bluuebunny/crossref_metadata_2025 huggingface dataset:
NOT ALL CELL-FREE MITOCHONDRIAL DNA IS EQUAL IN TRAUMA PATIENTS
Authors: Briggs Gabrielle D. , Gelzinnis Scott , Meakes Simone , King Kate L. , Balogh Zsolt J.
Published: September 2022

Mitochondrial DNA (mtDNA) acts as a proinflammatory damage-associated molecular pattern that stimulates innate immune activation via Toll-like receptor 9, similarly to bacterial DNA. A number of clinical studies have measured elevated cell-free mtDNA in the plasma of trauma patients, thought to originate from tissue injury and inflammatory processes; however, the magnitude of this increase, the absolute concentration, and the association with poor outcomes varies considerably across studies. Measurements of cell-free mtDNA in healthy individuals have shown that the majority of “cell-free” mtDNA (>95%) can be centrifuged/filtered from plasma in the size range of 0.45 to 5 μm, suggesting that there are larger forms of mtDNA-containing complexes in the plasma that could be considered cell-free. Whether this is true for trauma patients (and other relevant disease states) and the clinical relevance of the larger forms of mtDNA is unknown. These findings from healthy individuals also suggest that the centrifugation speeds used to generate cell-free plasma (which are rarely consistent among studies) could result in mixed populations of cell-free mtDNA that could confound associations with outcomes. We demonstrate in this study of 25 major trauma patients that the majority of the cell-free mtDNA in trauma patient plasma (>95%) is removed after centrifugation at 16,000g. Despite the larger forms of mtDNA being predominant, they do not correlate with outcomes or expected parameters such as injury/shock severity, multiple organ failure, and markers of inflammation, whereas low-molecular-weight cell-free mtDNA correlates strongly with these variables.
Microbiological and molecular screening of Candida spp. isolated from genital tract of asymptomatic pregnant women
Authors: Bouglita Wafa , Rabhi Sameh , Raich Natacha , Bouabid Cyrine , Belghith Cyrine , Slimani Olfa , Hkimi Chaima , Ghedira Kais , Karess Roger E. , Guizani-Tabbane Lamia , Attia Leila , Rabhi Imen
Published: September 2022

Introduction.
Candida spp. may cause opportunistic infections called vulvovaginal candidiasis (VVC), which is estimated to be the second most common cause of vaginitis worldwide.

Gap Statement. Under various circumstances, VVC could compromise pregnancy outcomes. Emerging data suggests that VVC during pregnancy may be associated with increased risk of complications and congenital cutaneous candidiasis.

Aim. To assess the prevalence of Candida spp. in asymptomatic pregnant women and determine the susceptibility of the isolates to antifungal drugs.

Methodology. In a prospective cohort, 65 high vaginal swab samples of consented pregnant women. Candida isolates were identified using both microbiological and molecular tools and drug susceptibilities were profiled.

Results. The prevalence of VVC among our study participants was 37 %, 24 of the 65 asymptomatic pregnant women show Candida spp. colonization. C. albicans was the most common species 61 %, followed by C. glabrata 39 %. In addition, a significant fraction of the isolated colonies showed resistance to Fluconazole, with a ratio of 63 % for C. albicans isolates and 16 % for Candida glabrata isolates. Moreover, relative quantification of genes related to resistance to fluconazole, CDR1, ERG11 as well as HWP1, showed a significant change compared to controls.

Conclusion. Monitoring of vaginal Candida colonization before the third trimester of pregnancy, that could reduce congenital Candida colonization and risk of pregnancy complications.
Clinical and molecular response of AML harboring non-canonical FLT3 N676K driver mutations to contemporary FLT3 inhibitors
Authors: Roloff Gregory W. , Wen Frank , Ramsland Aubrianna , Artz Andrew S. , Kosuri Satyajit , Stock Wendy , Odenike Olatoyosi , Larson Richard A. , Liu Hongtao , Godley Lucy A. , Thirman Michael J. , Patel Anand A. , Daugherty Christopher K. , DuVall Adam S. , Nawas Mariam T. , Dworkin Emily , Wool Geoffrey D. , Fitzpatrick Carrie , Segal Jeremy P. , Wang Peng , Drazer Michael W.
Published: September 2022

