bluuebunny/crossref_metadata_2025 huggingface dataset:
ANTIMICROBIAL SUSCEPTIBILITY PATTERNS OF OF TRACHEAL TUBE ISOLATES FROM PATIENTS OF VENTILATOR ASSOCIATED PNEUMONIA (VAP) ADMITTED TO THE ICU OF A TERTIARY CARE HOSPITAL IN RAWALPINDI PAKISTAN
Authors: Baba Miriam Farooq , Abdullah Ramal , Iqbal Soman Nadim , Tariq Maryam , Ali Muhammad Moaaz , Hassan Mohammad , Kaleem Fatima , Abbasi Shahid Ahmed
Published: April 2023

The respiratory system is a complex interconnected functionality which consists of a series of branching tubules and the lungs containing many alveoli. The alveoli are highly vascularized to provide a large surface area for gaseous exchange. The investigation was conducted in the Fauji Foundation Hospital’s Department of Microbiology from November 2019 to June 2022.. The various bacterial strains that were recovered from a total of 802 mechanically intubated individuals make up the data presented in this study.Acinetobacterspp 270 (34%),Pseudomonsspp 165(21%), andKlebsiellaspp 95 (12%) were the most frequently isolated bacteria. Main Gram-positive organisms isolated includedMethicillin-Resistant Staphylococcus aureus66 (8%), Enterococcus 48 (6%).MRSAwas 100% sensitive to Vancomycin, but only 97% sensitive to the Linezolid. TheAcinetobacterspp found in the tracheal tubes was reported to be 77% sensitive to Polymyxin B.
Optimizing Detection and Deep Learning-based Classification of Pathological High-Frequency Oscillations in Epilepsy
Authors: Monsoor Tonmoy , Zhang Yipeng , Daida Atsuro , Oana Shingo , Lu Qiujing , Hussain Shaun A. , Fallah Aria , Sankar Raman , Staba Richard J. , Speier William , Roychowdhury Vwani , Nariai Hiroki
Published: April 2023

Objective

This study aimed to explore sensitive detection methods and deep learning (DL)-based classification for pathological high-frequency oscillations (HFOs)

Methods

We analyzed interictal HFOs (80-500 Hz) in 15 children with medication-resistant focal epilepsy who underwent resection after chronic intracranial electroencephalogram via subdural grids. The HFOs were assessed using the short-term energy (STE) and Montreal Neurological Institute (MNI) detectors and examined for pathological features based on spike association and time-frequency plot characteristics. A DL-based classification was applied to purify pathological HFOs. Postoperative seizure outcomes were correlated with HFO-resection ratios to determine the optimal HFO detection method.

Results

The MNI detector identified a higher percentage of pathological HFOs than the STE detector, but some pathological HFOs were detected only by the STE detector. HFOs detected by both detectors exhibited the most pathological features. The Union detector, which detects HFOs identified by either the MNI or STE detector, outperformed other detectors in predicting postoperative seizure outcomes using HFO-resection ratios before and after DL-based purification.

Conclusions

HFOs detected by standard automated detectors displayed different signal and morphological characteristics. DL-based classification effectively purified pathological HFOs.

Significance

Enhancing the detection and classification methods of HFOs will improve their utility in predicting postoperative seizure outcomes.

HIGHLIGHTS

HFOs detected by the MNI detector showed different traits and higher pathological bias than those detected by the STE detector

HFOs detected by both MNI and STE detectors (the Intersection HFOs) were deemed the most pathological

A deep learning-based classification was able to distill pathological HFOs, regard-less of the initial HFO detection methods
Preprint: Towards Smart Glasses for Facial Expression Recognition Using OMG and Machine Learning
Authors: Kiprijanovska Ivana , Stankoski Simon , Broulidakis M. John , Archer James , Fatoorechi Mohsen , Gjoreski Martin , Nduka Charles , Gjoreski Hristijan
Published: April 2023

