bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: a missed case of chronic Q fever infective endocarditis demonstrating the ongoing diagnostic challenges
Authors: Grey Victoria , Simos Peter , Runnegar Naomi , Eisemann Jared
Published: November 2023

Diagnosis of chronic Q fever is often difficult for clinicians, particularly in the presence of a second pathology. In addition to the chronic constitutional symptoms, the most common manifestations of chronic Q fever include infective endocarditis and endovascular infection. We describe a case of prosthetic valve infective endocarditis caused by both

Streptococcus sanguinis

and Coxiella burnetti on a background of a previous aortic graft and bioprosthetic aortic valve replacement 2 years earlier. The diagnosis of chronic Q fever infective endocarditis was delayed because the significance of the abnormal valve histology from the patient’s previous surgery was initially overlooked. It was only after the patient had relapsed on appropriate therapy for the

S. sanguinis

prosthetic valve endocarditis that a subsequent review of the operative valve histology, along with the patient’s epidemiological risk factors, led to consideration of an additional culture-negative cause for infective endocarditis. Histological examination of the valve tissue had shown exophytic fibrin vegetations and acute inflammation. Further clinical assessment revealed previous exposure to Q fever and C. burnetti DNA was detected via polymerase chain reaction on the valve tissue. Q fever infective endocarditis must be considered if valves are inflamed or have vegetations with a subsequent negative culture. It should also still be considered in the presence of an alternative bacteraemia if the patient has risk factors for exposure.
Thyroid hyperplasia and neoplasm adverse events associated with GLP-1 receptor agonists in FDA Adverse Event Reporting System
Authors: Makunts Tigran , Joulfayan Haroutyun , Abagyan Ruben
Published: November 2023

Glucagon receptor-like peptide receptor agonists, GLP-1 RAs, are one of the most commonly used drugs for type-2 diabetes mellitus. The clinical guidelines recommend GLP-1 RAs as adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, obesity, and other cardiometabolic conditions. The weight loss seen in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment. Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled black boxed warning of the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of most recent postmarketing safety data is warranted to quantify thyroid hyperplasia and neoplasms instances. In this study we analyzed over eighteen million reports from United States Food and Drug Administration Adverse Event Reporting System and identified 17,653 relevant GLP-1 RA monotherapy reports to provide the evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA as monotherapy when compared to patients taking sodium-glucose cotransporter-2 inhibitor monotherapy.
Re-emergence of Sylvatic Dengue 2 during an outbreak in Southeastern Senegal, Kedougou 2020
Authors: Dieng Idrissa , Diarra Maryam , Sadio Bacary Djilocalisse , Gaye Alioune , Sow Bocar , Dior Ndione Marie Henriette , Diallo Diawo , Ndiaye Mignane , Diallo Amadou , Sankhe Safietou , Faye Martin , Diop Boly , Sall Amadou Alpha , Fall Gamou , Faye Oumar , Loucoubar Cheikh , Faye Ousmane , Weaver Scott C. , Diallo Mawlouth , Barry Mamadou Aliou , Diagne Moussa Moise
Published: November 2023

Dengue outbreaks in West Africa, linked to urban cycle viruses, pose a significant public health threat. In 2020, a sylvatic Dengue 2 outbreak in Kedougou, southeastern Senegal, resulted in 59 confirmed cases, suggesting these strains may not require additional adaptation but could re-emerge into urban transmission cycles in the region.
Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease
Authors: Curtis David
Published: November 2023

An important issue pertinent to the analysis of sequence data to detect association between rare variants in a gene and a given phenotype is the ability to annotate nonsynonymous variants in terms of their likely importance as affecting protein function. While a number of software tools attempt to do this, AlphaMissense was recently released and was shown to have good performance using benchmarks based on variants causing severe disease and on functional assays. Here, we assess the performance of AlphaMissense across 18 genes which had previously demonstrated association between rare coding variants and hyperlipidaemia, hypertension or type 2 diabetes. Ability to detect association, expressed as the signed log p value (SLP) was compared between AlphaMissense and 43 other annotation methods. The results demonstrated marked variability between genes regarding the extent to which nonsynonymous variants contributed to evidence for association and also between the performance of different methods of annotating the nonsynonymous variants. Although AlphaMissense produced the highest SLP on average across genes, it produced the maximum SLP for only 4 genes. For some genes, other methods produced a considerably higher SLP and there were examples of genes where AlphaMissense produced no evidence for association while another method performed well. The marked inconsistency across genes means that it is difficult to decide on an optimal method of analysis of sequence data. The fact that different methods perform well for different genes suggests that if one wished to use sequence data for individual risk prediction then gene-specific annotation methods should be used. It would be desirable to have the ability to recognise characteristics of a gene which could facilitate the selection of an annotation method which would best discriminate variants of interest within that gene.

