bluuebunny/crossref_metadata_2025 huggingface dataset:
“Subzone-Counting” Method in Asian Facial Liposuction: A Retrospective Study
Authors: Gu Tianyi , Zhang Xiaoyu , Yu Panxi , Ma Jiguang , Wang Shujie
Published: August 2023

Background:

Facial liposuction is a popular and reliable procedure for patients with subcutaneous fat accumulation pursuing the ideal face shape. However, complications like irregularities and asymmetry are still problems for plastic surgeons. To lower the incidence of the above complications, we developed the “subzone-counting” method. In this study, this technique was introduced and evaluated.

Methods:

By several lines all parallel to the earlobe-mouth corner line, the liposuction area was subdivided into several subzones. With consistent negative pressure, the paths of the cannula trip in all subzones were also parallel to the earlobe-mouth corner line. An objective index could be obtained by counting the number of aspiration in every subzone. Based on this index, the real-time adjustment was made to achieve smoothness and symmetry.

Results:

This study identified 32 Chinese patients who accepted this method between January 2019 and January 2021. The follow-up ranged from 6 to 44 months. Twenty-nine and 3 patients were satisfied and somewhat satisfied with the postoperative outcome, respectively. No patient was unsatisfied with the outcome. And no major complication was reported.

Conclusions:

The “subzone-counting” method is safe and effective for facial liposuction. The approach helps intraoperative judgment and adjustment. According to the real-time counting results, contour smoothness and bilateral symmetry can be easily achieved and less dependent on the surgeon’s experience.
Management of Traumatic Brain Injury in Older Adults: What You Need to Know
Authors: Ghneim Mira , Stein Deborah M.
Published: August 2023

Older adults represent the fastest growing population in the United States (US) and this portion of the population is expected to double to more than 80 million by 2050.1 Currently, older adults have more active lifestyles, therefore are at an increased risk of injury.2 Older adults currently represent 23% of trauma admissions.3 This number is projected to increase to 39% by 2050.3 In fact, over the last decade, unintentional injuries have climbed from the 9th to the 7th leading cause of death among older adults. Traumatic brain injury (TBI) accounts for over 200,000 cases annually.4 The consequences of TBI in older adults are severe with high mortality rates5 and significant cognitive and functional impairment for survivors.6–8 Many who were previously independent in their daily activities become dependent on assistance after sustaining a TBI.2 Moreover, older adults experience accelerated cognitive decline, sleep disturbances, and depression following a TBI, which can further hinder their recovery.9 The financial impact of TBI on patients, caregivers, and the health care system is substantial, with annual hospital charges exceeding 8.2 billion for the treatment of TBI in older adults.10 This review aims to highlight the specific considerations and challenges faced by older adults with TBI.
Brain Tuberculoma: A fifty-two-year-old woman case report
Authors: Shankar Gokul S , Nair Sreeja , Jacob Teena , Idikula Mercy John
Published: August 2023

Tuberculoma of the brain is one of the most severe extrapulmonary forms that affect patients less than 40 years of age. They are space-occupying masses of granulomatous tissue that result from haematogenous spread from a distant focus of tuberculous infection by Mycobacterium tuberculosis. Symptoms and radiologic features being nonspecific usually leads to misdiagnosis and mimics a variety of other infectious diseases. Anti- Tubercular drugs are essential for the successful treatment of cerebral tuberculomas. A 52-year-old woman with known co-morbidities and chronic kidney disease presented with complaints of disoriented talk, vomiting, fever, and decreased response since 1 day. The initial radiological imaging showed ring-enhancing lesions and a differential diagnosis of septic emboli, vasculitis, and tuberculosis was considered. A repeat MRI suggested Tuberculoma. CSF studies showed predominant lymphocytes with elevated protein. CBNAAT & AFB smears of CSF were negative. The patient was started on anti-tuberculous drugs and steroids. But did not respond to the treatment and twelve days later, a brain biopsy was taken and sent for cultures. She deteriorated progressively and died 14 days after admission. Twelve days after her demise, the Mycobacterial culture of the brain biopsy specimen grew Mycobacterium tuberculosis.
Clarifying Cognitive Control Deficits in Psychosis via Drift Diffusion Modeling
Authors: Shen Chen , Calvin Olivia L. , Rawls Eric , Redish A. David , Sponheim Scott R.
Published: August 2023

Cognitive control deficits are consistently identified in individuals with schizophrenia and other psychotic psychopathologies. In this analysis, we delineated proactive and reactive control deficits in psychotic psychopathology via hierarchical Drift Diffusion Modeling (hDDM). People with psychosis (PwP; N=123), their first-degree relatives (N=79), and controls (N=51) completed the Dot Pattern Expectancy task, which allows differentiation between proactive and reactive control. PwP demonstrated slower drift rates on proactive control trials suggesting less efficient use of cue information for proactive control. They also showed longer non-decision times than controls on infrequent stimuli sequences suggesting slower perceptual processing. An explainable machine learning analysis indicated that the hDDM parameters were able to differentiate between the groups better than conventional measures. Through DDM, we found that cognitive control deficits in psychosis are characterized by slower motor/perceptual time and slower evidence-integration primarily in proactive control.
Long-term Trajectories of Depressive Symptoms in Deployed Military Personnel: A 10-year prospective study
Authors: Plas Xandra , Bruinsma Bastiaan , van Lissa Caspar J. , Vermetten Eric , van Lutterveld Remko , Geuze Elbert
Published: August 2023