The treatment of acute myeloid leukemia (AML) has been enhanced by the development and regulatory approval of a series of novel agents, including midostaurin and gilteritinib (FLT3 inhibitors), venetoclax (BCL2 inhibitor), ivosidenib (IDH1 inhibitor), and enasidenib (IDH2 inhibitor). A difficulty that has arisen in the era of molecular therapies, however, is determining the efficacy of these agents for patients with AML harboring atypical driver mutations. The non-canonical FLT3 p.N676K variant was initially described as an acquired resistance mechanism in patients with FLT3 internal tandem duplication (ITD) mutations who were treated with midostaurin. Clinical data from patients with the FLT3 N676K mutations are limited. Here, we detail our experience caring for nine different patients with AML harboring FLT3 N676K at the University of Chicago. Seven of nine (78%) individuals received intensive induction chemotherapy, with FLT3 inhibitors utilized in three patients upfront and five patients during subsequent lines of treatment. With the use of FLT3 inhibitors, we noted reduction, and in some instances, complete molecular suppression of detectable FLT3 N676K variant allele fraction (VAF) on NGS, underscoring the activity of FLT3 inhibitors in this population regardless of line of therapy. Individuals with FLT3 N676K-mutated AML who received FLT3 inhibitors had longer median survival (940 days) than those who did not (408 days), however, the difference was not significant likely due to small size of the study (p = 0.2). The presence of concurrent canonical FLT3 mutations was associated with loss of treatment response. In silico visualization models of the FLT3 tyrosine kinase domain in the presence of gilteritinib demonstrate that the mechanism of N676K-mediated resistance is not due to disruption of FLT3 inhibitor binding at the ATP-binding site but rather influenced by other allosteric forces on protein structure. In conclusion, this is the largest study to date demonstrating that the atypical FLT3 N676K driver mutation is sensitive to contemporary FLT3 inhibitors, such as midostaurin and gilteritinib. Our data suggest that FLT3 inhibitors should be included in both the upfront induction setting as well as in the relapsed/refractory setting for patients harboring the FLT3 N676K mutation.
Predictors of 30-Day Readmission & Reoperations Post Strictureplasty in Crohn’s Disease: A NSQIP Retrospective Review and Analysis
Authors: Patel Apar S. , Satchel Emma K. , Guru Swadha , Hart Rachel , Serniak Nicholas , Byrne Raphael , Cagir Burt
Published: September 2022

INTRODUCTION

Strictureplasty, introduced in 1978, has been suggested as an alternative to small bowel resection for cases of intestinal obstruction involving multiple segments, such as in Crohn’s disease. Despite research supporting the operation, little is known about outcomes after strictureplasty. Specifically, 30-day readmission and reoperation rates, which are widely recognized as surrogates for quality of surgical care have not been studied for this procedure. We sought to study the rate of, as well as factors associated with 30-day outcomes, including readmission and reoperation.

METHODS

We used the National Surgical Quality Improvement Program (NSQIP) participant user files (PUF) for the years 2012-2020. Primary Current Procedural Terminology (CPT) code “44615” was used to identify patients undergoing strictureplasty as their principal procedure. The outcomes of interest included related thirty-day readmissions and reoperations, non-routine discharge, and prolonged length of stay (LOS). Multivariable analyses were performed to identify factors associated with each outcome.

RESULTS

A total of 535 patients were identified with mean age 44.14 years (SD= 15.74). 52.5% were female. Thirty-day related readmission and reoperation rates were 9% (n=48) and 6% (n=32) respectively. Average LOS was 8.16 days (SD= 6.9). Non-routine discharge rate was4.2% (n=21). On multivariable logistic regression, factors associated with 30-day readmissions included longer operative time (OR 1.00, 95% CI 1.00-1.01, p=0.0008) and any surgical site infection (SSI) (OR 6.4, 95% CI 2.89-14.2, p<0.001). Increased LOS (OR 1.7, 95%CI 1.03-1.11, p=0.0009) and SSI (OR 28.1, 95%CI 10.44-75.47, p<0.001) were associated with 30-day related reoperation. Predictors of non-routine discharge included older age (65+ vs 18-40: OR 30.72, 95%CI 3.14-300.74, p=0.003) and longer LOS (OR 1.09, 95%CI 1.03-1.14, 0.0009). Factors associated with increased odds of prolonged LOS included higher ASA class (OR 3.29, 95%CI 2.10-5.14, p<0.001), longer operative time (1.00, 95%CI 1.00-1.01, p=0.0008) and SSI (OR 3.05, 95%CI 1.57-5.90, p=0.0009). Factors associated with lower odds of prolonged LOS included male sex (OR 0.56, 96%CI 0.36-0.88, p=0.011) and preoperative steroid use (OR 0.62, 95%CI 0.38-0.99, p=0.04).

CONCLUSION

Our analyses indicate that among patients undergoing strictureplasty, longer operative time, wound complications, and longer length of stay are associated with increased odds of readmission and reoperation within 30 days. These findings may be important for hospitals, providers, payors, and other stakeholders in further refining standards of quality of care for patients undergoing strictureplasty.
IS ESPORTS ASSOCIATED WITH INCREASED HEALTH RISKS? A CROSS-SECTIONAL COMPARISON OF MUSCULOSKELETAL PAIN PREVALENCE AMONG YOUNG DANISH ESPORTS PLAYERS AND HANDBALL PLAYERS
Authors: Hansen Frederik Sand , Lyngs Mathias , Lauridsen Mathias Dyg Hyllested , Straszek Christian Lund
Published: September 2022

Background

There is a high prevalence of musculoskeletal (MSK) pain and extensive training volume among professional and amateur esport players. MSK pain has been found to limit esports participation in 6% of players. Further, there is an increasing concern that the training volume may lead to activity-limiting burnout in esports. However, it remains to be investigated if MSK pain and activity-limiting burnout is more prevalent in esports compared to traditional sports such as handball. The objectives were 1) to compare MSK pain prevalence between esports players and handball players and 2) to investigate if MSK pain is associated with training volume in the two groups.