This research has been conducted using the UK Biobank Resource.
Threat of shock increases distractor susceptibility during the short-term maintenance of visual information
Authors: Casalvera Abigail , Goodwin Madeline , Lynch Kevin , Teferi Marta , Patel Milan , Grillon Christian , Ernst Monique , Balderston Nicholas L
Published: November 2023

BACKGROUND

Work on anxiety related attention control deficits suggests that elevated arousal impacts the ability to filter out distractors. To test this, we designed a task to look at distractor suppression during periods of threat. We administered trials of a visual short-term memory (VSTM) task, during periods of unpredictable threat, and hypothesized that threat would impair performance during trials where subjects were required to filter out large numbers of distractors.

METHOD

Experiment 1 involved fifteen healthy participants who completed one study visit. They performed four runs of a VSTM task comprising 32 trials each. Participants were presented with an arrow indicating left or right, followed by an array of squares. They were instructed to remember the target side and disregard the distractors on the off-target side. A subsequent target square was shown, and participants indicated whether it matched one of the previously presented target squares. The trial conditions included 50% matches and 50% mismatches, with an equal distribution of left and right targets. The number of target and distractor squares varied systematically, with high (4 squares) and low (2 squares) target and distractor conditions. Trials alternated between periods of safety and threat, with startle responses recorded using electromyography (EMG) following white noise presentations.

Experiment 2 involved twenty-seven healthy participants who completed the same VSTM task inside an MRI scanner during a single study visit. The procedure mirrored that of Experiment 1, except for the absence of white noise presentations.

RESULTS

For Experiment 1, subjects showed significantly larger startle responses during threat compared to safe period, supporting the validity of the threat manipulation. However, results suggested that the white noise probes interfered with performance. For Experiment 2, we found that both accuracy was affected by threat, such that distractor load negatively impacted accuracy only in the threat condition.

CONCLUSION

Overall, these findings suggest that threat affects distractor susceptibility during the short-term maintenance of visual information. The presence of threat makes it more difficult to filter out distracting information. We believe that this is related to hyperarousal of parietal cortex, which has been observed during unpredictable threat.
Low Positive Social Determinants of Health Exposure Amplifies the Association between Allostatic Load and Risk of Cardiovascular Mortality in Cancer and Non-Cancer Patients
Authors: Bhave Aditya , Reddy Ritu , Moore Justin X. , Nain Priyanshu , Datta Biplab , Nettles Darryl , Seth Lakshya , Jiang Stephanie , Patel Vraj , Malik Sarah , Weintraub Neal , Al-Kindi Sadeer G , Ganatra Sarju , Dani Sourbha , Gomez-Valencia Javier , Wang Xiaoling , Guha Avirup
Published: November 2023

Background

High allostatic load (AL) is associated with an increased risk of cardiovascular death (CVD), but little is known about how social determinants moderate this relationship.

Methods

We conducted a retrospective cohort analysis of the National Health and Nutrition Examination Survey years 1999-2010 linked with the National Death Index. We fit age, race, and sex-adjusted Fine & Gray models to calculate sub-distribution hazard ratios (SHR) of CVD among adults exposed to high versus low levels of positive social determinants of health (PSDOH), stratified by high and low AL status.

Results

Among 22,775 participants, 1,939 (8.5%) had a cancer history. In the full cohort, low PSDOH was associated with 38% increased risk of CVD among high AL adults (SHR: 1.38, 95% CI: 1.22 - 1.56) and 57% increased risk among low AL adults (SHR: 1.57, 95% CI: 1.32 - 1.87). Among adults with no cancer history, low PSDOH was associated with 36% increased risk among high AL adults (SHR: 1.36, 95% CI: 1.19 – 1.55) and 59% increased risk among low AL adults (SHR: 1.59, 95% CI: 1.32 – 1.92). In the cancer cohort, low PSDOH was associated with 77% increased risk among high AL adults (SHR: 1.77, 95% CI: 1.32 – 2.37) and 73% increased risk among low AL adults (SHR: 1.73, 95% CI: 1.02 – 2.94).

Conclusions

Low PSDOH amplified the association between AL and CVD in all cohorts, with the highest risk increases among adults with cancer history. This suggests that socioeconomic-related distress supersedes biological changes from AL in relation to CVD.
The Clinimetric Profile of 11 Generic Quality Indicators for Appropriate Antibiotic Use in Hospitalized Patients in Indonesia
Authors: Tunjungputri Rahajeng N. , Lie Khie Chen , Susilo Adityo , Nainggolan Freddy C. , Jasirwan Chyntia O.M. , Hidayat Rudy , Purnamasari Dyah , Sinto Robert , Nelwan Erni J.
Published: November 2023

Background

One of the efforts in antibiotic stewardship for limiting antibiotic resistance is the assessment of the quality of antibiotic use. To date, the quality and appropriateness of antibiotic use in Indonesia, a low-middle-income non-European country, have not yet been assessed using proven quality indicators (QIs). One recommended tool to measure appropriate empiric antibiotic use in hospitalized patients is the generic QIs reported by van den Boschet. al., which demonstrated good validity and generalizability.

Objective

The aim of this study is to assess the clinimetric profile of 11 generic QIs based on van den Boschet. al. in admitted adult patients receiving empiric antibiotics in Indonesian hospitals.