Background

Military missions are associated with an increased risk of depression. Understanding the long-term development of depressive symptoms after deployment is important to improve decision-making regarding deployment and mental health policies in the military. Therefore, this study aims to investigate trajectories of depressive symptoms from pre- to post-deployment and assess the role of specific factors, such as demographics, early life trauma, posttraumatic stress disorder (PTSD) symptoms and deployment stressors, in the Dutch army.

Methods

The study includes a cohort of 1032 military men and women deployed to Afghanistan between 2005 and 2008. From pre-to 10 years post-deployment (across 6 distinct time points), depressive and PTSD symptoms were assessed using the Symptom CheckList-90 (SCL-90) and the Self-Rating Inventory for PTSD (SRIP) respectively. Demographics, early trauma, and deployment experiences were collected at baseline and after deployment, respectively. Latent Class Growth Analysis was used to explore heterogeneity in developmental trajectories of depressive symptoms over time.

Results

The study identified four trajectories for depressive symptoms: resilient (65%), intermediate-stable (20%), symptomatic-chronic (9%), and late-onset-increasing (6%). The late-onset-increasing group had the highest proportion of individuals younger than 21 years. In addition, the resilient group was less likely to have experienced deployment stressors and the symptomatic-chronic group reported more early life traumas compared to the other groups. For individuals classified in trajectories with higher levels of depressive symptoms, PTSD symptoms were higher at all time points.

Conclusions

Multiple trajectories for depressive symptoms were identified in a military sample up to 10 years after deployment. These trajectories were associated with age, early trauma, deployment stressors and PTSD symptoms. The majority of the sample fell within the resilient trajectory, supporting the notion that deployed military personnel possess a high level of resilience. Overall, these findings provide valuable insights and a foundation for further research in this area.
Post-recovery health domain scores among outpatients by SARS-CoV-2 testing status during the pre-Delta period
Authors: King Jennifer P. , Chung Jessie R. , Donahue James G. , Martin Emily T. , Leis Aleda M. , Monto Arnold S. , Gaglani Manjusha , Dunnigan Kayan , Raiyani Chandni , Saydah Sharon , Flannery Brendan , Belongia Edward A.
Published: August 2023

Background

Symptoms of COVID-19 including fatigue and dyspnea, may persist for weeks to months after SARS-CoV-2 infection. This study compared self-reported disability among SARS-CoV-2-positive and negative persons with mild to moderate COVID-19-like illness who presented for outpatient care before widespread COVID-19 vaccination.

Methods

Unvaccinated adults with COVID-19-like illness enrolled within 10 days of illness onset at three US Flu Vaccine Effectiveness Network sites were tested for SARS-CoV-2 by molecular assay. Enrollees completed an enrollment questionnaire and two follow-up surveys (7–24 days and 2–7 months after illness onset) online or by phone to assess illness characteristics and health status. The second follow-up survey included questions measuring global health, physical function, fatigue, and dyspnea. Scores in the four domains were compared by participants’ SARS-CoV-2 test results in univariate analysis and multivariable Gamma regression.

Results

During September 22, 2020 – February 13, 2021, 2,712 eligible adults were enrolled, 1,541 completed the first follow-up survey, and 650 completed the second follow-up survey. SARS-CoV-2-positive participants were more likely to report fever at acute illness but were otherwise comparable to SARS-CoV-2-negative participants. At first follow-up, SARS-CoV-2-positive participants were less likely to have reported fully or mostly recovered from their illness compared to SARS-CoV-2-negative participants. At second follow-up, no differences by SARS-CoV-2 test results were detected in the four domains in the multivariable model.

Conclusion

Self-reported disability was similar among outpatient SARS-CoV-2-positive and -negative adults 2–7 months after illness onset.
A novel visual analysis interface enables integrative analyses of cancer transcriptomics data and iden-tifies potential markers of immunotherapy response via machine learning.
Authors: Kus Muhammet Emre , Sahin Cagatay , Kilic Emre , Askin Arda , Ozgur Mustafa Mert , Karahanogullari Gokhan , Aksit Ahmet , O'Connell Ryan M. , Ekiz H. Atakan
Published: August 2023