Methods

Eligible players had to engage in either structured esports or handball and be 15-25 years of age to participate in this questionnaire-based cross-sectional study. Esports players had to engage in esports primarily through a computer-based game. Demographic data, self-reported MSK pain prevalence, training volume, sleep patterns, physical activity level and activity-limiting pain and burnout were obtained through online questionnaires. The primary outcome was any MSK pain during the previous week (yes/no).

Results

76 esports players and 175 handball players were included. 48% of esports players and 80% of handball players experienced MSK pain during the previous week. The likelihood of MSK pain was significantly lower in esport compared to handball (OR 0.24, 95%CI [0.13-0.43], Chi2 p-value < 0.001). No significant differences in training volume among participants with or without MSK pain were found in neither esports (p-value = 0.727) nor in handball (p-value = 0.128). There was a significant difference in training volume with esports player practicing for additional 12 hours per week compared to handball players (p-value < 0.001). The occurrence of activity-limiting burnout was high in both esports (34%) and handball (37%).

Conclusion

These findings suggest that young esports players are not at increased health risk in terms of experiencing MSK pain compared to young players participating in handball. This despite esports players practiced their activity for 12 hours more per week compared to handball players. More than 1 in every 3 had experienced activity-limiting burnout in both esports and handball despite a significant difference in weekly training volume. This indicate that other factors besides type of activity and training volume may influence the occurrence of activity-limiting burnout.
Exploring patient acceptability of emerging intravitreal therapies for Geographic Atrophy: a mixed-methods study
Authors: Enoch Jamie , Ghulakhszian Arevik , Sekhon Mandeep , Crabb David P. , Taylor Deanna J. , Dinah Christiana
Published: September 2022

Purpose

The acceptability of emerging intravitreal therapies for patients with Geographic Atrophy (GA) is currently unknown. This study therefore aimed to: investigate whether regular intravitreal injections will be acceptable as treatment for GA patients; identify which attributes of current treatments in late stage development patients find less acceptable; and explore whether patient-related factors influence GA treatment acceptability.

Design

Exploratory, cross-sectional, mixed-methods study.

Participants

30 UK-based individuals with GA secondary to age-related macular degeneration (AMD), recruited from two London-based hospitals, interviewed in April-October 2021.

Methods

Participants responded to a structured questionnaire, as well as open-ended questions in a semi-structured interview. Quantitative data were analysed using descriptive statistics and non-parametric measures of correlation. Qualitative data were analysed using the framework method of analysis, informed by the Theoretical Framework of Acceptability.

Main outcome measures

Main quantitative measures were Likert-type scale responses about acceptability of GA treatments. Qualitative outcomes of interest related to participants’ hopes, concerns and understanding of the proposed new intravitreal treatments for GA.

Results

Twenty participants (67%) were female, and median (interquartile range (IQR)) age was 83 (78, 87) years. 37% of participants had foveal centre-involving GA, and better eye median (IQR) logMAR visual acuity was 0.30 (0.17, 0.58). Data suggested that 18 participants (60% (95% CI: 41-79%)) would accept the treatment if offered today, despite their awareness of potential drawbacks. Eight participants (27% (95% CI: 10-43%) were ambivalent or undecided about treatment, and four (13%) (95% CI: 0-26%) would be unlikely to accept treatment. Reducing the frequency of injections from monthly to every other month increased the proportion of participants who considered the treatments acceptable.

Qualitative data indicated that participants’ prioritisation of continuation with vision-specific activities influenced treatment acceptability. Conversely, factors limiting acceptability clustered around: the limited magnitude of treatment efficacy; concerns about side effects or the increased risk of neovascular AMD; and the logistical burden of regular clinic visits for intravitreal injections. Misunderstandings of potential benefits indicate the need for appropriately designed patient education tools to support decision-making.

Conclusions

Our study suggests a majority of participants would be positive about intravitreal treatment for GA, in spite of potential burdens.
STUNTING PREVENTION BASED ON HEALTH PROMOTION MODEL FROM PERSPECTIVE PHILOSOPHY OF SCIENCE: A LITERATURE REVIEW
Authors: Ain Hurun , Pandin Moses Glorino , Arief Yuni Sufyanti
Published: September 2022

Introduction

Stunting is one of the biggest nutritional problems in toddlers in Indonesia which is based on Nutrition Status Monitoring (PSG) data for the last three years. The factor that has a large influence on the incidence of stunting is the pattern of parental care when the child is at the age of 0-59 months. The aim of this study is to study stunting prevention from the perspective of the theory of health promotion model

Method

This study uses a literature review using PICOS framework. Articles were searched from 3 databases, namely PubMed, Sciencedirect, Proquest. The keywords used in the literature search were: 1) ((Stunting prevention) AND (pender’s) OR (health promotion model), 2) Stunting prevention AND pender’s OR health promotion model; 3) stunting prevention. The search is limited to publications in 2018-2022, free full text, in English, not Reviews. Then selected using the PRISMA diagram and obtained 14 articles. Quality assessment of 14 articles using JBI Critical Appraisal tools.

Result

Seven articles stated that the determinant factor of stunting was the low education of parents (mothers) which resulted in poor parenting of children. Seven articles discussing the Health Promotion Model (HPM) theory can be used as a guide in providing education to improve health promotion.