Methods

This is an observational study with a cross-sectional design conducted at two government referral hospitals in Jakarta, Indonesia, from August 1, 2022, to February 2, 2023. Adult inpatients who received empiric antibiotics due to suspected infection for ≥24 hours were included in the study.

Results

In 500 inpatients from 2 hospitals, all QIs demonstrated good measurability with less than 10% of missing data. Ten QIs showed good applicability of >10%. Four QIs show good performance, while six QIs have significant potential for improvement (two blood cultures are obtained before empiric antibiotic treatment; culture sample is obtained from location suspected of infection; antibiotic is switched from intravenous to oral when clinically possible; antibiotics are stopped when there is no evidence of infection; a guideline is available and renewed every three years; and a guideline is adjusted to the local resistance pattern) making them priority targets for interventions to enhance the quality of antibiotic use in Indonesia. All QIs display good inter-observer reliability, and no moderate or strong correlations are found between QIs.

Conclusion

The clinimetric assessment of QIs is imperative before their implementation in any setting different from their country of origin. Of the 11 generic QIs, 10 demonstrated good reliability and applicability at two hospitals in Indonesia. Future intervention studies can utilize these generic QIs to measure improvement in the appropriateness of antibiotic use.
Examining Risk Factors Related to Cardiac Rehabilitation Cessation Among Advanced Heart Failure Patients
Authors: Sidhu Sharnendra K. , Kadosh Bernard S. , Haas François , Tang Ying , Sweeney Greg , Pierre Alicia , Whiteson Jonathan , Katz Edward , Reyentovich Alex , Dodson John A.
Published: November 2023

Background

Cardiac rehabilitation (CR) has shown benefits in heart transplant and left ventricular assist device (LVAD) recipients, but variable patterns of attendance remain poorly understood. We therefore aimed to describe CR adherence and factors associated with cessation in this population.

Methods

We performed a retrospective review of heart transplant and LVAD recipients who attended at least one CR session at a tertiary medical center (2013-2022). Complete adherence was defined as attending all 36 CR sessions. Primary reasons for cessation prior to 36 sessions were recorded. We compared post-operative complications and length of stay (following heart transplant or LVAD) between participants with and without complete adherence using logistic regression. In a subgroup analysis of participants with complete adherence, we compared changes in METs, exercise time, and peak VO2using paired-sample t tests.

Results

There were 137 heart transplant and LVAD recipients (median age 56.9 years, 73.7% male) who attended CR. Ninety-one percent either completed all 36 CR sessions or fewer than 24 sessions. Among those without complete adherence (n=74), 71.6% reported medical reasons and 15.0% reported personal reasons for cessation. Participants without complete adherence experienced more post-operative complications (43.9% vs 34.4%, p = 0.02) and major bleeding (22.7% vs 15.2%, p = 0.02) prior to enrolling in CR, but there were no other significant differences between groups. Participants with complete adherence experienced significant improvements in exercise time (160.9 seconds), METs (0.8), and peak VO2(1.5 mL/kg per min).

Conclusions

Among heart transplant and LVAD recipients, there was a bimodal distribution of CR attendance; nearly half completed all 36 sessions. Among those with complete adherence, there were significant improvements in exercise measures, underscoring the important benefits of CR in this population.
Machine Learning-Based Hyperglycemia Prediction: Enhancing Risk Assessment in a Cohort of Undiagnosed Individuals
Authors: Oyebola Kolapo , Ligali Funmilayo , Owoloye Afolabi , Erinwusi Blessing , Alo Yetunde , Musa Adesola , Aina Oluwagbemiga , Salako Babatunde
Published: November 2023

Background

Noncommunicable diseases (NCDs) continue to pose a significant health challenge globally, with hyperglycemia serving as a prominent indicator of potential diabetes. This study employed machine learning algorithms to predict hyperglycemia in a cohort of asymptomatic individuals and unraveled crucial predictors contributing to early risk identification.

Methods

This dataset included an extensive array of clinical and demographic data obtained from 195 asymptomatic adults residing in a suburban community in Nigeria. The study conducted a thorough comparison of multiple machine learning algorithms to ascertain the most effective model for predicting hyperglycemia. Moreover, we explored feature importance to pinpoint correlates of high blood glucose levels within the cohort.

Results

Elevated blood pressure and prehypertension were recorded in 8 (4%) and 18 (9%) individuals respectively. Forty-one (21%) individuals presented with hypertension (HTN), of which 34/41 (82.9%) were females. However, cohort-based gender adjustment showed that 34/118 (28.81%) females and 7/77 (9.02%) males were hypertensive. Age-based analysis revealed an inverse relationship between normotension and age (r = -0.88; P < 0.05). Conversely HTN increased with age (r = 0.53; P < 0.05), peaking between 50-59 years. Isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) were recorded in 16/195 (8.21%) and 15/195 (7.69%) individuals respectively, with females recording higher prevalence of ISH 11/16 (68.75%) while males reported a higher prevalence of IDH 11/15 (73.33%). Following class rebalancing, random forest classifier gave the best performance (Accuracy Score = 0.894; receiver operating characteristic-area under the curve (ROC-AUC) score = 0.893; F1 Score = 0.894) of the 27 model classifiers. The feature selection model identified uric acid and age as pivotal variables associated with hyperglycemia.

