with False Discovery Rate Control
Authors: Shi Yi , Peng Xueqiao , Liu Ruoqi , Sun Anna , Yang Yuedi , Zhang Ping , Zhang Pengyue
Published: June 2023

Adverse drug event (ADE) is a significant challenge in clinical practice. Many ADEs have not been identified timely after the approval of the corresponding drugs. Despite the use of drug similarity network demonstrates early success on improving ADE detection, false discovery rate (FDR) control remains unclear in its application. Additionally, performance of early ADE detection has not been explicitly investigated under the time-to-event framework. In this manuscript, we propose to use the drug similarity based posterior probability of null hypothesis for early ADE detection. The proposed approach is also able to control FDR for monitoring a large number of ADEs of multiple drugs. The proposed approach outperforms existing approaches on mining labeled ADEs in the US FDA’s Adverse Event Reporting System (FAERS) data, especially in the first few years after the drug initial reporting time. Additionally, the proposed approach is able to identify more labeled ADEs and has significantly lower time to ADE detection. In simulation study, the proposed approach demonstrates proper FDR control, as well as has better true positive rate and an excellent true negative rate. In our exemplified FAERS analysis, the proposed approach detects new ADE signals and identifies ADE signals in a timelier fashion than existing approach. In conclusion, the proposed approach is able to both reduce the time and improve the FDR control for ADE detection.
Population-level effectiveness of pre-exposure prophylaxis for HIV prevention among men who have sex with men in Montréal: a modelling study of surveillance and survey data
Authors: Doyle Carla M , Milwid Rachael M , Cox Joseph , Xia Yiqing , Lambert Gilles , Tremblay Cécile , Otis Joanne , Boily Marie-Claude , Baril Jean-Guy , Thomas Réjean , Blais Alexandre Dumont , Trottier Benoit , Grace Daniel , Moore David M. , Mishra Sharmistha , Maheu-Giroux Mathieu
Published: June 2023

Background

HIV pre-exposure prophylaxis (PrEP) has been recommended and partly subsidized in Québec since 2013. We aimed to evaluate the population-level impact of PrEP on HIV transmission among men who have sex with men (MSM) in Montréal over 2013-2021.

Methods

We used an agent-based mathematical model of sexual HIV transmission to estimate the fraction of HIV acquisitions averted by PrEP compared to a counterfactual scenario without PrEP. The model was calibrated to local MSM survey and cohort data and accounted for COVID-19 pandemic impacts on sexual activity, prevention, and care. To assess potential optimization strategies, we modelled hypothetical scenarios prioritizing PrEP to MSM with high sexual activity or aged ≤45 years, increasing coverage to levels achieved in Vancouver (where PrEP is free-of-charge), and improving retention.

Results

Over 2013-2021, the estimated annual HIV incidence decreased from 0.4 (90% credible interval [CrI]: 0.3-0.6) to 0.2 (90%CrI: 0.1-0.2) per 100 person-years. PrEP coverage in HIV-negative MSM remained low until 2015 (<1%). Afterward, coverage increased to a maximum of 10% (15% of those eligible for PrEP) and the cumulative fraction of HIV acquisitions averted over 2015-2021 was 20% (90%CrI: 11%-30%). The hypothetical scenarios modelled showed that PrEP could have averted up to 63% (90%CrI: 54%-70%) of acquisitions if coverage reached 10% in 2015 and 30% in 2019, like in Vancouver.

Interpretation

PrEP reduced population-level HIV transmission among Montréal MSM. However, our study suggests missed prevention opportunities and provides support for public policies that provide PrEP free-of-cost to MSM at high risk of HIV acquisition.
Cytosponge procedures produce fewer respiratory aerosols and droplets than oesophagogastro-duodenoscopies
Authors: Gordon George S.D. , Warburton Samantha , Parkes Sian , Kerridge Abigail , Parra-Blanco Adolfo , Ortiz-Fernandez-Sordo Jacobo , Fitzgerald Rebecca C.
Published: June 2023

Background and Aims

Oesophagogastro duodenoscopies (OGD) are aerosol generating procedures (AGP) that may spread respiratory pathogens. We aim to investigate production of airborne aerosols and droplets during Cytosponge procedures, which are being evaluated in large-scale research studies and NHS implementation pilots to reduce endoscopy backlogs.

Design and Methods

We measured 18 Cytosponge and 37 OGD procedures using a particle counter (diameters 0.3μm-25μm) taking measurements 10cm from the mouth. Two particle count analyses were performed: whole procedure and event-based.