The Cancer Genome Atlas (TCGA) initiative has been essential for revealing key mechanisms in hu-man cancer leading to the development of novel therapeutics. Analysis of the cancer transcriptomics data in the TCGA and other public repositories require coding skills that are associated with a steep learning curve for most non-specialists. To enable a wider utilization of these data, we introduce The Cancer Genome Explorer (TCGEx), a web-based visual data analysis interface that can perform a number of sophisticated analyses ranging from survival modeling and gene set enrichment analysis to unsupervised clustering and linear regression-based machine learning. In addition to providing access to preprocessed data from TCGA and immune checkpoint inhibition studies on cBioportal and CRI-iAtlas, the TCGEx platform allows users to upload and investigate their own data. Using this tool, we investigated the mo-lecular subsets of human melanoma and identified microRNAs associated with intratumoral interferon signaling. We validated these findings using independent data from clinical trials involving immune checkpoint inhibitors for melanoma and other cancers. Moreover, our analyses unveiled a subset of cytokines predictive of positive responses to diverse immune checkpoint inhibitors prior to treatment initiation. Built on the R/Shiny framework, TCGEx modules offer customizable features to tailor the analy-sis to different study contexts and help generate publication-ready plots. TCGEx is freely available at https://tcgex.iyte.edu.tr, and it provides an interactive solution to extract meaningful insights from cancer transcriptomics data and guide scientific inquiry.
Temperature sensitivity of bat antibodies links metabolic state with antigen-recognition diversity
Authors: Toshkova Nia , Zhelyzkova Violeta , Reyes-Ruiz Alejandra , Haerens Eline , de Castro Deus Marina , Lacombe Robin V. , Lecerf Maxime , Gonzalez Gaelle , Jouvenet Nolwenn , Planchais Cyril , Dimitrov Jordan D.
Published: August 2023

Bat immune system features multiple unique properties such as dampened inflammatory responses and increased tissue protection, explaining their long lifespan and tolerance to viral infections. Here, we demonstrated that body temperature fluctuations corresponding to different physiological states in bats exert a dramatic impact on their antibody repertoires. At elevated temperatures typical for flight, IgG fromMyotis myotisandNyctalus noctulashowed elevated antigen binding strength and diversity, recognizing both pathogen-derived antigens and autoantigens. The opposite was observed at temperatures reflecting inactive physiological states. This behavior was not observed for IgG antibodies of human and other mammals, or antibodies of birds. Importantly, diversification of bat antibody specificities resulted in preferential recognition of damaged endothelial and epithelial cells, indicating an anti-inflammatory function. The temperature-sensitivity of bat antibodies was mediated by the variable regions of immunoglobulin molecules. Additionally, we revealed specific molecular features of bat IgG such as low thermodynamic stability and implication of hydrophobic interactions in antigen binding as well as high prevalence of polyreactivity. Overall, our results extend the understanding of bat tolerance to disease and inflammation and highlight the link between metabolism and immunity. This might have important repercussions for human health in the future.
Scanpro: robust proportion analysis for single cell resolution data
Authors: Alayoubi Yousef , Bentsen Mette , Looso Mario
Published: August 2023

In higher organisms, individual cells respond to signals and perturbations by epigenetic regulation such as adjustment of gene expression. However, in addition to shifting their transcriptional profile, the adaptive response of cells can also lead to shifts in the proportions of different cell types. Recent methods such as scRNA-seq allow for the interrogation of expression on the single cell level, and can quantify individual cell type clusters within complex tissue samples. In order to identify clusters showing differential composition between different biological conditions, differential proportion analysis has recently been introduced. However, bioinformatics tools for robust proportion analysis of both replicated and unreplicated single cell datasets are critically missing. In this manuscript, we present Scanpro, a modular tool for proportion analysis, seamlessly integrating into widely accepted frameworks in the Python environment. Scanpro is fast, accurate, supports datasets without replicates, and is intended to be used by bioinformatics experts and beginners alike.
A Weights-based variant ranking pipeline for familial complex disorders
Authors: Ralli Sneha , Vira Tariq , Robles-Espinoza Carla Daniela , Adams David J. , Brooks-Wilson Angela R.
Published: August 2023

Identifying genetic susceptibility factors for complex disorders remains a challenging task. We have developed a weights-based pipeline to prioritize variants and genes in collections of small and large pedigrees where genetic heterogeneity is likely, but biological commonalities are plausible. TheWeights-based vAriantRanking inPedigrees (WARP) pipeline prioritizes variants using 5 weights: disease incidence rate, number of cases in a family, genome fraction shared amongst cases in a family, allele frequency and variant deleteriousness. Weights, except for the population allele frequency weight, are normalized between 0 to 1. Weights are combined multiplicatively to produce family-specific-variant weights that are then averaged across all families in which the variant is observed to generate a multifamily weight. Sorting multifamily weights in descending order creates a ranked list of variants and genes for further investigation. WARP was validated using familial melanoma sequence data from the European Genome-phenome Archive. The pipeline identified variation in known germline melanoma genesPOT1, MITFandBAP1in 4 out of 13 families (31%). Analysis of the other 9 families identified several interesting genes, some of which might have a role in melanoma. WARP provides an approach to identify disease predisposing genes in studies with small and large pedigrees.
ReducedPIN1gene expression in neocortical and limbic brain regions in female Alzheimer’s patients correlates with cognitive and neuropathological phenotypes
Authors: de Ávila Camila , Suazo Crystal , Nolz Jennifer , Cochran J. Nicholas , Wang Qi , Velazquez Ramon , Dammer Eric , Readhead Benjamin , Mastroeni Diego
Published: August 2023