This study aimed to evaluate the use of novel optomyography (OMG) based smart glasses, OCOsense™, for the monitoring and recognition of facial expressions. Experiments were conducted on data gathered from 27 young adult participants, who performed facial expressions varying in intensity, duration, and head movement. The facial expressions included smiling, frowning, raising the eyebrows, and squeezing the eyes. The statistical analysis demonstrated that: (i) OCO™ sensors based on the principles of OMG can capture distinct variations in cheek and brow movements with a high degree of accuracy and specificity; (ii) Head movement does not have a significant impact on how well these facial expressions are detected. The collected data were also used to train a machine learning model to recognise the four facial expressions and when the face enters a neutral state. We evaluated this model in conditions intended to simulate real-world use, including variations in expression intensity, head movement and glasses position relative to the face. The model demonstrated an overall accuracy of 93% (0.90 f1-score) – evaluated using a leave-one-subject-out cross-validation technique.
Pulmonary Hypertension Classification using Artificial Intelligence and Chest X-Ray:ATA AI STUDY-1
Authors: Kıvrak Tarık , Yagmur Burcu , Erken Hilal , Kocakaya Derya , Tuncer Turker , Doğan Şengül , Yaman Orhan , Sinan Umit Yasar , Sekerci Sena Sert , Yayla Cagri , Iyigun Ufuk , Kis Mehmet , Karaca Ozkan , Yesil Emrah , Yuce Ersoy Elif Ilkay , Tak Bahar Tekin , Oz Ahmet , Kaplan Mehmet , Ulutas Zeynep , Aslan Gamze Yeter , Eren Nihan Kahya , Turhan Caglar Fatma Nihan , Solmaz Hatice , Ozden Ozge , Gunes Hakan , Kocabas Umut , Yenercag Mustafa , Isık Omer , Yesilkaya Cem , Kaya Ali Nail , Omur Sefa Erdi , Sahin Anil , In Erdal , Berber Nurcan Kırıcı , Dogan Cigdem Ileri , Poyraz Fatih , Kaya Emin Erdem , Gumusdag Ayca , Kumet Omer , Kaya Hakki , Sarikaya Remzi , Tan Seda Turkan , Arabaci Hidayet Ozan , Guvenc Rengin Cetin , Yeni Mehtap , Avci Burcak Kılıckıran , Yilmaz Dilek Cicek , Celik Ahmet , Ekici Berkay , Erkan Aycan Fahri , Baris Veysel Ozgur , Seker Taner , Böyük Ferit , Can Mehmet Mustafa , Gungor Hasan , Simsek Hakki , Yildizeli Bedrettin , Kobat Mehmet Ali , Akbulut Mehmet , Zoghi Mehdi , Kozan Omer
Published: April 2023

An accurate diagnosis of pulmonary hypertension (PH) is crucial to ensure that patients receive timely treatment. One of the used imaging models to detect pulmonary hypertension is the X-ray. Therefore, a new automated PH-type classification model has been presented to depict the separation ability of deep learning for PH types. We retrospectively enrolled 6642 images of patients with PH and the control group. A new X-ray image dataset was collected from a multicentre in this work. A transfer learning-based image classification model has been presented in classifying PH types. Our proposed model was applied to the collected dataset, and this dataset contains six categories (five PH and a non-PH). The presented deep feature engineering (computer vision) model attained 86.14% accuracy on this dataset. According to the extracted ROC curve, the average area under the curve rate has been calculated at 0.945. Therefore, we believe that our proposed model can easily separate PH and non-PH X-ray images.
Updating reproduction number estimates for mpox in the Democratic Republic of Congo using surveillance data
Authors: Charniga Kelly , McCollum Andrea M. , Hughes Christine M. , Monroe Benjamin , Kabamba Joelle , Lushima Robert Shongo , Likafi Toutou , Nguete Beatrice , Pukuta Elisabeth , Muyamuna Elisabeth , Tamfum Jean-Jacques Muyembe , Karhemere Stomy , Kaba Didine , Nakazawa Yoshinori
Published: April 2023

Incidence of human mpox has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen’s transmissibility in DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus’ epidemic potential and inform outbreak control strategies. We used the R packagevimesto identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease’s serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number,Rt, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimatedRtof 0.82 (95% CI: 0.79 – 0.85) and a rate of 132 (95% CI: 122 – 143) spillovers per year assuming a reporting rate of 0.25. This estimate ofRtis larger compared to most previous estimates. One potential explanation for this result is thatRtcould have increased in DRC over time due to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982.Rtcould be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province.
Cohort profile: Recruitment and retention in a prospective cohort of Canadian health care workers during the Covid-19 pandemic
Authors: Cherry Nicola , Adisesh Anil , Burstyn Igor , Durand-Moreau Quentin , Galarneau Jean-Michel , Labrèche France , Ruzycki Shannon , Zadunayski Tanis
Published: April 2023

Purpose

Health care workers (HCWs) were recruited early in 2020 to chart effects on their health as the COVID-19 pandemic evolved. The aim was to identify modifiable workplace risk factors for infection and mental ill-health.

Participants

Participants were recruited from four Canadian provinces, physicians (MDs) in Alberta, British Columbia, Ontario and Quebec, registered nurses (RNs), licensed practical nurses (LPNs) and health care aides (HCAs) in Alberta and personal support workers (PSWs) in Ontario. Volunteers gave blood for serology testing before and after vaccination. Cases with COVID-19 were matched with up to 4 referents in a nested case-referent study.

Findings to Date

4964/5130 (97%) of those recruited joined the longitudinal cohort: 1442 MDs, 3136 RNs, 71 LPNs, 235 PSWs, 80 HCAs. Overall, 3812 (77%) were from Alberta. Pre-pandemic risk factors for mental ill-health and respiratory illness differed markedly by occupation. Participants completed questionnaires at recruitment, fall 2020, spring 2021, and spring 2022. By the 4thcontact, 127 had retired, moved away or died, for a response rate of 89% (4299/4837). 4567/4864 (92%) received at least one vaccine shot: 2752/4567 (60%) gave post-vaccine blood samples. Ease of accessing blood collection sites was a strong determinant of participation. Among 533 cases and 1697 referents recruited to the nested case-referent study, risk of infection at work decreased with widespread vaccination.