Results

Direct comparison with duration-standardised OGD procedures shows Cytosponge procedures produce 2.16x reduction (p<0.001) for aerosols and no significant change for droplets (p=0.332). Event-based analysis shows particle production is driven by throat spray (aerosols:138.1x reference, droplets:16.2x), which is optional, and removal of Cytosponge (aerosols:14.6x, droplets:62.6x). Cytosponge coughing produces less aerosols than OGD (2.82x,p<0.05).

Conclusions

Cytosponge procedures produce significantly less aerosols and droplets than OGD procedures and thus reduce two potential transmission routes for respiratory viruses.
Enhancing Kidney Failure Analysis: Web Application Development for Longitudinal Trajectory Clustering
Authors: Gu Yuan , Gong Yishu , Wang Mingyue , Jiang Song , Li Chen , Yuan Zheng
Published: June 2023

Kidney failure is a critical health condition with significant impact on patient well-being and healthcare systems worldwide. Analyzing the longitudinal trajectory of kidney function is crucial for understanding disease progression, predicting outcomes, and personalizing treatment strategies. This paper proposes a novel approach utilizing latent longitudinal trajectory clustering techniques by incorporating survival information to analyze kidney failure and explore patterns within patient populations. Besides, we also developed a web application to provide visualize and intuitive way to explore the relationship between estimated glomerular filtration rate (EGFR) progression and survival outcomes, helping researchers and clinicians gain valuable insights. By identifying distinct subgroups, this analysis can aid in early detection, risk stratification, and treatment optimization. The proposed methodology holds promise for improving patient care and outcomes in the field of nephrology.
Pangenome graphs improve the analysis of rare genetic diseases
Authors: Groza Cristian , Schwendinger-Schreck Carl , Cheung Warren A. , Farrow Emily G. , Thiffault Isabelle , Lake Juniper , Rizzo William B. , Evrony Gilad , Curran Tom , Bourque Guillaume , Pastinen Tomi
Published: June 2023

Rare DNA alterations that cause heritable diseases are only partially resolvable by clinical next-generation sequencing due to the difficulty of detecting structural variation (SV) in all genomic contexts. Long-read, high fidelity genome sequencing (HiFi-GS) detects SVs against reference genomes with increased sensitivity and also enables the assembly of personal and graph genomes. We leveraged standard reference genomes, publicly available human haploid assemblies (n=94), together with a large collection of HiFi-GS data from a rare disease program (Genomic Answers for Kids, GA4K, n=574 assemblies). These data allowed us to build a deep population graph genome distinguishing very rare SVs from recurrent polymorphisms. Using graphs to discover SVs, we obtained a higher level of reproducibility than that obtained by the standard reference approach. We observed over 200,000 SV alleles unique to the rare disease GA4K cohort, including nearly 1,000 rare variants that impact coding sequence. With improved specificity for rare SVs, we isolate 30 candidate SVs in phenotypically prioritized genes, including known disease SVs. We isolate novel diagnostic SV inKMT2Ein a patient demonstrating use of personal assemblies coupled with pangenome graphs as a new handle for rare disease genomics.
Prefrontal Cortex Astroglia Modulate Anhedonia-like Behavior
Authors: Codeluppi S.A. , Xu M. , Bansal Y. , Lepack A.E. , Duric V. , Chow M. , Muir J. , Bagot R.C. , Licznerski P. , Wilber S.L. , Sanacora G. , Sibille E. , Duman R.S. , Pittenger C. , Banasr M.
Published: June 2023

Reductions of astroglia expressing glial fibrillary acidic protein (GFAP) are consistently found in the prefrontal cortex (PFC) of patients with depression and in rodent chronic stress models. Here, we examine the consequences of PFC GFAP+ cell depletion and cell activity enhancement on depressive-like behaviors in rodents. Using viral expression of diphtheria toxin receptor in PFC GFAP+ cells, which allows experimental depletion of these cells following diphtheria toxin administration, we demonstrated that PFC GFAP+ cell depletion induced anhedonia-like behavior within 2 days and lasting up to 8 days, but no anxiety-like deficits. Conversely, activating PFC GFAP+ cell activity for 3 weeks using designer receptor exclusively activated by designer drugs (DREADDs) reversed chronic restraint stress-induced anhedonia-like deficits, but not anxiety-like deficits. Our results highlight a critical role of cortical astroglia in the development of anhedonia and further support the idea of targeting astroglia for the treatment of depression.
Quality control of variant peptides identified through proteogenomics- catching the (un)usual suspects
Authors: Raj Anurag , Aggarwal Suruchi , Yadav Amit Kumar , Dash Debasis
Published: June 2023