Conclusion

good parenting behavior can be improved by increasing mother’s knowledge through providing education using HPM theory as a basis
Responding to disruption: Exploring the transition to telehealth in mental-health occupational therapy during the COVID-19 pandemic
Authors: Duffy Aislinn , Boyle Bryan , Gorman Eoin , Hayes Sarah
Published: September 2022

Background

COVID-19 presented significant challenges for occupational therapy (OT) services in Ireland. Public health guidelines necessitated a transition of services from face-to-face delivery to the use of telehealth modalities. Telehealth has yet to be extensively researched within mental health OT, with a particular need for an increased understanding of therapeutic processes when conducted remotely.

Aim

To explore the experiences of occupational therapists transitioning to telehealth service provision.

Material and Methods

This study employed a qualitative, descriptive design to examine the experiences of therapists transitioning from face-to-face to telehealth services within a mental health service. Data was collected using comprehensive, semi-structured interviews with four participants and analysed thematically.

Results

This study yielded three major themes: 1) responding to disruption, 2) reconsidering practice with technology and 3) therapeutic use of the ‘virtual self’.

Conclusions

Adaptation to telehealth provision requires planned, gradual transition but offers unique opportunities for therapeutic engagement. How space is considered in therapy as well as therapists’ communication styles are components of practice which are altered when conducted remotely.

Significance

The disruption caused by COVID-19 presented opportunities for considering the delivery of OT services. As services emerge from social restrictions it is likely that their recent experiences will be utilised in reconfiguring the future delivery of mental-health OT services.
ELISL: Early-Late Integrated Synthetic Lethality Prediction in Cancer
Authors: Tepeli Yasin , Seale Colm , Gonçalves Joana
Published: September 2022

Anti-cancer therapies based on synthetic lethality (SL) exploit tumor vulnerabilities for treatment with reduced side effects. Since simultaneous loss-of-function of SL genes causes cell death, tumors with known gene disruptions can be treated by targeting SL partners. Computational selection of promising SL candidates amongst all gene combinations is key to expedite experimental screening. However, current SL prediction models: (i) only use tissue type-specific molecular data, which can be scarce/noisy, limiting performance for some cancers; and (ii) often rely on shared SL patterns across genes, showing sensitivity to prevalent gene selection bias. We propose ELISL, Early-Late Integrated models for SL prediction using forest ensembles. ELISL models ignore shared SL patterns, and integrate context-specific data from cancer cell lines or tumor tissue with context-free functional associations derived from protein sequence. ELISL outperformed existing methods and was more robust to selection bias in 8 cancer types, with prominent contribution from sequence. We found better survival for patients whose tumors carried simultaneous mutations in a BRCA gene together with an ELISL-predicted SL gene from the HH, FGF, or WNT families. ELISL thus arises as a promising strategy to discover SL interactions with therapeutic potential.
Mitochondrial metabolism and body condition of naturally infected sunfish (Lepomis gibbosus)
Authors: Mélançon Vincent , Breton Sophie , Bettinazzi Stefano , Levet Marie , Binning Sandra A.
Published: September 2022

Parasites can affect host behavior, cognition, locomotion, body condition and many other physiological traits. Changes to host aerobic metabolism are likely responsible for these parasite-induced performance alterations. Whole-organism metabolic rate is underpinned by cellular energy metabolism driven most prominently by the mitochondria. However, few studies have explored how mitochondrial enzymatic activity relates to body condition and parasite infection despite being a putative site for metabolic disruptions related to health status. We studied correlations among natural parasite infection, host body condition and the activity of key mitochondrial enzymes in target organs from wild-caught pumpkinseed sunfish (Lepomis gibbosus) to better understand the cellular responses of fish hosts to endoparasite infection. Enzymatic activities in the gills, spleen, and brain of infected fish were not significantly related to parasite infection or host body condition. However, the activity of cytochrome C oxidase, an enzyme involved in oxidative phosphorylation, in fish hearts was higher in individuals with lower body condition. Activities of citrate synthase, complexes I and III and carnitine palmitoyltransferase were also significantly different among organ types. These results provide preliminary information regarding the likely mitochondrial pathways affecting host body condition, the maintenance energetic requirements of different organs and their specific dependency on particular mitochondrial pathways. These results help pave the way for future studies on the effects of parasite infection on mitochondrial metabolism.
Ciliary propulsion and metachronal coordination in reef coral larvae
Authors: Poon Rebecca N. , Westwood Timothy A. , Laeverenz-Schlogelhofer Hannah , Brodrick Emelie , Craggs Jamie , Keaveny Eric E. , Jékely Gáspár , Wan Kirsty Y.
Published: September 2022

Larval dispersal is critical to the survival of coral reefs. As the only motile stage of the reproductive cycle, coral larvae choose a suitable location to settle and mature into adult corals. Here, we present the first detailed study of ciliary propulsion in the common stony reef coral Acropora millepora. Using high-speed, high-resolution imaging, particle image velocimetry, and electron microscopy, we reveal the arrangement of the densely packed cilia over the larval body surface, and their organisation into diaplectic (transversely propagating) metachronal waves. We resolve the individual-cilium’s beat dynamics and compare the resultant flows with a computational model of a ciliary array, and show that this form of ciliary metachronism leads to near-maximal pumping efficiency.
Genomic glucocorticoid receptor effects guide acute stress-induced delayed anxiety and basolateral amygdala spine plasticity in rats
Authors: Novaes Leonardo S. , Bueno-de-Camargo Leticia M. , Shigeo-de-Almeida Amadeu , Juliano Vitor A. L. , Goosens Ki , Munhoz Carolina D.
Published: September 2022