Women have a higher incidence of Alzheimer’s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify the molecular networks that underpin the sex-associated risk of AD. Recent efforts have identifiedPIN1as a key regulator of tau phosphorylation signaling pathway. Pin1is the only gene, to date, that when deleted can cause both tau and Aβ-related pathologies in an age-dependent manner. We analyzed multiple brain transcriptomic datasets focusing on sex differences inPIN1mRNA levels, in an aging and AD cohort, which revealed reducedPIN1levels driven by females. Then, we validated this observation in an independent dataset (ROS/MAP) which also revealed thatPIN1is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function, in females only. Additional analysis revealed a decrease inPIN1in subjects with mild cognitive impairment (MCI) compared with aged individuals, again, driven predominantly by female subjects. Our results show that while both male and female AD patients show decreasedPIN1expression, changes occur before the onset of clinical symptoms of AD in females and correlate to early events associated with AD risk (e.g., synaptic dysfunction). These changes are specific to neurons, and may be a potential prognostic marker to assess AD risk in the aging population and even more so in AD females with increased risk of AD.

Graphical abstract
Ischemic and hemorrhagic stroke lesion environments differentially alter the glia repair potential of neural progenitor cell and immature astrocyte grafts
Authors: Adewumi Honour O , Berniac Gabriela I , McCarthy Emily A , O’Shea Timothy M
Published: August 2023

Using cell grafting to direct glia-based repair mechanisms in adult CNS injuries represents a potential therapeutic strategy for supporting functional neural parenchymal repair. However, glia repair directed by neural progenitor cell (NPC) grafts is dramatically altered by increasing lesion size, severity, and mode of injury. To address this, we studied the interplay between astrocyte differentiation and cell proliferation of NPCin vitroto generate proliferating immature astrocytes (ImA) using hysteretic conditioning. ImA maintain proliferation rates at comparable levels to NPC but showed robust immature astrocyte marker expression including Gfap and Vimentin. ImA demonstrated enhanced resistance to myofibroblast-like phenotypic transformations upon exposure to serum enriched environmentsin vitrocompared to NPC and were more effective at scratch wound closurein vitrocompared to quiescent astrocytes. Glia repair directed by ImA at acute ischemic striatal stroke lesions was equivalent to NPC but better than quiescent astrocyte grafts. While ischemic injury environments supported enhanced survival of grafts compared to healthy striatum, hemorrhagic lesions were hostile towards both NPC and ImA grafts leading to poor survival and ineffective modulation of natural wound repair processes. Our findings demonstrate that lesion environments, rather than transcriptional pre-graft states, determine the survival, cell-fate, and glia repair competency of cell grafts applied to acute CNS injuries.
Respiratory syncytial virus-associated hospital admissions by deprivation levels among children and adults in Scotland
Authors: Osei-Yeboah Richard , Zhu Fuyu , Wang Xin , Nair Harish , Campbell Harry
Published: August 2023

Background

Socioeconomic deprivation may predispose individuals to respiratory tract infections (RTI). We aimed to estimate the number and rate of RSV-associated hospitalisations by socioeconomic status using the Scottish Index of Multiple Deprivation (SIMD).

Methods

Using national routine healthcare records and virological surveillance from 2010-2016, we used a time-series linear regression model and a direct measurement based on ICD-10 coded diagnoses to estimate RSV-associated hospitalisations by SIMD level and age and compared to influenza-associated hospitalisations.

Results

Using the model-based approach, we estimated an annual average rate per 1000 of 0.76 (95%CI: 0.43-0.90) for individuals of all ages in the least deprived group (5thquintile of SIMD) to 1.51 (1.03-1.79) for the most deprived group (1stquintile). Compared with the least deprived group, we estimated that the rate ratio (RR) was 1.96 (95%CI: 1.23-3.25), 1.60 (1.0- 2.66), 1.35 (0.85-2.25), and 1.12 (0.7-1.85) in the 1stto 4thquintile. The pattern of RSV- associated RTI hospitalisation rates variation with SIMD was most pronounced in children aged 2 years and below. The ICD-10 direct measurement approach provided much lower rates than the model-based approach but yielded similar RR estimates between SIMD groups.