Future Plans

Serology results (concentration of immunoglobulin G (IgG)) together with demographic data will be entered into the publicly accessible database compiled by the Canadian Immunology Task Force. Linkage with provincial administrative health databases will permit case validation, investigation of longer-term sequalae of infection and comparison with community controls. Analysis of the existing dataset will concentrate on effects on IgG of medical condition, medications and stage of pregnancy, and the role of occupational exposures and supports on mental health during the pandemic.

Strengths and limitations

Recruitment of a broad spectrum of health care workers close to the start of the COVID-19 pandemic through their professional organizations

Consent to link to records held by public health departments allows for validation of self-reports of vaccinations and episodes of COVID-19 infection

Repeated contacts permit charting the evolution of anxiety, depression and sources of stress through the course of the pandemic

The inclusion of a nested case-referent study allows exposure reporting in near real time

The absence of good denominator data limits the ability to examine recruitment bias

N=4216
SARS-CoV-2 occurrence in white-tailed deer throughout their range in the conterminous United States
Authors: Bevins Sarah N. , Chipman Richard B. , Beckerman Scott F. , Bergman David L. , Collins Derek T. , Deliberto Thomas J. , Eckery Joshua P. , Ellis Jeremy W. , Gosser Allen L. , Heale Jonathon D. , Klemm Jason M. , Lantz Kristina , Linder Timothy J. , Oswald Mitch , Pleszewski Robert , Quintanal Christopher A. , Ringenberg Jourdan M. , Weir Kelsey R. , Torchetti Mia K. , Lenoch Julianna B. , Chandler Jeffrey C. , Shriner Susan A.
Published: April 2023

Broad-scale data show SARS-CoV-2 occurrence in white-tailed deer throughout much of their range in the conterminous United States and reinforce findings of considerable SARS-CoV-2 infection and exposure. Results shed light on both current infections and prior exposure, with prevalence decreasing over time and seroprevalence increasing.

One-Sentence Summary

White-tailed deer are infected with, and have been exposed to, SARS-CoV-2 throughout their range in the conterminous US.
Clinical severity in Parkinson’s disease is determined by decline in cortical compensation
Authors: Johansson Martin E. , Toni Ivan , Kessels Roy P.C. , Bloem Bastiaan R. , Helmich Rick C.
Published: April 2023

Dopaminergic dysfunction in the basal ganglia, particularly in the post-commissural putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e., bradykinesia) in Parkinson’s disease. However, striatal dopamine loss fails to account for inter-individual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that inter-individual differences in clinical severity are determined by compensatory cortical mechanisms, and not just by basal ganglia dysfunction.

Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson’s disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes: diffuse-malignant (n=42), intermediate (n=128), or mild motor-predominant (n=150). Second, we used the total bradykinesia score across the entire sample as a continuous measure.

Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared to controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical bradykinesia scores. This indicates a limited role for striatal dysfunction in shaping inter-individual differences in symptom severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and to controls. Furthermore, parieto-premotor activity was inversely related to bradykinesia, which points to a compensatory role.

We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes inter-individual variability in symptom severity in Parkinson’s disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.
T helper-1 activation via interleukin-16 is a key phenomenon in the acute phase of severe, first-episode major depressive disorder and suicidal behaviors
Authors: Almulla Abbas F. , Abo Algon Ali Abbas , Tunvirachaisakul Chavit , Al-Hakeim Hussein K. , Maes Michael
Published: April 2023

Background

Immune-inflammatory pathways in major depressive disorder are confined to the major dysmood disorder (MDMD) phenotype (Maes et al., 2022). No studies have addressed the immune profile of first episode MDMD (FE-MDMD).

Methods

This study examines 48 cytokines/chemokines/growth factors, and classical M1, alternative M2, T helper (Th)-1, Th-2, and Th-17 phenotypes, immune-inflammatory response system (IRS), compensatory immunoregulatory system (CIRS), and neuro-immunotoxicity profiles in the acute phase of FE-MDMD (n=71) versus healthy controls (40).

Results

FE-MDMD patients show significantly activated M1, M2, Th-1, IRS, CIRS, and neurotoxicity, but not Th-2 or Th-17, profiles compared to controls. FE-MDMD is accompanied by Th-1 polarization, while there are no changes in M1/M2 or IRS/CIRS ratios. The top single indicator of FE-MDMD was by far interleukin (IL)-16, followed at a distance by TRAIL, IL-2R, tumor necrosis factor (TNF)-β. The severity of depression and anxiety was strongly associated with IRS (positively) and Th-2 (inversely) profiles, whereas suicidal behavior was associated with M1 activation. Around 56-60% of the variance in depression, anxiety, and suicidal behavior scores was explained by IL-16, platelet-derived growth factor (PDGF) (both positively), and IL-1 receptor antagonist (inversely). Increased neurotoxicity is mainly driven by IL-16, TNF-α, TRAIL, IL-6 and chemokine (CCL2, CCL11, CXCL1, CXCL10) signaling. Antidepressant-treated patients show an increased IRS/CIRS ratio as compared with drug-naïve FE-MDMD patients.