Anxiety, a state related to anticipatory fear, can be adaptive in the face of environmental threats or stressors. However, anxiety can also become persistent and manifest as anxiety-and stress-related disorders, such as generalized anxiety or post-traumatic stress disorder (PTSD). In rodents, systemic administration of glucocorticoids (GCs) or short-term restraint stress induces anxiety-like behaviors and dendritic branching within the basolateral complex of the amygdala (BLA) ten days later. Additionally, increased arousal-related memory retention mediated by elevated GCs requires concomitant noradrenaline (NE) signaling, both acting in the BLA. It is unknown whether GCs and NE play a role in the delayed acute stress-induced effects on behavior and BLA dendritic plasticity. Here, inhibiting corticosterone (CORT) elevation during two hours of restraint stress prevents stress-induced increases in delayed anxiety-like behavior and BLA dendritic spine density in rats. Also, we show that the delayed acute stress-induced effects on behavior and morphological alterations are critically dependent on genomic glucocorticoid receptor (GR) actions in the BLA. Unlike CORT, the pharmacological enhancement of NE signaling in the BLA was insufficient to drive delayed anxiety-related behavior. Nonetheless, the delayed anxiety-like behavior ten days after acute stress requires NE signaling in the BLA during stress exposure. Therefore, we define the essential roles of two stress-related hormones for the late stress consequences, acting at two separate times: CORT, via GR, immediately during stress and NE, via beta-adrenoceptors, during the expression of delayed anxiety.

Significance Statement

The dysregulation in orchestrating and finetuning major stress-related neural circuitries leads to enhanced reactivity and other altered ways of coping with threatening situations, predisposing humans to multiple psychiatric disorders, including anxiety and PTSD. Given the tremendous burden of affective disorders, we must advance our understanding of stress neurobiology and translate this into improved treatments. Here we showed that the absence of neuronal genomic GR signaling in the BLA prevented delayed effects on anxiety-like behavior and dendritic spine density ten days after stressor exposure. We also demonstrate that CORT, via GR and immediately at stress and NE, via beta-adrenoceptors, during the expression of delayed behavior contribute to the late stress consequences.
Identification of Ensifer meliloti genes required for survival during peat-based bioinoculant maturation by STM-seq
Authors: Lozano Mauricio J. , Mogro Ezequiel G. , Salas M. Eugenia , Erdozain Sofía A. , Zuber Nicolás E. , Becker Anke , Lagares Antonio
Published: September 2022

Rhizobial inoculants are sold either as rhizobia within a liquid matrix; or as rhizobia adhered to granules composed of peat prill or finely ground peat moss. During the production of peat-based inoculants, immediately after mixing the rhizobia culture with partially dry sterile peat, the inoculant is stored for a period of 4-5 weeks, inducing a series of changes that results in an increased capability of the rhizobia to survive in the seeds. The number of viable rhizobia on preinoculated seeds at the point of sale, however, is often a limiting factor, as is the inefficiency of the inoculant bacteria to compete with the local rhizobia for the host colonization. In the present work, we used STM-seq for the genomewide screening of Ensifer meliloti mutants affected in the survival during the maturation of peat-based inoculant formulations. Through this approach, we identified hundreds of genes that proved to be relevant to this process. These results also provide a base knowledge that could be used to more completely understand the survival mechanisms used by rhizobia during the maturation of peat-based inoculants, as well as for the design of new inoculant formulations.

Highlights

Rhizobial inoculants provide an ecological means of nitrogen fertilization compatible with the implementation of sustainable agricultural practices. Their successful usage, however, suffers from two main limitations: the low number of viable rhizobia on preinoculated seeds at the point of sale, and the inefficiency to compete with the local rhizobia for host colonization. Here, we used a high-throughput mutant-screening technology, STM-seq, to uncover which rhizobial genes are involved in the rhizobial survival during the preparation and storage of peat-based inoculant formulations. Our findings provide useful information about the stresses faced by rhizobia during peat-inoculant maturation and storage, which could assist both for the selection of better rhizobial strains, and for the improvement of the inoculant formulations.