Conclusion

Higher RSV hospitalisation rates are seen in the Scottish population of higher deprived levels. The differences between deprivation levels are most pronounced in infants and young children.
Probing the DCAF12 interactions with MAGEA3 and CCT5 C-terminal degrons
Authors: Righetto Germanna Lima , Yin Yanting , Vu Victoria , Duda David , Szewczyk Magdalena , Zeng Hong , Li Yanjun , Loppnau Peter , Mei Tony , Li Yen-Yen , Seitova Alma , Brazeau Jean-Francois , Barsyte-Lovejoy Dalia , Santhakumar Vijayaratnam , Chaudhry Charu , Halabelian Levon
Published: August 2023

DCAF12 is the substrate recognition component of the CRL4 E3 ligase complex that can recognize C-terminal double-glutamic acid degrons to promote degradation of its cognate substrates via the ubiquitin proteasome system. MAGEA3 and CCT5 proteins were reported to be cellular targets of DCAF12. To further characterize the DCAF12 interactions with both MAGEA3 and CCT5, we developed a suite of biophysical and a proximity-based cellular NanoBRET assays showing that both MAGEA3 and CCT5 C-terminal degron peptides interact with DCAF12 in nanomolar affinityin vitro andin cells. Furthermore, we report here the 3.17 Å cryo-EM structure of DCAF12-DDB1-MAGEA3 complex revealing the key DCAF12 residues involved in C-terminal degron recognition and binding. Our study provides new tools and resources to enable the discovery of small molecule handles targeting the WDR domain of DCAF12 for future PROTAC design and development.
Non-monotonic Relationship between Mutation Rate and Speed of adaptation under Antibiotic Exposure inEscherichia coli
Authors: Shibai Atsushi , Izutsu Minako , Kotani Hazuki , Furusawa Chikara
Published: August 2023

The mutation is a fundamental source of biological evolution that create genetic variation in populations. Mutations can create new advantageous traits, but also potentially interfere with pre-existing organismal functions. Therefore, organisms may have evolved their mutation rates to appropriate levels to maintain or improve their fitness. In this study, we aimed to experimentally quantify the relationship between mutation rate and the speed of antibiotic resistance evolution. We conducted experimental evolution using twelveEscherichia colimutator strains with increased mutation rates and five antibiotics. Our results showed that the highest mutation rate did not necessarily lead to the highest speed of adaptation, indicating a non-monotonic relationship between the speed of drug resistance evolution and mutation rate as expected. Moreover, this relationship was observed to differ among drugs, with significant differences in peak size observed between bacteriostatic and bactericidal antibiotics. We also successfully reproduced the mutation-rate dependence of the speed of adaptation using numerical simulation of a population dynamics model. These findings offer significant insights into the mutation rate’s evolution concomitant with the development of antibiotic resistance.
Temporal dissociation between local and global functional adaptations of the maternal brain to childbirth: A longitudinal assessment
Authors: Lotter Leon D. , Nehls Susanne , Losse Elena , Dukart Juergen , Chechko Natalia
Published: August 2023

The maternal brain undergoes significant reorganization during birth and the postpartum period. However, the temporal dynamics of these changes remain unclear. Using resting-state functional magnetic resonance imaging, we report on local and global brain function alterations in 75 mothers in their first postpartum week, compared to 23 nulliparous women. In a subsample followed longitudinally for the next six months, we observed a temporal and spatial dissociation between changes observed at baseline (cluster mass permutation: pFWE < .05). Local activity and connectivity changes in widespread neocortical regions persisted throughout the studied time period (ANCOVAs vs. controls: pFDR < .05), with preliminary evidence linking these alterations to behavioral and psychological adaptations (interaction effect with postpartum time: uncorrected p < .05). In contrast, the initially reduced whole-brain connectivity of putamen-centered subcortical areas returned to control levels within six to nine weeks postpartum (linear and quadratic mixed linear models: pFDR < .05). The whole-brain spatial colocalization with hormone receptor distributions (Spearman correlations: pFDR < .05) and preliminary blood hormone associations (interaction effect with postpartum time: uncorrected p < .05) suggested that the postpartum restoration of progesterone levels may underlie this rapid normalization. These observations enhance our understanding of healthy maternal brain function, contributing to the identification of potential markers for pathological postpartum adaptation processes, which in turn could underlie postpartum psychiatric disorders.
Risk of urban Mayaro virus (Alphavirus: Togaviridae) transmission: isAedes aegyptia competent vector?
Authors: Beranek Mauricio Daniel , Giayetto Octavio , Fischer Sylvia , Diaz Adrián Luis
Published: August 2023

Mayaro virus (MAYV) is an emerging pathogen endemic in Latin America and is the causative agent of fever and polyarthritis. Urban transmission depends on its ability to be transmitted byAedes aegyptiand to be amplified by humans. The aim of this study was to evaluate the susceptibility to infection and transmission and the presence of barriers to infection in different populations ofAe. aegyptifor MAYV.Ae. aegyptieggs were collected from Córdoba, Buenos Aires and Rosario Cities (Argentina). Females were infected with five viral loads of MAYV strain (1 to 6 log10PFU/ml) and maintained for 8 days. The presence of infectious viral particles in body, legs, and saliva was detected by plaquing assay in Vero cell monolayers. Through a bibliographic search,Ae. aegyptipopulation data from Perú were incorporated and tested with different viral doses of MAYV. We build dose-response curves forAe. aegyptipopulations to estimate infection (IR), dissemination (DR) and transmission (TR) based on MAYV viral loads detected in humans to estimate transmission risk occurring in an urban environment. The overall IR and DR were significantly associated with the viral doses and were not significantly affected by population origin. We found IR ranging for 3 to 84% (ID50% were higher than 5.5 log10PFU/ml) and a DR reached 78% (DD50% higher than 6.0 log10PFU/ml). The percentage of dissemination based on the infected mosquitoes ranged from 60 to 86% while the percentage of transmission based on disseminated mosquitoes ranged from 11 to 60%. Our results indicate thatAe. aegyptipopulations are not competent vectors for MAYV because they need higher viral doses than those developed by humans (3.9 – 4.5 log10PFU/ml) to become infected. Only a very low proportion of infected mosquitoes with high 5 log10PFU/ml are capable of transmitting it.
Conserved and tissue-specific immune responses to biologic scaffold implantation
Authors: DeStefano Sabrina , Josyula Aditya , Faust Mondreakest , Fertil Daphna , Lokwani Ravi , Ngo Tran B. , Sadtler Kaitlyn
Published: August 2023