Variant peptides resulting from translation of single nucleotide polymorphisms (SNPs) can lead to aberrant or altered protein functions and thus hold translational potential for disease diagnosis, therapeutics and personalized medicine. Variant peptides detected by proteogenomics are fraught with high number of false positives. Class-specific FDR along with ad-hoc post-search filters have been employed to tackle this issue, but there is no uniform and comprehensive approach to assess variant quality. These protocols are mostly manual or tedious, and not accessible across labs. We present a software tool, PgxSAVy, for the quality control of variant peptides. PgxSAVy provides a rigorous framework for quality control and annotations of variant peptides on the basis of (i) variant quality, (ii) isobaric masses, and (iii) disease annotation. PgxSAVy was able to segregate true and false variants with 98.43% accuracy on simulated data. We then used ∼2.8 million spectra (PXD004010 and PXD001468) and identified 12,705 variant PSMs, of which PgxSAVy evaluated 3028 (23.8%), 1409 (11.1%) and 8268 (65.1%) as confident, semi-confident and doubtful respectively. PgxSAVy also annotates the variants based on their pathogenicity and provides support for assisted manual validation. In these datasets, it identified previously found variants as well some novel variants not seen in original studies. The confident variants identified the importance of mutations in glycolysis and gluconeogenesis pathways in Alzheimer’s disease. The analysis of proteins carrying variants can provide fine granularity in discovering important pathways. PgxSAVy will advance personalized medicine by providing a comprehensive framework for quality control and prioritization of proteogenomics variants.

Availability

PgxSAVy is freely available athttps://github.com/anuragraj/PgxSAVy

Key Points

Variant peptide in proteogenomics have high rates of false positives

class-specific FDR is not sufficiently effective, and tedious manual filtering is not scalable

We developed PgxSAVy for automated quality control and disease annotation of variant peptides from proteogenomics search results

PgxSAVy was validated using simulation data and manually annotated variant PSMs

Independent application on large datasets on Alzheimer’s and HEK cell lines demonstrated that PgxSAVy discovered known and novel mutations with important biological roles.

Graphical Abstract
rCRUX: A Rapid and Versatile Tool for Generating Metabarcoding Reference libraries in R
Authors: Curd Emily E. , Gal Luna , Gallego Ramon , Nielsen Shaun , Gold Zachary
Published: June 2023

Key to making accurate taxonomic assignments are curated, comprehensive reference barcode databases. However, the generation and curation of such databases has remained challenging given the large and continuously growing volumes of DNA sequence data and novel reference barcode targets. Monitoring and research applications require a greater diversity of specialized gene regions and targeted taxa to meet taxonomic classification goals then are currently curated by professional staff. Thus, there is a growing need for an easy to implement tool that can generate comprehensive metabarcoding reference libraries for any bespoke locus. We address this need by reimagining CRUX from the Anacapa Toolkit and present the rCRUX package in R. The typical workflow involves searching for plausible seed amplicons (get_seeds_local() orget_seeds_remote()) by simulatingin silicoPCR to acquire seed sequences containing a user-defined primer set. Next these seeds are used to iteratively blast search seed sequences against a local NCBI formatted database using a taxonomic rank based stratified random sampling approach (blast_seeds()) that results in a comprehensive set of sequence matches. This database is dereplicated and cleaned (derep_and_clean_db()) by identifying identical reference sequences and collapsing the taxonomic path to the lowest taxonomic agreement across all matching reads. This results in a curated, comprehensive database of primer specific reference barcode sequences from NCBI. We demonstrate that rCRUX provides more comprehensive reference databases for the MiFish Universal Teleost 12S, Taberlet trnl, and fungal ITS locus than CRABS, METACURATOR, RESCRIPt, and ECOPCR reference databases. We then further demonstrate the utility of rCRUX by generating 16 reference databases for metabarcoding loci that lack dedicated reference database curation efforts. The rCRUX package provides a simple to use tool for the generation of curated, comprehensive reference databases for user-defined loci, facilitating accurate and effective taxonomic classification of metabarcoding and DNA sequence efforts broadly.
A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease
Authors: Li Guansheng , Qiang Yuhao , Li He , Li Xuejin , Buffet Pierre A. , Dao Ming , Karniadakis George Em
Published: June 2023