Conclusions

Random Forest classifier identified significant clinical correlates associated with hyperglycemia, offering valuable insights for early detection of diabetes and informing the design and deployment of therapeutic interventions. However, to achieve a more comprehensive understanding of each feature’s contribution to blood glucose levels, modeling additional relevant clinical features in larger datasets could be beneficial.
More than expected: extracellular waveforms and functional responses in monkey LGN
Authors: Sun Shi Hai , Killian Nathaniel J. , Pezaris John S.
Published: November 2023

Unlike the exhaustive determination of cell types in the retina, key populations in the lateral geniculate nucleus of the thalamus (LGN) may have been missed. Here, we have begun to characterize the full range of extracellular neuronal responses in the LGN of awake monkeys using multi-electrodes during the presentation of colored noise visual stimuli to identify any previously overlooked signals. Extracellular spike waveforms of single units were classified into seven distinct classes, revealing previously unrecognized diversity: four negative-dominant classes that were narrow or broad, one triphasic class, and two positive-dominant classes. Based on their mapped receptive field (RF), these units were further categorized into either magnocellular (M), parvocellular (P), koniocellular (K), or non-RF (N). We found correlations between spike shape and mapped RF and response characteristics, with negative and narrow spiking waveform units predominantly associated withPandNRFs, and positive waveforms mostly linked toMRFs. Responses from positive waveforms exhibited shorter latencies, larger RF sizes, and were associated with larger eccentricities in the visual field than the other waveform classes. Additionally,Ncells, those without an estimated RF, were consistently responsive to the visually presented mapping stimulus at a lower and more sustained rate than units with an RF. These findings suggest that the LGN cell population may be more diverse than previously believed.

Significance statement

This study uncovers evidence for an intricate diversity of neuronal responses within the lateral geniculate nucleus (LGN), challenging conventional classifications and revealing previously overlooked populations. By characterizing extracellular spike waveforms and revising receptive field classifications, we provide novel insights into LGN function. Our findings have significant implications for understanding early visual processing mechanisms and interpreting extracellular signals in neural circuits. Furthermore, we identify non-receptive field units, prompting exploration into their functional roles and broader implications for visual and non-visual computations. This study not only advances our understanding of LGN organization but also highlights the importance of considering recording biases in electrophysiological studies. Overall, our work opens new avenues for interdisciplinary research and contributes to advancing our knowledge of neural dynamics in the visual system.
Discovery of a novel MarR-type transcriptional regulator that controls cell death inBacillus subtilisbiofilms
Authors: McClennen Gillian , Angelini Leticia Lima , Fox Gabriel , Godoy-Carter Veronica , Chai Yunrong
Published: November 2023

Pulcherriminic acid (PA) is a cyclic-L-leu-L-leu di-peptide produced byBacillus subtilisduring biofilm formation. When secreted, PA strongly chelates extracellular iron and forms a reddish- brown pigment, pulcherrimin. Production of pulcherriminic acid and formation of pulcherrimin modulate iron homeostasis inB. subtilis. Pulcherriminic acid also functions as an antioxidant to protect cells from increasing oxidative stress during biofilm formation. We previously showed that PA is involved in gene regulation, differentially regulating hundreds of genes inB. subtilis. One of the strongly upregulated genes by PA isyhjH, encoding a putative MarR-type transcription repressor. In this study, we characterized the regulation of theyhjHgene by PA, by PchR, a known transcription repressor for PA biosynthesis, and by YhjH itself. We also found that high expression ofyhjHtriggers rapid cell lysis inB. subtilis. Results from RNA-seq suggest that YhjH differentially regulates about 180 genes, among which there is a significant number of prophage genes. Lastly, we propose that YhjH be re-named as PcdR, for “pulcherriminic acidcelldeathregulator”.
Neural patterns associated with mixed valence feelings differ in consistency and predictability throughout the brain
Authors: Vaccaro Anthony G. , Wu Helen , Iyer Rishab , Shakthivel Shruti , Christie Nina C. , Damasio Antonio , Kaplan Jonas
Published: November 2023

Mixed valence feelings, defined by the simultaneous presence of positive and negative affect, remain understudied in neuroscience. We used functional magnetic resonance imaging to investigate subjects watching an animated short film known to induce mixed feelings. These same subjects were asked to identify the time periods during which they had experienced positive, negative, and mixed feelings. Using Hidden-Markov models, we found that activity in the insula, amygdala, nucleus accumbens, and anterior cingulate allowed us to predict the onset of new feeling states as determined by individual self-report. Further analyses found spatiotemporally unique and consistent neural patterns in the insular cortex for univalent states, but not for mixed valence states. However, ventromedial prefrontal cortex and anterior cingulate exhibited unique neural consistency for both univalent and mixed valence states. This study is the first to reveal direct evidence for a neurally consistent representation of mixed feelings in the central nervous system.
scNODE : Generative Model for Temporal Single Cell Transcriptomic Data Prediction
Authors: Zhang Jiaqi , Larschan Erica , Bigness Jeremy , Singh Ritambhara
Published: November 2023