Conclusions

FE-MDMD is accompanied by positive regulation of the IRS mainly driven by Th-1 polarization and T cell activation (via binding of IL-16 to CD4), and TNF, chemokine, and growth factor signaling.
Different Physical Parameters in the Bonds between Platelet Glycoprotein Ibalpha with von Willebrand factor and with Coagulant Factor XI -Results from the Molecular Dynamic Simulation-
Authors: Nakayama Masamitsu , Goto Shinichi , Takemoto Satoko , Oka Hideki , Yokota Hideo , Takagi Shu , Goto Shinya
Published: April 2023

Background: Both von Willebrand factor (VWF) and coagulation factor XI (FXI) bind with platelet membrane glycoprotein (GP) Ibalpha. However, the differences in the physical parameters in the bonds between VWF-GPIbalpha and FXI-GPIbalpha mediating different biological functions are unclear. Methods: The FXI molecule was arranged in 9 different initial positions around the structure of GPIbalpha bound to VWF. The position coordinate and velocity vectors of all atoms constructing VWF, GPIbalpha, and FXI were calculated in each 2 femto (10-15) second using the Chemistry at HARvard Macromolecular Mechanics (CHARMM) force field. The physical parameters of VWF-GPIbalpha and FXI-GPIbalpha bonds were calculated by molecular dynamic (MD) simulations. Results: MD calculation revealed 2.8 to 11.3 times greater positional fluctuations in atoms constructing FXI-GPIbalpha as compared to those constructing VWF-GPIbapha (RMSDs: 5.9{plus minus}1.5 to 18.1{plus minus}7.9 Å for FXI-GPIbalpha vs 1.6{plus minus}0.1 to 2.1{plus minus}0.3 Å for VWF-GPIbalpha). The absolute value of non-covalent binding energy generated in FXI-GPIbalpha (65.5{plus minus}79.7 to 517.6{plus minus}54.2 kcal/mol) was smaller than that generated in VWF-GPIbalpha (678.5{plus minus}58.3 to 1000.4{plus minus}75.1 kcal/mol). The binding structure of VWF-GPIbalpha was stable and was only minimally influenced by the presence of FXI-GPIbalpha binding. Conclusions: Our MD calculation results revealed that atoms constructing the VWF-GPIbalpha bond are physically more stable and produce more non-covalent binding energy than the bond of FXI-GPIbalpha. The physical parameters in the VWF-GPIbalpha bond were not largely influenced by FXI binding with GPIbalpha.
PaxDB 5.0: curated protein quantification data suggests adaptive proteome changes
Authors: Huang Qingyao , Szklarczyk Damian , Wang Mingcong , Simonovic Milan , von Mering Christian
Published: April 2023

The “Protein Abundances Across Organisms” database (PaxDB) is an integrative meta-resource dedicated to protein abundance levels, in tissue-specific or whole-organism proteomes. PaxDB focuses on computing best-estimate abundances for proteins in normal/healthy contexts, and expresses abundance values for each protein in “parts per million” (ppm) in relation to all other protein molecules in the cell. The uniform data re-processing, quality scoring, and integrated orthology relations have made PaxDB one of the preferred tools for comparisons between individual datasets, tissues or organisms. In describing the latest version 5.0 of PaxDB, we particularly emphasise the data integration from various types of raw data, and how we expanded the number of organisms and tissue groups as well as the proteome coverage. The current collection of PaxDB includes 831 original datasets from 170 species, including 22 Archaea, 81 Bacteria and 67 Eukaryota. Apart from detailing the data update, we also show a comparative analysis of the human proteome subset of PaxDB against the two most widely-used human proteome data resources: Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx). Lastly, we present a use case of PaxDB, showing how protein abundance data can be used to study the evolution of relative amino acid usage in Fungi.
The structure of a hibernating ribosome in a Lyme disease pathogen
Authors: Sharma Manjuli R. , Manjari Swati R. , Agrawal Ekansh K. , Keshavan Pooja , Koripella Ravi K. , Majumdar Soneya , Marcinkiewicz Ashley L. , Lin Yi-Pin , Agrawal Rajendra K. , Banavali Nilesh K.
Published: April 2023

The spirochete bacterial pathogenBorrelia(Borreliella) burgdorferi(Bbu) affects more than 10% of the world population and causes Lyme disease in about half a million people in the US annually. Therapy for Lyme disease includes antibiotics that target theBburibosome. We determined the structure of theBbu70S ribosome by single particle cryo-electron microscopy (cryo-EM) at a resolution of 2.9 Å, revealing its distinctive features. In contrast to a previous study suggesting that the single hibernation promoting factor protein present inBbu(bbHPF) may not bind to its ribosome, our structure reveals a clear density for bbHPF bound to the decoding center of the small ribosomal 30S subunit. The 30S subunit has a non-annotated ribosomal protein, bS22, that has been found only in mycobacteria and Bacteroidetes so far. The protein bL38, recently discovered in Bacteroidetes, is also present in theBbularge 50S ribosomal subunit. The protein bL37, previously seen only in mycobacterial ribosomes, is replaced by an N-terminal α-helical extension of uL30, suggesting that the two bacterial ribosomal proteins uL30 and bL37 may have evolved from one longer uL30 protein. The longer uL30 protein interacts with both the 23S rRNA and the 5S rRNA, is near the peptidyl transferase center (PTC), and could impart greater stability to this region. Its analogy to proteins uL30m and mL63 in mammalian mitochondrial ribosomes also suggests a plausible evolutionary pathway for expansion of protein content in mammalian mitochondrial ribosomes. Computational binding free energies are predicted for antibiotics, bound to the decoding center or PTC and are in clinical use for Lyme disease, that account for subtle distinctions in antibiotic-binding regions in theBburibosome structure. Besides revealing unanticipated structural and compositional features for theBburibosome, our study thus provides groundwork to enable ribosome-targeted antibiotic design for more effective treatment of Lyme disease.
Screening and identification of key biomarkers in diabetic kidney disease and its complications: Evidence from bioinformatics and next generation sequencing data analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: April 2023