Being the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, there are relatively fewer works on investigating how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of a set of key factors that are expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as five-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a ‘clustering effect’, where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.
Chronic intermittent hypoxia induced-dysmetabolism is associated with hepatic oxidative stress, mitochondrial dysfunction and inflammation
Authors: Fernandes Joana L. , Martins Fátima O. , Olea Elena , Prieto-Lloret Jesus , Braga Patrícia C. , Sequeira Catarina O. , Pereira Sofia A. , Alves Marco G. , Rocher Asunción , Conde Silvia V.
Published: June 2023

The association between obstructive sleep apnea (OSA) and metabolic disorders is well-established but the underlying mechanisms that elucidate this relationship remain incompletely understood. Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O2) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. HF diet reduced mitochondrial density and hepatic antioxidant capacity. CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.
After wounding, a G-protein coupled receptor promotes the restoration of tension in epithelial cells
Authors: Han Ivy , Hua Junmin , White James S , O'Connor James T , Nassar Lila S. , Tro Kaden J , Page-McCaw Andrea , Hutson M. Shane
Published: June 2023

The maintenance of epithelial barrier function involves cellular tension, with cells pulling on their neighbors to maintain epithelial integrity. Wounding interrupts cellular tension, which may serve as an early signal to initiate epithelial repair. To characterize how wounds alter cellular tension, we used a laser-recoil assay to map cortical tension around wounds in the epithelial monolayer of the Drosophila pupal notum. Within a minute of wounding, there was widespread loss of cortical tension along both radial and tangential directions. This tension loss was similar to levels observed with Rok inactivation. Tension was subsequently restored around the wound, first in distal cells and then in proximal cells, reaching the wound margin about 10 minutes after wounding. Restoring tension required the GPCR Mthl10 and the IP3 receptor, indicating the importance of this calcium signaling pathway known to be activated by cellular damage. Tension restoration correlated with an inward-moving contractile wave that has been previously reported; however, the contractile wave itself was not affected by Mthl10 knockdown. These results indicate that cells may transiently increase tension and contract in the absence of Mthl10 signaling, but that pathway is critical for fully resetting baseline epithelial tension after it is disrupted by wounding.
Genome wide assessment of genetic diversity and transcript variations in 17 accessions of the model diatomPhaeodactylum tricornutum
Authors: Timothée Chaumier , Yang Feng , Manirakiza Eric , Ait-Mohamed Ouardia , Wu Yue , Chandola Udita , Jesus Bruno , Piganeau Gwenael , Groisillier Agnès , Tirichine Leila
Published: June 2023

Diatoms, a prominent group of phytoplankton, have a significant impact on both the oceanic food chain and carbon sequestration, thereby playing a crucial role in regulating the climate. These highly diverse organisms show a wide geographic distribution across various latitudes. In addition to their ecological significance, diatoms represent a vital source of bioactive compounds that are widely used in biotechnology applications. In the present study, we investigated the genetic and transcriptomic diversity of 17 accessions of the model diatomPhaeodactylum tricornutumincluding those sampled a century ago as well as more recently collected accessions. The analysis of the data reveals a higher genetic diversity and the emergence of novel clades, indicating an increasing diversity within theP. tricornutumpopulation structure, compared to the previous study and a persistent long-term balancing selection of genes in old and newly sampled accessions. However, the study did not establish a clear link between the year of sampling and genetic diversity, thereby, rejecting the hypothesis of loss of heterozygoty in cultured strains. Transcript analysis identified novel transcript including non-coding RNA and other categories of small RNA such as PiwiRNAs. Additionally, transcripts analysis using differential expression as well as Weighted Gene Correlation Network Analysis has provided evidence that the suppression or downregulation of genes cannot be solely attributed to loss of function mutations. This implies that other contributing factors, such as epigenetic modifications, may play a crucial role in regulating gene expression. Our study provides novel genetic resources, which are now accessible through the platform PhaeoEpiview (https://PhaeoEpiView.univ-nantes.fr), that offer both ease of use and advanced tools to further investigate microalgae biology and ecology, consequently enriching our current understanding of these organisms.
Detection of Patients at Risk of Enterobacteriaceae Infection Using Graph Neural Networks: a Retrospective Study
Authors: Gouareb Racha , Bornet Alban , Proios Dimitrios , Pereira Sónia Gonçalves , Teodoro Douglas
Published: June 2023