Abstract

Measurement of single-cell gene expression at different timepoints enables the study of cell development. However, due to the resource constraints and technical challenges associated with the single-cell experiments, researchers can only profile gene expression at discrete and sparsely-sampled timepoints. This missing timepoint information impedes downstream cell developmental analyses. We proposescNODE, an end-to-end deep learning model that can predictin silicosingle-cell gene expression at unobserved timepoints.scNODEintegrates a variational autoencoder (VAE) with neural ordinary differential equations (ODEs) to predict gene expression using a continuous and non-linear latent space. Importantly, we incorporate a dynamic regularization term to learn a latent space that is robust against distribution shifts when predicting single-cell gene expression at unobserved timepoints. Our evaluations on three real-world scRNA-seq datasets show thatscNODEachieves higher predictive performance than state-of-the-art methods. We further demonstrate thatscNODE’s predictions help cell trajectory inference under the missing timepoint paradigm and the learned latent space is useful forin silicoperturbation analysis of relevant genes along a developmental cell path. The data and code are publicly available athttps://github.com/rsinghlab/scNODE.
Multi-level framework to assess social variation in response to ecological and social factors: modeled with coral gobies
Authors: Froehlich Catheline Y.M. , Heatwole Siobhan J. , Klanten O. Selma , Hing Martin L. , Hildebrandt Courtney A. , Smith Jemma O. , Wong Marian Y.L.
Published: November 2023

1.

Understanding variation in social organization that does not have a strong phylogenetic signal represents a key focus of research in behavioural and evolutionary ecology. In light of this, we established a sociality framework that identifies four categories of variation in social organisation that range from large-scale to fine-scale and can each be related to various ecological factors: (1) forms of sociality, (2) degree of sociality, (3) social plasticity, and (4) within-group plasticity. We modelled this framework by quantifying the four categories of variation over time, space and disturbance regime using multiple species of coral-dwelling gobies from the genusGobiodon. Gobies are a particularly interesting model system as they vary in social structure, have within-group cooperation and form mutualistic relationships with their coral hosts which are vulnerable to climatic disturbances. We found that gobies varied in forms of sociality – from being solitary, to paired or group-living depending on location and disturbance regime. Only low or moderate degrees of sociality were observed in gobies, and this was influenced by location or disturbance regime depending on species. Gobies were more often solitary or pair-forming than group-forming (which became extremely rare) in a high disturbance regime whereas they were more often found in groups in a moderate disturbance regime. The size of coral hosts affected the social plasticity of gobies, and corals were smaller due to climatic disturbances. Gobies did not exhibit within-group social plasticity, as there were no changes to the structure of size-based hierarchies or sex allocation patterns with location or disturbance regime. Lastly, by combining the four categories of variation, we find that there is a high loss of sociality in coral-dwelling gobies due environmental disturbances, which likely affects overall goby survival as living in groups can improve survival and fitness. By using our structured framework, we identified which categories of social variation were influenced by ecological factors like location and disturbance. This framework therefore provides an excellent tool for predicting future responses of animal societies to environmental stressors.
The extinction crisis of the world’s amphibians is easing rapidly
Authors: van de Pol Martijn
Published: November 2023

A recent paper (Nature622, 308–14)1analysed changes in the extinction risk of 7,102 amphibian species from 1980 to 2004 to 2022 using the Red List Index2,3(RLI) of the International Union for the Conservation of Nature (IUCN). It concluded that the global amphibian extinction crisis has not abated. However, this conclusion appears too pessimistic and not supported by the data. Rather, it is a result of intrinsic limitations of the RLI. These limitations have implications well beyond amphibians, as the RLI is used worldwide for policy, for example as a headline indicator for the Kunming-Montreal Global Biodiversity Framework4.
Organ-on-a-Chip Fabrication using Dynamic Photomask
Authors: Ching Terry , Chang Shu-Yung , Toh Yi-Chin , Hashimoto Michinao
Published: November 2023

Organ-on-a-chip (OoC) technology is a powerful tool for creating physiologically relevant microscale models applicable to biomedical studies. Despite the advances in OoC technology, its fabrication method still primarily relies on soft lithography, which (1) lacks the adaptability to accommodate dynamic cell culture (e.g., spheroids and organoid culture) and (2) has a long design-to-prototype cycle that lowers its manufacturability. To overcome these challenges, we developed a system to fabricate OoC (consisting of microchannels and multiple cell types in a well-defined spatial arrangement) dynamically using a digital photomask aligned with a microchamber. Our approach used a pre-defined microfluidic chamber customized by xurography and cell-laden microfluidic channels photopatterned by a digital photomask; the entire design-to-prototype cycle was achieved within two hours. The versatility of our approach offered previously unattainable crucial features in the fabrication of OoC, including a gradual change in the height of the microchannels, and real-time modification of channel designs to trap live tissues (e.g., spheroids). In summary, this work highlights a versatile system to fabricate OoC that can accommodate various design requirements of microenvironments of specific organ tissues. We envision the effectiveness of our system for the rapid fabrication of OoC to contribute to the wide adoption of the technology for therapeutic screening and elucidation of disease mechanisms in both academic and industrial settings.
Long chain omega-3 fatty acid intake in pregnancy and risk of type 1 diabetes in the offspring: Two large Scandinavian pregnancy cohorts – MoBa and DNBC
Authors: Lund-Blix Nicolai A. , Bjerregaard Anne A. , Tapia German , Størdal Ketil , Brantsæter Anne Lise , Strøm Marin , Halldorsson Thorhallur I. , Granstrøm Charlotta , Svensson Jannet , Joner Geir , Skrivarhaug Torild , Njølstad Pål R. , Olsen Sjurdur F. , Stene Lars C.
Published: November 2023