Diabetic patients are prone to diabetic kidney disease (DKD), which may cause cardiovascular damage, hypertension and obesity, and reduce quality of life. As a result, the life quality of patients was seriously reduced. However, the pathogenesis of diabetic kidney disease (DKD) has not been fully elucidated, and current treatments remain inadequate. Therefore, it is essential to explore the molecular mechanism of DKD and its complications. Next Generation Sequancing (GSE217709) dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were picked out by R software. Then Gene ontology (GO) and REACTOME pathway enrichment analysis were performed by g:Profiler database, protein–protein interaction (PPI) of DEGs was constructed by Human Integrated Protein-Protein Interaction rEference (HIPPIE) database. Module analysis was carried out by Cytoscape plug-in PEWCC. Subsequently, miRNA-hub gene regulatory network and TF-hub gene regulatory network were performed by miRNet database and NetworkAnalyst database. Finally, validation of hub genes was performed by receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. In total, 958 DEGs, including 479 up regulated and 479 down regulated genes, were identified. The GO and pathway enrichment changes of DEGs were mainly enriched in biological regulation, multicellular organismal process, signaling by GPCR and extracellular matrix organization. Ten hub genes (HSPA8, HSP90AA1, HSPA5, SDCBP, HSP90B1, VCAM1, MYH9, FLNA, MDFI and PML) associated with DKD and its complications were identified. Bioinformatics analysis is a useful tool to explore the molecular mechanism and pathogenesis of DKD and its complications. The identified hub genes may participate in the onset and development of DKD and its complications and serve as therapeutic targets.
Disulfiram Exerts anti-pulmonary Fibrosis Effect by Activating PGE2 Synthesis
Authors: Pei Xiaolin , Zheng Fangxu , Li Yin , Lin Zhoujun , Zhang Yupeng , Han Xiao , Feng Ya , Li Fei , Yang Juan , Li Tianjiao , Tian Zhenhuan , Cao Ke , Ren Dunqiang , Li Chenggang
Published: April 2023

Idiopathic pulmonary fibrosis (IPF) is marked with the replacement of normal alveolar tissue by thicker and harder fibrous material, damaged exchange ability. Currently, nintedanib and pirfenidone, are the only FDA-approved drugs with limited efficacy for IPF, which indicated an urgent need to explore new therapies. Disulfiram (DSF), an acetaldehyde dehydrogenase inhibitor, used as anti-alcohol treatment. Despite reported with anti-hepatic fibrosis effect of DSF, the underlying mechanism remains unclear. In our study, DSF exhibited regulative impact on abnormal proliferation, EMT and ECM production in cell models of IPF including primary DHLF-IPF cells and TGF-β1-stimulated A549 cells. The absence of COX-2 was restored by DSF treatment, together with elevated prostaglandin biosynthesis both in vitro and in vivo models of IPF. Furthermore, the anti-fibrotic effect of DSF was impeded with COX-2 knockdown or pharmacological inhibition in TGF-β1-stimulated A549 cells, however, exogenous PGE2 reclaimed with anti-EMT function. In established animal model of IPF, DSF ameliorated declined lung function and histopathological changes, and restrained the lung hydroxyproline content. Together, these findings suggest that the anti-fibrotic effect of DSF was achieved through re-activation of COX-2 mediated PGE2 biosynthesis. The above results suggest that DSF can be applied therapeutically in fibrotic conditions.
The effect of removing repeat-induced overlaps inde novoassembly
Authors: Shirali Hossein Zade Ramin , Abeel Thomas
Published: April 2023

Determining accurate genotypes is important for associating phenotypes to genotypes.De novogenome assembly is a critical step to determine the complete genotype for species for which no reference exists yet. The main challenge ofde novoeukaryote genome assembly, particularly plant genomes, are repetitive DNA sequences within their genomes. The introduction of third generation sequencing and corresponding long reads has promised to resolve repeat-related problems. While there have been notable improvements, reads originating from these repeats are still creating errors because they introduce false overlaps in the assembly graph. This study focuses on analyzing the effect of repeats onde novoassembly and improving performance of existingde novoassembly algorithms by removing repeat-induced overlaps. First, we show the possible improvements in de novo assembly with removing repeat-induced overlaps. Then we propose several methods for detecting and removing repeat-induced overlaps and evaluate their performance on several simulated datasets.
Genetic insights into the association between inflammatory bowel disease and Alzheimer’s disease
Authors: Zeng Lu , White Charles C. , Bennett David A. , Klein Hans-Ulrich , De Jager Philip L.
Published: April 2023