Graphical Abstract
Improving animal behaviors through a neural interface with deep reinforcement learning
Authors: Li Chenguang , Kreiman Gabriel , Ramanathan Sharad
Published: September 2022

Artificial neural networks have performed remarkable feats in various domains but lack the flexibility and generalization power of biological neural networks. Given their different capabilities, it would be advantageous to build systems where both network types can synergistically interact. As proof-of-principle, we show how to create such a hybrid system and harness it to improve animal performance on biologically relevant tasks. Using optogenetics, we interfaced the nervous system of the nematodeCaenorhabditis eleganswith a deep reinforcement learning agent, enabling the animal to navigate to targets and enhancing its food search ability. Agents adapted to strikingly different sites of neural integration and learned site-specific activations to improve performance on a target-finding task. The animal plus agent displayed cooperative computation and generalized to novel environments. This work constitutes a demonstration of how to improve task performance in animals using artificial intelligence interfaced with a nervous system.
Heat Hardening of a Larval Amphibian is Dependent on Acclimation Period and Temperature
Authors: Dallas Jason , Warne Robin W.
Published: September 2022

The thermal tolerance–plasticity trade-off hypothesis states that acclimation to warmer environments increases basal thermal tolerance in ectotherms but reduces plasticity in coping with acute thermal stress characterized as heat hardening. We examined the potential trade-off between basal heat tolerance and hardening plasticity, measured as critical thermal maximum (CTmax) of a larval amphibian, Lithobates sylvaticus, in response to differing acclimation temperatures (15° and 25°C) and periods (3 or 7 days). A hardening treatment applied 2 hours before CTmax assays induced pronounced plastic hardening responses in the cool, 15°C treatment after 7 days of acclimation, compared to controls. Warm acclimated larvae at 25°C, by contrast, exhibited minor hardening responses, but significantly increased basal thermal tolerance. These results support the trade-off hypothesis and fill a knowledge gap in larval amphibian thermal plasticity. Elevated environmental temperatures induce acclimation in heat tolerance yet constrains ectotherm capacity to cope with further acute thermal stress.

Summary Statement

A larval amphibian follows the trade-off hypothesis such that the group with the highest basal heat tolerance displays the lowest hardening response and vice-versa.
Comparison of Mitogenomic and Mitochondrial Markers for the Phylogenetic and Evolutionary Study of Marmosets, with special focus on captive Callithrix jacchus
Authors: Fonseca João L.G. , del Rosario Ricardo C. H. , de Oliveira Maria Adélia Borstelmann , Feng Guoping , Igayara Claudia S. , McCarroll Steven A. , Nicola Patricia A. , Pereira Luiz C. M. , Rogers Jeffery , Roos Christian , Malukiewicz Joanna
Published: September 2022

Marmosets, especially Callithrix jacchus, are becoming valuable, high-demand biomedical models but their supply outside of their native Brazil is limited. Thus, uncovering the ancestry and biogeographic origins of captive marmosets is an essential task to optimize their biomedical use. Such information facilitates assessing standing levels of captive marmoset genetic diversity, identifying hybrids, and maintaining genetic diversity of captive marmoset populations. Here, we present 16 newly sequenced mitochondrial genomes from marmosets with C. jacchus phenotypes from international biomedical and animal supply facilities. We combine these new data with publicly available sequences to compare usage of mitogenome and the mtDNA control region for determining the ancestry and diversity of captive marmosets. MtDNA control region and mitogenome haplotypes from all 16 newly sequenced marmosets grouped within C. jacchus phylogenetic clades. Overall, phylogenies based on mitogenomes rather than the control region showed better resolved branching patterns with stronger statistical support within C. jacchus clades. However, both mtDNA markers show that C. jacchus is the sister clade to the phylogenetic C. penicillata Caatinga biome clade. Callithrix jacchus mtDNA control region haplotypes showed the highest haplotype and nucleotide diversity, and were intermediate in terms of per sequence theta and polymorphic sites. The larger number of available Callithrix mtDNA control region sequences relative to mitogenomes was used to determine ancestral mtDNA haplotype biogeographic origins. However, biogeographic origins for many C. jacchus haplotypes including those from international captive facilities could not be determined, which we attributed to unknown provenance information from natural C. jacchus populations. Given our results, we encourage increased sampling and genomic sequencing efforts for natural C. jacchus populations in Brazil, and utilizing the mitogenome over other mtDNA markers for phylogenetic-based analyses. Further, combining marmoset mitogenomic data with phenotypic and nuclear genomic data will greatly enhance the biomedical use of marmosets.
Novel mitochondrial genome rearrangements including duplications and extensive heteroplasmy could underlie temperature adaptations in Antarctic Notothenioid Fishes
Authors: Minhas Bushra Fazal , Beck Emily A. , Cheng C.-H. Christina , Catchen Julian
Published: September 2022

Mitochondrial genomes are known for their compact size and conserved gene order, however, recent studies employing long-read sequencing technologies have revealed the presence of atypical mitogenomes in some species. In this study, we assembled and annotated the mitogenomes of five Antarctic notothenioids, including four icefishes (Champsocephalus gunnari, C. esox, Chaenocephalus aceratus, andPseudochaenuchthys georgianus) and the cold-specializedTrematomus borchgrevinki. Antarctic notothenioids are known to harbor some rearrangements in their mt genomes, however the extensive duplications in icefishes observed in our study have never been reported before. In the icefishes, we observed duplications of the protein coding geneND6, two transfer RNAs, and the control region with different copy number variants present within the same individuals and with someND6duplications appearing to follow the canonical Duplication-Degeneration-Complementation (DDC) model inC. esoxandC. gunnari. In addition, using long-read sequencing and k-mer analysis, we were able to detect extensive heteroplasmy inC. aceratusandC. esox. We also observed a large inversion in the mitogenome ofT. borchgrevinki, along with the presence of tandem repeats in its control region. This study is the first in using long-read sequencing to assemble and identify structural variants and heteroplasmy in notothenioid mitogenomes and signifies the importance of long-reads in resolving complex mitochondrial architectures. Identification of such wide-ranging structural variants in the mitogenomes of these fishes could provide insight into the genetic basis of the atypical icefish mitochondrial physiology and more generally may provide insights about their potential role in cold adaptation.
Gene expression has distinct associations with brain structure and function in major depressive disorder
Authors: Liu Shu ,   the DIRECT Consortium, Abdellaoui Abdel , Verweij Karin J.H. , van Wingen Guido A.
Published: September 2022

Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well as brain anatomy and function are influenced by genetic factors, but the role of gene expression remains unclear. Here we investigated how cortical gene expression contributes to structural and functional brain abnormalities in MDD. We compared the gray matter volume and resting-state functional measures in a Chinese sample of 848 MDD patients and 749 healthy controls, and we then associated these case-control differences with cortical variation of gene expression. While whole gene expression was positively associated with structural abnormalities, it was negatively associated with functional abnormalities. We observed the relationships of expression levels with brain abnormalities for individual genes, and found that transcriptional correlates of brain structure and function showed opposite relations with gene dysregulation in postmortem cortical tissue from MDD patients. We further identified genes that were positively or negatively related to structural abnormalities as well as functional abnormalities. The MDD-related genes were enriched for brain tissue, cortical cells, and biological pathways. These findings suggest that distinct genetic mechanisms underlie structural and functional brain abnormalities in MDD, and highlight the importance of cortical gene expression for the development of cortical abnormalities.
Assessing the Mediterranean diet adherence during pregnancy: practical considerations based on the associations with cardiometabolic risk
Authors: Flor-Alemany Marta , Migueles Jairo H. , Acosta-Manzano Pedro , Marín-Jiménez Nuria , Baena-García Laura , Aparicio Virginia A
Published: September 2022

Objective

The aim of the present study was to provide practical considerations for assessing MD adherence during pregnancy based on the association with cardiometabolic risk.

Study design

Longitudinal study

Main outcome measures

A food frequency questionnaire was fulfilled by 152 pregnant women at the 16th gestational week (g.w.). We calculated the Mediterranean Food Pattern (MFP), the MD Scale (MDScale), the Short MD questionnaire (SMDQ), the MD Score (MedDietScore), and the MD scale for pregnant women (MDS-P). The cardiometabolic risk score consisted of pre-pregnancy body mass index, blood pressure, glucose, triglycerides, and high-density lipoprotein-cholesterol (at 16th and 34th g.w.).

Results

Multiple linear regression models showed that the MFP, the MedDietScore, and the SMDQ were associated with lower cardiometabolic risk at the 16th and 34th g.w. (β’s: - 0.193 to -0.415, all p<0.05); and the MDS-P at the 34th g.w. (β=-0.349, p<0.01). A comparison of these models with the J test showed that the MFP and the MedDietScore outperformed the SMDQ at the 16th g.w. (p’s<0.05); while the MedDietScore outperformed the SMDQ, MFP, and MDS-P (p’s<0.05) at the 34th g.w. Receiver-Operating-Characteristic-derived thresholds for the MFP, MedDietScore and MDS-P indices were 21, 30, and 6 points, respectively, to identify women with high cardiometabolic risk.

Conclusion

The MFP and MedDietScore are recommended to assess MD adherence during pregnancy, as these showed the strongest associations with cardiometabolic risk. Our validated thresholds might assist in the detection of poor dietary patterns during pregnancy.
Network feature-based phenotyping of leaf venation robustly reconstructs the latent space
Authors: Iwamasa Kohei , Noshita Koji
Published: September 2022

Despite substantial variation in leaf vein architectures among angiosperms, a typical hierarchical network pattern is shared within clades. Functional demands constrain the network structure of leaf venation, generating a biased distribution in the morphospace. Although network structures and their diversity are crucial for understanding angiosperm venation, previous studies have relied on simple morphological measurements (e.g., length, diameter, branching angles, and areole area) and their derived statistics to quantify phenotypes. In this study, we developed a simple, high-throughput phenotyping workflow for the quantification of vein networks and identified leaf venation-specific morphospace patterns. The proposed method involves four processes: leaf image acquisition using a feasible system, leaf vein segmentation based on a deep neural network model, network extraction as an undirected graph, and network feature calculation. To demonstrate the proposed method, we applied it to images of non-chemically treated leaves of five species for classification based on network features alone, with an accuracy of 90.6%. By dimensionality reduction, a one-dimensional morphospace, along which venation shows variation in loopiness, was identified for both untreated and cleared leaf images, suggesting that patterns of venation are determined by a functional trade-off. The proposed network feature-based method is a useful morphological descriptor, providing a quantitative representation of the topological aspects of venation and enabling inverse mapping to leaf vein structures. Accordingly, our approach is promising for analyses of the functional and structural properties of veins.