Background

Long-chain marine omega-3 fatty acids (eicosapentaenoic acid; EPA and docosahexaenoic acid; DHA) have anti-inflammatory effects. Dietary intake of EPA and DHA in pregnancy was associated with lower offspring risk of asthma in a randomized trial, and lower risk of type 1 diabetes in the offspring in retrospective observational studies.

Aim

We aimed to investigate whether higher intakes of EPA and DHA during pregnancy is associated with a lower type 1 diabetes risk in children in two of the world’s largest birth cohorts.

Methods

The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on EPA and DHA intake during pregnancy using validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries.

Results

There was no association between the sum of EPA and DHA intake during pregnancy and offspring risk of type 1 diabetes (hazard ratio per g/d of intake: 1.00 in both MoBa and DNBC, pooled 95% CI: 0.88-1.14). Adjustment for potential cofounders and robustness analyses gave very similar results.

Conclusion

The hypothesis that a higher maternal omega-3 fatty acid intake during pregnancy reduce the risk of offspring type 1 diabetes was not supported.
Associations between Social Contact, Sleep and Dietary Patterns Among Children: A Cross-Sectional Study
Authors: Mühlematter Christophe , Beaugrand Matthieu , Markovic Andjela , Kurth Salome
Published: November 2023

Social isolation in adults can be associated with altered sleep and eating behavior. This study aimed to investigate the interactions between the extent of social contact, eating behavior and sleep in infants and preschool children. In an observational study, 439 caregivers of 562 children aged 0-6 years provided information on sleep (i.e., duration, latency, bedtimes and nighttime awakenings), eating behaviors (i.e., meal size, consumption of sweet snacks, salty snacks, fruits and vegetables) and social contact (i.e., quarantine status, household size, social activities) during the Covid-19 pandemic (April 2020). In infants (0-3 years), the change in meal size and consumption of snacks, fruits, and vegetables did not significantly relate to the extent of social contact. For preschool children (3-6 years), a trend was observed, suggesting that quarantine status was associated with increased meal size. Changes in sleep duration, sleep latency, bedtimes and nighttime awakenings from before to during the pandemic were not significantly linked to the 3 variables quantifying social contact in both age groups. The study highlights that, contrary to expectations, the extent of social contact has negligible associations with infants’ and preschool children’s sleep and eating behaviors. These findings indicate that other factors beyond social isolation play a role in shaping children’s eating habits and sleep patterns.
Genetic studies of gestational diabetes mellitus in 21,813 Chinese women
Authors: Zhu Huanhuan , Xiao Han , Li Linxuan , Yang Meng , Cai Mingzhi , Zhou Jieqiong , Zeng Jingyu , Zhou Yan , Lan Xianmei , Liu Jiuying , Qian Xiaobo , Zhong Yuanyuan , Liu Panhong , Zhang Xinyi , Lin Ying , Cao Zhongqiang , Mei Hong , Cai Xiaonan , Hu Liqin , Zhou Rui , Xu Xun , Yang Huanming , Wang Jian , Jin Xin , Zhou Aifen
Published: November 2023

Gestational diabetes mellitus (GDM) is a common complication of pregnancy with adverse effects on both mothers and fetuses. The relationship between GDM and clinical information has been largely investigated; however, the role of laboratory features and genetic components in GDM are relatively understudied, especially in the Chinese population. In this study, we recruited 21,813 pregnant Chinese women and investigated the risk factors for GDM from both environmental and genetic aspects. In addition to the serum fasting glucose and urine glucose measured in the first trimester, our study revealed the close relations of γ-glutamyl transferase, prealbumin, and uric acid to GDM. The GWAS and subsequent conditional & joint association analysis identified four genome-wide significant SNPs, rs35261542, rs4712530, rs3781637, and rs12225378, mapped onCDKAL1andMTNR1B. The allele frequencies of the latter three SNPs showed substantial differences in European and East Asian populations. The ancient DNA analysis demonstrated that mutation of rs3781637 was originally appeared in an ancient Chinese in the Holocene period. This result might provide useful reference for explaining the distinct genetic background of GDM in different populations. Considering both clinical measurements and genetic components, we constructed an early prediction model for GDM by using only a dozen indicators and achieved acceptable prediction performance. We believe that our study will certainly become an important reference for the genetic study of GDM and will have important implications for elucidating the genetic mechanisms of GDM.
Primate origins of human event cognition
Authors: Wilson Vanessa A. D. , Sauppe Sebastian , Brocard Sarah , Ringen Erik , Daum Moritz M. , Wermelinger Stephanie , Gu Nianlong , Andrews Caroline , Isasi-Isasmendi Arrate , Bickel Balthasar , Zuberbühler Klaus
Published: November 2023