Myeloid cells, including monocytes, macrophages, microglia, dendritic cells and neutrophils are a part of innate immune system, playing a major role in orchestrating innate and adaptive immune responses. Both Alzheimer’s disease (AD) and inflammatory bowel disease (IBD) susceptibility loci are enriched for genes expressed in myeloid cells, but it is not clear whether these myeloid risk factors are shared between the two diseases. Leveraging results of genome-wide association studies, we investigated the causal effect of IBD (including ulcerative colitis (UC) and Crohn’s disease (CD)) variants on AD and its endophenotypes. Microglia and monocyte expression Quantitative Trait Locus (eQTLs) were used to examine the functional consequences of IBD and AD variants. Our results revealed distinct sets of genes and pathways of AD and IBD susceptibility loci. Specifically, AD loci are enriched for microglial eQTLs, while IBD loci are enriched for monocyte eQTLs. However, we also found that genetically determined IBD is associated with a protective effect against AD (p<0.03). Yet, a genetic propensity for the CD subtype is associated with increased amyloid accumulation (beta=7.14, p-value=0.02) and susceptibility to AD. Susceptibility to UC was associated with increased deposition of TDP-43 (beta=7.58, p-value=6.11×10-4). The relation of these gastrointestinal inflammatory disease to AD is therefore complex; while the different subsets of susceptibility variants preferentially affect different myeloid cell subtypes, there do appear to be certain shared pathways and the possible protective effect of IBD susceptibility on the risk of AD which may provide therapeutic insights.
Facilitating Healing for Black Women Experiencing Gendered Racism and Traumatic Stress: The Moderation of Psychosocial Resources
Authors: Williams Tiffany R. , Erving Christy L. , Frierson Whitney , Gao Fanchen , Bass Jeffery E , Martin Reniece , Mitchell Taeja
Published: April 2023

Black women must navigate a tumultuous sociopolitical terrain while simultaneously managing their psychological health. Experiences of gendered racism increase Black women’s vulnerability to psychological distress. Gendered racial microaggressions, a specific type of microaggression, account for the intricate ways racism and sexism intersect. The association between Black women’s experiences of gendered racial microaggressions and traumatic stress was investigated among 201 Black female-identified undergraduate and graduate students attending a Historically Black College or University. Whether psychosocial resources (i.e., resilience, social support, mastery, self-esteem) moderated the linkage between gendered racial microaggressions and traumatic stress was also examined. Gendered racial microaggressions were positively associated with traumatic stress. The microaggression Assumptions of Beauty and Sexual Objectification was the most strongly associated with traumatic stress, followed by Angry Black Woman. Resilience and mastery were protective factors, reducing the influence of gendered racial microaggressions on traumatic stress. In addition, high levels of social support reduced the impact of Assumptions of Beauty and Sexual Objectification on traumatic stress. To foster healing and posttraumatic growth for Black women, psychologists must decolonize their understanding and treatment of mental illness. Practice and research implications are discussed.
nELISA: A high-throughput, high-plex platform enables quantitative profiling of the secretome
Authors: Dagher Milad , Ongo Grant , Robichaud Nathaniel , Kong Jinglin , Rho Woojong , Teahulos Ivan , Tavakoli Arya , Bovaird Samantha , Merjaneh Shahem , Tan Andrew , Edwardson Kiran , Scheepers Christelle , Ng Andy , Hajjar Andy , Sow Baly , Vrouvides Michael , Lee Andy , DeCorwin-Martin Philippe , Rasool Shafqat , Huang JiaMin , Erps Timothy , Coffin Spencer , Han Yu , Chandrasekaran Srinivas Niranj , Miller Lisa , Kost-Alimova Maria , Skepner Adam , Singh Shantanu , Carpenter Anne E. , Munzar Jeffrey , Juncker David
Published: April 2023

We present the nELISA, a high-throughput, high-fidelity, and high-plex protein profiling platform. DNA oligonucleotides are used to pre-assemble antibody pairs on spectrally encoded microparticles and perform displacement-mediated detection. Spatial separation between non-cognate antibodies prevents the rise of reagent-driven cross-reactivity, while read-out is performed cost-efficiently and at high-throughput using flow cytometry. We assembled an inflammatory panel of 191 targets that were multiplexed without cross-reactivity or impact on performance vs 1-plex signals, with sensitivities as low as 0.1pg/mL and measurements spanning 7 orders of magnitude. We then performed a large-scale secretome perturbation screen of peripheral blood mononuclear cells (PBMCs), with cytokines as both perturbagens and read-outs, measuring 7,392 samples and generating ∼1.5M protein datapoints in under a week, a significant advance in throughput compared to other highly multiplexed immunoassays. We uncovered 447 significant cytokine responses, including multiple putatively novel ones, that were conserved across donors and stimulation conditions. We also validated the nELISA’s use in phenotypic screening, and propose its application to drug discovery.
Neural speech tracking benefit of lip movements predicts behavioral deterioration when the speaker’s mouth is occluded
Authors: Reisinger Patrick , Gillis Marlies , Suess Nina , Vanthornhout Jonas , Haider Chandra Leon , Hartmann Thomas , Hauswald Anne , Schwarz Konrad , Francart Tom , Weisz Nathan
Published: April 2023