While Enterobacteriaceae bacteria are commonly found in healthy human gut, their colonisation of other body parts can potentially evolve into serious infections and health threats. We aim to design a graph-based machine learning model to assess risks of inpatient colonisation by multi-drug resistant (MDR) Enterobacteriaceae. The colonisation prediction problem was defined as a binary classification task, where the goal is to predict whether a patient is colonised by MDR Enterobacteriaceae in an undesirable body part during their hospital stay. To capture topological features, interactions among patients and healthcare workers were modelled using a graph structure, where patients are described by nodes and their interactions by edges. Then, a graph neural network (GNN) model was trained to learn colonisation patterns from the patient network enriched with clinical and spatiotemporal features. The GNN model predicts colonisation risk with an AUROC of 0.93 (95% CI: 0.92-0.94), 7% above a logistic regression baseline (0.86 [0.85-0.87]). Comparing different graph topologies, the configuration that considers only in-ward edges (0.93 [0.92-0.94]) outperforms the configurations that include only out-ward edges (0.86 [0.85-0.87]) and both edges (0.90 [0.89-0.91]). For the top-3 most prevalent MDR Enterobacteriaceae, the AUROC varies from 0.92 (0.90-0.93) forEscherichia coliup to 0.95 (0.92-0.98) forEnterobacter cloacae, using the GNN – in-ward model. Topological features via graph modelling improves the performance of machine learning models for Enterobacteriaceae colonisation prediction. GNNs could be used to support infection prevention and control programmes to detect patients at risk of colonisation by MDR Enterobacteriaceae and other bacteria families.
The effect of screening on the health burden of chlamydia: An evaluation of compartmental models based on person-days of infection
Authors: Farrell Jack , Spolyar Owen , Greenhalgh Scott
Published: June 2023

Sexually transmitted diseases are detrimental to the health and economic well-being of society. Consequently, predicting impending outbreaks and identifying effective disease interventions through the use of epidemiological tools, such as compartmental models, is of the utmost importance. Unfortunately, traditional compartmental models, specifically the differential equation models attributed to the work of Kermack and McKendrick, require either a duration of infection that follows the exponential or Erlang distribution, despite the biological invalidity of such assumptions. As these assumptions negatively impact the quality of model predictions, alternative approaches are required that capture the variability in the duration of infection, along with its associated effects on the trajectory of disease, and in the evaluation of disease interventions. So, we apply an entirely new family of differential equation compartmental models based on the quantity, “person-days of infection,” to predict the trajectory of a disease. Importantly, this new family of models can alternative duration of infection distributions. As proof of concept, we calibrate our model to recent trends of chlamydia incidence in the United States and utilize a general statistical distribution that features periodic hazard rates. We then evaluate how increasing sexually transmitted disease screening rates alter predictions of incidence and saves disability adjusted life-years over a 5-year horizon. Our findings illustrate that increasing the annual screening rate of chlamydia from 35% to 40%-70% would annually avert 6.1-40.3 incidence and 1.68-11.14 disability adjusted life-years per 1000 people. This suggests increasing the screening rate of sexually transmitted diseases in the United States would greatly aid in ongoing public health efforts to curtail the rising trends in preventable sexually transmitted diseases.
Benchmarking local genetic correlation estimation methods using summary statistics from genome-wide association studies
Authors: Zhang Chi , Zhang Yiliang , Zhang Yunxuan , Zhao Hongyu
Published: June 2023

Local genetic correlation evaluates the correlation of genetic effects between different traits across genetic variants in a local region. It has been proven informative for understanding the genetic similarities of complex traits beyond that captured by global genetic correlation calculated across the whole genome. Several summary-statistics-based approaches have been developed for estimating local genetic correlation, includingρ-hess, SUPERGNOVA, and LAVA. However, there has not been a comprehensive evaluation of these methods to offer practical guidelines on the choices of these methods. In this study, we conduct benchmark comparisons of the performance of these three methods through extensive simulation and real data analyses. We focus on two technical difficulties in estimating local genetic correlation: sample overlaps across traits and local linkage disequilibrium (LD) estimates when only the external reference panels are available. Our simulations suggest that the type-I error and estimation accuracy are highly dependent on the estimation of the local LD matrix. These observations are corroborated by real data analyses of 31 complex traits. Overall, our results offer insights into post-GWAS local correlation studies and highlight issues that demand future methodology developments.
Effect of mangrove-sword bean-food bar on weight and Weight-for-Age Z-score in under-five children after landslide disaster
Authors: Fatmah  , Utomo Suyud Warno
Published: June 2023