Human language relies on a rich cognitive machinery, partially shared with other animals. One key mechanism, decomposing events into causally-linked agent-patient roles, however, has remained elusive with no known animal equivalent. In humans, agent-patient relations in event cognition drive how languages are processed neurally and expressions structured syntactically. We compared visual event tracking between humans and great apes, using stimuli that would elicit causal processing in humans. After accounting for attention to background information, we found similar gaze patterns to agent-patient relations in all species, mostly alternating attention to agents and patients, presumably in order to learn the nature of the event, and occasionally privileging agents under specific conditions. Six-month-old infants, in contrast, did not follow agent-patient relations and attended mostly to background information. We conclude that event role tracking, a cognitive foundation of syntax, evolved long before language but requires time and experience to become ontogenetically available.

Significance statement

Human adults and great apes, but not human infants, track natural events as agent-patient relations, a cognitive foundation for syntax.
Towards modeling genome-scale knowledge in the global ocean
Authors: Régimbeau Antoine , Aumont Olivier , Bowler Chris , Guidi Lionel , Jackson George A. , Karsenti Eric , Memery Laurent , Tagliabue Alessandro , Eveillard Damien
Published: November 2023

Earth System Models (ESMs) highly simplify their representation of biological processes, leading to major uncertainty in climate change impacts. Despite a growing understanding of molecular networks from genomic data, describing how changing phytoplankton physiology affects the production of key metabolites remains elusive. Here we embed a genome-scale model within a state-of-the-art ESM to deliver an integrated understanding of how gradients of nutritional constraints modulate metabolic reactions and molecular physiology. Applied to the prevalent marine cyanobacteriaProchlorococcus, we find that glycogen and lipid storage can be understood as a consequence of acclimation to environmental gradients. Given the pressing need to assess how biological diversity influences biogeochemical functions, genome-enabled ESMs allow the quantification of the contribution of modeled organisms to the production of dissolved organic carbon and its molecular composition.
Simplest Model of Nervous System. I. Formalism
Authors: Sinitskiy Anton V.
Published: November 2023

This study presents a novel, highly simplified model of the nervous system, inspired by one hypothetical scenario of its origin. The model is designed to accommodate both mathematical derivations and numerical simulations, offering a template for studying generalized principles and dynamics beyond the specifics of the referenced origin scenario. The model offers a holistic perspective by treating the nervous system and the environment (in their simplest forms) as parts of one system and, together with a companion paper, notes the key role of evolutionary factors (in this model, predator evasion) in shaping the properties of the nervous system. To emphasize these fundamental principles, some aspects, such as the highly dimensional nature of the networks or detailed molecular mechanisms of their functioning, are omitted in the current version. Analytically, the model facilitates insights into the stationary distribution as a solution to the Fokker-Planck equation and the corresponding effective potential and rotation (solenoidal) terms. Numerically, it generates biologically plausible (given its high abstraction) solutions and supports comprehensive sampling with limited computational resources. Noteworthy findings from the study include limitations of the commonly used weak noise approximation and the significance of rigorous mathematical analysis over heuristic interpretations of the potential. We hope that this abstract model will serve as a fruitful tool for better understanding a complete set of principles for modeling nervous systems.
A Personalized Probabilistic Approach to Ovarian Cancer Diagnostics
Authors: Ban Dongjo , Housley Stephen N. , Matyunina Lilya V. , McDonald L. DeEtte , Bae-Jump Victoria L. , Benigno Benedict B. , Skolnick Jeffrey , McDonald John F.
Published: November 2023

Objective

The identification/development of a machine learning (ML)-based classifier that utilizes metabolic profiles of serum samples to accurately identify individuals with ovarian cancer (OC).

Methods

Serum samples collected from 431 OC patients and 133 normal women at four geographic locations were analyzed by mass spectrometry. Reliable metabolites were identified using recursive feature elimination (RFE) coupled with repeated cross-validation (CV) and used to develop a consensus classifier able to distinguish cancer from non-cancer. The probabilities assigned to individuals by the model were used to create a clinical tool that assigns a likelihood that an individual patient sample is cancer or normal.

Results

Our consensus classification model is able to distinguish cancer from control samples with 93% accuracy. The frequency distribution of individual patient scores was used to develop a clinical tool that assigns a likelihood that an individual patient does or does not have cancer.

Conclusions

An integrative approach using metabolomic profiles and ML-based classifiers has been employed to develop a clinical tool that assigns a probability that an individual patient does or does not have OC. This personalized/probabilistic approach to cancer diagnostics is more clinically informative and accurate than traditional binary (yes/no) tests and represents a promising new direction in the early detection of OC.