1.

Upon implantation into a patient, any biomaterial induces a cascade of immune responses that influences the outcome of that device. This cascade depends upon several factors, including the composition of the material itself and the location in which the material is implanted. There is still significant uncertainty around the role of different tissue microenvironments in the immune response to biomaterials and how that may alter downstream scaffold remodeling and integration. In this study, we present a study evaluating the immune response to decellularized extracellular matrix materials within the intraperitoneal cavity, the subcutaneous space, and in a traumatic skeletal muscle injury microenvironment. All different locations induced robust cellular recruitment, specifically of macrophages and eosinophils. The latter was most prominent in the subcutaneous space. Intraperitoneal implants uniquely recruited B cells that may alter downstream reactivity as adaptive immunity has been strongly implicated in the outcome of scaffold remodeling. These data suggest that the location of tissue implants should be taken together with the composition of the material itself when designing devices for downline therapeutics.
Identifying signals of memory from observations of animal movements
Authors: Kim Dongmin , Thompson Peter R , Wolfson David , Merkle Jerod , Oliveira-Santos L. G. R. , Forester James D. , Avgar Tal , Lewis Mark A. , Fieberg John
Published: August 2023

Incorporating memory (i.e., some notion of familiarity or experience with the landscape) into models of animal movement is a rising challenge in the field of movement ecology. The recent proliferation of new methods offers new opportunities to understand how memory influences movement. However, there are no clear guidelines for practitioners wishing to parameterize the effects of memory on moving animals. We review approaches for incorporating memory into Step-Selection Analyses (SSAs), a frequently used movement modeling framework. Memory-informed SSAs can be constructed by including spatial-temporal covariates (or maps) that define some aspect of familiarity (e.g., whether, how often, or how long ago the animal visited different spatial locations) derived from long-term telemetry data. We demonstrate how various familiarity covariates can be included in SSAs using a series of coded examples in which we fit models to wildlife tracking data from a wide range of taxa. We discuss how these different approaches can be used to address questions related to whether and how animals use information from past experiences to inform their future movements. We also highlight challenges and decisions that the user must make when applying these methods to their tracking data. By reviewing different approaches and providing code templates for their implementation, we hope to inspire practitioners to investigate further the importance of memory in animal movements using wildlife tracking data.
Benchmarking of Small Molecule Feature Representations for hERG, Nav1.5, and Cav1.2 Cardiotoxicity Prediction
Authors: Arab Issar , Egghe Kristof , Laukens Kris , Chen Ke , Barakat Khaled , Bittremieux Wout
Published: August 2023

In the field of drug discovery, there is a substantial challenge in seeking out chemical structures that possess desirable pharmacological, toxicological, and pharmacokinetic properties. Complications arise when drugs interfere with the functioning of cardiac ion channels, leading to serious cardiovascular consequences. The discontinuation and removal of numerous approved drugs from the market or at late development stages in the pipeline due to such inhibitory effects further highlight the urgency of addressing this issue. Consequently, the early prediction of potential blockers targeting cardiac ion channels during the drug discovery process is of paramount importance. This study introduces a deep learning framework that computationally determines the cardiotoxicity associated with the voltagegated potassium channel (hERG), the voltage-gated calcium channel (Cav1.2), and the voltage-gated sodium channel (Nav1.5) for drug candidates. The predictive capabilities of three feature representations—molecular fingerprints, descriptors, and graph-based numerical representations— are rigorously benchmarked. Additionally, a novel training and evaluation dataset framework is presented, enabling predictive model training of drug off-target cardiotoxicity using a comprehensive and large curated dataset covering these three cardiac ion channels. To facilitate these predictions, a robust and comprehensive small molecule cardiotoxicity prediction tool named CToxPred has been developed. It is made available as open source under the permissive MIT license athttps://github.com/issararab/CToxPred.
A 3D-printed and freely available device to measure the zebrafish optokinetic response before and after injury
Authors: Hermans Ashley , Tajnai Sophia , Tieman Allison , Young Sarah , Franklin Ashley , Horutz Mackenzie , Henle Steven
Published: August 2023