Observing lip movements of a speaker is known to facilitate speech understanding, especially in challenging listening situations. Converging evidence from neuroscientific studies shows enhanced processing of audiovisual stimuli. However, the interindividual variability of this visual benefit and its consequences on behavior are unknown. Here, we analyzed source-localized magnetoencephalographic (MEG) responses from normal-hearing participants listening to audiovisual speech with or without an additional distractor speaker. Using temporal response functions (TRFs), we show that neural responses to lip movements are, in general, enhanced when speech is challenging. After conducting a crucial control for speech acoustics, we show that lip movements effectively contribute to higher neural speech tracking, particularly when a distractor speaker is present. However, the extent of this visual benefit varied greatly among participants. Probing the behavioral relevance, we show that individuals who benefit more from lip movement information in terms of neural speech tracking, show a stronger drop in performance and an increase in perceived difficulty when the mouth is occluded by a surgical face mask. By contrast, no effect was found when the mouth was not occluded. We provide novel insights on how the benefit of lip movements in terms of neural speech tracking varies among individuals. Furthermore, we reveal its behavioral relevance by demonstrating negative consequences for behavior when visual speech is absent. Our results also offer potential implications for future objective assessments of audiovisual speech perception.
A new ‘CFS tracking’ paradigm reveals uniform suppression depth regardless of target complexity or salience
Authors: Alais David , Coorey Jacob , Blake Randolph , Davidson Matthew J.
Published: April 2023

When the eyes view separate and incompatible images, the brain suppresses one image and promotes the other into visual awareness. Periods of interocular suppression can be prolonged during continuous flash suppression (CFS) - when one eye views a static ‘target’ while the other views a complex dynamic stimulus. Measuring the time needed for a suppressed image to break CFS (bCFS) has been widely used to investigate unconscious processing, and the results have generated controversy regarding the scope of visual processing without awareness. Here, we address this controversy with a new ‘CFS tracking’ paradigm (tCFS) in which the suppressed monocular target steadily increases in contrast until breaking into awareness (as in bCFS) after which it decreases until it again disappears (reCFS), with this cycle continuing for many reversals. Unlike bCFS, tCFS provides a measure of suppression depth by quantifying the difference between breakthrough and suppression thresholds. tCFS confirms that: (i) breakthrough thresholds indeed differ across target types (e.g., faces vs gratings, as bCFS has shown) – but (ii) suppression depth does not vary across target types. Once the breakthrough contrast is reached for a given stimulus, all stimuli require a strikingly uniform reduction in contrast to reach the corresponding suppression threshold. This uniform suppression depth points to a single mechanism of CFS suppression, one that likely occurs early in visual processing because suppression depth was not modulated by target salience or complexity. More fundamentally, it shows that variations in bCFS thresholds alone are insufficient for inferring whether the barrier to achieving awareness exerted by interocular suppression is weaker for some categories of visual stimuli compared to others.

Significance statement

Research on unconscious vision has proliferated recently, often employing the continuous flash suppression (CFS) method in which rapidly changing shapes viewed by one eye suppress the other eye’s image from awareness. If that suppressed image is progressively strengthened in contrast it will eventually break suppression and emerge into visible awareness. Low breakthrough thresholds are claimed to indicate unconscious processing during suppression. We introduce a method that quantifies breakthrough thresholds and suppression thresholds, thus providing a lower bound missing from previous CFS research. Comparing various image types, including those claimed to undergo unconscious processing, all images show equal suppression when both thresholds are measured. We thus find no evidence of differential unconscious processing and conclude reliance on breakthrough thresholds is misleading without considering suppression thresholds and leads to spurious claims about unconscious processing.
Botanicals impact the bifidogenic effect and metabolic outputs ofin vitrofiber fermentation by gut-derived microbiota in individual-specific ways
Authors: Deemer Dane G. , Voreades Noah , Goodwin Ben , Bron Peter A. , Lindemann Stephen R.
Published: April 2023

Modern diets typically contain dramatically lower fiber content compared to traditional hunter-gatherer and agrarian diets, and this trend is paralleled by an enhanced frequency of chronic diseases. Despite national nutrition policy and education instructing Americans on the beneficial health value of increasing daily fiber consumption, a “fiber gap” still persistently exists. Fortification of product groups frequently consumed by a large proportion of society provides an attractive strategy to close this “fiber gap” and may have the potential to concomitantly reverse the detrimental health effects exacerbated by our modern diets. Besides prebiotic fibers, products can contain several other functional components, such as botanicals. However, the vast majority of studies have investigated functional components in isolation. For instance, preferential fermentation of specific prebiotic fibers by bifidobacteria has been clearly established, both in terms of their increased abundance in the gut microbiome and the elevated levels of beneficial metabolites, including short chain fatty acids (SCFAs) produced directly (acetate) or through interactions with other microbiota members (resulting in butyrate and propionate production). The impact of other components present in functional product blends on this bifidogenic effect are largely unexplored. Here, we investigated the fiber and botanical blends included in OLIPOP, a functional soda, in anin vitrogut fermentation model. Our data revealed that the blend of inulins and resistant dextrins promoted growth of bifidobacteria across gut microbiota from four donors, even those with small initial populations. In addition, botanicals interacted with fiber fermentation in donor-specific ways, in some cases strongly enhancing fermentation rate and production of SCFAs. Our data suggest that botanicals can modify the rate and microbial and metabolic fates of prebiotic fiber fermentation, and suggest that future studies should examine such interactions in greater detail.
A 1.5 Mb continuous endogenous viral region in the arbuscular mycorrhizal fungusRhizophagus irregularis
Authors: Zhao Hongda , Zhang Ruixuan , Wu Junyi , Meng Lingjie , Okazaki Yusuke , Hikida Hiroyuki , Ogata Hiroyuki
Published: April 2023