Author Summary

Leaf venation exhibits diverse network structures among taxa and conservation within taxa, reflecting complex evolutionary processes involving functional, developmental, and structural constraints. We used network features to characterize hierarchical and complex venation patterns. We analyzed 479 non-chemically treated leaves of five species and demonstrated that network features contain sufficient information for species classification. Furthermore, we identified biased distribution patterns in the leaf venation morphospace by characterizing leaf samples from both untreated and cleared leaf images. These results improve our understanding of morphological constraints and functional trade-offs shaping divergence in leaf venation. Our approach provides a basis for similar analyses in various fields targeting reticulate networks, which are ubiquitous in nature, including biomimetics, generative design, and microfluidics.
Barcode-free prediction of cell lineages from scRNA-seq datasets
Authors: Eisele A.S. , Tarbier M. , Dormann A.A. , Pelechano V. , Suter D.M.
Published: September 2022

The integration of lineage tracing with scRNA-seq has transformed our understanding of gene expression heritability during development, regeneration, and disease. However, lineage tracing is technically demanding and most existing scRNA-seq datasets are devoid of lineage information. Here we introduce Gene Expression Memory-based Lineage Inference (GEMLI), a computational pipeline allowing to predict cell lineages over several cell divisions solely from scRNA-seq datasets. GEMLI leverages genes displaying conserved expression levels over cell divisions, and allows i.a. identifying cell lineages in a broad range of cultured cell types, in intestinal organoids, and in crypts from adult mice. GEMLI recovers GO-terms enriched for heritable gene expression, allows to discriminate symmetric and asymmetric cell fate decisions and to reconstruct individual cellular structures from pooled scRNA-seq datasets. GEMLI considerably extends the pool of datasets from which lineage information can be obtained, thereby facilitating the study of gene expression heritability in a broad range of contexts. GEMLI is available at (https://github.com/UPSUTER/GEMLI).
mRNA-based generation of marmoset PGCLCs capable of differentiation into gonocyte-like cells
Authors: Kubiura-Ichimaru Musashi , Penfold Christopher , Kojima Kazuaki , Dollet Constance , Yabukami Haruka , Semi Katsunori , Takashima Yasuhiro , Boroviak Thorsten , Kawaji Hideya , Woltjen Knut , Minoda Aki , Sasaki Erika , Watanabe Toshiaki
Published: September 2022

Primate germ cell development remains largely unexplored due to limitations in sample collection and the long duration of development. In mice, primordial germ cell-like cells (PGCLCs) derived from pluripotent stem cells (PSCs) can develop into functional gametes by in vitro culture or in vivo transplantation. Such PGCLC-mediated induction of mature gametes in primates is highly useful for understanding human germ cell development. Since marmosets generate functional sperm earlier than other species, recapitulating the whole male germ cell development process is technically more feasible. Here, we induced the differentiation of iPSCs into gonocyte-like cells via PGCLCs in marmosets. First, we developed an mRNA transfection-based method to efficiently generate PGCLC. Subsequently, to promote PGCLC differentiation, xenoreconstituted testes (xrtestes) were generated in the mouse kidney capsule. PGCLCs show progressive DNA demethylation and stepwise expression of developmental marker genes. This study provides an efficient platform for the study of marmoset germ cell development.

Highlights

An mRNA transfection-based PGCLC induction method is developed

Marmoset PGCLCs are efficiently induced from iPSCs

Marmoset PGCLCs differentiate into gonocyte-like cells in mouse kidneys

Developmentally regulated expression and demethylation are recapitulated

eTOC blurb

Watanabe et al. efficiently induced marmoset primordial germ cell-like cells (PGCLCs) using an mRNA transfection-based approach. PGCLCs further develop into gonocyte-like cells in the xenoreconstituted testes constructed under mouse kidney capsules. This system faithfully reproduced in vivo developmental processes (e.g., stage-specific expression of developmentally regulated genes and DNA demethylation).
The impact of COVID-19 on prior and current learning
Authors: Rudin Joel , D'Intino Robert , Fleming Robert , Nicholson Jennifer , Jovanovski Straso
Published: September 2022

Purpose

The purpose of this paper is to measure the effects of COVID-19 on student learning. Using boundary theory and border theory, the authors hypothesize that learning will be highest in 2019, the year before the pandemic, and lowest in 2020, the year that the pandemic began.

Design/methodology/approach

Participants were business students at an American university. The authors administered the same 88-question multiple-choice exam in a capstone course in May 2019, May 2020, and May 2021. Ten questions measured learning in the capstone course (current learning), and the remaining questions assessed learning from prerequisite courses (prior learning). Any year-to-year differences in test scores may be attributed to the effects of COVID-19.

Findings

Current learning was exactly as hypothesized. It was highest in 2019 and lowest in 2020. Prior learning appeared to be completely unaffected by the pandemic. It increased slightly but insignificantly throughout the three years. The authors conclude that home–school boundary and border problems caused by the pandemic inhibited the ability of students to remember what they had recently learned but did not prevent them from demonstrating knowledge of information that they had acquired in pervious semesters.

Originality/value

The authors add value to the body of knowledge about the effects of COVID-19 on student learning because (1) our dependent variable is cognitive. Most other studies have modeled attitudinal dependent variables such as satisfaction; and (2) this sample is located within the United States. Most other research has utilized participants in other countries and their results may not generalize to the American context.