Zebrafish have eyes similar to humans, making them a beneficial model organism for studying vision. However, zebrafish are different in that they can regenerate their optic nerve after injury, which most other animals cannot. Measuring vision in people who have communicative ability is achieved using eye charts. Because fish cannot use an eye chart, we utilize the optokinetic response (OKR) that is present in virtually all vertebrates to determine if a zebrafish has eyesight. To this end, we have developed an inexpensive OKR setup that uses 3D-printed and off-the-shelf parts. This setup has been designed and used by undergraduate researchers and is also scalable to a classroom lab setup. We demonstrate that this setup is fully functional for assessing OKR, and we use it to illustrate the return of the OKR following optic nerve injury in adult zebrafish.
Novel Insights into the Aortic Mechanical Properties of Mice Modeling Hereditary Aortic Diseases
Authors: Dubacher Nicolo , Sugiyama Kaori , Smith Jeffrey D. , Nussbaumer Vanessa , Csonka Máté , Ferenczi Szilamér , Kovács Krisztina J. , Caspar Sylvan M. , Lamberti Lisa , Meienberg Janine , Yanagisawa Hiromi , Sheppard Mary B. , Matyas Gabor
Published: August 2023

OBJECTIVE

Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.

APPROACH AND RESULT

We used two mouse models of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) ofEfemp2and three CRISPR/Cas9-engineered knock-in models (Ltbp1,Mfap4, andTimp1). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture. The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, theLtbp1,Mfap4, andTimp1knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.

CONCLUSIONS

Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force- focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.

Highlights

Assay to measure the aortic rupture force as read-out for the biomechanical integrity identified weakened murine thoracic aorta prior to micro- and macroscopic changes inFbn1+/C1041Gmice.

Despite reducing aneurysm growth, losartan treatment did not have any impact on the aortic rupture force ofFbn1mgR/mgRmice modeling MFS.

Smooth-muscle-cell-knock-out ofEfemp2significantly impaired the rupture force of the murine ascending aorta.

Aortic rupture force measurements could clarify the causality of novel candidate gene(s)/variant(s) in mouse models of aortic diseases.

Graphical Abstract
MarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer
Authors: Wang Xiaoying , Duan Maoteng , Li Jingxian , Ma Anjun , Xu Dong , Li Zihai , Liu Bingqiang , Ma Qin
Published: August 2023

Rare cell populations are key in neoplastic progression and therapeutic response, offering potential intervention targets. However, their computational identification and analysis often lag behind major cell types. To fill this gap, we introduced MarsGT: Multi-omics Analysis for Rare population inference using Single-cell Graph Transformer. It identifies rare cell populations using a probability-based heterogeneous graph transformer on single-cell multi-omics data. MarsGT outperformed existing tools in identifying rare cells across 400 simulated and four real human datasets. In mouse retina data, it revealed unique subpopulations of rare bipolar cells and a Müller glia cell subpopulation. In human lymph node data, MarsGT detected an intermediate B cell population potentially acting as lymphoma precursors. In human melanoma data, it identified a rare MAIT-like population impacted by a high IFN-I response and revealed the mechanism of immunotherapy. Hence, MarsGT offers biological insights and suggests potential strategies for early detection and therapeutic intervention of disease.
LC-UV/RI-MS2as the analytical platform for bioconversion of sustainable carbon sources: a showcase of 1,4-butanediol plastic monomer degradation usingUstilago trichophora
Authors: Phan An N.T. , Prigolovkin Lisa , Blank Lars M.
Published: August 2023

Plastic usage by microbes as a carbon source is a promising strategy to increase the recycling quota. 1,4-butanediol (BDO) is a common monomer derived from polyesters and polyurethanes. It presents in the complex mixture from the plastic degradation process. In this study,Ustilago trichophorawas found to be an efficient cell-factory to valorize BDO. To investigate product formation byU. trichophora, we refined the traditional ion exclusion liquid chromatography method by examining eluent, eluent concentrations, oven temperatures, and organic modifiers to make the chromatography compatible with mass spectrometry. An LC-UV/RI-MS2method is presented here to identify and quantify extracellular metabolites in the cell cultures. With this method, we successfully identified thatU. trichophorasecreted malic acid, succinic acid, erythritol, and mannitol into the culture medium. Adaptive laboratory evolution followed by medium optimization significantly improvedU. trichophoragrowth on BDO and especially malic acid production. Overall, the carbon yield on the BDO substrate was approximately 33% malic acid. This is the first report on a Ustilaginaceae fungus that was able to convert BDO into versatile chemical building blocks. SinceU. trichophorais not genetically engineered, it is a promising microbial host to produce malic acid from BDO, thereby contributing to the development of the envisaged sustainable bioeconomy.
Human sensorimotor resting state beta events and 1/f response show good test-retest reliability
Authors: Pauls Amande , Nurmi Pietari , Ala-Salomäki Heidi , Renvall Hanna , Kujala Jan , Liljeström Mia
Published: August 2023