HIGHLIGHTS

Predictive models derived from machine learning (ML) analyses of serum metabolic profiles can accurately (PPV 93%) detect ovarian cancer (OC).

Only a minority of the most predictively informative metabolites are currently annotated (7%).

Lipids predominate among the most predictively informative metabolites currently annotated.

The frequency distribution of model-derived patient scores can be used to develop a useful clinical tool for the diagnosis of OC.
Role of the medial agranular cortex in unilateral spatial neglect
Authors: Ishii Daisuke , Osaki Hironobu , Yozu Arito , Yamamoto Tatsuya , Yamamoto Satoshi , Miyata Mariko , Kohno Yutaka
Published: November 2023

Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among the various lesion positions, acute severity was higher with the lesion in the intermediate rostrocaudal position. On the other hand, the recovery from USN-like behavior after this phase tended to be slower in cases with more rostral lesions in the AGm. Additionally, no motor paralysis was observed in any of the mice with lesions in each AGm. These results suggest that the intermediate rostrocaudal position of the AGm may significantly influence selection of the direction, regardless of the areas to which it is connected. On the contrary, recovery from USN-like behavior may be dependent on the areas to which it is connected.

Highlights

Lesion of the rodent medial agranular cortex (AGm) results in unilateral spatial neglect (USN).

In the acute phase, the severity was higher with lesions in the intermediate AGm position.

Recovery from somatosensory USN tended to be slower with rostral AGm lesions.

Recovery from USN may depend on sensory modalities associated with the connected areas.

Our results revealed location-dependent differences in attentional functions within the AGm.
Isogenic iPSC-derived proximal and distal lung-on-chip models: Tissue- and virus-specific immune responses in human lungs
Authors: Yadav Sachin , Fujimoto Kazuya , Takenaga Toru , Takahashi Senye , Muramoto Yukiko , Mikawa Ryuta , Noda Takeshi , Gotoh Shimpei , Yokokawa Ryuji
Published: November 2023

Micro-physiological systems (MPS) are set to play a vital role in preclinical studies, particularly in the context of future viral pandemics. Nonetheless, the development of MPS is often impeded by the scarcity of reliable cell sources, especially when seeking various organs or tissues from a single patient for comparative analysis of the host immune response. Herein, we developed human airway-on-chip and alveolus-on-chip models using induced pluripotent stem cell (iPSC)-derived isogenic lung progenitor cells. Both models demonstrated the replication of two different respiratory viruses, namely SARS-CoV-2 and Influenza, as well as related cellular damage and innate immune responses-on-chip. Our findings reveal distinct immune responses to SARS-CoV-2 in the proximal and distal lung-on-chip models. The airway chips exhibited a robust interferon (IFN)-dependent immune response, whereas the alveolus chips exhibited dysregulated IFN activation but a significantly upregulated chemokine pathway. In contrast, Influenza virus infection induced a more pronounced immune response and cellular damage in both chip models compared to SARS-CoV-2. Thus, iPSC-derived lung-on-chip models may aid in quickly gaining insights into viral pathology and screening potential drugs for future pandemics.
Assessing Age-Related Decline in Anti-Bacterial Immune Responses Using an Ex-vivo Assay in African Turquoise Killifish (Nothobranchius furzeri)
Authors: Morabito Gabriele , Dávila Aleman Francisco Daniel , Valenzano Dario Riccardo
Published: November 2023

Ex-vivo immune functional assays serve as essential tools for uncovering the intricate molecular mechanisms behind immune responses, both intrinsic and extrinsic, across a diverse spectrum of conditions and interventions. In this study, we devised an innovative assay aimed at quantifying anti-bacterial responses in immune cells from the primary immune organ of small teleosts. Our model of choice is the the African turquoise killifish (Nothobranchius furzeri), which has emerged as a prominent model system in the field of biology of aging, because of its natural short lifespan and the broad range of aging-related dysfunctions. Using our novel ex vivo assay, we tested age-associated differences in immune cell functionality, measured as anti-bacterial responses in young and aged turquoise killifish. Our results show that the ability to inhibit bacterial growth declines in cells extracted from aged killifish, compared to young killifish. This ex-vivo assay, designed for rapid measures of immune effector responses, holds the potential to be a scalable tool for assessing the cellular and molecular basis for anti-microbial immune responses under a range of interventions.
In search of elite travel: visual communication of luxury hotels
Authors: Michael Noela , Fusté-Forné Francesc
Published: November 2023

Purpose

The relationships between luxury and tourism are manifested in meaningful customer experiences which are focused on exclusive products and services. This paper aims to examine the visual communication of hotels in the Middle East to identify what luxury features are represented.

Design/methodology/approach

The digital communication of four luxury hotels in the United Arab Emirates was analysed based on a visual content and semiotic analysis of their Instagram’s posts (N = 1,866).

Findings

Results show that customers and views of the hotel and from the hotel are the most representative features of the social media communication of luxury hotels.

Originality/value

Theoretical and practical implications derived from the results are described, and opportunities for further research are identified in relation to digital marketing communication and the effect on consumers in hospitality and tourism.