Most fungal viruses are RNA viruses and no double-stranded DNA virus that infects fungi is known to date. A recent study detected DNA polymerase genes that originated from large dsDNA viruses in the genomes of basal fungi, suggestive of the existence of dsDNA viruses capable of infecting fungi. In this study, we searched for viral infection signatures in chromosome-level genome assemblies of the arbuscular mycorrhizal fungusRhizophagus irregularis. We identified a continuous 1.5 Mb putative viral region on a chromosome inR. irregularisstrain 4401. Phylogenetic analyses revealed that the viral region is related to viruses in the familyAsfarviridaeof the phylumNucleocytoviricota. Single-copy marker genes fromNucleocytoviricotawere detected as single-copy genes in the viral region. Furthermore, this viral region was absent in the genomes of four otherR. irregularisstrains and had fewer signals of fungal transposable elements than the other genomic regions. These results suggest a recent and single insertion of a large dsDNA viral genome in the genome of this fungal strain, providing strong evidence of the recent infection of the fungus by a dsDNA virus.
Ontogeny shapes individual specialization
Authors: Hertel Anne G. , Albrecht Jörg , Selva Nuria , Sergiel Agnieszka , Hobson Keith A. , Janz David M. , Mulch Andreas , Kindberg Jonas , Hansen Jennifer E. , Frank Shane C. , Zedrosser Andreas , Mueller Thomas
Published: April 2023

Individual dietary specialization, where individuals occupy a subset of a population’s wider dietary niche, is a key factor determining a species resilience against environmental change. However, the ontogeny of individual specialization, as well as associated underlying social learning, genetic, and environmental drivers, remain poorly understood. Using a multigenerational dataset of female European brown bears (Ursus arctos) followed since birth, we discerned the relative contributions of environmental similarity, genetic heritability, maternal effects, and offspring social learning from the mother to individual specialization. Individual specialization accounted for 43% of phenotypic variation and spanned half a trophic position, with individual diets ranging from omnivorous to carnivorous. The main determinants of dietary specialization were social learning during rearing (13%), environmental similarity (9%), maternal effects (11%), and permanent between-individual effects (8%), whereas the contribution of genetic heritability was negligible. The trophic position of offspring closely resembled the trophic position of their mothers during the first 3-4 years of independence, but this relationship ceased with increasing time since separation. Our study shows that social learning and maternal effects are as important for individual dietary specialization as environmental composition. We propose a tighter integration of social effects into future studies of range expansion and habitat selection under global change that, to date, are mostly explained by environmental drivers.
Investigation of refractive index dynamics during embryo development using digital holographic microscopy
Authors: Dwapanyin George O. , Chow Darren J. X. , Tan Tiffany C. Y. , Dubost Nicolas S. , Morizet Josephine M. , Dunning Kylie R. , Dholakia Kishan
Published: April 2023

Embryo quality is a crucial factor affecting live birth outcomes. However, an accurate diagnostic for embryo quality remains elusive in thein vitrofertilization clinic. Determining physical parameters of the embryo may offer key information for this purpose. Here, we demonstrate that digital holographic microscopy (DHM) can rapidly and non-invasively assess the refractive index of mouse embryos. We showed that DHM can detect spatio-temporal changes in refractive index during embryo development that are reflective of its lipid content. As accumulation of intracellular lipid is known to compromise embryo health, DHM may prove beneficial in developing an accurate, non-invasive, multimodal diagnostic.
Phenotype control techniques for Boolean gene regulatory networks
Authors: Plaugher Daniel , Murrugarra David
Published: April 2023

Modeling cell signal transduction pathways via Boolean networks (BNs) has become an established method for analyzing intracellular communications over the last few decades. What’s more, BNs provide a course-grained approach, not only to understanding molecular communications, but also for targeting pathway components that alter the long-term outcomes of the system. This has come to be known asphenotype control theory. In this review we study the interplay of various approaches for controlling gene regulatory networks such as: algebraic methods, control kernel, feedback vertex set, and stable motifs. The study will also include comparative discussion between the methods, using an established cancer model of T-Cell Large Granular Lymphocyte (T-LGL) Leukemia. Further, we explore possible options for making the control search more efficient using reduction and modularity. Finally, we will include challenges presented such as the complexity and the availability of software for implementing each of these control techniques.