Neurological conditions affecting the sensorimotor system have a profound impact on individuals’ physical independence and are associated with a considerable socioeconomic burden. Reliable functional biomarkers allowing early diagnosis of these conditions or targeting treatment and rehabilitation can reduce this burden. Magnetoencephalography (MEG) can non-invasively measure the brain’s salient rhythmic patterns such as the somatomotor (‘rolandic’) rhythm. This rhythm shows intermittent high amplitude ‘events’ in the beta (14-30 Hz) frequency range which predict behavior across tasks and species and are altered by neurological diseases affecting the sensorimotor system. Thus, the sensorimotor resting beta phenotype is a promising candidate biomarker of sensorimotor function. A prerequisite for use as a biomarker is that it can be quantified reliably across different measurement sessions. Here, using MEG, we assessed the test-retest stability of spontaneously occurring sensorimotor power spectral characteristics, including both aperiodic (1/f) as well as beta band fluctuations (‘beta events’) in a cohort of 50 healthy human controls. Test-retest reliability across two separate measurement sessions was assessed using the intraclass correlation coefficient (ICC). Beta events were determined using a thresholding-based approach on a narrow-band filtered amplitude envelope obtained using Morlet wavelet decomposition across a range of parameters (recording length, amplitude threshold and filtering bandwidth). We find that both aperiodic power spectral features as well as several beta event characteristics show good to excellent testretest stability. Especially aperiodic component power spectral features (ICC 0.77-0.88), but also measures of beta event amplitude (ICC 0.74-0.82) were found to be very stable, while measures of individual beta event duration were less reliable, especially for the left hemisphere (ICC right ∼0.7, left ∼0.55). Recordings of 2-3 minutes were sufficient to obtain stable results for most parameters. Important for potential clinical applications, automatization of beta event extraction was successful in 86 % of cases. Beta event rate and duration measures were more sensitive to analysis parameters than the measures of event amplitude. The results suggest the sensorimotor beta phenotype is a stable feature of an individual’s resting brain activity even for short, 2-3 minute recordings which can be easily measured in patient populations, facilitating its use as a potential clinical biomarker.
Leveraging collaborations to increase the impact of food sharing platforms
Authors: Michelini Laura , Grieco Cecilia , Dentchev Nikolay
Published: August 2023

Purpose

The purpose of the paper is to explore how collaborations can increase the impact of food sharing platforms, which offer the potential to reduce food waste by facilitating contact between suppliers and consumers. With this comes the need to address the twofold challenge of being digital and having an economic and social-environmental mission. Thus, adopting a system perspective and recognizing stakeholders as part of a value network can maximize the generated impact.

Design/methodology/approach

A multiple case study analysis has been conducted on 12 food sharing platforms. Data have been collected through semi-structured interviews, triangulated with internal and external documents and content analysed.

Findings

The research outlines the systems of collaboration found in food sharing platforms characterized by two levels of actors (platform players and business players) and five different types of collaboration that can help platforms maximize their impact (boosting the network effect; capturing value; enhancing the business model; extending the type of impact; and scaling up).

Originality/value

The research offers important contributions for the advancement of the field, adding evidence on the opportunities offered by collaborations to generate impact for business and society in the context of the sharing economy and food industry. The research allows to identify the concept of “sustainability-oriented sharing platforms” as a subset of sharing economy platforms characterized by a dual mission and related challenges. From a managerial point of view, the study highlights how designing and implementing collaborations with the stakeholders can increase platforms' impact consistently with the life cycle and short- and long-term perspectives.
Board chairman characteristics and impression management: an empirical investigation. Further analysis
Authors: Al-Sayani Yahya Mohammed , Al-Matari Ebrahim Mohammed , Mohamad Nor Mohamad Naimi , Amran Noor Afza , Alsayani Mohammed Ahmed
Published: August 2023

Purpose

The purpose of this study is to look at the structure of the interactions between the board of directors’ chairman qualities such as chairman independence, tenure, ethnicity, age- and impression management (IM).

Design/methodology/approach

The research population consists of non-financial Malaysian companies listed on Bursa Malaysia’s Main Market, using data gathered via annual reports and DataStream. The study relies on the ordinary least square regression to test the direct relationships between the directors’ chairman characteristics and IM. Moreover, robustness and sensitivity tests were used to examine the effectiveness of chairman characteristics with IM. Furthermore, the results rely on the FGLS regression as an additional test. The study found that chairman independence, chairman ethnicity and chairman age have a significant impact on IM.

Findings

The results reveal that chairman independence has a negative association with qualitative IM (IMSC1). Moreover, chairman ethnicity has a positively significant relationship with qualitative IM (IMSC1) and quantitative IM (IMSC2). Also, the effectiveness of chairman characteristics has a negative and significant association with IMSC1.

Originality/value

The primary goal of this paper is to fill a gap in the literature and to open up opportunities for more in-depth research on the subject. So far, there has been no research into the impact of the board chairman’s (BC) personality on IM. This study serves as a warning to policymakers, businesses and their stakeholders, as well as researchers, about the importance of BC characteristics, which may impede the effectiveness of corporate governance mechanisms. The paper provides a framework for investigating these characteristics in the context of IM.