Special attention needs to be given to under-five children who have specific needs due to their lower ability to prepare for disasters. Simple, ready-to-eat, and tasty food that meets the micronutrient needs of the groups is needed. The study aimed to assess the effect of the food bar made fromapi-apimangrove (Avicennia marina) and sword bean (Canavalia ensiformis) blends on the weight and Weight-for-Age Z (WAZ) score after landslide disaster. A non randomized pre-post intervention study was performed on 34 under-five children affected by landslide disaster during 15 days. Subjects were divided into intervention (api-apimangrove-sword beanfood bars) and control groups (sword bean food bars). Both groups received the food bars for 15 days. Education on balanced nutrition for under-five children was provided to all subjects’ mothers in the study. The study revealed that most mothers of under-five children liked mangrove-sword bean food bar from the aroma, taste, texture, and color in the hedonic test. The intervention group experienced weight gain (0.32 kg) and WAZ score (0.73) were greater compared with the control group. There were significant difference in weight and WAZ score changes of the under-five children accompanied by a significant increases in mothers’ knowledge on the balanced nutrition for under-five children and food bar total consumption. No significant differences of macronutrient consumption, except fat intake between pre-post study were found.Api-apimangrove-sword beanfood bar can be an emergency food alternative for disaster vulnerable group communities affected by natural disasters. Future studies may wish to consider examining the issue using pregnant women as the research subjects.
Neuronal expression of human amyloid-β and Tau drives global phenotypic and multi-omic changes inC. elegans
Authors: Holcom Angelina , Fuentealba Matias , Sivapatham Renuka , King Christina D. , Osman Hadley , Foulger Anna , Bhaumik Dipa , Schilling Birgit , Furman David , Andersen Julie K. , Lithgow Gordon J.
Published: June 2023

Alzheimer’s disease (AD) and Alzheimer’s related diseases (ADRD) are prevalent age-related neurodegenerative disorders characterized by the accumulation of amyloid-β (Aβ) plaques and Tau neurofibrillary tangles. The nematodeCaenorhabditis elegans (C. elegans) serves as an invaluable model organism in diseases of old age-due to its rapid aging. Here we performed an unbiased systems analysis of aC. elegansstrain expressing both Aβ and Tau proteins within neurons. We set out to determine if there was a phenotypic interaction between Aβ and Tau. In addition, we were interested in determining the temporal order of the phenotypic and multi-omic (geromic) outcomes. At an early stage of adulthood, we observed reproductive impairments and mitochondrial dysfunction consistent with disruptions in mRNA transcript abundance, protein solubility, and metabolite levels. Notably, the expression of these neurotoxic proteins exhibited a synergistic effect, leading to accelerated aging. Our findings shed light on the close relationship between normal aging and ADRD. Specifically, we demonstrate alterations to metabolic functions preceding age-related neurotoxicity, offering a resource for the development of new therapeutic strategies.
Adult-onset CNS sulfatide deficiency causes sex-dependent metabolic disruption in aging
Authors: Qiu Shulan , He Sijia , Wang Jianing , Wang Hu , Bhattacharjee Anindita , Li Xin , Saeed Moawiz , Dupree Jeffrey L. , Han Xianlin
Published: June 2023

The interconnection between obesity and central nervous system (CNS) neurological dysfunction has been widely appreciated. Accumulating evidence demonstrates that obesity is a risk factor for CNS neuroinflammation and cognitive impairment. However, the extent to which CNS disruption influences peripheral metabolism remains to be elucidated. We previously reported that myelin-enriched sulfatide loss leads to CNS neuroinflammation and cognitive decline. In this study, we further investigated the impact of CNS sulfatide deficiency on peripheral metabolism while considering sex- and age-specific effects. We found that female sulfatide-deficient mice gained significantly more body weight, exhibited higher basal glucose levels, and were glucose intolerant during glucose-tolerance test (GTT) compared to age-matched controls under a normal diet, whereas male sulfatide-deficient mice only displayed glucose intolerance at a much older age compared to female sulfatide-deficient mice. Mechanistically, we found the increased body weight was associated with increased food intake and elevated neuroinflammation, especially in the hypo-thalamus, in a sex-specific manner. Our results suggest that CNS sulfatide deficiency leads to sex-specific alterations in energy homeostasis via dysregulated hypothalamic control of food-intake.